Degradation agents and uses thereof
By designing compounds that specifically target the Ras protein, binding to and enhancing its degradation, the problem of poor efficacy of existing therapeutic agents against the Ras protein, especially the G12C mutant Ras, has been solved. This has enabled effective inhibition and degradation of various Ras mutants, thus improving the efficacy of cancer treatment.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- KUMQUAT BIOSCIENCES INC
- Filing Date
- 2024-10-31
- Publication Date
- 2026-06-16
AI Technical Summary
Existing therapeutic agents have difficulty effectively targeting and degrading Ras proteins, especially G12C mutant Ras, leading to limited efficacy in cancer treatment and problems with drug resistance.
A class of compounds has been developed that are designed as Ras protein degraders that specifically target Ras protein by binding to and enhancing its degradation. These compounds can bind to a variety of Ras mutants and wild-type Ras, including G12C, G12D, G12S, G13D, and G12V, and utilize specific chemical structures to bind to and enhance the degradation of Ras protein.
It achieves effective inhibition and degradation of multiple Ras mutants, improves the efficacy of cancer treatment, reduces drug resistance, and provides additional advantages for the diagnosis, prognosis, and treatment of various diseases.
Smart Images
Figure CN122228262A_ABST
Abstract
Claims
1. A compound of formula (A0): (A0)， Or a pharmaceutically acceptable salt or solvate thereof, wherein: Z 1 Selected from N and N(R) B1b ); Z 2 Selected from C(R) B2 ) and C(O); Z B5 Selected from C(R) B9 )2 and O; Z 6 Selected from C(R) B6 ), C(R B6 2. N and N(R) B6b ); Z 7 Selected from C(R) B7 ) and N(R B7b ); Z 8 Selected from C(R) B8 ), C(R B8 )2 and N; Q 2 It is optionally controlled by one or more R B20 Replaced 4- to 12-membered heterocycles; J 1 Selected from key, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -O-, -N(R) B12 -, -C(O)-, -N(R) B12 )C(O)-、-C(O)N(R B12 )-, -S-, -S(O)2-, -S(O)-, -P(O)R B12 -、-N(R B12 )S(O)2-、-N(R B12 )S(O)-、-N(R B12 )P(O)R B12 -、-S(O)2N(R B12 )-、-S(O)N(R B12 )-、-P(O)R B12 N(R B12 )-, -OS(O)2-, -OS(O)-, -OP(O)R B12 -, -S(O)2O-, -S(O)O- and -P(O)R B12 O-, where C 1-6 Alkylene, C 2-6 imidene group, C 2-6 The ynyl group, 2- to 6-membered heteroalkyl group, 3- to 6-membered heteroenyl group, and 3- to 6-membered heteroynyl group are optionally separated by one or more R groups. B20 replace; J 2 Selected from key, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, wherein -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)- optionally separated by one or more R B20 replace; J 3 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, each of which is optionally divided by one or more R B20 replace; DG is a degradation enhancer; n1 is selected from 1, 2, and 3; R B1b R B6b and R B7b Independently selected from hydrogen, -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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), -C(O)OR B12 -C(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) are optionally separated by one, two or three R B20 replace; R B2 R B6 R B7 and R B8 Each time it appears, it is independently selected from hydrogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B12 -SR B12 -N(R) B12 (R) B13 -C(O)OR B12 -OC(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)N(R B12 (R) B13 ), -N(R B12 )C(O)OR B12 -N(R) B12 )S(O)2R B12 -C(O)R B12 -S(O)R B12 -OC(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)R B12 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) optionally separated by one or more R B20 replace; R B9 Each time it appears, it is independently selected from hydrogen and R. B20 ; R B12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3 to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle) optionally surrounded by one or more R groups B20 replace; R B13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; or R groups attached to the same nitrogen atom B12 and R B13 Formed optionally by one or more R B20 Replaced 3- to 10-membered heterocycles; R B20 Each time it appears, it is independently selected from halogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 - and -S(=O)(=NR B22 )N(R B22 (R) B23 ); where two R atoms connected to the same or adjacent atoms B20 Optional connection to form C 3-12 Carbon rings or 3 to 12-membered heterocycles; 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), C 3-12 The carbocyclic ring and the 3 to 12-membered heterocycle are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 ) and -S(=O)(=NR B22 )N(R B22 (R) B23 ); R B21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle), or two R groups B21 Together with the carbon atoms they are attached to, they form C 3-12 A carbocyclic or 3 to 12-membered heterocyclic ring, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and -OH; R B22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocyclic rings); R B23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R groups attached to the same nitrogen atom B22 and R B23 Formation of 3- to 10-membered heterocycles; and This indicates a single or double bond, such that all valences are satisfied.
