title: Evaluation of tert-butyl isosteres: case studies of physicochemical and pharmacokinetic properties, efficacies, and activities.
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.
authors: Laboratorium für Organische Chemie, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich (Switzerland).
authors: Matthias V
authors: MV
authors: Westphal
authors: Bernd T
authors: BT
authors: Wolfstädter
authors: Jean-Marc
authors: JM
authors: Plancher
authors: John
authors: J
authors: Gatfield
authors: Erick M
authors: EM
authors: Carreira
mesh_terms: D002073:Butanes / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D055808:Drug Discovery; D054879:Halogenation; D006801:Humans; D008745:Methylation; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002073:Butanes; D013457:Sulfur Compounds; C046888:butane
keywords: drug analogues; isosterism; metabolic stability; pentafluorosulfanyl; structure-property relationships