Discovery of potent and orally available malonyl-CoA decarboxylase inhibitors as cardioprotective agents

…, G Yang, E O'Leary, M Barbosa, R Barr…

Index: Cheng, Jie-Fei; Huang, Yujin; Penuliar, Richard; Nishimoto, Masahiro; Liu, Larry; Arrhenius, Thomas; Yang, Guang; O'Leary, Eoin; Barbosa, Miguel; Barr, Rick; Dyck, Jason R. B.; Lopaschuk, Gary D.; Nadzan, Alex M. Journal of Medicinal Chemistry, 2006 , vol. 49, # 14 p. 4055 - 4058

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Citation Number: 27

Abstract

Discovery of 5-(1, 1, 1, 3, 3, 3-hexafluoro-2-hydroxypropan-2-yl)-4, 5-dihydroisoxazole-3- carboxamides as a new class of malonyl-coenzyme A decarboxylase (MCD) inhibitors is described. tert-Butyl 3-(5-(1, 1, 1, 3, 3, 3-hexafluoro-2-hydroxypropan-2-yl)-4, 5- dihydroisoxazole-3-carboxamido) butanoate (5, CBM-301940) exhibited excellent potency and in vivo PK/ADME properties. It is the most powerful stimulant of glucose oxidation ...