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KR-20260062926-A - Substituted condensed tricyclic amine compounds and their use as RAS inhibitors

KR20260062926AKR 20260062926 AKR20260062926 AKR 20260062926AKR-20260062926-A

Abstract

The present disclosure provides a compound of formula (Vc), a pharmaceutically acceptable salt thereof, and a method of using the same. The compound and the method have various applications as therapeutic, diagnostic, and research tools. In particular, the compositions and methods of the present invention are useful for reducing the signaling output of oncogenic proteins. .

Inventors

  • 우, 바오겐
  • 런, 핑다
  • 리, 리안셩

Assignees

  • 컴쿼트 바이오사이언시즈 인크.

Dates

Publication Date
20260507
Application Date
20240628
Priority Date
20230630

Claims (20)

  1. Compound of the following chemical formula (Vc): (Vc), Or as a pharmaceutically acceptable salt or solvate thereof, in the food: X is selected from C(R 6 ) and N; A is a hexavalent heteroaryl containing 1, 2, or 3 ring nitrogen atoms; R1 is hydrogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered heterocyclic), -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)OC(O)R 12 , -C(O)O-( C1-6 alkyl)-OR 15 , -( C1-6 alkyl)-OR 15 , -C(O) R12 , -C(O)N( R12 )( R13 ), -C(O)C(O)N( R12 )( R13 ), -S(O) 2R12 , -S(O)(NR12)R12 , -S (O) 2N (R12)( R13 ), and -S(O)( NR12 )N( R12 )( R13 ), selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl , 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered heterocyclic ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic ring) are optionally substituted with 1, 2, or 3 R 20 groups; R2 , R5 , and R8 are, in each case, hydrogen, halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered hetero ring), -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring), -OR12 , -OR15 , -O-( C1-6 alkyl) -OR15 , -SR12 , -N( R12 )( R13 ), -C(O) OR12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O) 2 R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), -S(O)(NR Independently selected from 12 )N(R 12 )(R 13 ), and -OCH 2 C(O)OR 12 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered hetero ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring) are optionally substituted with 1, 2, or 3 R 20 ; R3 is, in each case, a halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered hetero ring), -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring), -OR12 , -OR15 , -O-( C1-6 alkyl) -OR15 , -SR12 , -N( R12 )( R13 ), -C(O) OR12 , -OC(O)N( R12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O) 2 R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 Independently selected from )(R 13 ), and -OCH 2 C(O)OR 12 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered hetero ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring) are optionally substituted with 1, 2, or 3 R 20 ; Here, two R3 are optionally taken together with the atoms or atoms to which they are attached to form a C3-8 carbon ring or a 3 to 8 heteroring, each of which is optionally substituted with one, two, or three R20 ; furthermore, two R3 are optionally taken together to form =O, = NR12 , or =C( R14 ) 2 ; R 4 is a halogen, -CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered hetero ring), -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring), -OR 12 , -OR 15 , -O-(C 1-6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O) 2 R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), and selected from -OCH 2 C(O)OR 12 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered hetero ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring) are optionally substituted with 1, 2, or 3 R 20 ; R4 and R5 form a C4-8 carbon ring or a 4 to 8-membered heteroring together with the atoms to which they are attached, each of which is optionally substituted with 1, 2, or 3 R20 ; R3 and R4 form a 4 to 8-membered heteroring together with the atoms to which they are attached, optionally substituted with 1, 2, or 3 R20 ; R6 is hydrogen, halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered heterocyclic), -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic), -OR12 , -OR15 , -O-( C1-6 alkyl) -OR15 , -SR12 , -SF5 , -N( R12 )( R13 ), -C(O) OR12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O) 2 R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), -S(O)(NR 12 )N(R Selected from 12 )(R 13 ), and -OCH 2 C(O)OR 12 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered hetero ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring) are