Granted Patent B2

US 12,202,824 · App. 17/816,855 · Granted Jan 21, 2025

Inventors: Jack Alexander Terrett (San Francisco, CA); Huifen Chen (Burlingame, CA); Lea Constantineau-Forget (Montreal, CA); Robin Larouche-Gauthier (Montreal, CA); Luce Lépissier (Montreal, CA); Francis Beaumier (Montreal, CA); Martin Déry (Montreal, CA); Chantal Grand-Maître (Montreal, CA); Claudio Sturino (L'ile-Bizard, CA); Matthew Volgraf (Oakland, CA); Elisia Villemure (Oakland, CA)

Assignee: Genentech, Inc.

C07D413/14A61K31/427A61P11/00A61P23/00A61P25/00A61P29/00C07D471/04C07D473/30C07D487/04C07D498/04C07D513/04

Abstract

Claims (43)

1. A compound of formula (II)

or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,

wherein:

A is: substituted or unsubstituted 6-6 fused bicyclic heteroaryl which may be partially saturated; substituted or unsubstituted 5-6 fused bicyclic heteroaryl which may be partially saturated; or substituted and unsubstituted 6-5 fused bicyclic heteroaryl which may be partially saturated;

X is methylene;

R 1 is: H; or C 1-6 alkyl; and

R 4 is: substituted or unsubstituted phenyl; substituted or unsubstituted heteroaryl; or substituted or unsubstituted naphthyl;

or R 1 and R 4 may together form an unsubstituted or substituted C 3-6 cylcoalkyl fused to a substituted or unsubstituted phenyl; substituted or unsubstituted heteroaryl; or substituted or unsubstituted naphthyl.

2. The compound of claim 1 , wherein A is selected from:

wherein:

each R 2 is independently: H; D; —C 1-4 alkyl; —C 1-4 haloalkyl; C 1-4 alkoxy; —CN, halo; —C(O)CH 3 ; —NH 2 ; NHC 1-4 alkyl wherein the C 1-4 alkyl optionally comprises an oxygen heteroatom or an —OH substitutent; —NHC(O)—C 1-4 alkyl; —NHCH 2 C(O)N(C 1-4 alkyl) 2 ; benzylamino; and —NH—C 4-6 heterocylo comprising an oxygen heteroatom;

each R 3 is independently: H; D; —C 1-4 alkyl; —C 1-4 haloalkyl; —CN; NR 14 R 15 ; or halo;

p is 0, 1 or 2;

q is 0 or 1;

R 14 and R 15 are each independently: H; substituted or unsubstituted —C 1-4 alkyl; substituted or unsubstituted —C(O)—C 1-4 alkyl; substituted or unsubstituted C 3-6 cycloalkyl; substituted or unsubstituted 3- to 6-membered heterocycloalkyl; substituted or unsubstituted —C 1-4 heteroalkyl; —C(O)NR 16 R 17 ; substituted or unsubstituted —C 1-4 alkyl-C(O)NR 16 R 17 ; substituted or unsubstituted phenyl; or substituted or unsubstituted benzyl;

or R 14 and R 15 together with the atoms to which they are attached may form a 4-, 5-, 6- or 7-membered ring that optionally includes one additional heteroatom selected from O, N and S; and

R 16 and R 17 each are independently H and C 1-4 alkyl.

3. The compound of claim 2 , wherein A is:

4. The compound of claim 3 , wherein A is:

5. The compound of claim 2 , wherein each R 2 is independently H; —CH 3 ; —CN; -halo; —NH 2 ; —NHCH 3 ; NHCH 2 CH 3 ; —NHCH 2 CH 2 CH 2 OH; —NHCH 2 CH 2 OCH 3 ; —NHC(O)CH 3 ; —NHCH 2 C(O)N(CH 3 ) 2 ;

and p is 0 or 1.

6. The compound of claim 1 , wherein A is:

7. The compound of claim 1 , wherein A is:

8. The compound of claim 1 , wherein A is:

9. The compound of claim 1 , wherein A is:

10. The compound of claim 1 , wherein R 4 is:

wherein:

each R 18 is independently selected from H, halogen, —OH, —C 1-4 alkyl, —C 1-4 haloalkyl, —CN, halo, C 1-4 haloalkoxy, C 1-4 alkoxy, —SO 2 —C 1-4 alkyl, —C 1-4 alkylCN, C 1-4 aldehyde, —SF 5 , C 1-4 ketone, unsubstituted or substituted C 3-6 cycloalkyl, unsubstituted or substituted phenyl, unsubstituted or substituted heteroaryl, fused aryl, and fused heteroaryl; and k is from 0 to 3.

11. The compound claim 10 , wherein each R 18 is independently: H; Cl; —OCHF 2 ; —OCF; —OCH 3 ; or —CN.

12. The compound claim 10 , wherein each R 18 is independently fluoro or chloro.

13. The compound of claim 1 , wherein R 4 is:

wherein:

each R 10 is independently: H; halogen; —CN; —OH; C 1-4 alkyl; substituted or unsubstituted C 3-6 cycloalkyl; C 1-4 haloalkyl; C 1-4 haloalkoxy; C 1-4 alkoxy; —SO 2 —C 1-4 alkyl; C 1-4 alkyl CN; C 1-4 aldehyde; C 1-4 ketone; —S—C 1-4 haloalkyl; substituted or unsubstituted 5- to 6-membered heteroaryl; substituted or unsubstituted 4- to 6-membered hetercycloalkyl; or substituted or unsubstituted C 5-6 aryl; and

each u is independently 0, 1, 2 or 3.

14. The compound of claim 1 , wherein R 4 is:

15. A pharmaceutical composition, comprising a compound as described in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

16. The compound of claim 1 , wherein A is:

17. The compound of claim 1 , wherein:

A is:

 and

R 4 is

wherein:

each R 18 is independently selected from H, halogen, —OH, —C 1-4 alkyl, —C 1-4 haloalkyl, —CN, halo, C 1-4 haloalkoxy, C 1-4 alkoxy, —SO 2 —C 1-4 alkyl, —C 1-4 alkylCN, C 1-4 aldehyde, —SF 5 , C 1-4 ketone, unsubstituted or substituted C 3-6 cycloalkyl, unsubstituted or substituted phenyl, unsubstituted or substituted heteroaryl, fused aryl, and fused heteroaryl; and k is from 0 to 3.

Continuity (7)

References Cited (137)