CA-3291799-A1 - PYRIMIDO MACROHETEROCYCLIC COMPOUND AS WEE1-YES DUAL-TARGET INHIBITOR AND USE THEREOF

Abstract

Disclosed in the present invention for the first time is a novel pyrimido macroheterocyclic compound having a WEE1 and Yes dual-target inhibitory activity. Specifically disclosed are a compound having a structure as shown in formula (I) as a WEE1 and YES dual-target inhibitor or a pharmaceutically acceptable salt, solvate, hydrate, or isotope substitute thereof, or an isomer thereof and a polymorph thereof. [Image disponible dans le document PDF, Image available in the PDF document]

Inventors

• Long Zhang
• Zhangming NIU

Assignees

• MINDRANK AI LTD.

Dates

Publication Date

20260301

Application Date

20240510

Priority Date

20230510

Claims (1)

1. <pat:ClaimStatement>CLAIMS</pat:ClaimStatement> <pat:Claims com:id="claims"> <pat:Claim com:id="CLM-00001"> <pat:ClaimNumber>1</pat:ClaimNumber> <pat:ClaimText>1. A compound represented by formula (I), a pharmaceutically acceptable salt, a solvate, an enantiomer, an isotopically substituted compound, or a polymorph thereof: [Image disponible dans le document PDF, Image available in the PDF document] formula (I), wherein <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>0</mn></msub><annotation encoding="application/x-tex">X_0</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>1</mn></msub><annotation encoding="application/x-tex">X_1</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>2</mn></msub><annotation encoding="application/x-tex">X_2</annotation></semantics></math> are each independently selected from -C(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mi>x</mi></msub><annotation encoding="application/x-tex">R_x</annotation></semantics></math>)- and -N-; L₃, L₄, L₅, L₆, and L₇ are identical or different and are independently absent, or selected from single bond, double bond, alkyne bond, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(R_{d1})(R_{d2})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(R_{d1})(R_{d2})C(R_{d1})(R_{d2})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>O</mi><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-OC(R_{d1})(R_{d2})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>O</mi></mrow><annotation encoding="application/x-tex">-C(R_{d1})(R_{d2})O</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(=O)N(R_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(=O)N(R_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(=O)N(R_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(=O)N(R_{d3})</annotation></semantics></math>-, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>$-C(=O)N(R_$</math> <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">N(R_{d3})C(=O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-N(R_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>N</mi><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(=NR_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>S</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><msub><mo stretchy="false" form="postfix">)</mo><mn>2</mn></msub><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-S(=O)_2N(R_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>S</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><msub><mo stretchy="false" form="postfix">)</mo><mn>2</mn></msub></mrow><annotation encoding="application/x-tex">-N(R_{d3})S(=O)_2</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(R_{d1})(R_{d2})N(R_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-N(R_{d3})C(R_{d1})(R_{d2})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-N(R_{d3})C(R_{d1})(R_{d2})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-N(R_{d3})C(R_{d1})(R_{d2})</annotation></semantics></math>- O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -N-, -CH-, -S(=O)-, and -S(=O)₂-; L is absent or is selected from O, S, CH₂, C(O), S(O), S(O)₂, NH, C(O)NH, and NHC(O); ring C is heterocyclyl unsubstituted or substituted with R₀; R₀ is independently selected from H, deuterium, halogen, alkyl, haloalkyl, deuterated alkyl, cycloalkyl, heterocyclyl, alkoxyalkyl, alkynyl, acetyl, methanesulfonyl, and phosphoryl; further, hydrogen(s) on R₀ is(are) optionally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; each R₂ or each R₅ may be identical or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH, -NH₂, -COOH, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocyclyl, carboxyl or carboxyl surrogate substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, aryl, and heteroaryl; or any two <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math> or any two R₅, together with the carbon atoms to which they are attached on the rings, form a 3- to 8-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure may be optionally selected from an aromatic ring structure, a heteroaromatic ring structure, an alicyclic structure, a heterocyclic structure, a fused-ring structure, a spiro-ring structure, and a bridged-ring structure, wherein the alicyclic structure, the heterocyclic structure, the fused-ring structure, the spiro-ring structure, or the bridged-ring structure may contain zero or more unsaturated alkene bonds; further, hydrogen(s) on R₂ or R₅ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; or any two R₂ or any two R₅, together with the carbon atoms to which they are attached, form 5- to 6- membered heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8-membered saturated or partially saturated heterocyclyl, wherein hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocycloalkyl is optionally substituted with a group selected from hydrogen, deuterium, halogen, -CN, -OH, CF₃, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, -NH₂, -NHC_1-6 alkyl, -N(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl)₂, =O, and saturated or partially saturated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-6}</annotation></semantics></math> cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; R₁, R_d1, R_d2, and R_x are independently selected from hydrogen, deuterium, halogen, cyano, oxo (=O), amino, hydroxyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylamino, aryl, heteroaryl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>N</mi><mo>,</mo><mi>N</mi></mrow><annotation encoding="application/x-tex">N,N</annotation></semantics></math>-di(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl)amino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfinyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkylamino, C_3-10 cycloalkoxy, C_3-10 cycloalkylacyl, C_3-10 cycloalkoxyacetyl, C_3-10 cycloalkylsulfonyl, and C_3-10 cycloalkylsulfinyl, wherein the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, - CN, -OH, CF₃, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, -NH₂, -NHC_1-6 alkyl, -N(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl)₂, oxy, and saturated or partially saturated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-6}</annotation></semantics></math> cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally further substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; or R_d1 and R_d2, or R_d1 and R₅, together with the carbon atoms to which they are attached, may form 5- to 6-membered aryl or heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8-membered saturated or partially saturated heterocyclyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, and OCH₂CH₃; <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><annotation encoding="application/x-tex">R_{d3}</annotation></semantics></math> is optionally and independently selected from hydrogen, NH₂, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cyclohydrocarbyl, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocyclyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cyclohydrocarbyl, or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocyclyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> ₁₀ cycloalkyl or C_3-10 heterocycloalkyl is further optionally substituted with one or more substituents selected from hydrogen, deuterium, halogen, oxo, CN, OH, and C_3-10 saturated or partially saturated cycloalkyl or heterocyclyl; the hetero represents any heteroatom optionally and independently selected from O, N, S, P, S=O, and S(=O)₂ and isotopes thereof; the halogen is optionally and independently selected from F, Cl, Br, and I and isotopes thereof; m is an integer optionally selected from 0, 1, 2, 3, and 4; n is an integer optionally selected from 0, 1, 2, 3, 4, and 5; and q is an integer optionally selected from 0, 1, 2, and 3. