Synthesis and Pharmacological Evaluation of Indole Derivatives as Deaza Analogues of Potent Human Neutrophil Elastase Inhibitors

Letizia Crocetti, Igor A. Schepetkin, Giovanna Ciciani, Maria Paola Giovannoni, Gabriella Guerrini, Antonella Iacovone, Andrey Ivanovich Khlebnikov, Liliya N. Kirpotina, Mark T. Quinn, Claudia Vergelli

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
JournalDrug Development Research
DOIs
Publication statusAccepted/In press - 2016
Externally publishedYes

Fingerprint

Secretory Proteinase Inhibitory Proteins
Indazoles
Pharmacology
Inhibitory Concentration 50
Research
indole

Keywords

  • Human neutrophil elastase (HNE)
  • Indoles
  • Inhibitors

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Synthesis and Pharmacological Evaluation of Indole Derivatives as Deaza Analogues of Potent Human Neutrophil Elastase Inhibitors. / Crocetti, Letizia; Schepetkin, Igor A.; Ciciani, Giovanna; Giovannoni, Maria Paola; Guerrini, Gabriella; Iacovone, Antonella; Khlebnikov, Andrey Ivanovich; Kirpotina, Liliya N.; Quinn, Mark T.; Vergelli, Claudia.

In: Drug Development Research, 2016.

Research output: Contribution to journalArticle

Crocetti, Letizia ; Schepetkin, Igor A. ; Ciciani, Giovanna ; Giovannoni, Maria Paola ; Guerrini, Gabriella ; Iacovone, Antonella ; Khlebnikov, Andrey Ivanovich ; Kirpotina, Liliya N. ; Quinn, Mark T. ; Vergelli, Claudia. / Synthesis and Pharmacological Evaluation of Indole Derivatives as Deaza Analogues of Potent Human Neutrophil Elastase Inhibitors. In: Drug Development Research. 2016.
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AU - Ciciani, Giovanna

AU - Giovannoni, Maria Paola

AU - Guerrini, Gabriella

AU - Iacovone, Antonella

AU - Khlebnikov, Andrey Ivanovich

AU - Kirpotina, Liliya N.

AU - Quinn, Mark T.

AU - Vergelli, Claudia

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