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Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2008 Aug 01; Vol. 18 (15), pp. 4339-43. Date of Electronic Publication: 2008 Jun 28. - Publication Year :
- 2008
-
Abstract
- Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.
- Subjects :
- Administration, Oral
Animals
Carboxylic Acids chemistry
Cholestasis metabolism
Cholestasis pathology
Crystallography, X-Ray
DNA-Binding Proteins chemistry
Disease Models, Animal
Dogs
Gastric Mucosa metabolism
Haplorhini
Isoxazoles chemistry
Mice
Molecular Conformation
Molecular Structure
Naphthalenes chemistry
Rats
Receptors, Cytoplasmic and Nuclear chemistry
Stomach drug effects
Structure-Activity Relationship
Transcription Factors chemistry
Carboxylic Acids chemical synthesis
Carboxylic Acids pharmacology
Cholestasis drug therapy
DNA-Binding Proteins agonists
Isoxazoles chemical synthesis
Isoxazoles pharmacology
Naphthalenes chemical synthesis
Naphthalenes pharmacology
Receptors, Cytoplasmic and Nuclear agonists
Transcription Factors agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 18
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 18621523
- Full Text :
- https://doi.org/10.1016/j.bmcl.2008.06.073