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Bioorg Med Chem Lett. 2006 Feb;16(3):695-700. Epub 2005 Oct 27.

Design and synthesis of heterocyclic malonyl-CoA decarboxylase inhibitors.

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1
Department of Chemistry, Chugai Pharma USA, LLC, 6275 Nancy Ridge Drive, San Diego, CA 92121, USA. jcheng@trlusa.com

Abstract

We have previously reported the discovery of small molecule inhibitors of malonyl-CoA decarboxylase (MCD) as novel metabolic modulators, which inhibited fatty acid oxidation and consequently increased the glucose oxidation rates in the isolated working rat hearts. MCD inhibitors were also shown to improve cardiac efficiency in rat and pig demand-induced ischemic models through the mechanism-based modulation of energy metabolism. Herein, we describe the design and synthesis of a series of novel heterocyclic MCD inhibitors with a preference for substituted imidazole and isoxazole.

PMID:
16257202
DOI:
10.1016/j.bmcl.2005.10.020
[Indexed for MEDLINE]
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