Design and Optimization
of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase
1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide
Phenylcyclohexylacetic Acid (AZD7687)

Alan M. Birch (2012893); Alma Redzic (687228); Andreas Nordin (2012902); Andrew V. Turnbull (1845709); Annika U. Petersson (1773541); Bo T. Lindmark (2012905); Charles
J. O’Donnell (2012908); Clare D. Hammond (2012899); Jan W. Eriksson (2012872); Johanna Vinblad (2012884); Jonas
G. Barlind (2012878); Linda K. Buckett (2012887); Magnus J. Johansson (1773544); Pablo Morentin
Gutierrez (2012917); Paul D. Kemmitt (1763374); Petra Johannesson (2012890); Ragnar Hovland (2012881); Robert D. M. Davies (1436602); Roger J. Butlin (2012875); Susan Birtles (2012911); Tobias A. Noeske (2012914); Udo A. Bauer (2012896)

Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)

Abstract

A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound <b>30</b> (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers

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Last time updated on 16/03/2018