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KR-20260065838-A - Cap analogues and methods of using the same

KR20260065838AKR 20260065838 AKR20260065838 AKR 20260065838AKR-20260065838-A

Abstract

Novel tetranucleotide and trinucleotide cap analogs and methods for their preparation and use are described herein. Additionally, RNA molecules comprising a 5'-cap are described herein, wherein the 5'-cap comprises the tetranucleotide or trinucleotide cap analog described herein. A method for inducing a therapeutic effect in a subject is also described herein, said method comprising the step of administering an RNA molecule comprising a tetranucleotide or trinucleotide cap analog to a subject. The tetranucleotide and trinucleotide cap analogs have chemical formulas (I) and (II).

Inventors

  • 쉬, 춘핑
  • 자오, 찬펑
  • 레베데프, 알렉산드르 브이.
  • 일리체프, 일리야 블라디미로비치
  • 랑, 헝위앤

Assignees

  • 트리링크 바이오테크놀로지스, 엘엘씨

Dates

Publication Date
20260511
Application Date
20240906
Priority Date
20230906

Claims (20)

  1. Compound of chemical formula (I): (I); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula: B1 , B2 , and B3 are each independently natural, modified, or non-natural nucleoside bases; Ring A is a substituted or unsubstituted cycloalkylene, a substituted or unsubstituted heterocycloalkylene, a substituted or unsubstituted arylene, or a substituted or unsubstituted heteroarylene; X 1 and X 2 are each independently -O-, -CH 2- , -CX 2- , -N(R 101 )-, -BH-, or -S-; Y1 , Y2 , Y3 , Y4 , and Y5 are each independently O, S, or Se; R1 is independently hydrogen, -C(O) R1A , -C(O) OR1A , -OR1A , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R2 is independently hydrogen, -C(O) R2A , -C(O) OR2A , -OR2A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or R1 and R2 together with the nitrogen atoms to which they are connected form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl; R3 is hydrogen, -C(O) R3A , -C(O) OR3A , -OR3A , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 7 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 7A , -NR 7A R 7B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI₃ , -OCHCl₂ , -OCHBr₂ , -OCHI₂, -OCHF₂ , -OCH₂Cl, -OCH₂Br , -OCH₂I, -OCH₂F , -N₃ , -SF₅ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Each R 19 is independently hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br, -CH 2F , -CH 2I , -CN, -OR 19A , -NR 19A R 19B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R 7 and R 19 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; R 11 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 11A , -NR 11A R 11B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R 11 and R 19 together with the carbon atoms to which they are connected to form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R1A , R2A , R3A, R7A , R7B , R11A , R11B , R19A , and R19B is independently hydrogen, -CX3 , -CHX2, -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH , -NH2, -COOH, -CONH2, -NO2 , -SH, -SO3H , -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC = (O) NHNH2 , -NHC=(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O)OH, -NHOH, -OCX3 , -OCHX2 , -OCH 2 X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; The R7A and R7B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R11A and R11B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R19A and R19B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl: R 101 is hydrogen, oxo, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OH, -NH 2 , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; n is an integer from 0 to 3; X is -Cl, -Br, -I, or -F; However, the compound of chemical formula (I) is , or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or a compound other than a pharmaceutically acceptable salt, solvate, or hydrate thereof.
  2. In claim 1, a compound of the chemical formula (IA): (IA); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, B3 is a natural nucleoside base; R 4 is independently hydrogen, -C(O)R 4A , -C(O)OR 4A , -OR 4A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R5 is independently hydrogen, -C(O) R5A , -C(O) OR5A , -OR5A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or R4 and R5 together with the nitrogen atoms to which they are connected form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl; R 6 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 6A , -NR 6A R 6B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI₃ , -OCHCl₂ , -OCHBr₂ , -OCHI₂, -OCHF₂ , -OCH₂Cl, -OCH₂Br , -OCH₂I, -OCH₂F , -N₃ , -SF₅ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 