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

K Futatsugi,K Huard,D W Kung, J C Pettersen, D A Flynn,J R Gosset, G E Aspnes, R J Barnes, S Cabral, M S Dowling, D P Fernando,T C Goosen, W P Gorczyca, D Hepworth, M Herr, S Lavergne,Q Li, M Niosi, S T M Orr, I D Pardo, S M Perez, J Purkal, T J Schmahai,N Shirai,A M Shoieb, J Zhou, B Goodwin

MEDCHEMCOMM（2017）

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摘要

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.

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