Granted Patent B2

US 12,187,709 · App. 18/052,851 · Granted Jan 7, 2025

Inventors: Malcolm Huestis (San Francisco, CA); Michael John Lambrecht (Burlingame, CA); Jun Liang (Los Altos Hills, CA); Man Un Ung (San Mateo, CA); Xiaojing Wang (Belmont, CA); Jason Robert Zbieg (Montara, CA); Bing-Yan Zhu (Palo Alto, CA); Lisa Marie Barton (Burlingame, CA); Fabio Broccatelli (San Diego, CA); Georgette Marie Castanedo (South San Francisco, CA); Araz Jakalian (Montreal, CA); Robin Larouche-Gauthier (Montreal, CA); Arun Yadav (Montreal, CA)

Assignee: Genentech, Inc.

C07D403/12A61P35/00C07D401/14C07D403/14C07D405/14C07D409/14C07D493/08

Abstract

Claims (116)

1. A compound of formula (I),

wherein:

Q is a 5-membered heteroaryl, optionally substituted by one or more alkyl, cycloalkyl, hydroxyalkyl, or haloalkyl groups;

Y 1 and Y 2 are independently CH, CF, or N;

J is C(R 3 ) (R 4 ), wherein:

R 3 , R 4 are independently selected from: H, halogen, CN, OH, amino, and LR 2a , wherein L is O, NR 0 , CHR 0 , C(═O), or a bond, wherein Ro is H or alkyl, and R 2a is selected from alkyl, alkenyl, alkynyl, alkylcarboxy, cyanoalkyl, aminoalkyl, hydroxyalkyl, haloalkyl, and a 3-14 membered ring moiety, wherein at least one of R 3 and R 4 is not H; or

R 3 and R 4 together with the carbon atom to which they are both bonded form a 3-14 membered ring moiety,

wherein, if either of R 3 or R 4 is alkyl, haloalkyl, or hydroxyalkyl, R 3 or R 4 is optionally substituted by a 3-14 membered ring moiety;

and wherein, if either of R 3 or R 4 is, or is substituted by, a 3-14 membered ring moiety, or R 3 and R 4 together are a 3-14 membered ring moiety, the ring moiety is selected from:

a monocyclic ring, a fused bicyclic ring system, a bridged bicyclic ring system, and a spirocyclic ring system, and

wherein the ring moiety:

is optionally substituted by one or more groups independently selected from halogen, CN, amino, oxo, carbenyl, OH, or L 0 R 2b , wherein L 0 is CH 2 , C(═O), NH, O, S, S(═O), S(═O) 2 , or a bond, and R 2b is alkyl, cycloalkyl, heterocyclyl, alkenvyl, alkoxy, hydroxyalkyl, haloalkyl, cyanoalkyl, and aminoalkyl;

is saturated, or contains 1 or 2 in-ring double bonds, or is aryl;

is carbocyclic, heterocyclic, or heteroaryl; and

when the ring moiety is heterocyclic or heteroaryl, it comprises 1, 2 or 3 ring atoms that are independently selected from O, N, and S;

R 5 is selected from: H, halo, or L 1 -R 10 , wherein L 1 is —N(R 11 )—, —C(═O) N (R 11 ), O, S, carbonyl, or a bond, and wherein Rio and R 11 are independently H, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl, and when either of Rio and R 11 are not H, R 10 or R 11 is optionally substituted by one or more groups selected from: halo, CN, amino, oxo, OH, alkoxy, alkyl, perhaloalkyl, haloalkyl, heterocyclyl, aryl, and heteroaryl, or R 10 and R 11 together form a cycloalkyl or heterocyclyl ring, a spirocyclic ring, a fused bicyclic ring, or a bridged bicyclic ring, wherein the ring formed by R 10 and R 11 together is optionally substituted by one or more groups selected from halo, CN, amino, oxo, carbenyl, OH, alkoxy, alkyl, perhaloalkyl, or haloalkyl;