2. A compound of formula (A): (A)， Or a pharmaceutically acceptable salt or solvate thereof, wherein: Z 1 Selected from N and N(R) B1b ); Z 2 Selected from C(R) B2 ) and C(O); Z 6 Selected from C(R) B6 ), C(R B6 2. N and N(R) B6b ); Z 7 Selected from C(R) B7 ) and N(R B7b ); Z 8 Selected from C(R) B8 ), C(R B8 )2 and N; Q 2 It is optionally controlled by one or more R B20 Replaced 4- to 12-membered heterocycles; J 1 Selected from key, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -O-, -N(R) B12 -, -C(O)-, -N(R) B12 )C(O)-、-C(O)N(R B12 )-, -S-, -S(O)2-, -S(O)-, -P(O)R B12 -、-N(R B12 )S(O)2-、-N(R B12 )S(O)-、-N(R B12 )P(O)R B12 -、-S(O)2N(R B12 )-、-S(O)N(R B12 )-、-P(O)R B12 N(R B12 )-, -OS(O)2-, -OS(O)-, -OP(O)R B12 -, -S(O)2O-, -S(O)O- and -P(O)R B12 O-, where C 1-6 Alkylene, C 2-6 imidene group, C 2-6 The ynyl group, 2- to 6-membered heteroalkyl group, 3- to 6-membered heteroenyl group, and 3- to 6-membered heteroynyl group are optionally separated by one or more R groups. B20 replace; J 2 Selected from key, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, wherein -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)- optionally separated by one or more R B20 replace; J 3 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, each of which is optionally divided by one or more R B20 replace; DG is a degradation enhancer; n1 is selected from 1, 2, and 3; R B1b R B6b and R B7b Independently selected from hydrogen, -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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), -C(O)OR B12 -C(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) are optionally separated by one, two or three R B20 replace; R B2 R B6 R B7 and R B8 Each time it appears, it is independently selected from hydrogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B12 -SR B12 -N(R) B12 (R) B13 -C(O)OR B12 -OC(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)N(R B12 (R) B13 ), -N(R B12 )C(O)OR B12 -N(R) B12 )S(O)2R B12 -C(O)R B12 -S(O)R B12 -OC(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)R B12 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) optionally separated by one or more R B20 replace; R B9 Each time it appears, it is independently selected from hydrogen and R. B20 ; R B12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3 to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle) optionally surrounded by one or more R groups B20 replace; R B13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; or R groups attached to the same nitrogen atom B12 and R B13 Formed optionally by one or more R B20 Replaced 3- to 10-membered heterocycles; R B20 Each time it appears, it is independently selected from halogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 - and -S(=O)(=NR B22 )N(R B22 (R) B23 ); where two R atoms connected to the same or adjacent atoms B20 Optional connection to form C 3-12 Carbon rings or 3 to 12-membered heterocycles; 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), C 3-12 The carbocyclic ring and the 3 to 12-membered heterocycle are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 ) and -S(=O)(=NR B22 )N(R B22 (R) B23 ); R B21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle), or two R groups B21 Together with the carbon atoms they are attached to, they form C 3-12 A carbocyclic or 3 to 12-membered heterocyclic ring, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and -OH; R B22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocyclic rings); R B23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R groups attached to the same nitrogen atom B22 and R B23 Formation of 3- to 10-membered heterocycles; and This indicates a single or double bond, such that all valences are satisfied.
