Title:
SUBSTITUTED PYRIDIN-4-ONES AND THEIR USE AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS.
Document Type and Number:
WIPO Patent Application WO/2003/013528
Kind Code:
A1
Abstract:
GnRH receptor antagonists of formula (I) are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof, including stereosomers, prodrugs and pharmaceutically acceptable salts thereof, wherein: A is O or a bond; n is 1, 2, 3 or 4; R¿1? and R¿2? are the same or different and independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocycle, substituted heterocycle, heterocyclealkyl, susbstituted heterocyclealkyl, -C(R¿8?)(=NR¿9?) or -C(NR¿10?R¿11?)(=NR¿9?); or R¿1? and R¿2? taken together with the nitrogen atom to which they are attached form a heterocycle or a substituted heterocycle; R¿3a? and R¿3b? are the same or different and, at each occurrence, independently hydrogen, alkyl, substituted alkyl, alkoxy, alkylthio, alkylamino, aryl, substituted aryl, arylakyl, substituted arylalkyl, heterocycle, substituted heterocycle, heterocyclealkyl, substituted heterocyclealkyl, -COOR¿12? or -CONR¿10?R¿11?; or R¿3ab? and R¿3b? taken together with the carbon atom to which they are attached form a homocycle, substituted homocycle, heterocycle or substituted heterocycle; or R¿3a? and the carbon to which it is attached taken together with R¿1? and the nitrogen to which it is attached form a heterocycle or substituted heterocycle; R¿4? is hydrogen, alkyl or substituted alkyl; R¿5? is arylalkyl, substituted arylalkyl, heteroarylalkyl or substituted heteroalalkyl; R¿6? is aryl, substituted aryl, heteroaryl or substituted heteroaryl; R¿7? is hydrogen, alkyl or substituted alkyl; R¿8?, R¿9?, R¿10? and R¿11? are the same or different and, at each occurrence, independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocycle, substituted heterocycle, heterocyclealkyl or substituted heterocyclealkyl, and R¿12? is hydrogen, alkyl or substituted alkyl.
Inventors:
TUCCI FABIO C (US)
CONNORS PATRICK J (US)
ZHU YUN-FEI (US)
CHEN CHEN (US)
CONNORS PATRICK J (US)
ZHU YUN-FEI (US)
CHEN CHEN (US)
Application Number:
PCT/US2002/024643
Publication Date:
February 20, 2003
Filing Date:
August 02, 2002
Export Citation:
Assignee:
NEUROCRINE BIOSCIENCES INC (US)
TUCCI FABIO C (US)
CONNORS PATRICK J (US)
ZHU YUN-FEI (US)
CHEN CHEN (US)
TUCCI FABIO C (US)
CONNORS PATRICK J (US)
ZHU YUN-FEI (US)
CHEN CHEN (US)
International Classes:
A61K31/439; A61K31/4418; A61K31/443; A61K31/4436; A61K31/4439; A61K31/444; A61K31/455; A61K31/4709; A61K31/4725; A61K31/496; A61K31/506; A61K31/52; A61K31/5377; A61P1/00; A61P5/00; A61P5/04; A61P13/08; A61P15/00; A61P17/00; A61P25/20; A61P35/00; A61P37/02; A61P43/00; C07D211/86; C07D213/68; C07D213/69; C07D213/74; C07D213/80; C07D401/06; C07D401/12; C07D405/12; C07D409/04; C07D409/14; C07D413/06; C07D413/14; C07D453/02; C07D453/06; C07D473/24; (IPC1-7): A61K31/45; A61K31/443; A61K31/4436; A61K31/4439; A61K31/444; A61P5/04; C07D213/68; C07D213/69; C07D401/12; C07D405/12; C07D409/04; C07D409/12; C07D453/02; C07D487/04
Domestic Patent References:
| WO2001055119A2 | 2001-08-02 | |||
| WO2001029044A1 | 2001-04-26 | |||
| WO1998055470A1 | 1998-12-10 |
Other References:
CHO N ET AL: "Discovery of a Novel, Potent and Orally Active Nonpeptide Antagonist of the Human Luteinizing Hormone Releasing Hormone (LHRH) Receptor", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 41, no. 22, 22 October 1998 (1998-10-22), pages 4190 - 4195, XP002156492, ISSN: 0022-2623
Attorney, Agent or Firm:
Hermanns, Karl R. (Suite 6300 701 Fifth Avenu, Seattle WA, US)
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