Granted Patent B2

US 11,407,749 · App. 17/119,488 · Granted Aug 9, 2022

Inventors: Liangxing Wu (Wilmington, DE); Bo Shen (Garnet Valley, PA); Jingwei Li (Westfield, NJ); Zhenwu Li (Wilmington, DE); Kai Liu (Chadds Ford, PA); Fenglei Zhang (Berwyn, PA); Wenqing Yao (Chadds Ford, PA)

Assignee: Incyte Corporation

C07D471/04C07D487/04

Abstract

Claims (83)

1. A compound of Formula (II):

or a pharmaceutically acceptable salt thereof, wherein:

one of Y 1 and Y 2 is N and the other of Y 1 and Y 2 is C;

X 1 is N or CR 1 ;

X 2 is N or CR 2 ;

X 3 is N or CR 3 ;

X 5 is N or CR 5 ;

X 6 is N or CR 6 ;

R 1 , R 2 and R 8 are each independently selected from H, C 1-4 alkyl, C 3-4 cycloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo, CN, OH, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, NH 2 , —NH—C 1-4 alkyl, —N(C 1-4 alkyl) 2 , NHOR 10 , C(O)R 10 , C(O)NR 10 R 10 , C(O)OR 10 , OC(O)R 10 , OC(O)NR 10 R 10 , NR 10 C(O)R 10 , NR 10 C(O)OR 10 , NR 10 C(O)NR 10 R 10 , C(═NR 10 )R 10 , C(═NR 10 )NR 10 R 10 , NR 10 C(═NR 10 )NR 10 R 10 , NR 10 S(O)R 10 , NR 10 S(O) 2 R 10 , NR 10 S(O) 2 NR 10 R 10 , S(O)R 10 , S(O)NR 10 R 10 , S(O) 2 R 10 , and S(O) 2 NR 10 R 10 , wherein each R 10 is independently selected from H and C 1-4 alkyl optionally substituted with 1 or 2 groups independently selected from halo, OH, CN and C 1-4 alkoxy; and wherein the C 1-4 alkyl, C 3-4 cycloalkyl, C 2-4 alkenyl and C 2-4 alkynyl of R 1 , R 2 or R 8 are each optionally substituted with 1 or 2 substituents independently selected from halo, OH, CN and C 1-4 alkoxy;

R 9 is C 1-4 alkyl, halo, CN, OH, cyclopropyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, NH 2 , —NH—C 1-4 alkyl, —N(C 1-4 alkyl) 2 , NHOR 11 , C(O)R 11 , C(O)NR 11 R 11 , C(O)OR 11 , OC(O)R 11 , OC(O)NR 11 R 11 , NR 11 C(O)R 11 , NR 11 C(O)OR 11 , NR 11 C(O)NR 11 R 11 , C(═NR 11 )R 11 , C(═NR 11 )NR 11 R 11 , NR 11 C(═NR 11 )NR 11 R 11 , NR 11 S(O)R 11 , NR 11 S(O) 2 R 11 , NR 11 S(O) 2 NR 11 R 11 , S(O)R 11 , S(O)NR 11 R 11 , S(O) 2 R 11 , and S(O) 2 NR 11 R 11 , wherein each R 11 is independently selected from H and C 1-4 alkyl optionally substituted with 1 or 2 halo, OH, CN or OCH 3 ;

R 3 , R 5 , R 6 and R 7 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , NHOR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NHR a , NR a R a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , C(═NR a )R a , C(═NR a )NR a R a , NR a C(═NR a )NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 3 , R 4 , R 5 , R 6 and R 7 are each optionally substituted with 1, 2, 3, or 4 R b substituents, with the proviso that at least one of R 3 , R 5 and R 6 is other than H;