R 1 is H, halo, haloalkyl, or cycloalkyl; and

Z is —L 2a NR 7 R 8 , wherein:

L 2a is —C(H) R 6a ;

R 6a =H, alkyl, cycloalkyl, haloalkyl or hydroxyalkyl;

R 7 is H; and

R 8 is L 3 R 9 , wherein:

L 3 =—(C(H)R 10 ) n —, —(C(H)R 10 ) n O—, or a bond, wherein n=1 or 2;

R 10 is selected from H and alkyl;

R 9 is selected from alkyl, haloalkyl, perhaloalkyl, hydroxyalkyl, aminoalkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, alkyl alkanoate, heterocyclyl, spirocyclyl ring system, fused ring system, bicyclyl ring system, a 5 or 6 member heteroaromatic ring, or a 3-10 member fused heteroaromatic ring system, and a bridged bicyclyl ring;

and wherein, R 8 is cycloalkyl, heterocyclyl, spirocyclyl, a fused bicyclyl, a bridged bicyclic ring, a 5 or 6 member heteroaromatic ring, or a 3-10 member fused heteroaromatic ring system, said ring or ring system is optionally substituted with one or more groups selected from: sulfonyl, halo, hydroxyl, alkoxy, alkyl, cycloalkyl, alkoxyalkyl, carbenyl, alkenyl, hydroxyalkyl, cyano, carboxyalkyl, or haloalkyl;

or an enantiomer, diastereomer or a pharmaceutically acceptable salt or solvate thereof.

2. The compound of claim 1 wherein R 5 is H.

3. The compound of claim 1 , wherein R 5 is selected from:

alkyl, alkoxy, alkylamino, cycloalkylamino, cycloalkyl, and cycloalkyloxy, any of which is optionally substituted by one or more groups independently selected from: halo, alkyl, cyano, hydroxyl, amino, and alkoxy.

4. The compound of claim 1 , wherein Y 1 and Y 2 are CH.

5. The compound of claim 1 , wherein Y 1 is N.

6. The compound of claim 1 , wherein R 1 is CF3.

7. The compound of claim 1 , wherein Q is 2-methyl triazol-1-yl or imidazolyl.

8. The compound of claim 1 , wherein Q is 2-methyl triazol-1-yl.

9. The compound of claim 1 , wherein Z is —C(H)R 6a NR 7 R 8 , and:

R 6a is H or methyl.

10. The compound of claim 1 , wherein Z is —C(H)R 6a NR 7 R 8 , and wherein:

R 6a is H or methyl;

R 7 is H; and

R 8 is cyclobutyl, optionally substituted with alkyl.

11. The compound of claim 1 , wherein R 3 is H or OH, and R 4 is selected from cyclobut-1-amino, 3-oxetanyl, cyclopropyloxy, cyclobutyloxy, and methoxy, and wherein R 4 is optionally substituted by one or more groups selected from: halo, alkyl, hydroxyl, and alkoxyl.

12. The compound of claim 1 , wherein R 3 and R 4 together with the carbon atom to which they are both bonded form a 3-8 membered ring moiety selected from: cyclobutyl, oxetanyl, cyclobutenyl, spiro [3.3] hept-2-yl, and 2-oxaspiro [3.3] hept-6-yl, wherein the ring moiety is optionally substituted by one or more groups independently selected from: halo, carbenyl, oxo, hydroxyl, cyano, alkyl, and alkoxy.

13. The compound of claim 1 , wherein R 3 and R 4 together with the carbon atom to which they are both bonded form an oxetan-3-yl ring or a cyclobutyl ring.

14. The compound of claim 1 , wherein R 3 and R 4 together with the carbon atom to which they are both bonded form a cycloalkyl ring substituted by one or more instances of methyl, ethyl, methoxy, acetyl, chloro, fluoro, fluromethyl, difluoromethoxy, trifluoromethoxy, methoxy-d3, cyanomethyl, or cyano.

