Granted Patent B2

US 12,281,126 · App. 17/418,353 · Granted Apr 22, 2025

Inventors: Nathanael S. Gray (Boston, MA); Tinghu Zhang (Brookline, MA); Nicholas Paul Kwiatkowski (Brookline, MA); Jie Jiang (Brookline, MA); Mingfeng Hao (Hefei, CN); Zhixiang He (Brookline, MA)

Assignee: Dana-Farber Cancer Institute, Inc.

C07D519/00A61K31/4162C07D487/04

Abstract

Claims (31)

1. A compound of Formula (I):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein:

Ring A is aryl, or heteroaryl;

R 1 is of the formula —NHC(O)CH═CH 2 or L 3 ;

wherein:

L 3 is a substituted or unsubstituted C 1-4 hydrocarbon chain;

m is 0 or 1;

L is a single bond or —C(═O)—;

one of R 9 and R 10 is hydrogen and the other is —(CH 2 ) N (CH 3 ) 2 ;

p is 0 or 1 such that when p=0, then D=piperidinyl, 1,2,3,4-tetrahydroisoquinolinyl, or

and when p=1, then D=tetrahydropyranyl or tetrahydrofuryl;

R 11 is substituted or unsubstituted alkyl; and

q is 0 or 1.

2. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein the compound is of the formula:

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

4. A compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein A is aryl.

5. A compound of claim 4 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein A is phenyl.

6. A compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein A is heteroaryl.

7. A compound of claim 6 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein A is selected from thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoquinolinyl, pyridinyl, and pyrimidinyl.

8. A compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R 1 is —NHC(O)CH═CH 2 .

9. A compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein p=0 and D=piperidinyl, 1,2,3,4-tetrahydroisoquinolinyl, or

10. A compound of claim 9 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein q=1 and R 11 is methyl.

11. A compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein p=1 and D=tetrahydropyranyl or tetrahydrofuryl.

12. A compound of claim 11 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein q=0.

13. A pharmaceutical composition comprising:

a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; and

a pharmaceutically acceptable excipient.

14. A kit comprising:

a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; and

instructions for using the compound, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof.

15. A method of inhibiting the activity of cyclin-dependent kinase 7 (CDK7) in a subject, biological sample, tissue, or cell, the method comprising administering to the subject or contacting the biological sample, tissue, or cell with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof.

Assignments (3)

Continuity (2)

References Cited (400)