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00002"> <pat:ClaimNumber>2</pat:ClaimNumber> <pat:ClaimText>2. The compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof as claimed in claim 1, wherein: <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>0</mn></msub><annotation encoding="application/x-tex">X_0</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>1</mn></msub><annotation encoding="application/x-tex">X_1</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>2</mn></msub><annotation encoding="application/x-tex">X_2</annotation></semantics></math> are each independently selected from -C(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mi>x</mi></msub><annotation encoding="application/x-tex">R_x</annotation></semantics></math>)- and -N-, wherein <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mi>x</mi></msub><annotation encoding="application/x-tex">R_x</annotation></semantics></math> is selected from H and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl (e.g., methyl); preferably, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>0</mn></msub><annotation encoding="application/x-tex">X_0</annotation></semantics></math> is -CH-; preferably, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>1</mn></msub><annotation encoding="application/x-tex">X_1</annotation></semantics></math> is <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mi>N</mi><annotation encoding="application/x-tex">N</annotation></semantics></math>; preferably, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>2</mn></msub><annotation encoding="application/x-tex">X_2</annotation></semantics></math> is <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mi>N</mi><annotation encoding="application/x-tex">N</annotation></semantics></math>. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00003"> <pat:ClaimNumber>3</pat:ClaimNumber> <pat:ClaimText>3. The compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof as claimed in claim 1 or 2, wherein: L is selected from O, S, and NH; preferably, L₃, L₄, L₅, L₆, and L₇ are identical or different and are independently absent, or selected from single bond, and the following groups unsubstituted or optionally substituted with one, two, or more R_d1: C_1-6 alkylene and C_2-6 alkenylene; preferably, L₃, L₄, L₅, L₆, and L₇ are identical or different and are independently absent, or selected from single bond, and the following groups unsubstituted or optionally substituted with one, two, or more R_d1: CH₂, CH₂CH₂, CH₂CH₂CH₂, CH=CH, and CH=CHCH₂; preferably, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>L</mi><mn>3</mn></msub><annotation encoding="application/x-tex">L_3</annotation></semantics></math> is <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(R_{d1})(R_{d1})</annotation></semantics></math>-, preferably <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>C</mi><msub><mi>H</mi><mn>3</mn></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mi>H</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(CH_3)(OH)</annotation></semantics></math>-; preferably, L₆ is vinylene, preferably cis-vinylene; preferably, L₄, L₅, and L₇ are identical or different and are independently CH₂; preferably, each <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><annotation encoding="application/x-tex">R_{d1}</annotation></semantics></math> is identical or different and is independently selected from H, OH, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl (e.g., methyl). </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00004"> <pat:ClaimNumber>4</pat:ClaimNumber> <pat:ClaimText>4. The compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof as claimed in any one of claims 1-3, wherein: ring C is heterocyclyl unsubstituted or substituted with R₀, wherein the heterocyclyl may be selected from piperidyl [Image disponible dans le document PDF, Image available in the PDF document] </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00005"> <pat:ClaimNumber>5</pat:ClaimNumber> <pat:ClaimText>5. The compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof as claimed in any one of claims 1-4, wherein: <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>0</mn></msub><annotation encoding="application/x-tex">R_0</annotation></semantics></math> is selected from H, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, deuterated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> haloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>H</mi><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">HC(O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>N</mi><msub><mi>H</mi><mn>2</mn></msub><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">NH_2C(O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl-C(O)-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy-C(O)-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>8</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-8}</annotation></semantics></math> cycloalkyl-C(O)-, and 3- to 8-membered heterocyclyl; preferably, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>0</mn></msub><annotation encoding="application/x-tex">R_0</annotation></semantics></math> is selected from H, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, deuterated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> haloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>H</mi><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">HC(O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>N</mi><msub><mi>H</mi><mn>2</mn></msub><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">NH_2C(O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl-<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">C(O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy-<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">C(O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-6}</annotation></semantics></math> cycloalkyl-<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">C(O)</annotation></semantics></math>-, and 3- to 6-membered heterocyclyl; [Image disponible dans le document PDF, Image available in the PDF document] preferably, R₀ is selected from H, methyl, ethoxy, trideuterated methyl, CF₃CH₂-, HC(O)-, CH₃C(O)-, , [Image disponible dans le document PDF, Image available in the PDF document] preferably, each R₁ is identical or different and is independently selected from H, deuterium, oxo (=O), C_1-6 alkyl, C_1-6 alkoxy, C_1-6 alkoxy-C(O)-, C_1-6 haloalkyl, C_1-6 haloalkoxy, C_1-6 alkylamino, C_6-10 aryl, and 5- to 10-membered heteroaryl; preferably, each R₁ is identical or different and is independently selected from H, deuterium, oxo (=O), C_1-6 alkyl, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy-<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">C(O)</annotation></semantics></math>-; preferably, each R₁ is identical or different and is independently selected from H, methyl, deuterium, oxo (=O), and [Image disponible dans le document PDF, Image available in the PDF document] preferably, each R₂ is identical or different and is independently selected from H, deuterium, oxo (=O), C_1-6 alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy-<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">C(O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> haloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> haloalkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>6</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{6-10}</annotation></semantics></math> aryl, and 5- to 10-membered heteroaryl; preferably, each <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math> is identical or