IP Library › Granted Patent US 8,349,841
Granted Patent B2
US 8,349,841 · App. 12/452,980 · Granted Jan 8, 2013

Vinyl-aryl derivatives for inflammation and immune-related uses

Assignee: Synta Pharmaceuticals Corp.
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Quick Facts
Patent No.
US 8,349,841
App. No.
12/452,980
Granted
Jan 8, 2013
Kind
B2
Abstract

The invention relates to compounds that are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders. In some embodiments, compounds of structural formula (I): or pharmaceutically acceptable salts, solvates, clathrates, or prodrugs thereof, are provided.

Claims (53)

1. A compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein:

X 1 and X 2 are N;

one of X 3 or X 6 is NR 29 , and the other is CH 2 ;

L is a linker selected from the group consisting of —NHCH 2 —, —CH 2 NH—, —NR 5 —C(O)—, —C(O)—NR 5 —, —NR 5 —C(S)—, —C(S)—NR 5 —, —NR 5 —C(NR 8 )—, —C(NR 8 )—NR 5 —, —NR 5 C(S)NR 5 —, —NR 5 C(NR 8 )NR 5 —, or —NR 5 CR a R b NR 5 —;

Y is a substituted phenyl, provided that Y is not substituted with —NHC(O)R 30 ;

R 1 is selected from the group consisting of H, a halo, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;

R 2 , for each occurrence is, hydrogen;

R a and R b , for each occurrence, are independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, cyano, nitro, halo, —OR 5 , —SR 5 , —NR 6 R 7 , —C(O)NR 6 R 7 , —NR 5 C(O)R 5 , —C(O)R 5 , —C(O)OR 5 , —OC(O)R 5 , —C(O)SR 5 , —SC(O)R 5 , —C(S)NR 6 R 7 , —NR 5 C(S)R 5 , —C(S)R 5 , —C(S)OR 5 , —OC(S)R 5 , —C(S)SR 5 , —SC(S)R 5 , —C(NR 8 )NR 6 R 7 , —NR 5 C(NR 8 )R 5 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —OC(NR 8 )R 5 , —C(NR 8 )SR 5 , —SC(NR 8 )R 5 , —OC(O)OR 5 , —OC(O)NR 6 R 7 , —NR 5 C(O)OR 5 , —NR 5 C(O)NR 6 R 7 , —SC(O)OR 5 , —SC(O)NR 6 R 7 , —SC(O)SR 5 , —NR 5 C(O)SR 5 , —OC(O)SR 5 , —OC(S)OR 5 , —OC(S)NR 6 R 7 , —NR 5 C(S)OR 5 , —NR 5 C(S)NR 6 R 7 , —SC(S)OR 5 , —SC(S)NR 6 R 7 , —SC(S)SR 5 , —NR 5 C(S)SR 5 , —OC(S)SR 5 , —OC(NR 8 )OR 5 , —OC(NR 8 )NR 6 R 7 , —NR 5 C(NR 8 )OR 5 , —NR 5 C(NR 8 )NR 6 R 7 , —SC(NR 8 )OR 5 , —SC(NR 8 )NR 6 R 7 , —SC(NR 8 )SR 5 , —NR 5 C(NR 8 )SR 5 , or —OC(NR 8 )SR 5 ;

R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;

R 6 and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6 and R 7 taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;

R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;

R 29 is —C(O)R 30 or an optionally substituted N-containing 6-membered aromatic ring;

R 30 is —H, —OR 5 , —SR 5 , —NR 6 R 7 , an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; and

m is 2.

2. The compound of claim 1 , wherein:

Y is substituted with one to two substituents that are each independently a lower alkyl or a halo.

3. The compound of claim 1 , wherein:

L is —NHCH 2 —, —CH 2 NH—, —NH—C(O)—, or —C(O)—NH—.

4. The compound of claim 1 , wherein:

X 3 is CH 2 and X 6 is NR 29 .

5. The compound of claim 1 wherein

Y is a difluorophenyl;

L is —NHC(O)—; and

R 1 is selected from the group consisting of halo or an optionally substituted lower alkyl.

6. The compound of claim 1 , wherein the compound is represented by one of the following structures:

wherein

each of X 7 , X 8 , X 9 , X 10 , and X 11 are independently CH or N, provided that at least one of X 7 , X 8 , X 9 , X 10 , or X 11 is N;

R 31 is halo, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; and

p is 1, 2, 3, 4 or 5.

7. The compound of claim 6 , wherein the compound is represented by one of the following structures:

8. The compound of claim 6 , wherein p is 1 or 2.

9. The compound of claim 6 , wherein each R 31 is independently a lower alkyl or a halo.

10. The compound of claim 9 , wherein each R 31 is halo.

11. The compound of claim 10 , wherein each R 31 is F.

12. The compound of claim 6 , wherein:

L is —NHCH 2 —, —CH 2 NH—, —NH—C(O)—, or —C(O)—NH—.

13. The compound of claim 6 , wherein:

(i) two of X 7 , X 8 , X 9 , X 10 , and X 11 are N; or

(ii) one of X 7 , X 8 , X 9 , X 10 , and X 11 is N.

14. The compound of claim 7 , wherein:

each R 31 is halo;

L is —NHC(O)—;

R 1 is selected from the group consisting of halo or an optionally substituted lower alkyl; and

two of X 7 , X 8 , X 9 , X 10 , and X 11 are N.

15. The compound of claim 14 , wherein each R 31 is F.

16. The compound of claim 1 , wherein the compound is 2,6-difluoro-N-(5-(4-methyl-1-(pyrimidin-2-yl)-1,2,5,6-tetrahydropyridin-3-yl)pyrazin-2-yl)benzamide hydrochloride.

17. A pharmaceutical composition, comprising a compound of claim 1 , and

a pharmaceutically acceptable carrier.

18. The compound of claim 2 , wherein Y is a difluorophenyl.

19. The compound of claim 2 , wherein Y is 2,6-difluorophenyl.

20. The compound of claim 3 , wherein L is —NHC(O)—.

21. The compound of claim 12 , wherein L is —NHC(O)—.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 22, 2010
From: CHEN, SHOUJUN
To: SYNTA PHARMACEUTICALS CORP.
Reel/Frame 024570/0376 →
Continuity (3)
Provisional Application 60962823 · Aug 1, 2007
Related Publication 20100292252A1 · Nov 18, 2010
Related Publication 20120040997A9 · Feb 16, 2012