optionally substituted with 1, 2, or 3 R 20 ; R7 is selected from benzothiophenyl and thienopyridinyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from -OR 15 , -O-(C 1-6 alkyl )-OR 15 , -NH(C 1-6 alkyl)-OR 15 , -NHC(O)O-(C 1-6 alkyl)-OR 15 , (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-NH-, and R 20 ; m is 0, 1, 2, or 3, and; n is 1 or 2 and; R 12 is independently selected in each case from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12 heterocyclic), wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12 heterocyclic) are optionally substituted with 1, 2, or 3 R 20 ; R 13 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl in each case; R 12 and R 13 attached to the same nitrogen atom form a 3 to 10-membered heterocyclic group optionally substituted with one, two, or three R 20s ; R 14 is independently selected in each case from hydrogen, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12 heterocyclic ring), or two R 14s form a C 3-12 carbon ring or a 3 to 12 heterocyclic ring together with the carbon atoms to which they are attached, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12 heterocyclic ring), C 3-12 carbon ring, and 3 to 12 heterocyclic ring are optionally substituted with one, two, or three R 20s ; R 15 is independently selected from (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)R 12 , -P(O)(YR 16 )(ZR 17 ), and -CH 2 P(O)(YR 16 )(ZR 17 ) in each case; Y and Z are independently selected from -O- and -N(R 12 )- in each case; R16 and R17 are each independently selected from hydrogen, C1-6 alkyl, and phenyl in each case, wherein C1-6 alkyl and phenyl are hydrogen, -NO2 , -CN, C3-12 carbon ring, 3 to 12-membered heterocyclic ring, -OR12 , -SR12 , -N( R12 )( R13 ), -C(O) OR12 , -OC(O)N( R12 )( R13 ), -N( R12 )C(O)N( R12 )( R13 ), -N( R12 )C(O) OR12 , -N ( R12 )S(O) 2R12 , -N( R12 )S(O) 2N ( R12 )( R13 ), -SSR12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 ) 2 , -P(O)(R 12 ) 2 , -OP(O)(OR 12 ) 2 , Optionally substituted with 1, 2, or 3 substituents independently selected from =O, =S, and =NR 12 ; R 16 and R 17 are taken together with the atoms to which they are attached to form a 3 to 12-membered heterocyclic ring optionally substituted with 1, 2, or 3 R 20 ; R 20 is, in each case, hydrogen, oxo, -CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered heterocyclic), -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 ) 2 , -SF 5 , =N-OR 22 , =NN(R 22 )(R 23 ), -P(O)(R 22 )(R 23 ), -ON=R 22 , -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O) 2 R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -OS(O) 2 R 22 , -S(O) 2 R Independently selected from 22 , -S(O)(NR 22 )R 22 , -S(O) 2 N(R 22 )(R 23 )-, -S(O)(NR 22 )N(R 22 )(R 23 ), and -OCH 2 C(O)OR 22 ; two R 20 attached to the same or adjacent atoms are optionally combined to form a C 3-12 carbon ring or a 3- to 12 heteroring; Here, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered hetero ring), -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring), C3-12 carbon ring, and 3 to 12-membered hetero ring are halogen, oxo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -OR22 , -SR22 , -N( R22 )(R 23 ), =NR 22 , =C(R 21 ) 2 , -SF 5 , =N-OR 22 , =NN(R 22 )(R 23 ), -P(O)(R 22 )(R 23 ), -ON=R 22 , -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O) 2 R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), Optionally substituted with one or more substituents independently selected from -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 ) C (O)R 22 , -OS(O) 2 R 22 , -S(O) 2 R 22 , -S(O)(NR 22 )R 22 , -S(O) 2 N(R 22 )(R 23 ), and -S(O)(NR 22 )N(R 22 )(R 23 ); R 21 is independently selected in each case from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, -C 0-6 alkyl-(C 3-12 carbon ring), and -C 0-6 alkyl-(3 to 12 heterocyclic), or two R 21 are taken together with the carbon atoms to which they are attached to form a C 3-12 carbon ring or a 3 to 12 heterocyclic, each of which is optionally substituted with one, two, or three substituents independently selected from halogen, C 1-3 alkyl, C 1-3 haloalkyl, and -OH; R 22 is independently selected in each case from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, -C 0-6 alkyl-(C 3-12 carbon ring), and -C 0-6 alkyl-(3 to 12 heterocyclic ring); A compound or a pharmaceutically acceptable salt or solvate thereof, wherein R23 is independently selected from hydrogen and C1-6 alkyl in each case; and R22 and R23 attached to the same nitrogen atom form a 3 to 10-membered heterocyclic ring.