different and is independently selected from H and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl (e.g., methyl); preferably, each R₅ is identical or different and is independently selected from H, deuterium, oxo (=O), C_1-6 alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy-<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">C(O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> haloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> haloalkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>6</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{6-10}</annotation></semantics></math> aryl, and 5- to 10-membered heteroaryl; preferably, each <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>5</mn></msub><annotation encoding="application/x-tex">R_5</annotation></semantics></math> is identical or different and is independently selected from H and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl (e.g., methyl). </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00006"> <pat:ClaimNumber>6</pat:ClaimNumber> <pat:ClaimText>6. The compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof as claimed in any one of claims 1-5, having a structure of formula (II): [Image disponible dans le document PDF, Image available in the PDF document] (II), wherein L, L₃, L₄, L₅, L₆, L₇, X₀, X₁, X₂, R₀, R₁, R₂, R₅, m, n, and q are independently defined as described in any one of claims 1-5; preferably, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>0</mn></msub><annotation encoding="application/x-tex">X_0</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>1</mn></msub><annotation encoding="application/x-tex">X_1</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>2</mn></msub><annotation encoding="application/x-tex">X_2</annotation></semantics></math> are each independently selected from -C(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mi>x</mi></msub><annotation encoding="application/x-tex">R_x</annotation></semantics></math>)- and -N-; L₃, L₄, L₅, L₆, and L₇ are independently absent, or selected from single bond, double bond, alkyne bond, - <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">C(R_{d1})(R_{d2})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(R_{d1})(R_{d2})C(R_{d1})(R_{d2})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>O</mi><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-OC(R_{d1})(R_{d2})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>O</mi></mrow><annotation encoding="application/x-tex">-C(R_{d1})(R_{d2})O</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(=O)N(R_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-N(R_{d3})C(=O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-N(R_{d3})</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>N</mi><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(=NR_{d3})-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>S</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><msub><mo stretchy="false" form="postfix">)</mo><mn>2</mn></msub><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo>−</mo></mrow><annotation encoding="application/x-tex">-S(=O)_2N(R_{d3})-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>S</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><msub><mo stretchy="false" form="postfix">)</mo><mn>2</mn></msub><mo>−</mo></mrow><annotation encoding="application/x-tex">-N(R_{d3})S(=O)_2-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(R_{d1})(R_{d2})N(R_{d3})-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><msub><mi>R</mi><mrow><mi>d</mi><mn>2</mn></mrow></msub><mo stretchy="false" form="postfix">)</mo><mo>−</mo></mrow><annotation encoding="application/x-tex">-N(R_{d3})C(R_{d1})(R_{d2})-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>O</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-O-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>S</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-S-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>O</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(=O)O-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>O</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(=O)O-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>O</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(=O)O-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>O</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(=O)O-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>O</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(=O)O-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>O</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(=O)O-</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo><mi>O</mi><mo>−</mo></mrow><annotation encoding="application/x-tex">-C(=O)O-</annotation></semantics></math> <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>O</mi><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">OC(=O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(=O)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>S</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-C(=S)</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>N</mi></mrow><annotation encoding="application/x-tex">-N</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>C</mi><mi>H</mi></mrow><annotation encoding="application/x-tex">-CH</annotation></semantics></math>-, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>S</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-S(=O)</annotation></semantics></math>-, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>−</mo><mi>S</mi><mo stretchy="false" form="prefix">(</mo><mo>=</mo><mi>O</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">-S(=O)</annotation></semantics></math>₂-; L is optionally and independently selected from O, S, and NH; R₀ is independently selected from H, deuterium, halogen, alkyl, haloalkyl, deuterated alkyl, cycloalkyl, heterocyclyl, alkoxyalkyl, alkynyl, acetyl, methanesulfonyl, and phosphoryl; further, hydrogen(s) on R₀ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; each R₂ or each R₅ may be identical or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH, -NH₂, -COOH, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with C_3-10 cycloalkyl or C_3-10 heterocycloalkyl, C_2-10 heteroalkyl substituted with C_3-10 cycloalkyl, C_3-10 heterocyclyl, carboxyl or carboxyl surrogate substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, aryl, and heteroaryl; or any two <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math> or any two R₅, together with the carbon atoms to which they are attached on the rings, form a 3- to 8-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure may be optionally selected from an aromatic ring structure, a heteroaromatic ring structure, an alicyclic structure, a heterocyclic structure, a fused-ring structure, a spiro-ring structure, and a bridged-ring structure, wherein the alicyclic structure, the heterocyclic structure, the fused-ring structure, the spiro-ring structure, or the bridged-ring structure may contain zero or more unsaturated alkene bonds; further, hydrogen(s) on R₂ or R₅ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; or any two R₂ or any two R₅, together with the carbon atoms to which they are attached, form 5- to 6- membered heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8-membered saturated or partially saturated heterocyclyl, wherein hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocycloalkyl is optionally substituted with a group selected from hydrogen, deuterium, halogen, -CN, -OH, CF₃, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, -NH₂, -NHC_1-6 alkyl, -N(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl)₂, =O, and saturated or partially saturated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-6}</annotation></semantics></math> cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; R₁, R_d1, R_d2, and R_x are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C_1-10 alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylamino, aryl, heteroaryl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>N</mi><mo>,</mo><mi>N</mi></mrow><annotation