Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: potent acyl-CoA:cholesterol acyltransferase inhibitor with improved aqueous solubility

Hitoshi Ban; Masami Muraoka; Katsuhisa Ioriya; Naohito Ohashi

doi:10.1016/j.bmcl.2005.09.056

Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: potent acyl-CoA:cholesterol acyltransferase inhibitor with improved aqueous solubility

Bioorg Med Chem Lett. 2006 Jan 1;16(1):44-8. doi: 10.1016/j.bmcl.2005.09.056. Epub 2005 Oct 18.

Authors

Hitoshi Ban¹, Masami Muraoka, Katsuhisa Ioriya, Naohito Ohashi

Affiliation

¹ Research Division, Sumitomo Pharmaceuticals Co., Ltd 1-98, Kasugadenaka 3-chome, Konohana-ku, Osaka 554-0022, Japan. ban@sumitomopharm.co.jp

PMID: 16242323
DOI: 10.1016/j.bmcl.2005.09.056

Abstract

4-Aryl-1,8-naphthyridin-2(1H)-on-3-yl urea derivatives with hydrophilic groups were synthesized in order to improve aqueous solubility and pharmacokinetic property. SMP-797 possessing (4-aminophenyl)ureido and 3-(hydroxypropoxyphenyl) moieties showed potent ACAT inhibitory activity and excellent oral efficacy.

MeSH terms

Acyltransferases / chemistry
Administration, Oral
Anticholesteremic Agents / chemistry
Anticholesteremic Agents / pharmacology*
Drug Design*
Enzyme Inhibitors / pharmacology*
Humans
Hypercholesterolemia / drug therapy
Inhibitory Concentration 50
Models, Chemical
Molecular Structure
Naphthyridines / chemistry*
Naphthyridines / pharmacology*
Solubility
Sterol O-Acyltransferase / antagonists & inhibitors*
Temperature
Time Factors
Urea / analogs & derivatives*

Substances

Anticholesteremic Agents
Enzyme Inhibitors
Naphthyridines
SMP-797
Urea
Acyltransferases
Sterol O-Acyltransferase