Discovery of Potent and Orally Available Malonyl-coa Decarboxylase Inhibitors As Cardioprotective Agents.
From: Department of Chemistry, Chugai Pharma USA, LLC., 6275 Nancy Ridge Drive, San Diego, California 92121, USA. jcheng@trlusa.com
Journal of medicinal chemistry
- Publish Date: Jul 2006
- ISSN: 0022-2623
- Volume: 49
- Issue: 14
- Pages: 4055-8
- Medium: Print
- Language: English
- Citation (JAMA): Cheng Jie-Fei, Huang Yujin, Penuliar Richard, et al. Discovery of Potent and Orally Available Malonyl-coa Decarboxylase Inhibitors As Cardioprotective Agents.. J. Med. Chem. Jul 2006;49:4055-8
Abstract
Discovery of 5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydroisoxazole-3-carboxamides as a new class of malonyl-coenzyme A decarboxylase (MCD) inhibitors is described. tert-Butyl 3-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydroisoxazole-3-carboxamido)butanoate (5, CBM-301940) exhibited excellent potency and in vivo PK/ADME properties. It is the most powerful stimulant of glucose oxidation reported to date in isolated working rat hearts. Compound 5 improved the cardiac efficiency and function in a rat heart global ischemia/reperfusion model, suggesting MCD inhibitors may be useful for the treatment of ischemic heart diseases.
Mesh Headings (Keywords): Administration, Oral, Animals, Biological Availability, Carboxy-Lyases, Cardiotonic Agents, Crystallography, X-Ray, Isoxazoles, Molecular Conformation, Myocardial Ischemia, Myocardial Reperfusion, Rats, Rats, Sprague-Dawley, Stereoisomerism, Structure-Activity Relationship
Check for Full Text / PubMed Unique Identifier (PMID): 16821767
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.