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Metabolically Stable tert-Butyl Replacement

Barnes, David, Jain, Monish, Bell, Leslie, Ferreira, Suzie, Cohen, Scott, Chen, Xiao-Hui, Amin, Jakal, Snodgrass, Bradley and Hatsis, Panagiotis (2013) Metabolically Stable tert-Butyl Replacement. ACS Medicinal Chemistry Letters. ISSN 1948-5875


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-H’s from a tert-butyl group: replacing some H’s with F’s and increasing the s-character of the remaining C-H’s. This approach gave a trifluoromethylcyclopropyl group which increased metabolic stability. Trifluoromethylcyclopropyl-containing analogs had consistently higher metabolic stability in vitro and in vivo compared to their tert-butyl-containing counterparts.

Item Type: Article
Keywords: metabolic stability, metabolism, clearance, tertiary butyl, tert-butyl, t-butyl
Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14


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