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Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors.

Abstract：

:The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Chimenti F,Secci D,Bolasco A,Chimenti P,Granese A,Carradori S,Maccioni E,Cardia MC,Yáñez M,Orallo F,Alcaro S,Ortuso F,Cirilli R,Ferretti R,Distinto S,Kirchmair J,Langer T

doi

10.1016/j.bmc.2010.05.070

subject

Has Abstract

pub_date

2010-07-15 00:00:00

pages

5063-70

issue

14

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(10)00501-8

journal_volume

18

pub_type

杂志文章

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