Triazolopyridine compounds and uses thereof

1. A compound of Formula (IA):

or a pharmaceutically acceptable salt thereof, wherein:

A is

W is independently N or CR 4 ;

Y is independently N or CR 3 ;

Z is independently N or CR 1 ;

R 1 is independently H, halogen, or NH 2 ;

R 2 is independently H, OCH 3 , or halogen;

R 3 is independently H or halogen;

R 4 is independently H, halogen, CH 3 , or OCH 3 ;

R 5 is independently H, halogen, CH 3 , OH, OCH 3 , OCH 2 F, OCHF 2 , or OCF 3 ;

R 6 and R 7 are independently selected from: H and halogen;

R 8 is independently selected from: halogen, phenyl, and a 5- to 6-membered heteroaryl comprising carbon atoms and 1-4 heteroatoms selected from N, NR a , O, and S(O) p ; wherein said phenyl and heteroaryl are substituted with 0-4 R 8A ;

each R 8A is independently selected from: halogen, CN, OH, —(O) m —(C 1 -C 6 alkyl substituted with 0-1 R 8B ), C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, R 8C , —OR 8C , —C(═O)R 8D , NR 8E R 8F , —C(C 1 -C 4 alkyl)═N(C 1 -C 4 alkoxy), —C(═O)NR 8E R 8F , —NHC(═O)R 8D , —NHC(═O)NR 8E R 8F , —S(═O)R 8D , —S(═O) 2 R 8D , —S(═O) 2 NR 8E R 8F , —NHS(═O) 2 R 8D , —NR 8E (S(═O) 2 (C 1 -C 4 alkyl)), and —CR 8C R 8E R 8G ;

R 8B is independently selected from: CN, OH, NR e R f , C 1 -C 4 alkoxy, —C(═O)NR e R f , —NHC(═O)(C 1 -C 4 alkyl), —N(→O)(C 1 -C 4 alkyl) 2 , —S(═O) 2 (C 1 -C 4 alkyl), and a 4- to 6-membered heterocycloalkyl comprising carbon atoms and 1-2 heteroatoms selected from N, NR a , O, and S(O) p ; wherein said heterocycloalkyl is substituted with 0-2 R c ;

each R 8C is independently selected from: C 3 -C 6 cycloalkyl, phenyl, and a 4- to 7-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NR a , O, and S(O) p ; wherein each moiety is substituted with 0-2 R c ;

each R 8D is independently selected from: C 1 -C 4 alkyl and R 8C ;

R 8E and R 8G are, at each occurrence, independently selected from: H and C 1 -C 4 alkyl;

each R 8F is independently selected from: H and C 1 -C 4 alkyl substituted with 0-1 R d ;

each R a is independently selected from: H, →O, C 1 -C 4 alkyl substituted with 0-1 R b , —C(═O)H, —C(═O)(C 1 -C 4 alkyl), —CO 2 (C 1 -C 4 alkyl), C 3 -C 6 cycloalkyl, benzyl, and a 4- to 6-membered heterocycloalkyl comprising carbon atoms and 1-2 heteroatoms selected from N, NR g , O, and S(O) p ;

R b is independently selected from: halogen, OH, C 1 -C 4 alkoxy, and

each R c is independently selected from: ═O, halogen, OH, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and C 1 -C 4 haloalkoxy;

R d is independently selected from: OH and NR e R f ;

R e and R f are, at each occurrence, independently selected from: H and C 1 -C 4 alkyl;

R g is independently selected from: H, C 1 -C 4 alkyl, —C(═O)(C 1 -C 4 alkyl), and —CO 2 (C 1 -C 4 alkyl);

each p is independently selected from 0, 1 and 2; and

m is independently selected from 0 and 1.

2. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

each R 8A is independently selected from: halogen, CN, OH, —(O) m —(C 1 -C 6 alkyl substituted with 0-1 R 8B ), C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, R 8C , —C(═O)R 8D , NR 8F R 8F , —C(═O)NR 8F R 8F , —NHC(═O)R 8D , —NHC(═O)NR 8F R 8F , —S(═O)R 8D , —S(═O) 2 R 8D , —S(═O) 2 NHR 8F , —NHS(═O) 2 R 8D , —NR 8F (S(═O) 2 (C 1 -C 4 alkyl)), —O—C 3 -C 6 cycloalkyl, and

and

each R a is independently selected from: H, →O, C 1 -C 4 alkyl substituted with 0-1 R b , —C(═O)H, —C(═O)(C 1 -C 4 alkyl), —CO 2 (C 1 -C 4 alkyl), C 3 -C 6 cycloalkyl, benzyl,

3. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 1 is independently H, F, or Cl;

R 2 is independently H, OCH 3 , or F;

R 3 is independently H or F;

R 4 is independently H, F, CH 3 , or OCH 3 ;

R 5 is independently H, F, CH 3 , OH, OCH 3 , OCH 2 F, OCHF 2 , or OCF 3 ;

R 6 and R 7 are independently selected from: H and F; and

R a is independently selected from: H, C 1 -C 4 alkyl substituted with 0-1 R b , C 3 -C 6 cycloalkyl,

4. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 6 and R 7 are H;

R 8 is independently selected from: phenyl, and a 6-membered heteroaryl comprising carbon atoms and 1-2 heteroatoms selected from N and NR a ; wherein said phenyl and heteroaryl are substituted with 0-3 R 8A .

5. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 8 is independently selected from:

6. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 8 is independently selected from:

7. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 8 is independently selected from:

each R 8A is independently selected from: halogen, CN, OH, —(O) m —(C 1 -C 6 alkyl substituted with 0-1 R 8B ), C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NH 2 , —N(C 1 -C 4 alkyl) 2 , C 3 -C 6 cycloalkyl, —O—C 3 -C 6 cycloalkyl, —C(═O)(C 1 -C 4 alkyl), —C(═O)NH 2 , —C(═O)NH(C 1 -C 4 alkyl), —C(═O)N(C 1 -C 4 alkyl) 2 , —NHC(═O)(C 1 -C 4 alkyl), —NHC(═O)N(C 1 -C 4 alkyl) 2 , —S(═O)(C 1 -C 4 alkyl), —S(═O) 2 (C 1 -C 4 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 NH(C 1 -C 4 alkyl substituted with 0-1 OH), —S(═O) 2 N(C 1 -C 4 alkyl) 2 , —NHS(═O) 2 (C 1 -C 4 alkyl), —N(C 1 -C 4 alkyl)(S(═O) 2 (C 1 -C 4 alkyl)), tetrazolyl,

R 8B is independently selected from: CN, OH, C 1 -C 4 alkoxy, —N(C 1 -C 4 alkyl) 2 , —C(═O)NH(C 1 -C 4 alkyl), —C(═O)N(C 1 -C 4 alkyl) 2 , —NHC(═O)(C 1 -C 4 alkyl), —N(→O)(C 1 -C 4 alkyl) 2 , —S(═O) 2 (C 1 -C 4 alkyl), imidazolyl,

R a is independently selected from: H and C 1 -C 4 alkyl; and

R c is independently C 1 -C 4 alkyl.

8. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 8 is independently selected from:

each R 8A is independently selected from: halogen, CN, OH, —(O) m —(C 1 -C 6 alkyl substituted with 0-1 R 8B ), C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, N(C 1 -C 4 alkyl) 2 , C 3 -C 6 cycloalkyl, —O—C 3 -C 6 cycloalkyl, —C(═O)NH(C 1 -C 4 alkyl), —C(═O)N(C 1 -C 4 alkyl) 2 , —NHC(═O)(C 1 -C 4 alkyl), —NHC(═O)N(C 1 -C 4 alkyl) 2 , —S(═O) 2 (C 1 -C 4 alkyl), —N(C 1 -C 4 alkyl)(S(═O) 2 (C 1 -C 4 alkyl)),

R 8B is independently selected from: CN, OH, C 1 -C 4 alkoxy, —N(C 1 -C 4 alkyl) 2 , —C(═O)NH(C 1 -C 4 alkyl), —C(═O)N(C 1 -C 4 alkyl) 2 , —NHC(═O)(C 1 -C 4 alkyl), —S(═O) 2 (C 1 -C 4 alkyl), and

R a is independently selected from: H and C 1 -C 4 alkyl; and

R c is independently C 1 -C 4 alkyl.

9. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

W is independently N or CR 4 ;

R 1 is independently H or F;

R 2 is independently H or F;

R 3 is independently H or F;

R 4 is independently H or F;

R 5 is independently H or —OCH 3 ;

R 8A is independently selected from: C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, —N(C 1 -C 4 alkyl) 2 , C 3 -C 6 cycloalkyl, —O—C 3 -C 6 cycloalkyl,

and

R a is independently selected from: H and C 1 -C 4 alkyl.

10. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

W is independently CR 4 ;

R 4 is independently H or F;

R 8A is independently selected from: CH 3 , CH(CH 3 ) 2 , CH(CH 3 )(CH 2 CH 3 ), OCH 3 , OCH 2 CH 3 , OCH(CH 3 ) 2 , CHF 2 , N(CH 3 ) 2 , cyclopropyl, —O-cyclopropyl,

11. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 6 and R 7 are H;

R 8 is independently selected from:

each R 8A is independently selected from: C 1 -C 4 alkyl substituted with 0-1 OH, and C 1 -C 4 haloalkyl;

R a is independently selected from: H, C 1 -C 4 alkyl substituted with 0-1 R b , C 3 -C 6 cycloalkyl,

and

R b is independently selected from: OH and

12. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 1 is F.

13. The compound or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein said compound is selected from

14. A pharmaceutical composition, comprising one or more pharmaceutically acceptable carriers and a compound of claim 1 .

15. The pharmaceutical composition of claim 14 further comprising at least one additional therapeutic agent.

16. The pharmaceutical composition of claim 15 where said at least one additional therapeutic agent is selected from an anti-cancer agent, an immunomodulatory, an anti-allergic agent, an anti-emetic, a pain reliever, and a cytoprotective agent, and a combination thereof.

17. A method for treating a disease or disorder mediated by EED and/or PRC2, comprising the step of administering to a subject in need of such treatment a therapeutically effective amount of a compound according to claim 1 and wherein the disease is lymphoma.

18. The method of claim 17 , wherein the disease is diffused large B cell lymphoma or follicular lymphoma.