Metabolically stable tert-butyl replacement

D Barnes-Seeman, M Jain, L Bell…

Index: Barnes-Seeman, David; Jain, Monish; Bell, Leslie; Ferreira, Suzie; Cohen, Scott; Chen, Xiao-Hui; Amin, Jakal; Snodgrass, Brad; Hatsis, Panos ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 6 p. 514 - 516

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Citation Number: 27

Abstract

Susceptibility to metabolism is a common issue with the tert-butyl group on compounds of medicinal interest. We demonstrate an approach of removing all the fully sp3 C–Hs from a tert-butyl group: replacing some C–Hs with C–Fs and increasing the s-character of the remaining C–Hs. This approach gave a trifluoromethylcyclopropyl group, which increased metabolic stability. Trifluoromethylcyclopropyl-containing analogues had consistently ...