Document Detail

Discovery of a potent and selective free fatty acid receptor 1 (FFA1) agonist with low lipophilicity and high oral bioavailability.
MedLine Citation:
PMID:  23294321     Owner:  NLM     Status:  Publisher    
The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability and appreciable efficacy on glucose tolerance in mice.
Elisabeth Christiansen; Maria E Due-Hansen; Christian Urban; Manuel Grundmann; Johannes Schmidt; Steffen V F Hansen; Brian D Hudson; Mohamed Zaibi; Stine B Markussen; Ellen Hagesaether; Graeme Milligan; Michael A Cawthorne; Evi Kostenis; Matthias Kassack; Trond Ulven
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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