IP Library Granted Patent US 7,465,731
Granted Patent B2
US 7,465,731 · App. 11/199,453 · Granted Dec 16, 2008

HDAC inhibitor

Assignee: Astellas Pharma Inc.
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Quick Facts
Patent No.
US 7,465,731
App. No.
11/199,453
Granted
Dec 16, 2008
Kind
B2
Abstract

A compound having the formula (I): wherein R 1 is hydrogen, lower alkyl, lower alkenyl, lower or higher alkynyl, cyclo(lower)alkyl, cyclo(higher)alkyl, cyclo(lower)alkyl(lower)alkyl, cyclo(higher)alkyl(lower)alkyl, cyclo(lower)alkenyl(lower)alkyl, aryl-fused cyclo(lower)alkyl, lower alkoxy, acyl, aryl, ar(lower)alkoxy, ar(lower)alkyl, heteroar(lower)alkyl, amino, heteroaryl, heterocyclyl or heterocyclyl(lower)alkyl, which may be substituted with one or more suitable substituent(s), R 2 is hydrogen or lower alkyl, X is arylene, heterorarylene, cycloalkylene, heterocycloalkylene or aryl-fused cycloalkene, Y is arylene, heteroarylene, which may be substituted with one or more suitable substituent(s), Z lower alenylene, which may be substituted with lower alkyl or halogen, or a salt thereof. The compound is useful as a histone deacetylase inhibitor.

Claims (32)

1. A compound having the formula (I):

wherein

R 1 is hydrogen, lower alkyl, lower alkenyl, lower or higher alkynyl, cyclo(lower)alkyl, cyclo(higher)alkyl, cyclo(lower)alkyl(lower)alkyl, cyclo(higher)alkyl(lower)alkyl, cyclo(lower)alkenyl(lower)alkyl, aryl-fused cyclo(lower)alkyl, lower alkoxy, acyl, aryl, ar(lower)alkoxy, ar(lower)alkyl, heteroar(lower)alkyl, amino, heteroaryl, heterocyclyl or heterocyclyl(lower)alkyl, which may be substituted with one or more substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, amino, hydroxy, cyano, aryl, aryloxy, acyl, cyclo(lower)alkyl, heteroaryl, halo(lower)alkyl and halo(lower)alkoxy,

R 2 is hydrogen or lower alkyl,

X is pyrrolidinylene or piperidinylene,

Y is pyrazinylene, pyrimidinylene, or pyridazinylene, which may be substituted with one or more substituent(s) selected from the group consisting of halogen and lower alkyl,

Z is lower alkenylene, which may be substituted with lower alkyl or halogen, or a salt thereof.

2. The compound or salt thereof of claim 1 , wherein

R 1 is hydrogen, lower alkyl, lower alkenyl, lower or higher alkynyl, cyclo(lower)alkyl, cyclo(higber)alkyl, cyclo(lower)alkyl(lower)alkyl, cyclo(higher)alkyl(lower)alkyl, cyclo(lower)alkenyl(lower)alkyl, aryl-fused cyclo(lower)alkyl, lower alkoxy, acyl, aryl, ar(lower)alkoxy, ar(lower)alkyl, heteroar(lower)alkyl, amino, heteroaryl, heterocyclyl or heterocyclyl(lower)alkyl, which may be substituted with one or more substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, amino, hydroxy, cyano, aryl, aryloxy, acyl, cyclo(lower)alkyl, heteroaryl, halo(lower)alkyl and halo(lower)alkoxy, and

Z is vinylene, which may be substituted with lower alkyl or halogen.

3. The compound or salt thereof of claim 2 , wherein

R 1 is lower alkyl, cyclo(lower)alkyl, cyclo(lower)alkyl(lower)alkyl, acyl, aryl, ar(lower)alkyl, heteroar(lower)alkyl, heteroaryl or heterocyclyl, which may be substituted with one or more substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, amino, hydroxy, cyano, aryl, aryloxy, acyl, cyclo(lower)alkyl, heteroaryl, halo(lower)alkyl and halo(lower)alkoxy,

R 2 is hydrogen,

Z is vinylene, which may be substituted with methyl or fluorine.

