Assessing the Bioisosterism of the Trifluoromethyl Group with a Protease Probe

Abstract

The controversial bioisosterism of the trifluoromethyl group has been re-assessed by measuring the inhibitory potency of a set of barbiturates having CF3, CH3, CH3CH2, and (CH3)2CH groups as remote substituents occupying the bottom of the tight lipophilic tunnel-like S1′ pocket of collagenase B as a steric probe. The results support the recent hypothesis that the CF3 group is, in terms of bioisosterism, “smaller” than the isopropyl, larger than the methyl, and rather similar to the ethyl group. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.