Compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-2023149414-A1
Application number	US-202117795747-A
Country	US
Kind code	A1
Filing date	Jan 29, 2021
Priority date	Jan 29, 2020
Publication date	May 18, 2023
Grant date	—

Abstract

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

First claim

1 . A compound having the structure:

wherein m is 0, 1, 2, 3, or 4;
n is 0, 1, 2, 3, or 4;
R 1 is optionally substituted C 3 -C 8 branched alkyl, or R 1 combines with R 2 and the atoms to which they are attached to form a 5- to 7-membered ring;
each R 2 is, independently, halo, hydroxy, thiol, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted amino, or one R 2 combines with another R 2 and the atoms to which they are attached to form a 5- to 7-membered ring;
R 3 and R 5 are, independently, hydrogen or optionally substituted C 1 -C 6 alkyl;
R 4 is hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 1 -C 6 alkyl C 6 -C 10 aryl, or optionally substituted C 1 -C 6 alkyl C 2 -C 9 heteroaryl;
Het is 5- or 6-membered heterocycle;
R 6 is hydrogen, halo, cyano, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 1 -C 6 heteroalkyl, carboxyl, optionally substituted amide, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 9 heterocyclyl, or optionally substituted C 6 -C 10 aryl; and
R 7 is cyano, halo, optionally substituted C 1 -C 6 alkyl or optionally substituted C 1 -C 6 heteroalkyl,
or a pharmaceutically acceptable salt thereof.

2 . The compound of claim 1 , wherein R 3 is hydrogen.

3 . The compound of claim 1 , wherein R 5 is hydrogen.

4 . The compound of claim 1 , wherein R 4 is hydrogen.

5 . The compound of claim 1 , wherein R 4 is optionally substituted C 1 -C 6 heteroalkyl.

6 . The compound of claim 5 , wherein R 4 is

7 . The compound of claim 1 , wherein R 4 is optionally substituted C 1 -C 6 alkyl.

8 . The compound of claim 7 , wherein R 4 is methyl.

9 . The compound of claim 1 , wherein Het is

10 . The compound of claim 1 , wherein Het is

11 . The compound of claim 1 , wherein R 1 is iso-propyl,

12 . The compound of claim 1 , wherein m is 0, 1 or 2.

13 . (canceled)

14 . (canceled)

15 . The compound of claim 12 , wherein m is 1 or 2, and at least one R 2 is optionally substituted C 1 -C 6 alkyl or halo.

16 . The compound of claim 15 , wherein R 2 is methyl.

17 . The compound of claim 12 , wherein m is 1 or 2, and R 2 is optionally substituted C 1 -C 6 heteroalkyl.

18 . The compound of claim 17 , wherein R 2 is

19 . The compound of claim 1 , wherein R 1 combines with an R 2 and the atoms to which they are attached to form a 5- to 7-membered ring.

20 . The compound of claim 19 , wherein the compound has the structure of Formula Ia:

21 . (canceled)

22 . The compound of claim 12 , wherein m is 1 or 2 and R 2 is —NH 2 .

23 . The compound of claim 1 , wherein n is 0 or 1.

24 . (canceled)

25 . The compound of claim 1 , wherein n is 1, and R 7 is cyano.

26 . The compound of claim 1 , wherein R 6 is hydrogen, cyano, or optionally substituted C 1 -C 6 heteroalkyl.

27 . (canceled)

28 . (canceled)

29 . The compound of claim 26 , wherein R 6 is

30 . The compound of claim 1 , wherein R 6 is carboxyl.

31 . The compound of claim 1 , wherein R 6 is optionally substituted C 2 -C 9 heteroaryl.

33 . The compound of claim 1 , wherein R 6 is optionally substituted C 2 -C 9 heterocyclyl.

34 . The compound of claim 33 , wherein R 6 is

35 . The compound of claim 1 , wherein R 6 is C 6 -C 10 aryl.

36 . The compound of claim 35 , wherein R 6 is 3,5-dicyano-phenyl, 3-hydroxymethyl-5-cyano-phenyl, 3-cyano-phenyl, 3-hydroxymethyl-5-trifluoromethyl-phenyl, 3-chloro-phenyl, 3,5-dichloro-phenyl, 3-aminomethyl-phenyl,

 or 4-aminomethyl-phenyl.

37 . The compound of claim 1 , wherein the compound is any one of compounds 12-47 in Table 1a or 110-129 in Table 1b.

38 .- 175 . (canceled)

176 . A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.

177 .- 186 . (canceled)

187 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1 .

188 . The method of claim 187 , wherein the cancer is non-small cell lung cancer, colorectal cancer, bladder cancer, cancer of unknown primary, glioma, breast cancer, melanoma, non-melanoma skin cancer, endometrial cancer, esophagogastric cancer, pancreatic cancer, hepatobiliary cancer, soft tissue sarcoma, ovarian cancer, head and neck cancer, renal cell carcinoma, bone cancer, non-Hodgkin lymphoma, small-cell lung cancer, prostate cancer, embryonal tumor, germ cell tumor, cervical cancer, thyroid cancer, salivary gland cancer, gastrointestinal neuroendocrine tumor, uterine sarcoma, gastrointestinal stromal tumor, CNS cancer, thymic tumor, Adrenocortical carcinoma, appendiceal cancer, small bowel cancer, or penile cancer.

189 . The method of claim 187 , wherein the cancer is non-small cell lung cancer, colorectal cancer, bladder cancer, cancer of unknown primary, glioma, breast cancer, melanoma, non-melanoma skin cancer, endometrial cancer, or penile cancer.

190 . The method of claim 187 , wherein the cancer is non-small cell lung cancer.

191 . The method of claim 187 , wherein the cancer is soft tissue sarcoma.

192 . A method of treating melanoma, prostate cancer, breast cancer, bone cancer, renal cell carcinoma, or a hematologic cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1 .

193 . (canceled)

194 . (canceled)

195 . (canceled)

196 . A method of reducing the level and/or activity of BRG1 and/or BRM in a melanoma, pro

Assignees

• Foghorn Therapeutics Inc

Inventors

• Anthony Neville John
• Vaswani Rishi G
• Millan David Simon
• Schiller Shawn E R
• Wilson Kevin J

Classifications

• C07D277/46 Primary

  by carboxylic acids, or sulfur or nitrogen analogues thereof · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title