Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors

Pauline C Ting; Joe F Lee; Nicolas Zorn; Hyunjin M Kim; Robert G Aslanian; Mingxiang Lin; Michelle Smith; Scott S Walker; John Cook; Margaret Van Heek; Jean Lachowicz

doi:10.1016/j.bmcl.2012.12.040

Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors

Bioorg Med Chem Lett. 2013 Feb 15;23(4):985-8. doi: 10.1016/j.bmcl.2012.12.040. Epub 2012 Dec 21.

Authors

Pauline C Ting¹, Joe F Lee, Nicolas Zorn, Hyunjin M Kim, Robert G Aslanian, Mingxiang Lin, Michelle Smith, Scott S Walker, John Cook, Margaret Van Heek, Jean Lachowicz

Affiliation

¹ Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA. [email protected]

PMID: 23317570
DOI: 10.1016/j.bmcl.2012.12.040

Abstract

The structure-activity relationship studies of a novel series of carboxylic acid derivatives of pyridine-carboxamides as DGAT-1 inhibitors is described. The optimization of the initial lead compound 6 based on in vitro and in vivo activity led to the discovery of key compounds 10j and 17h.

MeSH terms

Amides / pharmacology*
Animals
Diacylglycerol O-Acyltransferase / antagonists & inhibitors*
Diacylglycerol O-Acyltransferase / metabolism
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Mice
Pyridines / pharmacology*
Structure-Activity Relationship

Substances

Amides
Enzyme Inhibitors
Pyridines
DGAT1 protein, human
Diacylglycerol O-Acyltransferase