  2. Compound of the following chemical formula (I): (I), Or as a pharmaceutically acceptable salt or solvate thereof, in the food: X is selected from C(R 6 ) and N; A is a hexavalent heteroaryl containing 1, 2, or 3 ring nitrogen atoms; R1 is hydrogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered heterocyclic), -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)OC(O)R 12 , -C(O)O-( C1-6 alkyl)-OR 15 , -( C1-6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered heterocyclic ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic ring) are optionally substituted with 1, 2, or 3 R 20 groups; R2 , R3 , R5 , R6 , and R8 are, in each case, hydrogen, halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered hetero ring), -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring), -OR12 , -OR15 , -O-( C1-6 alkyl) -OR15 , -SR12 , -N( R12 )( R13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O) 2 R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 Each is independently selected from -S(O)(NR 12 )N(R 12 )(R 13 ), and -OCH 2 C(O)OR 12 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered hetero ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring) are optionally substituted with 1, 2, or 3 R 20 ; Two R3s are optionally taken together with the atoms or atoms to which they are attached to form a C3-8 carbon ring or a 3 to 8 heteroring, each of which is optionally substituted with one, two, or three R20s ; wherein additionally, two R3s are optionally taken together to form =O, = NR12 , or =C( R14 ) 2 ; R 4 is a halogen, -CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered hetero ring), -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring), -OR 12 , -OR 15 , -O-(C 1-6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O) 2 R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), and selected from -OCH 2 C(O)OR 12 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered hetero ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring) are optionally substituted with 1, 2, or 3 R 20 ; R4 and R5 form a C4-8 carbon ring or a 4 to 8-membered heteroring together with the atoms to which they are attached, each of which is optionally substituted with 1, 2, or 3 R20 ; R3 and R4 form a 4 to 8-membered heteroring together with the atoms to which they are attached, optionally substituted with 1, 2, or 3 R20 ; R7 is a benzothiophenyl optionally substituted with 1 , 2, 3, or 4 substituents independently selected from -OR15, -O-( C1-6 alkyl) -OR15 , -NH( C1-6 alkyl) -OR15 , -NHC(O)O-( C1-6 alkyl) -OR15 , (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-NH-, and R20 ; m is 0, 1, 2, or 3, and; n is 1 or 2 and; R 12 is independently selected in each case from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12 heterocyclic), wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12 heterocyclic) are optionally substituted with 1, 2, or 3 R 20 ; R 13 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl in each case; R 12 and R 13 attached to the same nitrogen atom form a 3 to 10-membered heterocyclic group optionally substituted with one, two, or three R 20s ; R 14 is independently selected in each case from hydrogen, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12 heterocyclic ring), or two R 14s form a C 3-12 carbon ring or a 3 to 12 heterocyclic ring together with the carbon atoms to which they are attached, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12 heterocyclic ring), C 3-12 carbon ring, and 3 to 12 heterocyclic ring are optionally substituted with one, two, or three R 20s ; R 15 is independently selected from (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)R 12 , -P(O)(YR 16 )(ZR 17 ), and -CH 2 P(O)(YR 16 )(ZR 17 ) in each case; Y and Z are independently selected from -O- and -N(R 12 )- in each case; R16 and R17 are each independently selected from hydrogen, C1-6 alkyl, and phenyl in each case, wherein C1-6 alkyl and phenyl are hydrogen, -NO2 , -CN, C3-12 carbon ring, 3 to 12-membered heterocyclic ring, -OR12 , -SR12 , -N( R12 )( R13 ), -C(O) OR12 , -OC(O)N( R12 )( R13 ), -N( R12 )C(O)N( R12 )( R13 ), -N( R12 )C(O) OR12 , -N ( R12 )S(O) 2R12 , -N( R12 )S(O) 2N ( R12 )( R13 ), -SSR12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 ) 2 , -P(O)(R 12 ) 2 , -OP(O)(OR 12 ) 2 , Optionally substituted with 1, 2, or 3 substituents independently selected from =O, =S, and =NR 12 ; R 16 and R 17 are