Small structural changes of the imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitors produce an improved safety profile† ‡

Abstract

Preclinical pharmacokinetic, efficacy, and toxicology results are reported for a series of DGAT2 inhibitors for the potential treatment of hypertriglyceridemia.

Abstract

Small molecule DGAT2 inhibitors have shown promise for the treatment of metabolic diseases in preclinical models. Herein, we report the first toxicological evaluation of imidazopyridine-based DGAT2 inhibitors and show that the arteriopathy associated with imidazopyridine 1 can be mitigated with small structural modifications, and is thus not mechanism related.

Notes

†All authors were employed by Pfizer Inc. at the moment the experiments were conducted.

‡Electronic supplementary information (ESI) available: Protocols and supporting data for all experiments and compound preparation. See DOI: 10.1039/c6md00564k