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Sulfonimidamides as Sulfonamides Bioisosteres: Rational Evaluation through Synthetic, in Vitro, and in Vivo Studies with γ‐Secretase Inhibitors
Author(s) -
Sehgelmeble Fernando,
Janson Juliette,
Ray Colin,
Rosqvist Susanne,
Gustavsson Susanne,
Nilsson Linda I.,
Minidis Alexander,
Holenz Jörg,
Rotticci Didier,
Lundkvist Johan,
Arvidsson Per I.
Publication year - 2012
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.201200014
Subject(s) - in vivo , in vitro , chemistry , pharmacology , computational biology , stereochemistry , biochemistry , biology , genetics
The proof of the pudding: A proof‐of‐concept study using γ‐secretase inhibitors as a model has shown that sulfonimidamides act as bioisosteres for sulfonamides. Detailed in vitro and in vivo profiling reveal that the sulfonimidamide motif imparts desirable properties such as decreased lipophilicity and plasma protein binding, accompanied by increased solubility. Our data support a wider use of this unique functional group in the design of new pharmacologically active agents.