4. The compound or salt thereof of claim 3 , wherein

R 1 is ar(lower)alkyl or heteroar(lower)alkyl optionally substituted with lower alkyl, halogen, lower alkoxy, amino, hydroxy, cyano, aryl, aryloxy, acyl, cyclo(lower)alkyl, heteroaryl, halo(lower)alkyl or halo(lower)alkoxy.

5. The compound or salt thereof of claim 4 , wherein

R 1 is ar(lower)alkyl or heteroar(lower)alkyl optionally substituted with lower alkyl, halogen, lower alkoxy, di(lower)alkylamino, lower alkanoylamino, lower alkylsulfonylamino, hydroxy, cyano, arylcarbonyl, cyclo(lower)alkyl, halo(lower)alkyl or halo(lower)alkoxy, and

Z is vinylene.

6. The compound or salt thereof of claim 5 , wherein Y is pyrazinylene.

7. A pharmaceutical composition, comprising a compound or salt thereof according to ef claim 1 and a pharmaceutically acceptable, substantially non-toxic carrier or excipient.

8. A method for treating cirrhosis, acute promyelocytic leukaemia (APL), an organ transplant rejection, or a protozoal infection , which comprises administering an effective amount of a compound or salt thereof according to claim 1 to a human being or an animal in need thereof.

9. A pharmaceutical composition, comprising a compound or salt thereof according to claim 2 and a pharmaceutically acceptable, substantially non-toxic carrier or excipient.

10. A pharmaceutical composition, comprising a compound or salt thereof according to claim 3 and a pharmaceutically acceptable, substantially non-toxic carner or excipient.

11. A pharmaceutical composition, comprising a compound or salt thereof according to claim 4 and a pharmaceutically acceptable, substantially non-toxic carrier or excipient.

12. A pharmaceutical composition, comprising a compound or salt thereof according to claim 5 and a pharmaceutically acceptable, substantially non-toxic carrier or excipient.

13. A pharmaceutical composition, comprising a compound or salt thereof according to claim 6 and a pharmaceutically acceptable, substantially non-toxic carrier or excipient.

14. A method for treating cirrhosis, acute promyelocytic leukaemia (APL), an organ transplant rejection, or a protozoal infection, which comprises administering an effective amount of a compound or salt thereof according to claim 2 to a human being or an animal in need thereof.

15. A method for treating cirrhosis, acute promyelocytic leukaemia (APL), an organ transplant rejection, or a protozoal infection, which comprises administering an effective amount of a compound or salt thereof according to claim 3 to a human being or an animal in need thereof.

16. A method for treating cirrhosis, acute promyclocytic leukaemia (APL), an organ transplant rejection, or a protozoal infection, which comprises administering an effective amount of a compound or salt thereof according to claim 4 to a human being or an animal in need thereof.

17. A method for treating cirrhosis, acute promyelocytic leukaemia (APL), an organ transplant rejection, or a protozoal infection, which comprises administering an effective amount of a compound or salt thereof according to claim 5 to a human being or an animal in need thereof.

18. A method for treating cirrhosis, acute promyelocytic leukaemia (APL), an organ transplant rejection, or a protozoal infection, which comprises administering an effective amount of a compound or salt thereof according to claim 6 to a human being or an animal in need thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 17, 2005
From: ISHIBASHI, NAOKI; SAWADA, YUKI; URANO, YASUHARU; SATOH, SHIGEKI; INOUE, YOSHIKAZU; EIKYU, YOSHITERU; MUKOYOSHI, KOICHIRO; KAMIJO, KAZUNORI; SHIRAI, FUMIYUKI; TAKASUGI, HISASHI
To: ASTELLAS PHARMA INC.
Reel/Frame 017249/0464 →
Priority Claims (2)
AU 2004904487 · Aug 9, 2004 · national
AU 2004907228 · Dec 20, 2004 · national
Continuity (1)
Related Publication 20060052599A1 · Mar 9, 2006