15. A compound selected from the group consisting of:

(S)-2-(3-(cyclobutyl (hydroxy) (4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 2);

2-(6-(cyclopentylamino)-4-((1r,3r)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl) pyridin-2-yl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 9);

2-(3-((1s,3s)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 22);

2-(3-((1r,3r)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 23);

(1r,3r)-3-(4-methyl-4H-1,2,4-triazol-3-yl)-3-(3-(6-(((1-methylcyclobutyl)amino)methyl)-1-oxo-4-(trifluoromethyl) isoindolin-2-yl)phenyl)cyclobutanecarbonitrile (Compound 24);

2-(3-((1r,3r)-3-fluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 36);

(S)-6-((2-isopropyl-4-methylpiperazin-1-yl)methyl)-2-(3-(6-(4-methyl-4H-1,2,4-triazol-3-yl)-2-oxaspiro [3.3] heptan-6-yl)phenyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 41);

2-(6-(cyclopentylamino)-4-((1r,3r)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl) pyridin-2-yl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 52);

2-(6-(cyclopentyloxy)-4-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl) pyridin-2-yl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 54);

2-(3-(6-(4-methyl-4H-1,2,4-triazol-3-yl)-2-oxaspiro [3.3] heptan-6-yl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 65);

2-(6-(cyclopentylamino)-4-((1R,3R)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl) pyridin-2-yl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 70);

2-(3-(2-(4-methyl-4H-1,2,4-triazol-3-yl)-6-oxospiro [3.3] heptan-2-yl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 92);

2-(3-(6,6-difluoro-2-(4-methyl-4H-1,2,4-triazol-3-yl) spiro [3.3] heptan-2-yl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 94);

2-(3-((1s,3s)-3-fluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 95);

2-(3-((1r,3r)-3-(fluoromethyl)-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 101);

2-(3-((1s,3s)-3-(fluoromethyl)-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 102);

(S)-2-(3-(3,3-difluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclopentyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 106);

2-(3-((4r,6r)-6-(4-methyl-4H-1,2,4-triazol-3-yl)-1-oxaspiro [3.3] heptan-6-yl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 108);

4-(difluoromethyl)-2-(3-((1r,3r)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 117);

2-(3-((R)-((1r,3R)-3-fluorocyclobutyl) (4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 129);

2-(3-((R)-((1s,3S)-3-fluorocyclobutyl) (4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 130);

2-(3-((1r,3r)-3-chloro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 137);

2-(3-((1s,3s)-3-chloro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 138);

(R)-2-(3-(fluoro (4-methyl-4H-1,2,4-triazol-3-yl) (oxetan-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoro-methyl) isoindolin-1-one (Compound 150);

(R)-2-(3-((4-methyl-4H-1,2,4-triazol-3-yl) (oxetan-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 164);

(R)-2-(3-(1-(4-methyl-4H-1,2,4-triazol-3-yl)ethyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 170);

2-(3-((1r,3S)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-((S)-1-((1-methylcyclobutyl)amino)ethyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 185);

(R)-4-chloro-2-(3-((4-methyl-4H-1,2,4-triazol-3-yl) (oxetan-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 270);

4-(difluoromethyl)-2-(3-((1r,3r)-3-fluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 272);

4-chloro-2-(3-((1r,3r)-3-fluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 273);

4-chloro-2-(3-((1r,3S)-3-fluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-((S)-1-((1-methylcyclobutyl)amino)ethyl) isoindolin-1-one (Compound 312);

4-chloro-2-(3-((S)-((1r,3S)-3-fluorocyclobutyl) (4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 320);

2-(3-((1r,3r)-3-(difluoromethoxy)-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 334);

2-(3-((1s,3s)-3-(difluoromethoxy)-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 335);

(R)-2-(3-(cyclopropyl (4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 342);

