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Evaluation of tert ‐Butyl Isosteres: Case Studies of Physicochemical and Pharmacokinetic Properties, Efficacies, and Activities
Author(s) -
Westphal Matthias V.,
Wolfstädter Bernd T.,
Plancher JeanMarc,
Gatfield John,
Carreira Erick M.
Publication year - 2015
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.201402502
Subject(s) - trifluoromethyl , lipophilicity , metabolic stability , chemistry , pharmacokinetics , stereochemistry , drug , combinatorial chemistry , organic chemistry , pharmacology , biochemistry , medicine , in vitro , alkyl
Abstract The tert ‐butyl group is a common motif in medicinal chemistry. Its incorporation into bioactive compounds is often accompanied by unwanted property modulation, such as increased lipophilicity and decreased metabolic stability. Several alternative substituents are available for the drug discovery process. Herein, physicochemical data of two series of drug analogues of bosentan and vercirnon are documented as part of a comparative study of tert ‐butyl, pentafluorosulfanyl, trifluoromethyl, bicyclo[1.1.1]pentanyl, and cyclopropyl‐trifluoromethyl substituents.