Heterocyclic compounds as e3 ligase inhibitors
AssigneeAccutar Biotechnology Inc.
InventorsJi Liu, Yimin Qian, Pin Huang, Xiangyan Sun, Ke Liu, Jie Fan
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Abstract
The present disclosure relates to novel compounds that inhibit glucose-induced degradation-deficient (GID) E3 ligase, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of cancer and related diseases and conditions.
Claims30
A compound of Formula (1) or a tautomer, stereoisomer or a mixture of stereoisomers, or a pharmaceutically acceptable salt, or hydrate, or deuterated derivative thereof:
- wherein:
- Y1 is either:
- chosen from CH, N, and CX1, wherein X1 is a halogen, or
- Y1 and R1 together form an optionally substituted 3 to 7 membered saturated or unsaturated ring G, wherein the ring has 0 to 3 heteroatoms;
- Y2 is chosen from CH, N, and CX1, wherein X1 is a halogen;
- R1 is either:
- chosen from NHR5, H, and C1-C4 alkyl, wherein R5 is chosen from H and optionally substituted C1-C3 alkyl, or
- Y1 and R1 together form a 3 to 7 membered saturated or unsaturated ring G, wherein the ring has 0 to 3 heteroatoms;
- R2 is chosen from NHR6, H, and C1-C4 alkyl, wherein R6 is chosen from H and optionally substituted C1-C3 alkyl;
- and
- R3 and R4 are each independently chosen from hydrogen, an optionally substituted 5 to 7 membered ring, and optionally substituted C1-C3 alkyl;
- or
- R3 and R4 together form a 5 to 9 membered ring system D, wherein the ring is chosen from monocyclic rings and bicyclic rings, and wherein the monocyclic rings and bicyclic rings are optionally substituted with a halogen, a hydroxyl, an optionally substituted phenyl, an acetyl group, a 5 membered heteroaryl, an optionally substituted 9 membered heterobicyclic aryl, an optionally substituted benzimidazolone, and/or an optionally substituted C1-C3 alkyl.
A compound chosen from Formula (2) or a tautomer, stereoisomer or a mixture of stereoisomers, or a pharmaceutically acceptable salt, or hydrate, or deuterated derivative thereof:
- wherein:
- Y3 is chosen from CH, CH2, N, CO, and NH;
- Y4 is chosen from CH, N, and CH2;
- Y5 is chosen from CH, CH2, CNHR10, CO, N, 5 membered heteroaryl rings comprising two nitrogen atoms and three carbon atoms wherein the heteroaryl ring is optionally substituted with a methyl, and NH, wherein R10 is chosen from H and C1-C4 alkyl;
- Y6 is chosen from CH and CH2;
- Y7 is chosen from CH, N, and C—OH;
- R7 is absent or chosen from OH, halogen, 5 membered heteroaryl rings comprising two nitrogen atoms and three carbon atoms wherein the heteroaryl ring is optionally substituted with a methyl, and methyl;
- ring A is an aromatic or non-aromatic 6-membered heterocyclic ring;
- n is 0 or 1;
- ring system B is chosen from:
- 5 to 6 membered rings optionally comprising up to three nitrogen atoms, a sulfur atom, and/or an oxygen atom,
- bicyclic 9 or 10 membered rings comprising at least one aromatic ring, optionally comprising up to three nitrogen atoms, a sulfur atom, and/or a carbonyl, and
- bicyclic 7 or 8 membered aliphatic rings comprising an amine, and wherein ring system B is optionally substituted with up to two halogens, a methyl, and/or NH2;
- R8 is absent or chosen from:
- aliphatic amines comprising up to two nitrogen atoms, up to 7 carbon atoms, and optionally an alkoxy,
- N-substituted amides wherein at least one N-substituent comprises up to 7 carbon atoms and, optionally, an amine, a hydroxyl, and/or an alkoxy, and
- C-substituted carbonyls wherein the C-substituent comprises up to 6 carbon atoms and a tertiary amine;
- and wherein Formula (2) encompasses all tautomers, stereoisomers, isotopes, pharmaceutically acceptable salts, and mixtures thereof.
Dependencies are inferred from the claim text.