encoding="application/x-tex">N,N</annotation></semantics></math>-di(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl)amino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfinyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkylamino, C_3-10 cycloalkoxy, C_3-10 cycloalkylacyl, C_3-10 cycloalkoxyacetyl, C_3-10 cycloalkylsulfonyl, and C_3-10 cycloalkylsulfinyl, wherein the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, - CN, -OH, CF₃, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, -NH₂, -NHC_1-6 alkyl, -N(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl)₂, oxy, and saturated or partially saturated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-6}</annotation></semantics></math> cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally further substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; or R_d1 and R_d2, or R_d1 and R₅, together with the carbon atoms to which they are attached, may form 5- to 6-membered aryl or heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8-membered saturated or partially saturated heterocyclyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, and OCH₂CH₃; <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mrow><mi>d</mi><mn>3</mn></mrow></msub><annotation encoding="application/x-tex">R_{d3}</annotation></semantics></math> is optionally and independently selected from hydrogen, NH₂, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cyclohydrocarbyl, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocyclyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl; wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cyclohydrocarbyl, or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocyclyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> ₁₀ cycloalkyl or C_3-10 heterocycloalkyl is further optionally substituted with one or more substituents selected from hydrogen, deuterium, halogen, oxo, CN, OH, and C_3-10 saturated or partially saturated cycloalkyl or heterocyclyl; the hetero represents any heteroatom optionally and independently selected from O, N, S, P, S=O, and S(=O)₂ and isotopes thereof; the halogen is optionally and independently selected from F, Cl, Br, and I and isotopes thereof; m is an integer optionally selected from 0, 1, 2, 3, and 4; n is an integer optionally selected from 0, 1, 2, 3, 4, and 5; and q is an integer optionally selected from 0, 1, 2, and 3; preferably, the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof has a structure of formula (IA): [Image disponible dans le document PDF, Image available in the PDF document] formula (IA), wherein L, X₂, R₀, R₁, R₂, R₅, R_d1, m, n, and q are independently defined as described in any one of claims 1-5, and p is an integer optionally selected from 0, 1, 2, 3, and 4; preferably, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>2</mn></msub><annotation encoding="application/x-tex">X_2</annotation></semantics></math> is independently selected from -C(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mi>x</mi></msub><annotation encoding="application/x-tex">R_x</annotation></semantics></math>)- and -N-; L is optionally and independently selected from O, S, and NH; R₀ is independently selected from H, deuterium, halogen, alkyl, haloalkyl, deuterated alkyl, cycloalkyl, heterocyclyl, alkoxyalkyl, alkynyl, acetyl, methanesulfonyl, and phosphoryl; further, hydrogen(s) on R₀ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; each R₂ or each R₅ may be identical or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH, -NH₂, -COOH, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocyclyl, carboxyl or carboxyl surrogate substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, aryl, and heteroaryl; or any two <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math> or any two R₅, together with the carbon atoms to which they are attached on the rings, form a 3- to 8-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure may be optionally selected from an aromatic ring structure, a heteroaromatic ring structure, an alicyclic structure, a heterocyclic structure, a fused-ring structure, a spiro-ring structure, and a bridged-ring structure, wherein the alicyclic structure, the heterocyclic structure, the fused-ring structure, the spiro-ring structure, or the bridged-ring structure may contain zero or more unsaturated alkene bonds; further, hydrogen(s) on R₂ or R₅ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; or any two R₂ or any two R₅, together with the carbon atoms to which they are attached, form 5- to 6- membered heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8-membered saturated or partially saturated heterocyclyl, wherein hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocycloalkyl is optionally substituted with a group selected from hydrogen, deuterium, halogen, -CN, -OH, CF₃, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, -NH₂, -NHC_1-6 alkyl, -N(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl)₂, =O, and saturated or partially saturated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-6}</annotation></semantics></math> cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>1</mn></msub><annotation encoding="application/x-tex">R_1</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><annotation encoding="application/x-tex">R_{d1}</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mi>x</mi></msub><annotation encoding="application/x-tex">R_x</annotation></semantics></math> are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylamino, aryl, heteroaryl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>N</mi><mo>,</mo><mi>N</mi><mo>−</mo><mi>d</mi><mi>i</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub></mrow><annotation encoding="application/x-tex">N,N-di(C_{1-10}</annotation></semantics></math> alkyl)amino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfinyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkylamino, C_3-10 cycloalkoxy, C_3-10 cycloalkylacyl, C_3-10 cycloalkoxyacetyl, C_3-10 cycloalkylsulfonyl, and C_3-10 cycloalkylsulfinyl, wherein the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, - CN, -OH, CF₃, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, -NH₂, -NHC_1-6 alkyl, -N(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl)₂, oxy, and saturated or partially saturated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-6}</annotation></semantics></math> cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally further substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; or optionally, R_d1 and R₅, together with the carbon atoms to which they are attached, may form 5- to 6-membered aryl or heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8- membered saturated or partially saturated heterocyclyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, and OCH₂CH₃; the hetero represents any heteroatom optionally and independently selected from O, N, S, P, S=O, and S(=O)₂ and isotopes thereof; the halogen is optionally and independently selected from F, Cl, Br, and I and isotopes thereof; m is an integer optionally selected from 0, 1, 2, 3, and 4; n is an integer optionally selected from 0, 1, 2, 3, 4, and 5; q is an integer optionally selected from 0, 1, 2, and 3; and p is an integer optionally selected from 0, 1, 2, 3, and 4; preferably, the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof has a structure of formula (IB): [Image disponible dans le document PDF, Image available in the PDF document] formula (IB), wherein R₀, R₁, R₂, R₅, R_d1, m, n, and q are independently defined as described in any one of claims 1-5; preferably, R₀ is independently selected from H, alkyl, haloalkyl, deuterated alkyl, cycloalkyl, heterocyclyl, alkoxyalkyl, alkynyl, acetyl, methanesulfonyl, and phosphoryl; further, hydrogen(s) on R₀ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; each R₂ or each R₅ may be identical or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH, -NH₂, -COOH, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated cycloalkyl, C_3-10 saturated or