3. The compound, salt, or solvate according to any one of claims 1 to 2, wherein the degradation enhancer is capable of binding to proteins selected from: E3A, mdm2, APC, EDD1, SOCS / BC-box / eloBC / CUL5 / RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, H ERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von-Hippel-Lindau ubiquitin ligase), WWP1, WWP2, perkinin, MKRN1, CMA (molecular chaperone-mediated autophagy), SCFb-TRCP (jumping-hysteresis-F-box (β-TRCP) ubiquitin complex), b-TRCP (protein containing b-transduction repeat sequence), cIAP1 (cell inhibitor of apoptosis protein 1), APC / C (late-phase promoter complex / cell cycle body), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4C) RBN Ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadoline, iberdoline, and CC-885.
4. The compound, salt, or solvate according to any one of claims 1 to 2, wherein the degradation enhancer is capable of binding to proteins selected from the group consisting of: UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1.
5. The compound, salt, or solvate according to any one of the preceding claims, wherein DG is selected from: and , in: J 4 Selected from bonds, 2- to 10-membered heteroalkyl, 3- to 10-membered heteroenyl and 3- to 10-membered heteroynyl, wherein the 2- to 10-membered heteroalkyl, 3- to 10-membered heteroenyl and 3- to 10-membered heteroynyl are optionally separated by one or more R B20 replace; R B15 Selected from hydrogen, C 1-6 Alkyl, C 3-8 Carbon rings and 3 to 8-membered heterocycles, of which C 1-6 Alkyl, C 3-8 The carbon ring and 3 to 8-membered heterocycles are optionally separated by one or more R B20 replace; R B16 Selected from hydrogen, C 1-6 Alkyl, -OR B12 -C(O)OR B12 and -C(O)R B12 C 1-6 Alkyl groups are optionally surrounded by one or more R B20 replace; R B17 Selected from halogens, -CN, C 1-3 Alkyl, C 3-6 Carbon rings, 4- to 6-membered heterocycles, and -S(O)2CH3, wherein C 1-3 Alkyl, C 3-6 The carbon ring and 4- to 6-membered heterocycles are optionally separated by one or more R B20 replace; o1 is selected from 0, 1, and 2; p1 and q1 are independently selected from 1, 2, and 3; and X is selected from CH2 and C(O).
6. The compound, salt, or solvate according to any one of the preceding claims, wherein DG is .
7. A method for preparing a compound of formula (A0): (A0)， The method includes: (a) Reacting the compound of formula (a0) with a degradation enhancer under conditions that achieve LG release and the generation of the compound of formula (A0), (a0)， in: Z 1 Selected from N and N(R) B1b ); Z 2 Selected from C(R) B2 ) and C(O); Z B5 Selected from C(R) B9 )2 and O; Z 6 Selected from C(R) B6 ), C(R B6 2. N and N(R) B6b ); Z 7 Selected from C(R) B7 ) and N(R B7b ); Z 8 Selected from C(R) B8 ), C(R B8 )2 and N; Q 2 It is optionally controlled by one or more R B20 Replaced 4- to 12-membered heterocycles; J 1 Selected from key, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -O-, -N(R) B12 -, -C(O)-, -N(R) B12 )C(O)-、-C(O)N(R B12 )-, -S-, -S(O)2-, -S(O)-, -P(O)R B12 -、-N(R B12 )S(O)2-、-N(R B12 )S(O)-、-N(R B12 )P(O)R B12 -、-S(O)2N(R B12 )-、-S(O)N(R B12 )-、-P(O)R B12 N(R B12 )-, -OS(O)2-, -OS(O)-, -OP(O)R B12 -, -S(O)2O-, -S(O)O- and -P(O)R B12 O-, where C 1-6 Alkylene, C 2-6 imidene group, C 2-6 The ynyl group, 2- to 6-membered heteroalkyl group, 3- to 6-membered heteroenyl group, and 3- to 6-membered heteroynyl group are optionally separated by one or more R groups. B20 replace; J 2 Selected from key, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, wherein -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)- optionally separated by one or more R B20 replace; J 3 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, each of which is optionally divided by one or more R B20 replace; DG is a degradation enhancer; LG is a leaving group; n1 is selected from 1, 2, and 3; R B1b R B6b and R B7b Independently selected from hydrogen, -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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), -C(O)OR B12 -C(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) are optionally separated by one, two or three R B20 replace; R B2 R B6 R B7 and