US Patent:
20070265345, Nov 15, 2007
Inventors:
Amita Chaudhari - Collegeville PA, US
Dashyant Dhanak - Collegeville PA, US
Steven Knight - Collegeville PA, US
David Morgans - King of Prussia PA, US
Cynthia Parrish - College of Prussia PA, US
Assignee:
SMITHKLINE BEECHAM CORPORATION - Philadelphia PA
CYTOKINETICS - South San Francisco CA
International Classification:
A61K 31/17
A61K 31/165
A61P 35/00
A61P 37/00
A61P 43/00
A61P 9/00
C07C 233/00
C07C 273/18
C07C 275/00
US Classification:
514595000, 514618000, 564161000, 564054000
Abstract:
The invention is directed to certain biphenyl compounds. Specifically, the invention is directed to compounds according to Formula I: wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and Y are as defined below, and to pharmaceutically-acceptable salts thereof. The compounds of the invention are KSP inhibitors, particularly human KSP inhibitors, and can be useful for the treatment for a variety of diseases and conditions, such as cancer, hyperplasias, restenosis, cardiac hypertrophy, immune disorders, fungal disorders, and inflammation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting KSP and treatment of conditions associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. In an additional aspect, the invention provides methods of screening for compounds that will bind to a KSP kinesin, for example compounds that will displace or compete with the binding of the compounds of the invention. The methods comprise combining a labeled compound of the invention, a KSP kinesin, and at least one candidate agent and determining the binding of the candidate bioactive agent to the KSP kinesin. In a further aspect, the invention provides methods of screening for modulators of KSP kinesin activity. The methods comprise combining a compound of the invention, a KSP kinesin, and at least one candidate agent and determining the effect of the candidate bioactive agent on the KSP kinesin activity.