partially saturated heterocycloalkyl, C_1-10 alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocyclyl, carboxyl or carboxyl surrogate substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, aryl, and heteroaryl; or any two <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math> or any two R₅, together with the carbon atoms to which they are attached on the rings, form a 3- to 8-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure may be optionally selected from an aromatic ring structure, a heteroaromatic ring structure, an alicyclic structure, a heterocyclic structure, a fused-ring structure, a spiro-ring structure, and a bridged-ring structure, wherein the alicyclic structure, the heterocyclic structure, the fused-ring structure, the spiro-ring structure, or the bridged-ring structure may contain zero or more unsaturated alkene bonds; further, hydrogen(s) on R₂ or R₅ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; or any two R₂ or any two R₅, together with the carbon atoms to which they are attached, form 5- to 6- membered heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8-membered saturated or partially saturated heterocyclyl, wherein hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocycloalkyl is optionally substituted with a group selected from hydrogen, deuterium, halogen, -CN, -OH, CF₃, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy, -NH₂, -NHC_1-6 alkyl, -N(<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl)₂, =O, and saturated or partially saturated <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-6}</annotation></semantics></math> cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; R₁ and R_d1 are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C_1-10 alkyl, C_2- 10 alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylamino, aryl, heteroaryl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>N</mi><mo>,</mo><mi>N</mi><mo>−</mo><mi>d</mi><mi>i</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub></mrow><annotation encoding="application/x-tex">N,N-di(C_{1-10}</annotation></semantics></math> alkyl)amino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfinyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkoxy, C_3-10 cycloalkylacyl, C_3-10 cycloalkoxyacetyl, C_3-10 cycloalkylsulfonyl, and C_3-10 cycloalkylsulfinyl, wherein the alkyl, alkenyl, aryl, saturated or partially saturated cycloalkyl, and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, -CN, -OH, CF₃, C_1-6 alkyl, C_1-6 alkoxy, -NH₂, -NHC_1-6 alkyl, -N(C_1-6 alkyl)₂, oxy, and saturated or partially saturated C_3-6 cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally further substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; or optionally, R_d1 and R₅, together with the carbon atoms to which they are attached, may form 5- to 6- membered aryl or heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8-membered saturated or partially saturated heterocyclyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, and OCH₂CH₃; the hetero represents any heteroatom optionally and independently selected from O, N, S, P, S=O, and S(=O)₂ and isotopes thereof; the halogen is optionally and independently selected from F, Cl, Br, and I and isotopes thereof; m is an integer optionally selected from 0, 1, 2, 3, and 4; n is an integer optionally selected from 0, 1, 2, 3, 4, and 5; q is an integer optionally selected from 0, 1, 2, and 3; and p is an integer optionally selected from 0, 1, 2, 3, and 4; preferably, the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof has a structure of formula (IC): [Image disponible dans le document PDF, Image available in the PDF document] formula (IC), wherein <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>0</mn></msub><annotation encoding="application/x-tex">R_0</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>1</mn></msub><annotation encoding="application/x-tex">R_1</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mi>m</mi><annotation encoding="application/x-tex">m</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mi>n</mi><annotation encoding="application/x-tex">n</annotation></semantics></math> are independently defined as described in any one of claims 1-5; preferably, R₀ is independently selected from H, alkyl, haloalkyl, deuterated alkyl, cycloalkyl, heterocyclyl, alkoxyalkyl, alkynyl, acetyl, methanesulfonyl, and phosphoryl; further, hydrogen(s) on R₀ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; each R₂ may be identical or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH, -NH₂, -COOH, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> 10 cycloalkyl or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocyclyl, carboxyl or carboxyl surrogate substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, aryl, and heteroaryl; or any two <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math>, together with the carbon atoms to which they are attached on the ring form a 3- to 8-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure may be optionally selected from an aromatic ring structure, a heteroaromatic ring structure, an alicyclic structure, a heterocyclic structure, a fused-ring structure, a spiro-ring structure, and a bridged-ring structure, wherein the alicyclic structure, the heterocyclic structure, the fused-ring structure, the spiro-ring structure, or the bridged-ring structure may contain zero or more unsaturated alkene bonds; further, hydrogen(s) on R₂ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>1</mn></msub><annotation encoding="application/x-tex">R_1</annotation></semantics></math> is independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylamino, aryl, heteroaryl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mi>N</mi><mo>,</mo><mi>N</mi><mo>−</mo><mi>d</mi><mi>i</mi><mo stretchy="false" form="prefix">(</mo><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub></mrow><annotation encoding="application/x-tex">N,N-di(C_{1-10}</annotation></semantics></math> alkyl)amino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyloxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfonyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkylsulfinyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkylamino, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkylacyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkoxyacetyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkylsulfonyl, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkylsulfinyl, wherein the alkyl, alkenyl, aryl, saturated or partially saturated cycloalkyl, and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, -CN, -OH, CF₃, C_1-6 alkyl, C_1-6 alkoxy, -NH₂, -NHC_1-6 alkyl, -N(C_1-6 alkyl)₂, oxy, and saturated or partially saturated C_3-6 cycloalkyl, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkyl and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>6</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-6}</annotation></semantics></math> alkoxy are optionally further substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, OCH₂CH₃, and saturated or partially saturated C_3-6 cycloalkyl; or optionally, R_d1 and R₅, together with the carbon atoms to which they are attached, may form 5- to 6- membered aryl or heteroaryl, 3- to 8-membered saturated or partially saturated cycloalkyl, or 3- to 8-membered saturated or partially saturated heterocyclyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more groups selected from hydrogen, deuterium, halogen, oxo, CN, CF₃, OH, OCH₃, and OCH₂CH₃; the hetero represents any heteroatom optionally and independently selected from O, N, S, P, S=O, and S(=O)₂ and isotopes thereof; the halogen is optionally and independently selected from F, Cl, Br, and I and isotopes thereof; m is an integer optionally selected from 0, 1, 2, 3, and 4; and n is an integer optionally selected from 0, 1, 2, 3, and 4; preferably, the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof has a structure of formula (ID): [Image disponible dans le document PDF, Image available in the PDF document] formula (ID), wherein <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>0</mn></msub><annotation encoding="application/x-tex">R_0</annotation></semantics></math> and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math> are independently defined as described in any one of claims 1-5; preferably, R₀ is independently selected from H, alkyl, haloalkyl, deuterated alkyl, cycloalkyl, heterocyclyl, alkoxyalkyl, alkynyl, acetyl, methanesulfonyl, and phosphoryl; further, hydrogen(s) on R₀ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; R₂ is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH, -NH₂, -COOH, C_1-10 alkyl, C_2-10 alkenyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> alkynyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkoxy, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated cycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> saturated or partially saturated heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>1</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{1-10}</annotation></semantics></math> alkyl substituted with <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> cycloalkyl or <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>3</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{3-10}</annotation></semantics></math> heterocycloalkyl, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>C</mi><mrow><mn>2</mn><mo>−</mo><mn>10</mn></mrow></msub><annotation encoding="application/x-tex">C_{2-10}</annotation></semantics></math> heteroalkyl substituted with C_3-10 cycloalkyl, C_3-10 heterocyclyl, carboxyl or carboxyl surrogate substituted with C_1- ₁₀ alkyl, aryl, and heteroaryl; or any two R₂, together with the carbon atoms to which they are attached on the ring form a 3- to 8-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure may be optionally selected from an aromatic ring structure, a heteroaromatic ring structure, an alicyclic structure, a heterocyclic structure, a fused-ring structure, a spiro-ring structure, and a bridged-ring structure, wherein the alicyclic structure, the heterocyclic structure, the fused-ring structure, the spiro-ring structure, or the bridged-ring structure may contain zero or more unsaturated alkene bonds; further, hydrogen(s) on R₂ is(are) optionally and optimally substituted with one or more substituents selected from H, deuterium, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, OCH₃, carboxyl, OH, and CN; the hetero represents any heteroatom optionally and independently selected from O, N, S, P, S=O, and S(=O)₂ and isotopes thereof; and the halogen is optionally and independently selected from F, Cl, Br, and I and isotopes thereof; preferably, the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof has a structure of formula (III): [Image disponible dans le document PDF, Image available in the PDF document] (III), wherein ring C, L, X₀, X₁, X₂, R₁, R₂, R₅, R_d1, m, n, and q are independently defined as described in any one of claims 1-5; preferably, the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof has a structure of formula (IIIA): [Image disponible dans le document PDF, Image available in the PDF document] (IIIA), wherein L, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>X</mi><mn>2</mn></msub><annotation encoding="application/x-tex">X_2</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>0</mn></msub><annotation encoding="application/x-tex">R_0</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>1</mn></msub><annotation encoding="application/x-tex">R_1</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mn>2</mn></msub><annotation encoding="application/x-tex">R_2</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><msub><mi>R</mi><mrow><mi>d</mi><mn>1</mn></mrow></msub><annotation encoding="application/x-tex">R_{d1}</annotation></semantics></math> are independently defined as described in any one of claims 1-5; preferably, the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof has a structure represented by formula (IE): [Image disponible dans le document PDF, Image available in the PDF document] formula (IE). </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00007"> <pat:ClaimNumber>7</pat:ClaimNumber> <pat:ClaimText>7. The compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof as claimed in any one of claims 1-6, having a structure selected from: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , , , , , , Н , , , [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , , , , , , , , , • [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , , , , , , , , , , [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , , , , 7 7 , an preferably, having a structure selected from: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00008"> <pat:ClaimNumber>8</pat:ClaimNumber> <pat:ClaimText>8. A polymorph of the compound represented by formula (IE): [Image disponible dans le document PDF, Image available in the PDF document] formula (IE), wherein the polymorph is selected from a nonsolvate crystal form, a hydrate crystal form, and a metastable crystal form of compound IE; preferably, the nonsolvate crystal form may be a crystal form A, B, or C as described below; the hydrate crystal form may be a crystal form D, E, F, or G as described below; the metastable crystal form may be a crystal form H, I, J, K, L, M, N, O, P, or Q as described below; regarding the crystal form A: an X-ray powder diffraction pattern of the crystal form A comprises peaks at diffraction angles (20) of <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>5.10</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">5.10\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>15.72</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">15.72\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>15.25</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">15.25\pm0.2^{\circ}</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>20.53</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">20.53\pm0.2^{\circ}</annotation></semantics></math>; preferably, the crystal form A preferably further comprises peaks at diffraction angles (2θ) of 23.66±0.2°, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>23.92</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">23.92\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>17.47</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">17.47\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>20.14</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">20.14\pm0.2^{\circ}</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>24.44</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">24.44\pm0.2^{\circ}</annotation></semantics></math>; preferably, the crystal form A more preferably further comprises peaks at diffraction angles (2θ) of 26.66±0.2°, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>17.22</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">17.22\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>26.92</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">26.92\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>16.48</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">16.48\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>10.20</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">10.20\pm0.2^{\circ}</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>21.97</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">21.97\pm0.2^{\circ}</annotation></semantics></math>; preferably, the X-ray powder diffraction pattern of the crystal form A has the diffraction angles (<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>2</mn><mi>θ</mi></mrow><annotation encoding="application/x-tex">2\theta</annotation></semantics></math>) shown in Table 1, wherein the 20 angles have a margin of error of <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>±</mo><msup><mn>0.20</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">\pm 0.20^{\circ}</annotation></semantics></math>: Table 1 [Image disponible dans le document PDF, Image available in the PDF document] preferably, the crystal form A has the X-ray powder diffraction