Granted Patent B2

US 12,509,455 · App. 17/291,927 · Granted Dec 30, 2025

Inventors: Nathanael S. Gray (Boston, MA); Tinghu Zhang (Brookline, MA); Yao Liu (Brookline, MA); Zhixiang He (Brookline, MA); Mingfeng Hao (Hefei, CN); David Weinstock (Jamaica Plain, MA); Loretta Sze-Mun Li (Chicago, IL)

Assignee: Dana-Farber Cancer Institute, Inc.

C07D471/04A61K45/06C07D487/04

Abstract

Claims (71)

1 . A compound of Formula (I′):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, or stereoisomer thereof, wherein:

each instance of R A is independently halogen or substituted or unsubstituted alkyl;

each instance of R 1 is independently hydrogen or substituted or unsubstituted alkyl;

k is 0, 1, or 2;

is

R E is hydrogen;

R J is hydrogen;

Y A is N or CR B ;

Y B is N or CR B ;

Y C is N or CR B ;

Y D is N or CR B ; provided that no more than one of Y A , Y B , Y C , and Y D is N;

each instance of RB is independently hydrogen, halogen, substituted or unsubstituted alkyl, —OR 1 , or —CN;

is

X A is N or CR H ,

X B is N or CR H ,

X C is N or CR H ;

X D is N or CR H ; provided that no more than one of X A , X B , X C and X D is N;

each instance of R H is independently hydrogen;

R K is hydrogen or substituted or unsubstituted alkyl;

R C is hydrogen;

R G is

or hydrogen; and

each instance of R D is independently substituted or unsubstituted carbocyclyl;

or two instances of R D are joined together to form a substituted or unsubstituted; carbocyclic ring;

provided that the compound is not of the formula:

2 . The compound of claim 1 , wherein the compound is of Formula (I):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, or stereoisomer thereof, wherein:

each instance of R A is independently halogen or substituted or unsubstituted alkyl;

each instance of R 1 is independently hydrogen or substituted or unsubstituted alkyl;

k is 0, 1, or 2;

is

R E is hydrogen;

R J is hydrogen;

Y A is N or CR B ;

Y B is N or CR B ;

Y C is N or CR B ;

Y D is N or CR B ; provided that no more than one of Y A , Y B , Y C , and Y D is N;

each instance of RB is independently hydrogen, halogen, substituted or unsubstituted alkyl, —OR 1 , or —CN;

is

X A is N or CR H ;

X B is N or CR H ;

X C is N or CR H ;

X D is N or CR H ; provided that no more than one of X A , X B , X C and X D is N;

each instance of R H is independently hydrogen;

R C is hydrogen; and

each instance of R D is independently substituted or unsubstituted carbocyclyl;

or two instances of R D are joined together to form a substituted or unsubstituted, carbocyclic ring.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein

is

4 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein one instance of R A is—(substituted or unsubstituted alkylene) (substituted or unsubstituted heterocyclyl).

5 . The compound of claim 3 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein one instance of R A is—(substituted or unsubstituted, C 1-3 alkylene)-(substituted or unsubstituted piperazinyl) and the other instance of R A is —CF 3 .

6 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein k is 2.

7 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein

is

8 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein

is

9 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein

10 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein at least one instance of R B is halogen, substituted or unsubstituted alkyl, or —OR 1 .

11 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein at least one instance of R B is substituted or unsubstituted methyl.

12 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein

is

13 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein R K is hydrogen or substituted or unsubstituted C 1-6 alkyl.

14 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein two instances of R D are joined to form a substituted or unsubstituted carbocyclic ring.

15 . The compound of claim 2 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein the compound is of the formula:

16 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof.

17 . A pharmaceutical composition comprising:

a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof; and a pharmaceutically acceptable excipient.

18 . A kit comprising:

a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition thereof further comprising a pharmaceutically acceptable excipient; and

instructions for using the compound, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or the pharmaceutical composition.

Assignments (1)

Continuity (4)

References Cited (367)