R 4 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , NHOR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NHR a , NR a R a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , C(═NR a )R a , C(═NR a )NR a R a , NR a C(═NR a )NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 4 are each optionally substituted with 1, 2, 3, or 4 R b substituents;

or two adjacent R 7 substituents on the phenyl ring, taken together with the carbon atoms to which they are attached, form a fused phenyl ring, a fused 5-, 6- or 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 5-6 cycloalkyl ring, wherein the fused 5-, 6- or 7-membered heterocycloalkyl ring and fused 5- or 6-membered heteroaryl ring each have 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused phenyl ring, fused 5-, 6- or 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 5-6 cycloalkyl ring are each optionally substituted with 1 or 2 independently selected R q substituents;

each R a is independently selected from H, CN, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R a are each optionally substituted with 1, 2, 3, 4, or 5 R d substituents;

each R d is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, CN, NH 2 , NHOR e , OR e , SR e , C(O)R e , C(O)NR e R e , C(O)OR e , OC(O)R e , OC(O)NR e R e , NHR e , NR e R e , NR e C(O)R e , NR e C(O)NR e R e , NR e C(O)OR e , C(═NR e )NR e R e , NR e C(═NR e )NR e R e , S(O)R e , S(O)NR e R e , S(O) 2 R e , NR e S(O) 2 R e , NR e S(O) 2 NR e R e , and S(O) 2 NR e R e , wherein the C 1-4 alkyl, C 3-10 cycloalkyl and 4-10 membered heterocycloalkyl of R d are each further optionally substituted with 1-3 independently selected R q substituents;

each R b substituent is independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, OH, NH 2 , NO 2 , NHOR c , OR c SR c , C(O)R c , C(O)NR c R c , C(O)OR c , OC(O)R c , OC(O)NR c R c , C(═NR c )NR c R c , NR c C(═NR c )NR c R c , NHR c , NR c R c , NR c C(O)R c , NR c C(O)OR c , NR c C(O)NR c R c , NR c S(O)R c , NR c S(O) 2 R c , NR c S(O) 2 NR c R c , S(O)R c , S(O)NR c R c , S(O) 2 R c and S(O) 2 NR c R c ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R b are each further optionally substituted with 1-3 independently selected R d substituents;

each R c is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R c are each optionally substituted with 1, 2, 3, 4, or 5 R f substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, halo, CN, NHOR g , OR g , SR g , C(O)R g , C(O)NR g R g , C(O)OR g , OC(O)R g , OC(O)NR g R g , NHR g , NR g R g , NR g C(O)R g , NR g C(O)NR g R g , NR g C(O)OR g , C(═NR g )NR g R g , NR g C(═NR g )NR g R g , S(O)R g , S(O)NR g R g , S(O) 2 R g , NR g S(O) 2 R g , NR g S(O) 2 NR g R g , and S(O) 2 NR g R g ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R f are each optionally substituted with 1, 2, 3, 4, or 5 R n substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, CN, NHOR o , OR o , SR o , C(O)R o , C(O)NR o R o , C(O)OR o , OC(O)R o , OC(O)NR o R o , NHR o , NR o R o , NR o C(O)R o , NR o C(O)NR o R o , NR o C(O)OR o , C(═NR o )NR o R o , NR o C(═NR o )NR o R o , S(O)R o , S(O)NR o R o , S(O) 2 R o , NR o S(O) 2 R o , NR o S(O) 2 NR o R o , and S(O) 2 NR o R o ;

each R g is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R g are each optionally substituted with 1-3 independently selected R p substituents;

or any two R a substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 R h substituents independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-C 1-4 alkyl-, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo, CN, OR i , SR i , NHOR i , C(O)R i , C(O)NR i R i , C(O)OR i , OC(O)R i , OC(O)NR i R i , NHR i , NR i R i , NR i C(O)R i , NR i C(O)NR i R i , NR i C(O)OR i , C(═NR i )NR i R i , NR i C(═NR i )NR i R i , S(O)R i , S(O)NR i R i , S(O) 2 R i , NR i S(O) 2 R i , NR i S(O) 2 NR i R i , and S(O) 2 NR i R i , wherein the C 1-6 alkyl, C 3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-C 1-4 alkyl- of R h are each further optionally substituted by 1, 2, or 3 substituents independently selected from C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 2-4 alkenyl, C 2-4 alkynyl, halo, C 1-4 alkyl, C 1-4 haloalkyl, CN, NHOR k , OR k , SR k , C(O)R k , C(O)NR k R k , C(O)OR k , OC(O)R k , OC(O)NR k R k , NHR k , NR k R k , NR k C(O)R k , NR k C(O)NR k R k , NR k C(O)OR k , C(═NR k )NR k R k , NR k C(═NR k )NR k R k , S(O)R k , S(O)NR k R k , S(O) 2 R k , NR k S(O) 2 R k , NR k S(O) 2 NR k R k , and S(O) 2 NR k R k ; or two R h groups attached to the same carbon atom of the 4- to 10-membered heterocycloalkyl taken together with the carbon atom to which they are attached form a C 3-6 cycloalkyl or 4- to 6-membered heterocycloalkyl having 1-2 heteroatoms as ring members selected from O, N or S;