2-(3-((1r,3r)-3-acetyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 347);

2-(3-((1r,3r)-1-(4-methyl-4H-1,2,4-triazol-3-yl)-3-(trifluoromethoxy)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 351;

(S)-4-chloro-2-(3-(1-(4-methyl-4H-1,2,4-triazol-3-yl) propyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 359);

6-((S)-1-amino-2,2-dimethylpropyl)-2-(3-((1r,3S)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 361);

2-((1R,3s)-3-((S)-(4-methyl-4H-1,2,4-triazol-3-yl) (3-(6-(((1-methylcyclobutyl)amino)methyl)-1-oxo-4-(trifluoromethyl) isoindolin-2-yl)phenyl)methyl)cyclobutyl) acetonitrile (Compound 362);

2-((1R,3r)-3-((R)-(4-methyl-4H-1,2,4-triazol-3-yl) (3-(6-(((1-methylcyclobutyl)amino)methyl)-1-oxo-4-(trifluoromethyl) isoindolin-2-yl)phenyl)methyl)cyclobutyl) acetonitrile (Compound 364);

2-((1S,3s)-3-((R)-(4-methyl-4H-1,2,4-triazol-3-yl) (3-(6-(((1-methylcyclobutyl)amino)methyl)-1-oxo-4-(trifluoromethyl) isoindolin-2-yl)phenyl)methyl)cyclobutyl) acetonitrile (Compound 365);

2-(3-((1S,3S)-3-(methoxy-d3)-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 372);

2-(3-((1R,3R)-3-(methoxy-d3)-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 373);

4-chloro-2-(3-((1r,3s)-3-ethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 374);

4-chloro-2-(3-((1s,3r)-3-ethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 375);

(R)-2-(3-((3-fluorooxetan-3-yl) (4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 380);

(R)-2-(3-(fluoro (3-fluorooxetan-3-yl) (4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 404);

6-(((cyclobutylmethyl)amino)methyl)-2-(3-((1r3r)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 416);

6-((isobutylamino)methyl)-2-(3-((1r 3r)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-4-(trifluoromethyl)isoindolin-1-one(Compound 421);

6-(((1,1-difluorospiro[2.3]hexan-5-yl)amino)methyl)-2-(3-((1r 3r)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-4-(trifluoromethyl) isoindolin-1-one

(Compound 426);

6-(((6,6-difluorobicyclo[3.1.0] hexan-3-yl)amino)methyl)-2-(3-((1r3r)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-4-(trifluoromethyl) isoindolin-1-one

(Compound 427);

2-(3-((1s,3s)-3-chloro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-4-(difluoromethyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 446);

2-(3-((1r,3r)-3-chloro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-4-(difluoromethyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 447);

4-chloro-2-(3-((1r,3r)-3-chloro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 451);

2-(3-((1r,3s)-3-ethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 454);

2-(3-((1s,3r)-3-ethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 455); and

4-(difluoromethyl)-2-(3-((R)-((1s,3S)-3-fluorocyclobutyl) (4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl) isoindolin-1-one (Compound 459);

or a pharmaceutically acceptable salt thereof.

16. A method of treating a cancer, comprising administering to a subject in need thereof, a compound according to claim 1 .

17. The compound of claim 1 , selected from the group consisting of:

2-(3-((1s,3s)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 22);

2-(3-((1r,3r)-3-methoxy-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 23); and

(R)-2-(3-((5-methyl-1H-1,2,3-triazol-1-yl) (oxetan-3-yl)methyl)phenyl)-6-(((1-methylcyclobutyl)amino)methyl)-4-(trifluoromethyl) isoindolin-1-one (Compound 135);

or a pharmaceutically acceptable salt thereof.

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

19. A pharmaceutical composition comprising a compound of claim 15 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

20. A pharmaceutical composition comprising a compound of claim 17 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

Assignments (4)

Continuity (2)

References Cited (31)