R B8 Each time it appears, it is independently selected from hydrogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B12 -SR B12 -N(R) B12 (R) B13 -C(O)OR B12 -OC(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)N(R B12 (R) B13 ), -N(R B12 )C(O)OR B12 -N(R) B12 )S(O)2R B12 -C(O)R B12 -S(O)R B12 -OC(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)R B12 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) optionally separated by one or more R B20 replace; R B9 Each time it appears, it is independently selected from hydrogen and R. B20 ; R B12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3 to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle) optionally surrounded by one or more R groups B20 replace; R B13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; or R groups attached to the same nitrogen atom B12 and R B13 Formed optionally by one or more R B20 Replaced 3- to 10-membered heterocycles; R B20 Each time it appears, it is independently selected from halogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 - and -S(=O)(=NR B22 )N(R B22 (R) B23 ); where two R atoms connected to the same or adjacent atoms B20 Optional connection to form C 3-12 Carbon rings or 3 to 12-membered heterocycles; 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), C 3-12 The carbocyclic ring and the 3 to 12-membered heterocycle are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 ) and -S(=O)(=NR B22 )N(R B22 (R) B23 ); R B21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle), or two R groups B21 Together with the carbon atoms they are attached to, they form C 3-12 A carbocyclic or 3 to 12-membered heterocyclic ring, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and -OH; R B22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocyclic rings); R B23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R groups attached to the same nitrogen atom B22 and R B23 Formation of 3- to 10-membered heterocycles; and This indicates a single or double bond, such that all valences are satisfied.
8. A compound of formula (a0): (a0)， Or a pharmaceutically acceptable salt or solvate thereof, wherein: Z 1 Selected from N and N(R) B1b ); Z 2 Selected from C(R) B2 ) and C(O); Z B5 Selected from C(R) B9 )2 and O; Z 6 Selected from C(R) B6 ), C(R B6 2. N and N(R) B6b ); Z 7 Selected from C(R) B7 ) and N(R B7b ); Z 8 Selected from C(R) B8 ), C(R B8 )2 and N; Q 2 It is optionally controlled by one or more R B20 Replaced 4- to 12-membered heterocycles; J 1 Selected from key, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -O-, -N(R) B12 -, -C(O)-, -N(R) B12 )C(O)-、-C(O)N(R B12 )-, -S-, -S(O)2-, -S(O)-, -P(O)R B12 -、-N(R B12 )S(O)2-、-N(R B12 )S(O)-、-N(R B12 )P(O)R B12 -、-S(O)2N(R B12 )-、-S(O)N(R B12 )-、-P(O)R B12 N(R B12 )-, -OS(O)2-, -OS(O)-, -OP(O)R B12 -, -S(O)2O-, -S(O)O- and -P(O)R B12 O-, where C 1-6 Alkylene, C 2-6 imidene group, C 2-6 The ynyl group, 2- to 6-membered heteroalkyl group, 3- to 6-membered heteroenyl group, and 3- to 6-membered heteroynyl group are optionally separated by one or more R groups. B20 replace; J 2 Selected from key, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, wherein -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)- optionally separated by one or more R B20 replace; J 3 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, each of which is optionally divided by one or more R B20 replace; LG is selected from -OS(O)2R B4 and -OS(O)(NR B4b )R B4 ; n1 is selected from 1, 2, and 3; R B4 Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6 heteroalkyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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) and -N(R B12 (R) B13 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6 heteroalkyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) optionally separated by one or more R B20 replace; R B1b R B4b R B6b and R B7b Independently selected from hydrogen, -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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), -C(O)OR B12 -C(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) are optionally separated by one, two or three R B20 replace; R B2 R B6 R B7 and R B8 Each