Discovery of pyrrolopyridazines as novel DGAT1 inhibitors

Abstract

A new structural class of DGAT1 inhibitors was discovered and the structure-activity relationship was explored. The pyrrolotriazine core of the original lead molecule was changed to a pyrrolopyridazine core providing an increase in potency. Further exploration resulted in optimization of the propyl group at C7 and the discovery that the ester at C6 could be replaced by five-membered heterocyclic rings. The analogs prepared have DGAT1 IC 50 values ranging from >10 μM to 48 nM. © 2010 Elsevier Ltd. All rights reserved.