or any two R c substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;

or any two R e substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;

or any two R g substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;

or any two R o substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; and

each R e , R i , R k , R o or R p is independently selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 1-4 haloalkyl, C 2-4 alkenyl, and C 2-4 alkynyl, wherein the C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 2-4 alkenyl, and C 2-4 alkynyl of R e , R i , R k , R o or R p are each optionally substituted with 1, 2 or 3 R q substituents;

each R q is independently selected from OH, CN, —COOH, NH 2 , halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylthio, phenyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, NHR 12 , NR 12 R 12 , and C 1-4 haloalkoxy, wherein the C 1-4 alkyl, phenyl and 5-6 membered heteroaryl of R q are each optionally substituted with OH, CN, —COOH, NH 2 , C 1-4 alkoxy, C 3-10 cycloalkyl and 4-6 membered heterocycloalkyl and each R 12 is independently C 1-6 alkyl;

is a single bond or a double bond to maintain ring A being aromatic;

the subscript n is an integer of 1, 2, 3, 4 or 5; and

the subscript m is an integer of 1, 2 or 3.

2. The compound of claim 1 , having Formula (III):

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , having Formula (IV):

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , having Formula (V):

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , having Formula (VI):

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the moiety:

is selected from:

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 and R 5 , where applicable, are each H.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is N, X 2 is CH, X 3 , X 5 and X 6 are each CH, Y 1 is N and Y 2 is C.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is CH, X 2 is CH, X 3 , X 5 and X 6 are each CH, Y 1 is C and Y 2 is N.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is CH, X 2 is CH, X 3 and X 6 are each CH, X 5 is N, Y 1 is C and Y 2 is N.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is N, X 2 is CH, X 3 and X 6 are each N, X 5 is CH, Y 1 is N and Y 2 is C.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is N, X 2 is CH, X 3 and X 5 are each CH, X 6 is N, Y 1 is N and Y 2 is C.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is N, X 2 is CH, X 3 and X 6 are each CH, X 5 is N, Y 1 is N and Y 2 is C.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is N, X 2 is CH, X 5 and X 6 are each CH, X 3 is N, Y 1 is N and Y 2 is C.

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 and X 2 are each N, X 3 , X 5 and X 6 are each CH, Y 1 is C and Y 2 is N.

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 and X 2 are each N, X 3 is CH, X 5 is N, X 6 is CR 6 , Y 1 is C and Y 2 is N.

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is N, X 2 is CH, X 3 and X 5 are each CH, X 6 is CR 6 , Y 1 is N and Y 2 is C.

18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 and X 2 are each N, X 3 and X 5 are each CH, X 6 is CR 6 , Y 1 is N and Y 2 is C.

19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is —CH 2 —R b .

20. The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein R b is —NR c R c .

21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is 2-hydroxyethylaminomethyl, 2-hydroxyethyl(methyl)aminomethyl, 2-carboxypiperidin-1-ylmethyl, (cyanomethyl)aminomethyl, (S)-2-carboxypiperidin-1-ylmethyl or (R)-2-carboxypiperidin-1-ylmethyl.

