Granted Patent B2

US 12,336,981 · App. 18/073,768 · Granted Jun 24, 2025

Inventors: Kenneth W. Bair (Wellesley, MA); Timm R. Baumeister (Cambridge, MA); Alexandre J. Buckmelter (Acton, MA); Karl H. Clodfelter (Brighton, MA); Peter Dragovich (South San Francisco, CA); Francis Gosselin (South San Francisco, CA); Bingsong Han (Westwood, MA); Jian Lin (Acton, MA); Dominic J. Reynolds (Stoneham, MA); Bruce Roth (South San Francisco, CA); Chase C. Smith (Rutland, MA); Zhongguo Wang (Lexington, MA); Po-Wai Yuen (Beijing, CN); Xiaozhang Zheng (Lexington, MA)

Assignees: Valo Health, Inc.; Genentech, Inc.

A61K31/4355A61K31/4365A61K31/437A61K31/496A61K31/497A61K31/519A61K31/5377A61K31/55A61K45/06C07D471/04C07D487/04C07D491/04C07D491/048C07D495/04

Abstract

Claims (23)

1. A compound of Formula IIA:

or a pharmaceutically acceptable salt thereof, wherein:

R is heteroaryl comprising 1, 2, 3 or 4 heteroatom(s) independently selected from N, S or O, wherein said heteroaryl may be substituted by one or more substituents selected from the group consisting of amino, oxo, and halo, and wherein said heteroaryl can comprise one or more N-oxide(s) formed with a N atom member of said heteroaryl;

Ar is aryl;

R 1 is aryl, wherein:

said aryl is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of:

deuterium, halo, hydroxy, hydroxyalkyl, cyano, —(CH 2 ) m NR a R b , oxo, alkyl, cyanoalkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkyl-, alkenyl, alkynyl, alkynylalkoxy, —CONH 2 , —S-alkyl, —C(O)NH(alkyl), —C(O)N(alkyl) 2 , —C(O)NH(cycloalkyl), —C(O)NH(aryl), —C(O)N(aryl) 2 , arylalkyl-, arylalkoxy-, aryloxy-, cycloalkyl, heterocycloalkyl, aryl, (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-, —C(O) heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-, —S(O) 2 -alkyl, —S(O) 2 -aryl, —S(O) 2 —CH z F 3-z , —C(O)alkyl, —N(R 5 )—C(O)-alkyl, —N(R 5 )—C(O)-aryl, —S(O 2 )NH 2 , —S(O 2 )NH(alkyl), —S(O 2 )N(alkyl) 2 , —N(H)(SO 2 )(alkyl), and methylenedioxy, wherein each of said cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted by one or more halo, cyano, alkyl, or alkoxy and;

said aryl may optionally additionally be fused with independently selected aryl, heteroaryl, heterocycloalkyl or cycloalkyl to from a bicyclic or tricyclic group that may be substituted by one or more halo, cyano, alkyl, or alkoxy;

R 2 and R 3 are independently selected from the group consisting of H and deuterium;

R 5 is H, alkyl, or arylalkyl-;

z is 0, 1, or 2;

R a and R b are independently selected from the group consisting of H, alkyl, alkoxy, alkoxyalkyl and haloalkyl; and

m is 0, 1, 2, 3, 4, 5 or 6.

2. The compound of claim 1 , wherein R 1 is substituted aryl.

3. The compound of claim 1 , wherein R 1 is aryl, wherein said aryl is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of: halo, hydroxy, hydroxyalkyl, cyano, alkyl, alkynyl, alkynylalkoxy, alkoxyalkyl, alkoxy, haloalkyl, haloalkoxy, —C(O)NH(alkyl), —C(O)NH(cycloalkyl), —C(O)N(alkyl) 2 , arylalkoxy-, aryloxy-, cycloalkyl, heterocycloalkyl, aryl, (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-, —C(O) heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-, —S(O) 2 -alkyl, —S-alkyl, —C(O)alkyl, —S(O 2 )NH 2 , —S(O 2 )NH(alkyl), —S(O 2 )N(alkyl) 2 , and —N(H)(SO 2 )(alkyl), wherein each of said cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted by one or more halo, cyano, alkyl, or alkoxy.

4. The compound of claim 1 , wherein R 1 is aryl, wherein said aryl is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of halo, haloalkyl, and haloalkoxy.

5. The compound of claim 1 , wherein Ar is phenyl.

6. The compound of claim 1 , wherein R 2 and R 3 are each H.

7. The compound of claim 1 , wherein R is a monocyclic heteroaryl.

8. The compound of claim 1 , wherein R is pyridinyl.

9. The compound of claim 1 , wherein R is a 9- to 10-membered bicyclic heteroaryl groups containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O.

10. The compound of claim 1 , wherein the compound is 6-amino-N-({4-[(3,5-difluorobenzene)sulfonyl]phenyl}methyl)pyridine-3-carboxamide, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignments (9)

Continuity (12)

References Cited (156)