Identification of 2-aminooxazole amides as acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) inhibitors through scaffold hopping strategy

Hyunjin M Kim; Michelle D Smith; Jae-Hun Kim; Mary Ann Caplen; Tin Yau Chan; Brian A McKittrick; John A Cook; Margaret van Heek; Jean Lachowicz

doi:10.1016/j.bmcl.2013.09.048

Identification of 2-aminooxazole amides as acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) inhibitors through scaffold hopping strategy

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6410-4. doi: 10.1016/j.bmcl.2013.09.048. Epub 2013 Sep 25.

Authors

Hyunjin M Kim¹, Michelle D Smith, Jae-Hun Kim, Mary Ann Caplen, Tin Yau Chan, Brian A McKittrick, John A Cook, Margaret van Heek, Jean Lachowicz

Affiliation

¹ Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: hyunjin.kim@merck.com.

PMID: 24120540
DOI: 10.1016/j.bmcl.2013.09.048

Abstract

A scaffold hopping strategy was successfully applied in discovering 2-aminooxazole amides as potent DGAT1 inhibitors for the treatment of dyslipidemia. Further optimization in potency and PK properties resulted in a lead series with oral in vivo efficacy in a mouse postprandial triglyceridemia (PPTG) assay.

Keywords: DGAT1 inhibitors; Scaffold hopping; Treatment for dyslipidemia.

MeSH terms

Amides / pharmacology*
Animals
Diacylglycerol O-Acyltransferase / antagonists & inhibitors*
Enzyme Inhibitors / pharmacology*
Humans
Mice
Molecular Structure
Oxazoles / pharmacology*
Structure-Activity Relationship
Triglycerides / blood*

Substances

2-aminooxazole
Amides
Enzyme Inhibitors
Oxazoles
Triglycerides
Diacylglycerol O-Acyltransferase