time it appears, it is independently selected from hydrogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B12 -SR B12 -N(R) B12 (R) B13 -C(O)OR B12 -OC(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)N(R B12 (R) B13 ), -N(R B12 )C(O)OR B12 -N(R) B12 )S(O)2R B12 -C(O)R B12 -S(O)R B12 -OC(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)R B12 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) optionally separated by one or more R B20 replace; R B9 Each time it appears, it is independently selected from hydrogen and R. B20 ; R B12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3 to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle) optionally surrounded by one or more R groups B20 replace; R B13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; or R groups attached to the same nitrogen atom B12 and R B13 Formed optionally by one or more R B20 Replaced 3- to 10-membered heterocycles; R B20 Each time it appears, it is independently selected from halogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 - and -S(=O)(=NR B22 )N(R B22 (R) B23 ); where two R atoms connected to the same or adjacent atoms B20 Optional connection to form C 3-12 Carbon rings or 3 to 12-membered heterocycles; 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), C 3-12 The carbocyclic ring and the 3 to 12-membered heterocycle are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 ) and -S(=O)(=NR B22 )N(R B22 (R) B23 ); R B21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle), or two R groups B21 Together with the carbon atoms they are attached to, they form C 3-12 A carbocyclic or 3 to 12-membered heterocyclic ring, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and -OH; R B22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocyclic rings); R B23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R groups attached to the same nitrogen atom B22 and R B23 Formation of 3- to 10-membered heterocycles; and This indicates a single or double bond, such that all valences are satisfied.
9. A compound of formula (a): (a)， Or a pharmaceutically acceptable salt or solvate thereof, wherein: Z 1 Selected from N and N(R) B1b ); Z 2 Selected from C(R) B2 ) and C(O); Z 6 Selected from C(R) B6 ), C(R B6 2. N and N(R) B6b ); Z 7 Selected from C(R) B7 ) and N(R B7b ); Z 8 Selected from C(R) B8 ), C(R B8 )2 and N; Q 2 It is optionally controlled by one or more R B20 Replaced 4- to 12-membered heterocycles; J 1 Selected from key, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -O-, -N(R) B12 -, -C(O)-, -N(R) B12 )C(O)-、-C(O)N(R B12 )-, -S-, -S(O)2-, -S(O)-, -P(O)R B12 -、-N(R B12 )S(O)2-、-N(R B12 )S(O)-、-N(R B12 )P(O)R B12 -、-S(O)2N(R B12 )-、-S(O)N(R B12 )-、-P(O)R B12 N(R B12 )-, -OS(O)2-, -OS(O)-, -OP(O)R B12 -, -S(O)2O-, -S(O)O- and -P(O)R B12 O-, where C 1-6 Alkylene, C 2-6 imidene group, C 2-6 The ynyl group, 2- to 6-membered heteroalkyl group, 3- to 6-membered heteroenyl group, and 3- to 6-membered heteroynyl group are optionally separated by one or more R groups. B20 replace; J 2 Selected from key, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, wherein -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)- optionally separated by one or more R B20 replace; J 3 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Alynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroenyl, 3- to 6-membered heteroynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic)-, -(2 to 6-membered heteroalkyl)-(C 3-12 (Carbon ring)-, -C 0-6 Alkyl-(3 to 12-membered heterocyclic)- and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocyclic)-, each of which is optionally divided by one or more R B20 replace; LG is selected from -OS(O)2R B4 and -OS(O)(NR B4b )R B4 ; n1 is selected from 1, 2, and 3; R B4 Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6 heteroalkyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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) and -N(R B12 (R) B13 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2 to 6 heteroalkyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) optionally separated by one or more R B20 replace; R B1b R B4b R B6b and R B7b Independently selected from