intensities shown in Table 1; preferably, the crystal form A has an X-ray powder diffraction pattern substantially as shown in FIG. 1; preferably, according to DSC analysis, an endothermic peak appears when the crystal form A is heated to a peak temperature of about 180.86 °C; preferably, the crystal form A has a DSC profile substantially as shown in FIG. 2; preferably, the crystal form A has a TGA profile substantially as shown in FIG. 3; regarding the crystal form B: an X-ray powder diffraction pattern of the crystal form B comprises peaks at diffraction angles (20) of <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>10.33</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">10.33\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>5.18</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">5.18\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>13.69</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">13.69\pm0.2^{\circ}</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>18.72</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">18.72\pm0.2^{\circ}</annotation></semantics></math>; preferably, the crystal form B preferably further comprises peaks at diffraction angles (20) of <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>8.96</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">8.96\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>11.73</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">11.73\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>25.89</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">25.89\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>17.10</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">17.10\pm0.2^{\circ}</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>23.20</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">23.20\pm0.2^{\circ}</annotation></semantics></math>; preferably, the crystal form B more preferably further comprises peaks at diffraction angles (20) of <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>26.13</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">26.13\pm0.2^{\circ}</annotation></semantics></math>, preferably, the X-ray powder diffraction pattern of the crystal form B has the diffraction angles (<math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>2</mn><mi>θ</mi></mrow><annotation encoding="application/x-tex">2\theta</annotation></semantics></math>) shown in Table 2, wherein the <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>2</mn><mi>θ</mi></mrow><annotation encoding="application/x-tex">2\theta</annotation></semantics></math> angles have a margin of error of <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo>±</mo><msup><mn>0.20</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">\pm 0.20^{\circ}</annotation></semantics></math>: Table 2 [Image disponible dans le document PDF, Image available in the PDF document] preferably, the crystal form B has the X-ray powder diffraction intensities shown in Table 2; preferably, the crystal form B has an X-ray powder diffraction pattern substantially as shown in FIG. 4; preferably, according to DSC analysis, an endothermic peak appears when the crystal form B is heated to a peak temperature of about 179.71 °C; preferably, the crystal form B has a DSC profile substantially as shown in FIG. 5; preferably, the crystal form B has a TGA profile substantially as shown in FIG. 6; regarding the crystal form C: an X-ray powder diffraction pattern of the crystal form C comprises peaks at diffraction angles (20) of <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>5.39</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">5.39\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>12.05</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">12.05\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>9.70</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">9.70\pm0.2^{\circ}</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>18.00</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">18.00\pm0.2^{\circ}</annotation></semantics></math>; preferably, the crystal form C preferably further comprises peaks at diffraction angles (2θ) of 23.06±0.2°, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>21.21</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">21.21\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>17.30</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">17.30\pm0.2^{\circ}</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>17.14</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">17.14\pm0.2^{\circ}</annotation></semantics></math>, and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mn>25.09</mn><mo>±</mo><msup><mn>0.2</mn><mo>∘</mo></msup></mrow><annotation encoding="application/x-tex">25.09\pm0.2^{\circ}</annotation></semantics></math>; preferably, the crystal form C more preferably further comprises peaks at diffraction angles (2θ) of 22.39±0.2°, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00009"> <pat:ClaimNumber>9</pat:ClaimNumber> <pat:ClaimText>9. A preparation method for the polymorph as claimed in claim 8, comprising the following steps: step 1: dissolving or dispersing compound IE in a solvent; and step 2: stirring at 0-50 °C for crystallization; or adding an anti-solvent to a clear solution of the compound for precipitation; or slowly volatilizing a clear solution of the compound; wherein preferably, the compound IE is preferably the metastable crystal form H of compound IE; preferably, the solvent is water, an organic solvent, or a mixed solvent of water with the organic solvent, wherein the organic solvent is selected from alcohols, chloroalkanes, ketones, ethers, cyclic ethers, esters, alkanes, cycloalkanes, benzenes, amides, sulfoxides, and mixtures thereof; preferably, the organic solvent is selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, trifluoroethanol, acetonitrile, acetone, methyl ethyl ketone, methyl isobutyl ketone, 1,4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, N,N-dimethylformamide, N,N- dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, ethyl acetate, isopropyl acetate, dichloromethane, trichloromethane, trichloroethane, carbon tetrachloride, methyl tert-butyl ether, cyclopentyl methyl ether, 2- methoxyethyl ether, isopropyl ether, diethyl ether, n-heptane, n-hexane, isooctane, pentane, cyclohexane, cyclopentane, methylcyclohexane, benzene, toluene, xylene, and mixtures thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00010"> <pat:ClaimNumber>10</pat:ClaimNumber> <pat:ClaimText>10. Use of the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, or the isotopically substituted compound thereof as claimed in any one of claims 1-7 or the polymorph as claimed in claim 8 for the manufacturing of a medicament for the prevention and/or treatment of diseases associated with the WEE1 and/or Yes target(s), wherein: preferably, the diseases include tumors, inflammations, and autoimmune diseases (e.g., lupus erythematosus and psoriasis). </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00011"> <pat:ClaimNumber>11</pat:ClaimNumber> <pat:ClaimText>11. A pharmaceutical composition, comprising the compound, the pharmaceutically acceptable salt, the solvate, the enantiomer, the isotopically substituted compound, or the polymorph thereof as claimed in any one of claims 1-7 or the polymorph as claimed in claim 8 as an active ingredient and an auxiliary ingredient that enables the pharmaceutical composition to be suitable for being formulated as different pharmaceutical dosage forms such as liquid formulations (including oral liquids, injectable liquids, eye drops, etc.), solid formulations (including tablets, capsules, pills, granules, etc.), wherein the pharmaceutical composition is capable of being used for the manufacturing of a medicament for the prevention and/or treatment of diseases associated with the WEE1 and/or Yes target(s); preferably, the diseases include tumors, inflammations, and autoimmune diseases (e.g., lupus erythematosus and psoriasis). </pat:ClaimText> </pat:Claim> </pat:Claims>