14 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 14A , -NR 14A R 14B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Each R₄A , R₅A , R₆A, R₆B , R₁₄A , and R₁₄B is independently hydrogen, -CX₃ , -CHX₂ , -CH₂X , -C(O)OH, -C(O) NH₂ , -CN , -OH , -NH₂, -COOH, -CONH₂ , -NO₂, -SH, -SO₃H, -SO₄H , -SO₂NH₂ , -NHNH₂ , -ONH₂ , -NHC =(O)NHNH₂, -NHC =(O) NH₂ , -NHSO₂H , -NHC=(O)H, -NHC(O ) OH, -NHOH, -OCX₃ , -OCHX₂ , -OCH₂X , substituted or unsubstituted alkyl, substituted or unsubstituted Heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound in which the R6A and R6B substituents bonded to the same nitrogen atom can optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R14A and R14B substituents bonded to the same nitrogen atom can optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  3. In claim 1 or 2, a compound of formula (IB): (IB); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  4. In claim 1 or 2, a compound of formula (IC): (IC); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  5. In claim 1, a compound of chemical formula (ID): (ID); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R 4 is independently hydrogen, -C(O)R 4A , -C(O)OR 4A , -OR 4A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R5 is independently hydrogen, -C(O) R5A , -C(O) OR5A , -OR5A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or R4 and R5 together with the nitrogen atoms to which they are connected form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl; R 6 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 6A , -NR 6A R 6B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI₃ , -OCHCl₂ , -OCHBr₂ , -OCHI₂, -OCHF₂ , -OCH₂Cl, -OCH₂Br , -OCH₂I, -OCH₂F , -N₃ , -SF₅ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 12 is independently hydrogen, -C(O)R 12A , -C(O)OR 12A , -OR 12A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R 13 is independently hydrogen, -C(O)R 13A , -C(O)OR 13A , -OR 13A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or R 12 and R 13 together with the nitrogen atoms to which they are connected form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl; R 14 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 14A , -NR 14A R 14B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Each R₄A , R₅A , R₆A, R₆B , R₁₂A , R₃A , R₁₄A , and R₁₄B is independently hydrogen, -CX₃ , -CHX₂ , -CH₂X , -C(O)OH, -C(O) NH₂ , -CN, -OH, -NH₂ , -COOH, -CONH₂, -NO₂ , -SH , -SO₃H, -SO₄H , -SO₂NH₂ , -NHNH₂ , -ONH₂, -NHC =(O) NHNH₂ , -NHC =(O) NH₂ , -NHSO₂H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX₃ , -OCHX₂, -OCH₂X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound in which the R6A and R6B substituents bonded to the same nitrogen atom can optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R14A and R14B substituents bonded to the same nitrogen atom can optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  6. In claim 1 or 5, a compound of formula (IE): (IE); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  7. In claim 1 or 5, a compound of formula (IF): (IF); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  8. In claim 1, a compound of the chemical formula (IG): (IG); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R 4 is independently hydrogen, -C(O)R 4A , -C(O)OR 4A , -OR 4A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R5 is independently hydrogen, -C(O) R5A , -C(O) OR5A , -OR5A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or R4 and R5 together with the nitrogen atoms to which they are connected form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl; R 6 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 6A , -NR 6A R 6B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI₃ , -OCHCl₂ , -OCHBr₂ , -OCHI₂, -OCHF₂ , -OCH₂Cl, -OCH₂Br , -OCH₂I, -OCH₂F , -N₃ , -SF₅ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 15 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 15A , -NR 15A R 15B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 16 is independently hydrogen, -C(O)R 16A , -C(O)OR 16A , -OR 16A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; Each R₄A , R₅A , R₆A, R₆B , R₁₅A , R₁₅B , and R₁₆A is independently hydrogen, -CX₃ , -CHX₂, -CH₂X , -C(O)OH, -C(O)NH₂, -CN, -OH , -NH₂ , -COOH, -CONH₂, -NO₂ , -SH , -SO₃H , -SO₄H, -SO₂NH₂ , -NHNH₂ , -ONH₂ , -NHC =(O) NHNH₂ , -NHC =(O ) NH₂ , -NHSO₂H , -NHC=(O)H, -NHC(O)OH, -NHOH , -OCX₃, -OCHX₂ , -OCH₂X , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound in which the R6A and R6B substituents bonded to the same nitrogen atom can optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R15A and R15B substituents bonded to the same nitrogen atom can optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  9. In claim 1 or 8, a compound of the formula (IH): (IH); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  10. In claim 1 or 8, a compound of formula (IJ): (IJ); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  11. In claim 1, a compound of the chemical formula (IK): (IK); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R 6 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 6A , -NR 6A R 6B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI₃ , -OCHCl₂ , -OCHBr₂ , -OCHI₂, -OCHF₂ , -OCH₂Cl, -OCH₂Br , -OCH₂I, -OCH₂F , -N₃ , -SF₅ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 14 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 14A , -NR 14A R 14B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Each R6A , R6B , R14A , and R14B is independently hydrogen, -CX3 , -CHX2, -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2, -COOH , -CONH2, -NO2 , -SH, -SO3H , -SO4H , -SO2NH2, -NHNH2, -ONH2 , -NHC=(O) NHNH2 , -NHC =(O ) NH2 , -NHSO2H , -NHC=(O) H , -NHC(O)OH, -NHOH, -OCX3 , -OCHX2 , -OCH2X , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or an unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; The R6A and R6B substituents bonded to the same nitrogen atom may be optionally bonded to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; A compound in which R 14A and R 14B substituents bonded to the same nitrogen atom are optionally bonded to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  12. In claim 1 or 11, a compound of formula (IL): (IL); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  13. In claim 1 or 11, a compound of formula (IM): (IM); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  14. In claim 1, a compound of chemical formula (IN): (IN); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R 6 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 6A , -NR 6A R 6B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI₃ , -OCHCl₂ , -OCHBr₂ , -OCHI₂, -OCHF₂ , -OCH₂Cl, -OCH₂Br , -OCH₂I, -OCH₂F , -N₃ , -SF₅ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 15 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 15A , -NR 15A R 15B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 16 is independently hydrogen, -C(O)R 16A , -C(O)OR 16A , -OR 16A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; Each R6A , R6B , R15A , R15B , and R16A is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2, -COOH , -CONH2, -NO2 , -SH, -SO3H, -SO4H , -SO2NH2, -NHNH2 , -ONH2 , -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H, -NHC=(O) H , -NHC(O) OH , -NHOH, -OCX3 , -OCHX2 , -OCH2X , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; The R6A and R6B substituents bonded to the same nitrogen atom may be optionally bonded to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; A compound in which R 15A and R 15B substituents bonded to the same nitrogen atom are optionally bonded to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  15. In claim 1 or 14, a compound of the formula (IO): (IO); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  16. In claim 1 or 14, a compound of formula (IP): (IP); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  17. In claim 1, a compound of chemical formula (IQ): (IQ); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R 4 is independently hydrogen, -C(O)R 4A , -C(O)OR 4A , -OR 4A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R5 is independently hydrogen, -C(O) R5A , -C(O) OR5A , -OR5A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or R4 and R5 together with the nitrogen atoms to which they are connected form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl; R 6 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 6A , -NR 6A R 6B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI₃ , -OCHCl₂ , -OCHBr₂ , -OCHI₂, -OCHF₂ , -OCH₂Cl, -OCH₂Br , -OCH₂I, -OCH₂F , -N₃ , -SF₅ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 12 is independently hydrogen, -C(O)R 12A , -C(O)OR 12A , -OR 12A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R 13 is independently hydrogen, -C(O)R 13A , -C(O)OR 13A , -OR 13A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or R 12 and R 13 together with the nitrogen atoms to which they are connected form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl; R 15 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 15A , -NR 15A R 15B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Each