hydrogen, -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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), -C(O)OR B12 -C(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) are optionally separated by one, two or three R B20 replace; R B2 R B6 R B7 and R B8 Each time it appears, it is independently selected from hydrogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B12 -SR B12 -N(R) B12 (R) B13 -C(O)OR B12 -OC(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)N(R B12 (R) B13 ), -N(R B12 )C(O)OR B12 -N(R) B12 )S(O)2R B12 -C(O)R B12 -S(O)R B12 -OC(O)R B12 -C(O)N(R) B12 (R) B13 -C(O)C(O)N(R) B12 (R) B13 ), -N(R B12 )C(O)R B12 -S(O)2R B12 -S(O)(NR) B12 )R B12 -S(O)2N(R) B12 (R) B13 ) and -S(=O)(=NR B12 )N(R B12 (R) B13 ), where 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(2 to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3 to 12-membered heterocycle) and -(2 to 6-membered heteroalkyl)-(3 to 12-membered heterocycle) optionally separated by one or more R B20 replace; R B9 Each time it appears, it is independently selected from hydrogen and R. B20 ; R B12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3 to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle) optionally surrounded by one or more R groups B20 replace; R B13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; or R groups attached to the same nitrogen atom B12 and R B13 Formed optionally by one or more R B20 Replaced 3- to 10-membered heterocycles; R B20 Each time it appears, it is independently selected from halogen, 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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 B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 - and -S(=O)(=NR B22 )N(R B22 (R) B23 ); where two R atoms connected to the same or adjacent atoms B20 Optional connection to form C 3-12 Carbon rings or 3 to 12-membered heterocycles; 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 heteroynyl, -C 0-6 Alkyl-(C 3-12 Carbocyclic), -(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), C 3-12 The carbocyclic ring and the 3 to 12-membered heterocycle are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR B22 -SR B22 -N(R) B22 (R) B23 =NR B22 =C(R) B21 )2、-C(O)OR B22 -OC(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)N(R B22 (R) B23 ), -N(R B22 )C(O)OR B22 -N(R) B22 )S(O)2R B22 -C(O)R B22 -S(O)R B22 -OC(O)R B22 -C(O)N(R) B22 (R) B23 -C(O)C(O)N(R) B22 (R) B23 ), -N(R B22 )C(O)R B22 -S(O)2R B22 -S(O)(NR) B22 )R B22 -S(O)2N(R) B22 (R) B23 ) and -S(=O)(=NR B22 )N(R B22 (R) B23 ); R B21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocycle), or two R groups B21 Together with the carbon atoms they are attached to, they form C 3-12 A carbocyclic or 3 to 12-membered heterocyclic ring, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and -OH; R B22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3 to 12-membered heterocyclic rings); R B23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R groups attached to the same nitrogen atom B22 and R B23 Formation of 3- to 10-membered heterocycles; and This indicates a single or double bond, such that all valences are satisfied.
10. The compound, salt, solvate, or method according to any one of claims 1 to 8, wherein Z B5 It is C(R) B9 )2.
11. The compound, salt, solvate, or method according to any one of claims 1 to 10, wherein n1 is 1.
12. The compound, salt, solvate, or method according to any one of claims 1 to 11, wherein Q 2 It is optionally controlled by one or more R B20 Substituted 7- to 9-membered bridged bicyclic heterocyclic alkyl groups.
13. The compound, salt, solvate, or method according to claim 12, wherein... yes It is optionally controlled by one or more R B20 replace.
14. The compound, salt, solvate, or method according to any one of the preceding claims, wherein: Z 1 It is N, Z 2 It is C(R) B2 Z 6 It is C(R) B6 Z 7 It is C(R) B7 ), and Z 8 It is C(R) B8 ); Z 1 It is N, Z 2 It is C(R) B2 Z 6 It is N, Z 7 It is C(R) B7 ), and Z 8 It is C(R) B8 ); Z 1 It is N, Z 2 It is C(R) B2 Z 6 It is C(R) B6 )2、Z 7 It is N(R) B7b ), and Z 8 It is C(R) B8 )2; or Z 1 It is N(R) B1b Z 2 It is C(O), Z 6 It is C(R) B6 Z 7 It is C(R) B7 ), and Z 8 It is N.
