Granted Patent B2

US 12,612,425 · App. 17/671,436 · Granted Apr 28, 2026

Inventors: Wang Shen (San Mateo, CA); Jack Maung (Daly City, CA); Aimin Zhang (Castro Valley, CA); Xiaoling Zheng (Fremont, CA)

Assignee: Rakovina Therapeutics Inc.

C07F9/6584

Abstract

Claims (34)

1 . A method for the treatment of a condition which can be ameliorated by inhibition of PARP in an individual in need thereof, the method comprising administering to the individual an effective amount of a compound of formula (I):

wherein

R A and R B are taken together with the carbon atoms to which they are attached to form a substituted or unsubstituted 6-membered aromatic ring, wherein the substituted 6-membered aromatic ring is substituted by R F , wherein R F is hydrogen, halo, —CF 3 , unsubstituted C 1 -C 3 alkyl or unsubstituted C 1 -C 3 alkoxy;

each R 1 and R 2 is independently hydrogen, halo, hydroxy, unsubstituted C 1 -C 3 alkyl or unsubstituted C 1 -C 3 alkoxy;

Z is a 6-membered aryl substituted with R C and R P ;

R C is hydrogen, halo, —CF 3 , unsubstituted C 1 -C 3 alkyl or unsubstituted C 1 -C 3 alkoxy;

R P is a moiety of the formula (Ia) or (Ib):

each X is independently O, S or absent;

R D is hydrogen, substituted or unsubstituted alkyl, unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C(O)R 4 , —C(═N—CN)NR 8 R 9 or —C(O)NR 5 R 6 ;

R 4 is an unsubstituted alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy, or substituted or unsubstituted heterocyclyl;

each R 5 and R 6 is independently hydrogen, unsubstituted alkyl or unsubstituted cycloalkyl;

each R 8 and R 9 is independently hydrogen, unsubstituted alkyl or unsubstituted cycloalkyl, or R 8 and R 9 are taken together with the nitrogen to which they are attached to form an unsubstituted heterocyclyl;

R E is unsubstituted alkyl, unsubstituted cycloalkyl, unsubstituted aryl, or —OR 7 ; and

R 7 is an unsubstituted alkyl or unsubstituted cycloalkyl;

wherein the substituted alkyl, the substituted aryl, the substituted heteroaryl, and the substituted heterocyclyl are independently substituted by one, two, three, or more substituents, wherein the substituents are independently cyano, halo, haloalkyl, alkyl, alkylcarbonyl, cycloalkyl, or aryl; wherein said alkyl substituents are optionally substituted with hydroxyl,

or a pharmaceutically acceptable salt or solvate thereof,

wherein the condition is cancer selected from the group consisting of a breast cancer, an ovarian cancer and a cervical cancer.

2 . The method of claim 1 , wherein the cancer is a cancer which is deficient in HR dependent DNA DSB repair activity.

3 . The method of claim 1 , wherein the cancer is a BRCA-1 or BRCA-2 deficient tumor.

4 . The method of claim 1 , wherein the cancer is a PTEN mutated tumor.

5 . The method of claim 1 , wherein the compound is a compound of the formula (V):

wherein

each R 1 and R 2 is independently hydrogen, halo, hydroxy, unsubstituted C 1 -C 3 alkyl or unsubstituted C 1 -C 3 alkoxy;

R D is hydrogen, substituted or unsubstituted alkyl, unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; and

R F is hydrogen, halo, —CF 3 , unsubstituted C 1 -C 3 alkyl or unsubstituted C 1 -C 3 alkoxy;

wherein the substituted alkyl, the substituted aryl, the substituted heteroaryl, and the substituted heterocyclyl are independently substituted by one, two, three, or more substituents, wherein the substituents are independently cyano, halo, haloalkyl, alkyl, alkylcarbonyl, cycloalkyl, or aryl; wherein said alkyl substituents are optionally substituted with hydroxyl,

or a pharmaceutically acceptable salt or solvate thereof.

6 . The method of claim 1 , wherein R D is selected from the group consisting of:

7 . The method of claim 1 , wherein the compound is selected from the group consisting of:

8 . The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt or solvate thereof.

9 . The method of claim 1 , wherein the condition is a breast cancer.

10 . The method of claim 1 , wherein the condition is an ovarian cancer.

11 . The method of claim 1 , wherein the condition is a cervical cancer.

Assignments (3)

Continuity (6)

References Cited (137)