Synthesis and structure-activity relationship studies on a novel series of naphthylidinoylureas as inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT)

  • Bioorg Med Chem Lett. 2004 Mar 8;14(5):1309-11. doi: 10.1016/j.bmcl.2003.12.045.
Satoshi Ohnuma  1 ,  Masami Muraoka ,  Katsuhisa Ioriya ,  Naohito Ohashi
Affiliations
  • 1. Research Division, Sumitomo Pharmaceuticals Co. Ltd, 1-98 Kasugade Naka 3-chome, Konohana-ku, Osaka 554-0022, Japan. [email protected]
PMID: 14980688 DOI: 10.1016/j.bmcl.2003.12.045
Abstract

The synthesis and structure-activity relationships of N-phenyl-N'-[3-(4-phenylnaphthylidinoyl)]urea derivatives 3 as a novel structural class of potent ACAT inhibitors is described. A 3-methoxy group substituted on the naphthylidinone 4-phenyl ring, together with a 1-N-(n)butyl substitution, SM-32504 (3m), gave a potent ACAT Inhibitor, in vitro, respectively. The most potent compound, SM-32504 (3m), decreased the serum Cholesterol level significantly in a high fat and high cholesterol-fed mouse model.

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