15. The compound, salt, solvate, or method according to claim 14, wherein Z 1 It is N, Z 2 It is C(R) B2 Z 6 It is C(R) B6 Z 7 It is C(R) B7 ), and Z 8 It is C(R) B8 ).
16. The compound, salt, solvate, or method according to claim 14, wherein Z 1 It is N, Z 2 It is C(R) B2 Z 6 It is N, Z 7 It is C(R) B7 ), and Z 8 It is C(R) B8 ).
17. The compound, salt, solvate, or method according to any one of the preceding claims, wherein J 1 Selected from key, C 1-6 Alkylene, 2- to 6-membered heteroalkylene and -C(O)-, wherein C 1-6 Alkylenes and 2- to 6-membered heteroalkylenes are optionally separated by one or more R B20 replace.
18. The compound, salt, solvate, or method according to any one of the preceding claims, wherein J 1 It is -C(O)-.
19. The compound, salt, solvate, or method according to any one of the preceding claims, wherein J 2 It is a key.
20. The compound, salt, solvate, or method according to any one of the preceding claims, wherein J 3 Selected from C 1-6 Alkylenes and 2 to 6-membered heteroalkylenes, each of which is optionally bounded by one or more R B20 replace.
21. The compound, salt, solvate, or method according to any one of claims 1 to 16, wherein: J 1 It is -C(O)-; J 2 It is a key; and J 3 It is C 1-6 Alkylene.
22. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B2 It is -O(C 1-3 Alkylene (4 to 10-membered heterocycle), wherein the 4 to 10-membered heterocycle is optionally substituted by one, two or three independent substituents selected from the following: halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and =C(R) B21 )2, and where R B21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-3 alkyl.
23. The compound, salt, solvate, or method according to any one of claims 1 to 21, wherein R B2 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , and .
24. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B2 yes .
25. The compound, salt, solvate, or method according to any one of claims 1 to 21, wherein R B2 Selected from , , , , , , , , , , and .
26. The compound, salt, solvate, or method according to any one of claims 1 to 21, wherein R B2 yes .
27. The compound, salt, solvate, or method according to any one of claims 1 to 21, wherein R B2 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .
28. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B6 Is it halogen or C? 1-3 Halogenated alkyl groups.
29. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B7 Selected from C 6-12 aryl and 5 to 12 heteroaryl groups, each of which is optionally divided by one or more R B20 replace.
30. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B7 Selected from naphthyl, isoquinolinyl, indazole, benzothiazolyl, benzothiophene, phenyl, and pyridyl, each of which is optionally marked by one or more R... B20 replace.
31. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B7 It is substituted by one, two, three or four independent substituents selected from the following: halogen, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl, C 2-3 alkenyl, C 2-3 Alkyne group, -OR B22 -N(R) B22 (R) B23 ) and C 3-6 Cycloalkyl.
32. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B7 It is substituted by one, two, three or four independent substituents selected from the following: halogen, -CN, -CH3, -CH2CH3, -CH=CH2, -CF3, -C≡CH, -OH, -NH2 and -cyclopropyl.
33. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B7 Selected from , , , , , , , , , , , , , , , , , , and .
34. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B7 yes .
35. The compound, salt, solvate, or method according to any one of claims 1 to 28, wherein R B7 Selected from , , , , , , , and .
36. The compound, salt, solvate, or method according to any one of claims 1 to 28, wherein R B7 yes .
37. The compound, salt, solvate, or method according to any one of claims 1 to 28, wherein R B7 yes .
38. The compound, salt, solvate, or method according to any one of claims 1 to 28, wherein R B7 yes .
39. The compound, salt, solvate, or method according to any one of claims 1 to 28, wherein R B7 yes .
40. The compound, salt, solvate, or method according to any one of claims 1 to 28, wherein R B7 yes .
41. The compound, salt, solvate, or method according to any one of the preceding claims, wherein R B8 It is halogen.
42. The compound, salt, solvate, or method according to any one of claims 1 to 28, wherein: R B6 It is halogen; R B7 Selected from naphthyl, isoquinolinyl, indazole, benzothiazolyl, benzothiophene, phenyl, and pyridyl, each of which is optionally marked by one or more R... B20 Replace; and R B8 It is halogen.
