title: Synthesis and selective inhibitory activity against human COX-1 of novel 1-(4-substituted-thiazol-2-yl)-3,5-di(hetero)aryl-pyrazoline derivatives.
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.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, 00185 Rome, Italy. simone.carradori@uniroma1.it
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.forename: Celeste
authors.initials: C
authors.lastname: De Monte
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013844:Thiazoles; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human