Document Detail

Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor.
MedLine Citation:
PMID:  18477508     Owner:  NLM     Status:  MEDLINE    
A series of quinoline/naphthalene-difluoromethylphosphonates were prepared and were found to be potent PTP1B inhibitors. Most of these compounds bearing polar functionalities or large lipophilic residues did not show appreciable oral bioavailability in rodents while small and less polar analogs displayed moderate to good oral bioavailability. The title compound was found to have the best overall potency and pharmacokinetic profile and was found to be efficacious in animal models of diabetes and cancer.
Yongxin Han; Michel Belley; Christopher I Bayly; John Colucci; Claude Dufresne; Andre Giroux; Cheuk K Lau; Yves Leblanc; Daniel McKay; Michel Therien; Marie-Claire Wilson; Kathryn Skorey; Chi-Chung Chan; Giovana Scapin; Brian P Kennedy
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Publication Detail:
Type:  Journal Article     Date:  2008-04-29
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  18     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-30     Completed Date:  2008-07-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  3200-5     Citation Subset:  IM    
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada Ltd, PO Box 1005, Pointe-Claire-Dorval, Que., Canada.
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MeSH Terms
Combinatorial Chemistry Techniques
Diabetes Mellitus / chemically induced
Disease Models, Animal
Drug Design
Drug Screening Assays, Antitumor
Hydrocarbons, Halogenated / chemical synthesis*,  chemistry,  pharmacology*
Molecular Structure
Naphthalenes / chemical synthesis*,  chemistry,  pharmacology*
Neoplasms / chemically induced
Phosphonic Acids / chemical synthesis*,  chemistry,  pharmacology*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Reg. No./Substance:
0/((3-bromo-7-cyano-2-naphthyl)(difluoro)methyl)phosphonic acid; 0/Hydrocarbons, Halogenated; 0/Naphthalenes; 0/Phosphonic Acids; EC Tyrosine Phosphatase, Non-Receptor Type 1

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