Oxazole PPAR antagonist
US6506781B1 · kind B1 · utility
Assignee
Inventors
Key dates
| Filing date | Mar 7, 2002 |
| Grant date | Jan 14, 2003 |
| Priority date | — |
| Expiry date | Mar 7, 2022 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D417/12
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
A method is disclosed for rational design of a PPAR, FXR, LXR-alpha, or LXR-beta antagonist comprising chemical modification of a PPAR, FXR, LXR-alpha, or LXR-beta agonist to: a) prevent formation of a hydrogen bond between the agonist and tyrosine or histidine, or tryptophan involved in receptor activation; and/or b) displace the tyrosine or histidine, or tryptophan involved in receptor activation from its agonist bound position. Preferably, little or no additional changes are made in the structure of the agonist so that the resulting antagonist is a close structural analogue of the agonist. Specific examples of PPAR gamma antagonists designed and prepared using the method of this invention are compounds of Formula (I) or (II), or pharmaceutically acceptable salts or solvates thereof, where in Formula (I) X is O, S, or NH; and R is methyl, ethyl, n-propyl, i-propyl, cyclopropyl, n-butyl, phenyl, or —CH2OCH3 and wherein in Formula (II) X is C or N; and R is methyl, ethyl, n-propyl, i-propyl, —CH2OCH3, or —CO2CH3.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.