22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

2-({[2-(2-methylbiphenyl-3-yl)imidazo[1,2-a]pyridin-6-yl]methyl}amino)ethanol;

2-({[2-(2-methylbiphenyl-3-yl)indolizin-7-yl]methyl}amino)ethanol;

(2S)-1-{[2-(2-methylbiphenyl-3-yl)indolizin-7-yl]methyl}piperidine-2-carboxylic acid;

(2 S)-1-{[6-(2-methylbiphenyl-3-yl)pyrrolo[1,2-c]pyrimidin-3-yl]methyl}piperidine-2-carboxylic acid;

2-((6-(2-methylbiphenyl-3-yl)imidazo[1,2-b][1,2,4]triazin-2-yl)methylamino)ethanol;

2-((6-(2-methylbiphenyl-3-yl)imidazo[1,2-b][1,2,4]triazin-2-yl)methylamino)acetonitrile;

2-((6-(2-methylbiphenyl-3-yl)imidazo[1,2-b][1,2,4]triazin-2-yl)methylamino)acetamide;

2-(methyl((6-(2-methylbiphenyl-3-yl)imidazo[1,2-b][1,2,4]triazin-2-yl)methyl)amino)ethanol;

2-((8-methyl-2-(2-methylbiphenyl-3-yl)imidazo[1,2-a]pyridin-6-yl)methylamino)ethanol;

(S)-1-((8-methyl-2-(2-methylbiphenyl-3-yl)imidazo[1,2-a]pyridin-6-yl)methyl)piperidine-2-carboxylic acid;

2-((8-chloro-2-(2-methylbiphenyl-3-yl)imidazo[1,2-a]pyridin-6-yl)methylamino)ethanol;

2-({[2-(2-methylbiphenyl-3-yl)imidazo[1,2-a]pyrimidin-6-yl]methyl}amino)ethanol;

2-({[2-(2-methylbiphenyl-3-yl)imidazo[1,2-a]pyrazin-6-yl]methyl}amino)ethanol;

(S)-1-((2-(2-methylbiphenyl-3-yl)imidazo[1,2-b]pyridazin-6-yl)methyl)piperidine-2-carboxylic acid;

2-({[2-(2-methylbiphenyl-3-yl)imidazo[1,2-b]pyridazin-6-yl]methyl}amino)ethanol;

2-({[2-(2-methylbiphenyl-3-yl)[1,2,4]triazolo[1,5-a]pyridin-7-yl]methyl}amino)ethanol;

(2S)-1-{[2-(2-methylbiphenyl-3-yl)[1,2,4]triazolo[1,5-a]pyridin-7-yl]methyl}piperidine-2-carboxylic acid;

2-({[2-(2-methylbiphenyl-3-yl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]methyl}amino)ethanol;

(2S)-1-{[2-(2-methylbiphenyl-3-yl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]methyl}piperidine-2-carboxylic acid; and

2-({[5-methyl-2-(2-methylbiphenyl-3-yl)[1,2,4]triazolo[1,5-c]pyrimidin-7-yl]methyl}amino)ethanol.

23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

2-({[8-chloro-2-(2-methylbiphenyl-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]methyl}amino)ethanol;

2-({[8-[(2-methoxyethyl)amino]-2-(2-methylbiphenyl-3-yl) [1,2,4]triazolo[1,5-a]pyridin-6-yl]methyl}amino)ethanol;

4-[6-{[(2-hydroxyethyl)amino]methyl}-2-(2-methylbiphenyl-3-yl)[1,2,4]triazolo[1,5-a]pyridin-8-yl]butanenitrile;

[6-{[(2-hydroxyethyl)amino]methyl}-2-(2-methylbiphenyl-3-yl) [1,2,4]triazolo[1,5-a]pyridin-8-yl]acetonitrile;

2-(8-chloro-6-{[(2-hydroxyethyl)amino]methyl}[1,2,4]triazolo[1,5-a]pyridin-2-yl)-6-(2,3-dihydro-1,4-benzodioxin-6-yl)benzonitrile;

2-[2-cyano-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-6-{[(2-hydroxyethyl)amino]methyl}[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile; and

2-(8-(cyanomethyl)-6-{[(2-hydroxyethyl)amino]methyl}[1,2,4]triazolo[1,5-a]pyridin-2-yl)-6-(2,3-dihydro-1,4-benzodioxin-6-yl)benzonitrile.

24. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignments (1)

Continuity (10)

Cited By (6)

US 12,187,743 US 12,247,026 US 12,247,038 US 12,404,272 US 12,466,822 US 12,516,044