R₄A , R₅A , R₆A, R₆B , R₁₂A , R₃A , R₅A , and R₅B is independently hydrogen, -CX₃ , -CHX₂ , -CH₂X , -C(O)OH, -C(O) NH₂ , -CN, -OH, -NH₂ , -COOH, -CONH₂, -NO₂ , -SH , -SO₃H, -SO₄H , -SO₂NH₂ , -NHNH₂ , -ONH₂, -NHC =(O) NHNH₂ , -NHC =(O) NH₂ , -NHSO₂H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX₃ , -OCHX₂, -OCH₂X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; The R6A and R6B substituents bonded to the same nitrogen atom may be optionally bonded to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; A compound in which R 15A and R 15B substituents bonded to the same nitrogen atom are optionally bonded to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  18. In claim 1 or 17, a compound of the chemical formula (IR): (IR); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  19. In claim 1 or 17, a compound of formula (IS): (IS); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R8 independently represents hydrogen, halogen, -CCl3, -CBr3 , -CF3 , -Cl3, -CHCl2, -CHBr2 , -CHF2 , -CHI2 , -CH2Cl , -CH2Br , -CH2F , -CH2I, -CN, -OR8A , -NR8A , R8B , -COOH , -CONH2 , -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2 , -NHC(O) NHNH2 , -NHC (O)NH2, -NHSO2H, -NHC(O)R8A , -NHC ( O ) OH, -NHOH, -OCCl3 , -OCF3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8' independently represents hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br , -CH 2F, -CH 2I , -CN, -OR 8'A , -NR 8'A , R 8'B , -COOH , -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)R 8'A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 -OCBr3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2, -OCHF2 , -OCH2Cl , -OCH2Br, -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 9 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 9A , -NR 9A R 9B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)R 9A , -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R9 or R8 ' and R9 form a substituted or unsubstituted heterocycloalkylene together with the carbon atoms to which they are connected; R 10 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 10A , -NR 10A R 10B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R8 and R10 or R8 ' and R10 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; Each R8A , R8B , R8'A, R8'B , R9A , R9B , R10A , and R10B is independently hydrogen, -CX3 , -CHX2 , -CH2X , -C(O)OH, -C(O) NH2 , -CN, -OH, -NH2 , -COOH, -CONH2, -NO2 , -SH , -SO3H, -SO4H , -SO2NH2 , -NHNH2 , -ONH2, -NHC =(O) NHNH2 , -NHC =(O) NH2 , -NHSO2H , -NHC=(O)H, -NHC(O) OH , -NHOH, -OCX3 , -OCHX2, -OCH2X , substituted or Unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; A compound wherein the R 8A and R 8B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 8'A and R 8'B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; the R 9A and R 9B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; and the R 10A and R 10B substituents bonded to the same nitrogen atom may optionally bond to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.
  20. In claim 1, a compound of the chemical formula (IT): (IT); or its enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant; or as a pharmaceutically acceptable salt, solvate, or hydrate thereof, In the above formula, R 15 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 15A , -NR 15A R 15B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 16 is independently hydrogen, -C(O)R 16A , -C(O)OR 16A , -OR 16A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R 17 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 17A , -NR 17A R 17B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI 3 , -OCHCl 2 , -OCHBr 2 , -OCHI 2 , -OCHF 2 , -OCH 2Cl , -OCH 2Br , -OCH 2I , -OCH 2F , -N 3 , -SF 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 18 is independently hydrogen, -C(O)R 18A , -C(O)OR 18A , -OR 18A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; Each R 15A , R 15B , R 16A , R 17A , R 17B , and R 18A is independently hydrogen, -CX₃ , -CHX₂ , -CH₂X , -C(O)OH, -C(O) NH₂ , -CN, -OH, -NH₂ , -COOH, -CONH₂, -NO₂, -SH, -SO₃H , -SO₄H , -SO₂NH₂ , -NHNH₂, -ONH₂ , -NHC =(O ) NHNH₂ , -NHC=(O) NH₂ , -NHSO₂H , -NHC=(O)H, -NHC(O)OH, -NHOH , -OCX₃ , -OCHX₂, -OCH₂X , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; The R 15A and R 15B substituents bonded to the same nitrogen atom may be optionally bonded to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl; A compound in which R 17A and R 17B substituents bonded to the same nitrogen atom are optionally bonded to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.

