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Assessing the Bioisosterism of the Trifluoromethyl Group with a Protease Probe
Author(s) -
Jagodzinska Monika,
Huguenot Florent,
Candiani Gabriele,
Zanda Matteo
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800321
Subject(s) - trifluoromethyl , isopropyl , steric effects , chemistry , group (periodic table) , stereochemistry , potency , protease , medicinal chemistry , organic chemistry , biochemistry , enzyme , alkyl , in vitro
The controversial bioisosterism of the trifluoromethyl group has been re‐assessed by measuring the inhibitory potency of a set of barbiturates having CF 3 , CH 3 , CH 3 CH 2 , and (CH 3 ) 2 CH 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 CF 3 group is, in terms of bioisosterism, “smaller” than the isopropyl, larger than the methyl, and rather similar to the ethyl group.