taken together with the atoms to which they are attached to form a 3 to 12-membered heterocyclic ring optionally substituted with 1, 2, or 3 R 20 ; R 20 is, in each case, hydrogen, oxo, -CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered heterocyclic), -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 ) 2 , -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O) 2 R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -OS(O) 2 R 22 , -S(O) 2 R 22 , -S(O)(NR 22 )R 22 , -S(O) 2 N(R 22 )(R 23 )-, -S(O)(NR 22 Independently selected from )N(R 22 )(R 23 ), and -OCH 2 C(O)OR 22 ; two R 20 attached to the same or adjacent atoms are optionally combined to form a C 3-12 carbon ring or a 3- to 12 heteroring; Here, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered hetero ring), -(2 to 6-membered heteroalkyl)-(3 to 12-membered hetero ring), C3-12 carbon ring, and 3 to 12-membered hetero ring are halogen, oxo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -OR22 , -SR22 , -N( R22 )(R 23 ), =NR 22 , =C(R 21 ) 2 , -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O) 2 R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -OS(O) 2 R 22 , -S(O) 2 R 22 , Optionally substituted with one or more substituents independently selected from -S(O)(NR 22 )R 22 , -S(O) 2 N(R 22 )(R 23 ), and -S(O)(NR 22 )N(R 22 )(R 23 ); R 21 is independently selected in each case from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, -C 0-6 alkyl-(C 3-12 carbon ring), and -C 0-6 alkyl-(3 to 12 heterocyclic), or two R 21 are taken together with the carbon atoms to which they are attached to form a C 3-12 carbon ring or a 3 to 12 heterocyclic, each of which is optionally substituted with one, two, or three substituents independently selected from halogen, C 1-3 alkyl, C 1-3 haloalkyl, and -OH; R 22 is independently selected in each case from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, -C 0-6 alkyl-(C 3-12 carbon ring), and -C 0-6 alkyl-(3 to 12 heterocyclic ring); A compound or a pharmaceutically acceptable salt or solvate thereof, wherein R23 is independently selected from hydrogen and C1-6 alkyl in each case; and R22 and R23 attached to the same nitrogen atom form a 3 to 10-membered heterocyclic ring.
  3. In paragraph 1 or 2, X is a compound, salt, or solvate of C( R6 ).
  4. In paragraph 1 or 2, X is a compound, salt, or solvate in which X is N.
  5. In any one of claims 1 to 4, A is a compound, salt, or solvate selected from pyridinyl, pyridazinyl, pyrimidinyl, and pyrazinyl.
  6. In any one of paragraphs 1 to 4, A is a compound, salt, or solvate of pyridinyl.
  7. In any one of paragraphs 1 to 6, R1 is a compound, salt, or solvate in which R1 is hydrogen.
  8. A compound, salt, or solvate of any one of claims 1 to 7, wherein R7 is optionally benzo[b]thiophene-4-yl substituted with 1, 2, or 3 R20 .
  9. In any one of claims 1 to 8, R7 is a compound, salt, or solvate substituted with fluorine, -CN, and -NH2 .
  10. In any one of paragraphs 1 through 9, R 7 is Phosphorus, compound, salt, or solvate.
  11. In claim 1 or 2, having the structure of the following chemical formula (II-a): (II-a), A compound, salt, or solvate that is a pharmaceutically acceptable salt or solvate thereof.
  12. A compound, salt, or solvate according to any one of claims 1 to 11, wherein R3 is independently selected in each case from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 carbon ring, and 3 to 8 heterocyclic rings, each of which is optionally substituted with 1, 2, or 3 R20 .
  13. A compound, salt, or solvate according to any one of claims 1 to 11, wherein R3 is independently selected in each case from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 carbon ring, and 3 to 8 heterocyclic rings, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, -CN, -OH, and -OCH3.
  14. A compound, salt, or solvate according to any one of claims 1 to 13, wherein m is 0 or 1.
  15. A compound, salt, or solvate in any one of claims 1 to 11, wherein m is 0.
  16. In any one of claims 1 to 15, R6 and R8 are compounds, salts, or solvates independently selected from hydrogen, halogens, and C1-3 haloalkyls.
  17. In any one of paragraphs 1 to 16, R6 is a compound, salt, or solvate in which chlorine.
  18. In any one of paragraphs 1 to 17, R 8 is a compound, salt, or solvate of fluorine.
  19. A compound, salt, or solvate of any one of claims 1 to 18, wherein n is 1.
  20. In any one of claims 1 to 19, R2 is a compound, salt, or solvate in which -OR 12 .

