BICYCLIC PYRIMIDINES AND BICYCLIC 3,4-DIHYDROPYRIMIDINES AS INHIBITORS OF CELLULAR PROLIFERATION

Title:

BICYCLIC PYRIMIDINES AND BICYCLIC 3,4-DIHYDROPYRIMIDINES AS INHIBITORS OF CELLULAR PROLIFERATION

Document Type and Number:

WIPO Patent Application WO1999061444

Kind Code:

A3

Abstract:

This invention provides bicyclic heterocycles that are useful for treating cell proliferative disorders, such as cancer and restenosis, as well as angiogenesis and atherosclerosis. We have now discovered a group of bicyclic compounds that are potent inhibitors of cyclin-dependent kinases (cdks), growth factor-mediated kinases, and non-receptor kinases. The compounds are readily synthesized and can be administered by a variety of routes, including orally, and have sufficient bioavailability for clinical use. This invention provides compounds of Formula (I), where Z is N or CH; G is N or CH; W is NH, S, SO, or SO2, R<1> includes phenyl and substituted phenyl, R<2> includes alkyl and cycloalkyl, R<3> includes alkyl and hydrogen, R<8> and R<9> include hydrogen and alkyl, and the pharmaceutically acceptable salts thereof. This invention also provides pharmaceutical formulations comprising a compound of Formula (I) together with a pharmaceutically acceptable carrier, diluent, or excipient therefor.

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Inventors:

DOBRUSIN ELLEN MYRA (US)
HAMBY JAMES MARINO (US)
KRAMER JAMES BERNARD (US)
SCHROEDER MEL CONRAD (US)
SHOWALTER HOWARD DANIEL HOLLIS (US)
TOOGOOD PETER (US)
TRUMPP-KALLMEYER SUSANNE A (SE)

Application Number:

PCT/US1999/010187

Publication Date:

February 03, 2000

Filing Date:

May 10, 1999

Export Citation:

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Assignee:

WARNER LAMBERT CO (US)
DOBRUSIN ELLEN MYRA (US)
HAMBY JAMES MARINO (US)
KRAMER JAMES BERNARD (US)
SCHROEDER MEL CONRAD (US)
SHOWALTER HOWARD DANIEL HOLLIS (US)
TOOGOOD PETER (US)
TRUMPP KALLMEYER SUSANNE A (SE)

International Classes:

A61K31/505; A61K31/519; A61K31/5377; A61P9/00; A61P9/10; A61P17/06; A61P27/02; A61P35/00; A61P43/00; C07D221/00; C07D239/00; C07D471/04; C07D487/04; A61K; C07D; (IPC1-7): C07D487/04; C07D471/04; A61K31/505

Domestic Patent References:

WO1996034867A1	1996-11-07
WO1995019774A1	1995-07-27
WO1997038983A1	1997-10-23
WO1992020642A1	1992-11-26
WO1996015128A2	1996-05-23
WO1998033798A2	1998-08-06
WO1999009030A1	1999-02-25
WO1999006378A1	1999-02-11

Foreign References:

US5654307A	1997-08-05
EP0278686A1	1988-08-17
EP0021292A1	1981-01-07

Other References:

G. W. REWCASTLE ET AL., JOURNAL OF MEDICINAL CHEMISTRY, vol. 39, 1996, pages 1823 - 35, XP002046257
G. W. REWCASTLE TE AL., JOURNAL OF MEDICINAL CHEMISTRY, vol. 38, 1995, pages 3482 - 7, XP000673491

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