Small molecule inhibitors of TEAD transcription factors

Patent metadata

Field	Value
Publication number	US-12187722-B2
Application number	US-202017439735-A
Country	US
Kind code	B2
Filing date	Mar 13, 2020
Priority date	Mar 15, 2019
Publication date	Jan 7, 2025
Grant date	Jan 7, 2025

Abstract

The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.

First claim

What is claimed is:

1. A compound of Formula:

or a pharmaceutically acceptable salt thereof, wherein:
R N is H or C 1-6 alkyl;
R 1 is OH or OC 1-6 alkyl;
A 3 is CR 3 or N;
A 5 is CH or N;
A 7 is CH or N;
A 10 is CH or N;
R 3 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR al , C(O)NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ,
R 8 is Cy 8A , OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A ;
Cy 8A is a group of one of the following formulae:

and
R a1 , R b1 , R cl and R d1 are each independently selected from H, C 1-6 alkyl, HO—C 1-6 alkylene, C 1-6 alkoxy-C 1-6 alkylene, C 6-10 aryl, C 2-6 alkenyl and C 2-6 alkynyl.

2. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein A 3 is CR 3 .

3. The compound or pharmaceutically acceptable salt thereof of claim 2 , wherein R 3 is H, C 1-6 alkyl or C 1-6 haloalkyl.

4. The compound or pharmaceutically acceptable salt thereof of claim 2 , wherein R 3 is H.

5. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein A 3 is N.

6. The compound or pharmaceutically acceptable salt thereof claim 1 , wherein A 5 is CH.

7. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein A 5 is N.

8. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 1 is OH.

9. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R N is H.

10. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein A 7 is CH.

11. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein A 7 is N.

12. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 8 is NHCy 8A .

13. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein Cy 8A is a group of one of the following formulae:

14. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein A 10 is CH.

15. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein A 10 is N.

16. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 1 is OH.

17. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 1 is OC 1-6 alkyl.

18. The compound of claim 1 wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt of any of the foregoing.

19. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt of any of the foregoing.

20. A compound selected from the group consisting of:

Assignees

• Massachusetts Gen Hospital

Inventors

• Wu Xu
• Maiti Pranab
• Abbineni Chandrasekhar
• Talluri Krishna Chaitanya
• Panigrahi Sunil Kumar
• Jarugumilli Gopala Krishna
• Sun Yang

Classifications

• C07D213/82 Primary

  in position 3 · CPC title

• C07C211/55 Primary

  Diphenylamines · CPC title

• C07C2601/02

  with a three-membered ring · CPC title

• C07C2601/04

  with a four-membered ring · CPC title

• C07C2602/42

  the bicyclo ring system containing seven carbon atoms · CPC title