Description

Substituted condensed tricyclic amine compounds and their use as RAS inhibitors Cross-reference This application claims the benefit of U.S. Provisional Application No. 63/511,279 filed June 30, 2023; U.S. Provisional Application No. 63/513,796 filed July 14, 2023; U.S. Provisional Application No. 63/582,484 filed September 13, 2023; U.S. Provisional Application No. 63/600,560 filed November 17, 2023; and U.S. Provisional Application No. 63/646,597 filed May 13, 2024, the entire contents of each of said documents being incorporated herein by reference. Sequence list The present application includes a sequence list submitted electronically in XML format, the entirety of which is incorporated herein by reference. The XML copy created on June 20, 2024, is named 56690_771_601_SL.xml and has a size of 14,003 bytes. Cancer (e.g., tumors, neoplasms, metastases) is the second leading cause of death worldwide, with an estimated 10 million deaths annually. Many types of cancer are characterized by mutations in one or more proteins involved in various signaling pathways that lead to the uncontrolled growth of cancer cells. In some cases, it is known that about 25 to 30 percent of tumors carry rat sarcoma (Ras) mutations. In particular, mutations in the Kirsten Ras oncogene (K-Ras) are one of the most common Ras mutations detected in human cancers, including lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC). Ras proteins have long been considered "undruggable" due, in part, to their high affinity for their substrate, guanosine-5'-triphosphate (GTP), and/or to their smooth surfaces lacking any distinct target sites. Specific G12C Ras gene mutations have been formulated as drug-treatable targets, for which numerous G12C-specific inhibitors have been developed. However, because G12C mutations in Ras exhibit a much lower prevalence compared to other known Ras mutations such as G12D and G12V, the application of these therapies remains limited. Drug resistance and a lack of persistence impose additional limitations on these therapies. In light of the foregoing, there remains a significant need for the design of novel therapeutics and diagnostic agents capable of specifically targeting Ras, including wild-type Ras, mutants, and/or Ras-related proteins, to reduce Ras signaling output. Of particular interest are Ras inhibitors, including pan-Ras inhibitors capable of inhibiting two or more Ras mutants and/or wild-type Ras, as well as mutant-selective inhibitors that target mutant Ras proteins such as Ras G12D, G12C, G12S, G13D, and/or G12V, for the treatment of Ras-related diseases (e.g., cancer). Such compositions and methods may be particularly useful for treating a variety of diseases, including but not limited to cancers and neoplastic pathologies. The present disclosure addresses these needs and provides additional benefits applicable to the diagnosis, prognosis, and/or treatment of a wide range of diseases. In a given embodiment, the present disclosure relates to a compound of formula (I): (I), or provides a pharmaceutically acceptable salt or solvate thereof, and in the food: X is selected from C(R 6 ) and N; A is a hexavalent heteroaryl containing 1, 2, or 3 ring nitrogen atoms; R1 is hydrogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered heterocyclic), -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)OC(O)R 12 , -C(O)O-( C1-6 alkyl)-OR 15 , -( C1-6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S(O) 2 N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C 0-6 alkyl-(C 3-12 carbon ring), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 alkyl-(3 to 12-membered heterocyclic ring), and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic ring) are optionally substituted with 1, 2, or 3 R 20 groups; R2 , R3 , R5 , R6 , and R8 are, in each case, hydrogen, halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2 to 6-membered heteroalkyl, 3 to 6-membered heteroalkenyl, 3 to 6-membered heteroalkynyl, -C0-6 alkyl-( C3-12 carbon ring), -(2 to 6-membered heteroalkyl)-( C3-12 carbon ring), -C0-6 alkyl-(3 to 12-membered heterocyclic), -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic), -OR12 , -OR15 , -O-( C1-6 alkyl) -OR15 , -SR12 , -N( R12 )( R13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O) 2 R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O) 2 R 12 , -S(O)(NR 12 )R 12 , -S