Description

PYRIMIDO MACROHETEROCYCLIC COMPOUND AS WEE1-YES DUAL-TARGET INHIBITOR AND USE THEREOF The present disclosure claims priority of an International Application No. PCT/CN2023/093349 entitled "NOVEL" PYRIMIDO-HETEROCYCLIC COMPOUND AS WEE1 INHIBITOR AND USE THEREOF", and filed with the International Bureau of the World Intellectual Property Organization on May 10, 2023. TECHNICAL FIELD The present disclosure pertains to the field of medical chemistry and particularly discloses, for the first time worldwide, novel pyrimido-macroheterocyclic compounds capable of simultaneously inhibiting the WEE1 and Yes targets, compositions containing such compounds, and a method for manufacturing a medicament for the treatment or prevention of diseases associated with the WEE1 and/or Yes targets by using such compounds. BACKGROUND The cell cycle is a highly regulated and controlled process. A normal cell cycle has checkpoints in the G1/S, S, and G2/M phases to allow sufficient time for DNA damage repair. Normally, after DNA damage occurs in a cell, TP53 can perform checks in the G1/S phase of the cell, and the cell cannot enter the G2 phase until the damaged DNA is repaired. If TP53 is dysfunctional and cannot perform checks in the G1/S phase as it normally does, the cell enters the G2 phase, carrying the damaged DNA. WEE1, a member of the serine/threonine protein kinase family, plays an important regulatory role at the checkpoint of the G2/M phase of the cell cycle. The WEE1 kinase inhibits the activity of CDKs by phosphorylating the Tyr14 and Tyr15 of the CDKs, arresting the cell cycle in the G2/M phase, thereby allowing sufficient time for DNA damage repair in the cell. Inhibition of WEE1 eliminates the cell cycle arrest and causes the cell to enter mitosis prematurely, which leads to cell replication stress and improper mitotic progression. WEE1 is overexpressed in many types of cancer, including breast cancer, lung cancer, cervical cancer, head and neck cancer, ovarian cancer, prostate cancer, melanoma, leukemia, glioblastoma, medulloblastoma, liver cancer, and the like. The overexpression of WEE1 in cancer cells is a normal response to the elevated replication stress in cancer cells and has some correlation with tumor progression and low disease-free survival rates. Therefore, WEE1 inhibition has become a very promising cancer therapy, especially in conjunction with DNA damage treatment. Numerous studies have demonstrated that WEE1 and TP53 exhibit a synthetic lethal relationship. In tumor cells in which TP53 is inactivated due to mutation, the loss of the checking function of the G1/S phase makes the tumor cells highly dependent on the checks of the G2/M phase. In tumor cells lacking TP53 function, inhibiting WEE1 function disrupts damage repair, leading to the accumulation of errors and eventual apoptosis, thereby achieving an inhibitory effect on tumors. Therefore, WEE1 inhibitors have great synthetic lethal therapeutic value in cancers in which TP53 is mutated. Oral small molecule WEE1 inhibitors have been reported in some literature or patent publications, and some candidate compounds have entered clinical trials, for example, ZN-c3, AZD-1775, IMP 7068, Debio 0123, and the like. However, single-target Wee1 selective inhibitors generally show relatively poor efficacy in inhibiting tumor proliferation, and the majority of the clinical candidate molecules generally face relatively significant challenges regarding druggability, such as relatively low efficacy, poor selectivity, rapid metabolism, poor oral absorption, low bioavailability, narrow safety windows, and the like. Yes-associated protein (YAP) is a major transcriptional coactivator in the Hippo pathway. It binds to the transcription factor TEAD to regulate downstream targets related to cell proliferation and survival. Dysregulated YAP can cause metastasis and poor prognosis of aggressive tumors, including pancreatic cancer, gastric cancer, lung cancer, and the like. Therefore, Yes target inhibitors are likely to become a good tumor treatment strategy. Studies have shown that both Yes and Weel are co-overexpressed in many malignant tumors, such as pancreatic cancer, small-cell lung cancer, gastric cancer, bowel cancer, ovarian cancer, or the like, and play significant roles in the proliferation, invasion, and metastasis of these malignant tumors. This suggests that inhibitors that simultaneously inhibit the Yes and Weel targets can have better efficacy. However, up to the filing date of this application, compounds capable of simultaneously inhibiting the Yes and Wee1 targets have not been reported in literature or patent publications worldwide. Technical Effects The inventors have unexpectedly discovered for the first time that some of the novel pyrimido-macroheterocyclic compounds of the structure of formula (I) of the present disclosure can simultaneously inhibit the Yes and Wee1 targets. Compared to structurally known single-target Weel selective compounds, su