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Synthesis and Pharmacological Evaluation of Indole Derivatives as Deaza Analogues of Potent Human Neutrophil Elastase Inhibitors
Author(s) -
Crocetti Letizia,
Schepetkin Igor A.,
Ciciani Giovanna,
Giovani Maria Paola,
Guerrini Gabriella,
Iacovone Antonella,
Khlebnikov Andrei I.,
Kirpotina Liliya N.,
Quinn Mark T.,
Vergelli Claudia
Publication year - 2016
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21323
Subject(s) - elastase , pharmacology , chemistry , indole test , biological activity , biochemistry , in vitro , enzyme , medicine
Preclinical ResearchA number of N‐benzoylindoles were designed and synthesized as deaza analogs of previously reported potent and selective HNE inhibitors with an indazole scaffold. The new compounds containing substituents and functions that were most active in the previous series were active in the micromolar range (the most potent had IC 50 = 3.8 μM) or inactive. These results demonstrated the importance of N‐2 in the indazole nucleus. Docking studies performed on several compounds containing the same substituents but with an indole or an indazole scaffold, respectively, highlight interesting aspects concerning the molecule orientation and H‐bonding interactions, which could help to explain the lower activity of this new series. Drug Dev Res, 2016. © 2016 Wiley Periodicals, Inc.