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Synthesis and Selective Inhibitory Activity Against Human COX‐1 of Novel 1‐(4‐Substituted‐thiazol‐2‐yl)‐3,5‐di(hetero)aryl‐pyrazoline Derivatives
Author(s) -
Carradori Simone,
Secci Daniela,
Bolasco Adriana,
De Monte Celeste,
Yáñez Matilde
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200249
Subject(s) - pyrazoline , chemistry , aryl , selectivity , stereochemistry , chemical synthesis , combinatorial chemistry , in vitro , medicinal chemistry , organic chemistry , biochemistry , alkyl , catalysis
Abstract Novel 1‐(4‐ethyl carboxylate‐thiazol‐2‐yl)‐3,5‐di(hetero)aryl‐2‐pyrazoline derivatives were obtained by reacting 3,5‐di(hetero)aryl‐1‐thiocarbamoyl‐2‐pyrazolines with the ethyl ester of α‐bromo‐pyruvic acid. The synthesized compounds were confirmed by spectroscopic data and assayed to evaluate their in vitro ability to inhibit both isoforms of human cyclooxygenase (hCOX). Some derivatives (compounds 5 , 6 , 13 , 16 , and 17 ) displayed promising selectivity against hCOX‐1 in the micromolar range and were shown to have a selectivity index similar or better than the reference drugs (indometacin, diclofenac). The introduction of a phenyl or a 4‐F‐phenyl ring on the C5 associated with a 4‐substituted phenyl or a heteroaryl group on the C3 of (4‐substituted‐thiazol‐2‐yl)pyrazoline derivatives improved the activity against hCOX‐1. Thanks to these preliminary results it could be possible to extend our knowledge of the pharmacophoric requirements for the discovery of new pyrazoline‐based hCOX‐1 inhibitors.