Title:
FXR MODULATORS
Document Type and Number:
WIPO Patent Application WO2002020463
Kind Code:
A3
Abstract:
The present invention provides compounds, pharmaceutical compositions and methods that are useful in modulating the farnesoid X receptor (FXR). As FXR is involved in negatively controlling the expression level of cholesterol 7 alpha -hydroxylase (cyp7a), the rate-limiting enzyme involved in the oxidative metabolism of cholesterol into bile acids, the compounds described herein find utility in treating diseases associated with abnormally high or low cholesterol levels. In certain aspects, the FXR modulators (e.g., antagonists) described herein block the negative feed-back downregulation of cyp7a expression produced by certain cholic acids, the endogenous ligands for FXR. Moreover, as FXR forms heterodimers with the retinoid X receptor (RXR) in some cell types, modulation of the level of FXR activity in cells has a wide range of effects on a variety of biological processes which are mediated by RXR or other RXR-interacting proteins such as PPAR gamma and PPAR alpha . Thus, compounds described herein are useful in treating other biological activities such as obesity, diabetes, lipid associated disorders, cancer, inflammatory disorders, disorders involving a disrupted or dysfunctional epidermal barrier, and various other metabolic disorders.
Inventors:
HOUZE JONATHAN (US)
MCKENDRY SHARON (US)
GERGELY JOSHUA P (US)
XIA YI (US)
SHAN BEI (US)
KAYSER FRANK (US)
MCKENDRY SHARON (US)
GERGELY JOSHUA P (US)
XIA YI (US)
SHAN BEI (US)
KAYSER FRANK (US)
Application Number:
PCT/US2001/027239
Publication Date:
August 21, 2003
Filing Date:
August 31, 2001
Export Citation:
Assignee:
TULARIK INC (US)
HOUZE JONATHAN (US)
MCKENDRY SHARON (US)
GERGELY JOSHUA P (US)
XIA YI (US)
SHAN BEI (US)
KAYSER FRANK (US)
HOUZE JONATHAN (US)
MCKENDRY SHARON (US)
GERGELY JOSHUA P (US)
XIA YI (US)
SHAN BEI (US)
KAYSER FRANK (US)
International Classes:
A61P35/00; C07C233/75; C07C237/22; C07C311/19; C07C311/29; C07D209/48; C07D241/44; C07D279/02; (IPC1-7): C07C233/75; A61K31/16; A61P35/00; C07C237/22; C07C311/17; C07D209/48; C07D241/44; C07D279/02; C07K14/705
Domestic Patent References:
| WO1996034851A1 | 1996-11-07 | |||
| WO2000017159A1 | 2000-03-30 |
Foreign References:
| US5470982A | 1995-11-28 |
Other References:
DATABASE CROSSFIRE BEILSTEIN [online] Beilstein Institut zur Förderung der Chemischen Wissenschaften, Frankfurt am Main, DE; XP002225844, Database accession no. 463660
DATABASE CROSSFIRE BEILSTEIN [online] Beilstein Institut zur Förderung der Chemischen Wissenschaften, Frankfurt am Main, DE; XP002225845, Database accession no. 6451663
DATABASE CROSSFIRE BEILSTEIN [online] Beilstein Institut zur Förderung der Chemischen Wissenschaften, Frankfurt am Main, DE; XP002225845, Database accession no. 6451663
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