Description

Cap analogues and methods of using the same Cross-reference with priority applications This application claims priority to U.S. Provisional Application No. 63/536,844 filed on September 6, 2023, the entire disclosure of which is incorporated herein by reference. Technology field The field of the present invention relates to cap analogs and methods for preparing and using the same. Additionally, the present invention relates to using cap analogs to prepare 5'-capped RNA. In vitro transcribed messenger RNA (mRNA) has a number of in vivo applications, for example, vaccination in which mRNA encoding a specific antigen is administered to induce protective immunity in a patient; cell therapy in which mRNA is transfected ex vivo into cells to alter cell phenotype or function before delivering these altered cells to the patient; or replacement therapy in which mRNA encoding a therapeutic protein is administered to the patient. The primary structural element of mRNA molecules used in in vivo applications includes a cap structure on the 5'-terminus of the mRNA. Naturally occurring cap structures include 7-methylguanosine ( 7mG or m7G ) linked via a 5'- to 5'-triphosphate chain at the 5'-terminus of the mRNA molecule. The cap must be present for the mRNA to maintain template activity for protein synthesis. The chemical structure of the cap can regulate translation efficiency within the cell. Therefore, an effective cap structure is required. A novel cap structure is described herein, which can be used to produce 5'-capped mRNA. In one embodiment, a compound of formula (I) (I); or its enantiomers, mixtures of enantiomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants; or pharmaceutically acceptable salts, solvates, or hydrates thereof are provided herein; Here: B1 , B2 , and B3 are each independently natural, modified, or non-natural nucleoside bases; Ring A is a substituted or unsubstituted cycloalkylene, a substituted or unsubstituted heterocycloalkylene, a substituted or unsubstituted arylene, or a substituted or unsubstituted heteroarylene; X 1 and X 2 are each independently -O-, -CH 2- , -CX 2- , -N(R 101 )-, -BH-, or -S-; Y1 , Y2 , Y3 , Y4 , and Y5 are each independently O, S, or Se; R1 is independently hydrogen, -C(O) R1A , -C(O) OR1A , -OR1A , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R2 is independently hydrogen, -C(O) R2A , -C(O) OR2A , -OR2A , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or R1 and R2 together with the nitrogen atoms to which they are connected form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl; R3 is hydrogen, -C(O) R3A , -C(O) OR3A , -OR3A , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 7 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2 Cl, -CH 2 Br, -CH 2 F, -CH 2 I, -CN, -OR 7A , -NR 7A R 7B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3 H, -SO 4 H, -SO 2 NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2 H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI₃ , -OCHCl₂ , -OCHBr₂ , -OCHI₂, -OCHF₂ , -OCH₂Cl, -OCH₂Br , -OCH₂I, -OCH₂F , -N₃ , -SF₅ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Each R 19 is independently hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -Cl 3 , -CHCl 2 , -CHBr 2 , -CHF 2 , -CHI 2 , -CH 2Cl , -CH 2Br, -CH 2F , -CH 2I , -CN, -OR 19A , -NR 19A R 19B , -COOH, -CONH 2 , -NO 2 , -SH, -SO 3H , -SO 4H , -SO 2NH 2 , -NHNH 2 , -ONH 2 , -NHC(O)NHNH 2 , -NHC(O)NH 2 , -NHSO 2H , -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl 3 , -OCF 3 , -OCBr 3 , -OCI3 , -OCHCl2, -OCHBr2 , -OCHI2 , -OCHF2, -OCH2Cl , -OCH2Br , -OCH2I , -OCH2F , -N3 , -SF5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Or R 7 and R 19 together with the carbon atoms to which they are connected form a substituted or unsubstituted cycloalkylene or a substituted or unsubstituted heterocycloalkylene; R 11 is hydrogen, halogen, -CCl 3 , -CBr 3 , -CF 3 , -CI 3 , -CHCl 2