title: Synthesis and Pharmacological Evaluation of Indole Derivatives as Deaza Analogues of Potent Human Neutrophil Elastase Inhibitors.
abstract: Preclinical Research A 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 IC50  = 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.
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Crocetti
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT, 59717.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Schepetkin
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ciciani
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Giovannoni
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Guerrini
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Iacovone
authors.affiliation: Department of Biotechnology and Organic Chemistry, Tomsk Polytechnic University, Tomsk 634050, Russia and Department of Chemistry, Altai State Technical University, Barnaul, Russia.
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Khlebnikov
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT, 59717.
authors.forename: Liliya N
authors.initials: LN
authors.lastname: Kirpotina
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT, 59717.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Quinn
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vergelli
mesh_terms: D006801:Humans; D006860:Hydrogen Bonding; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D062105:Molecular Docking Simulation; D053491:Proteinase Inhibitory Proteins, Secretory / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D053491:Proteinase Inhibitory Proteins, Secretory; D019272:Leukocyte Elastase
keywords: human neutrophil elastase (HNE); indoles; inhibitors