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    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
19488928 - Antihyperglycaemic activity of alpha-amyrin acetate in rats and db/db mice.
20829708 - Evaluation of renal hypoxia in diabetic mice by bold mri.
12707408 - Glucose, glycation, and rage: implications for amplification of cellular dysfunction in...
15597878 - Time-dependent toxicity of fluoranthene to freshwater invertebrates and the role of bio...
19224198 - Enhanced susceptibility of cpt1c knockout mice to glucose intolerance induced by a high...
10522818 - New developments in the treatment of type 1 diabetes mellitus.
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    
Affiliation:
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada Ltd, PO Box 1005, Pointe-Claire-Dorval, Que., Canada. yongxin_han@merck.com
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Combinatorial Chemistry Techniques
Diabetes Mellitus / chemically induced
Disease Models, Animal
Drug Design
Drug Screening Assays, Antitumor
Haplorhini
Hydrocarbons, Halogenated / chemical synthesis*,  chemistry,  pharmacology*
Mice
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*
Rats
Chemical
Reg. No./Substance:
0/((3-bromo-7-cyano-2-naphthyl)(difluoro)methyl)phosphonic acid; 0/Hydrocarbons, Halogenated; 0/Naphthalenes; 0/Phosphonic Acids; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effects of amide constituents from pepper on adipogenesis in 3T3-L1 cells.
Next Document:  Synthesis and antitumor activity of benzils related to combretastatin A-4.