43. The compound, salt, solvate, or method according to any one of claims 1 to 21, wherein: R B2 Selected from , , , , and ; R B6 It is halogen; R B7 yes ;and R B8 It is halogen.
44. The compound, salt, solvate, or method according to any one of claims 1 to 21, wherein: R B2 Selected from and ; R B6 It is halogen; R B7 Selected from , , , and ;and R B8 It is halogen.
45. The compound, salt, solvate, or method according to any one of claims 1, 2, and 7, having the following formula: (A-7), where -J 1 -J 2 -J 3 -DG is ; R B7 Selected from , , , , , , , and ;and R B2 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , and .
46. The compound, salt, solvate, or method according to any one of claims 7 to 9, having the following formula: (a-7), where -J 1 -J 2 -J 3 -LG is , R B7 Selected from , , , , , , , and ;and R B2 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , and .
47. The compound, salt, solvate, or method according to claim 45 or 46, wherein R B7 Selected from , , , and .
48. The compound, salt, solvate, or method according to claim 45 or 46, wherein R B7 Selected from and .
49. The compound, salt, solvate, or method according to claim 45 or 46, wherein R B7 yes .
50. The compound, salt, solvate, or method according to claim 45 or 46, wherein R B7 yes .
51. The compound, salt, solvate, or method according to claim 45 or 46, wherein R B7 yes .
52. The compound, salt, solvate, or method according to any one of claims 45 to 51, wherein R B2 Selected from , , and .
53. The compound, salt, solvate, or method according to any one of claims 45 to 51, wherein R B2 yes .
54. The compound, salt, solvate, or method according to any one of claims 45 to 51, wherein R B2 yes .
55. The compound, salt, solvate, or method according to any one of claims 45 to 51, wherein R B2 yes .
56. The compound, salt, solvate, or method according to any one of claims 1, 7, and 8, wherein the compound is selected from the compounds in Table 1.
57. A selection from , , , , , , , , , , , , , , , , , , and The compound, or its pharmaceutically acceptable salt or solvation.
58. A selection from , , , , , , and The compound, or its pharmaceutically acceptable salt or solvation.
59. A selection from , and The compound, or its pharmaceutically acceptable salt or solvation.
60. A kind of formula The compound, or its pharmaceutically acceptable salt or solvation.
61. A selection from , , and The compound, or its pharmaceutically acceptable salt or solvation.
62. A pharmaceutical composition comprising a compound according to any one of claims 1 to 6 or 8 to 61, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.
63. A method of treating cancer in a subject of need, comprising administering to the subject a therapeutically effective amount of the compound according to any one of claims 1 to 6 or 8 to 61, or a pharmaceutically acceptable salt or solvate thereof.
64. A method for treating cancer involving a subject containing a Ras mutant protein, the method comprising: The Ras mutant protein of the object is inhibited by applying a compound according to any one of claims 1 to 6 or 8 to 61 to the object, wherein the compound is characterized in that, upon contact with the Ras mutant protein, the Ras mutant protein exhibits a reduced Ras signaling output.
65. The method according to claim 63 or 64, wherein the cancer is a solid tumor or a hematologic cancer.
66. A method for reducing the signal transduction output of a Ras protein, comprising contacting the Ras protein with an effective amount of a compound according to any one of claims 1 to 6 or 8 to 61, or a pharmaceutically acceptable salt or solvate thereof, thereby reducing the signal transduction output of the Ras protein.
67. The method of claim 66, wherein the compound binds covalently or non-covalently to the Ras protein, thereby reducing the signal transduction output of the Ras protein.
68. A method for inhibiting cell growth, comprising administering an effective amount of the compound according to any one of claims 1 to 6 or 8 to 61, or a pharmaceutically acceptable salt or solvate thereof, to cells expressing Ras protein, thereby inhibiting the growth of said cells.
69. The method according to any one of claims 63 to 68, wherein the application of an additional agent is included.