1,5-Diarylpyrrole-3-acetic Acids and Esters as Novel Classes of Potent and Highly Selective Cyclooxygenase-2 Inhibitors

Abstract

A small set of substituted 1,5-diarylpyrrole-3-acetic and -glyoxylic acid derivatives have been synthesized, and their cyclooxygenase (COX-1 and COX-2) inhibiting properties have been evaluated. Some compounds proved to be highly selective COX-2 inhibitors, and their affinity data have been rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-2 binding site.

Novel Ester and Acid Derivatives of the 1,5-Diarylpyrrole Scaffold as Anti-Inflammatory and Analgesic Agents. Synthesis and in Vitro and in Vivo Biological Evaluation

“…The activity of 10a-h was better than that of both the corresponding acids and ethyl esters. 23,24 Esters also proved to be very effective and long-lasting, in this test a relevant analgesia being still present 2 h after administration.…”

“…Analytical data, the melting point, and the 1 H NMR spectrum were consistent with those reported in the literature. [23][24][25][26] General Procedure for the Preparation of 1,5-Diarylpyrroles 14a,c,e,g. Following the Paal-Knorr reaction, 13 (0.58 g, 2.28 mmol) was dissolved in ethanol (2 mL) in a round-bottom flask equipped with a stir bar.…”

“…23,24,26 (iii) Substituents and the substitution pattern on the phenyl ring at N1 influenced activity in the following order: 3-F = 4-F > 3,4-diF > 4-OMe > H > 4-CF 3 > 4-CH 3 . [23][24][25][26][27] In this paper, we report the synthesis and biological activity of new derivatives 10a-h (Scheme 1 and Table 1), in which longer side chains were introduced at C3 on the basis of the hypothesis that such chains could better interact with hydrophobic residues of the carboxylate pocket of the receptor. [23][24][25][26] In particular, compounds 10a-h, bearing an isopropyl and an n-butyl ester function, a N1 phenyl ring with various substituents previously found to be important for activity (namely, 3-F, 3,4-diF, and 4-OCH 3 ), and a C5 p-methylsulfonyl phenyl moiety, showed outstanding activity.…”

Synthesis, biological evaluation and docking analysis of a new series of methylsulfonyl and sulfamoyl acetamides and ethyl acetates as potent COX-2 inhibitors

“…We have previously reported several studies on the design, synthesis and activity of pyrrole-based COX-2 inhibitors. [6][7][8][9][10][11][12] http://dx.doi.org/10.1016/j.bmc.2014.12.041 0968-0896/Ó 2015 Elsevier Ltd. All rights reserved.…”

Planejamento, síntese e avaliação biológica de derivados pirrólicos com potencial atividade antiinflamatória

“…Inúmeros derivados pirrólicos, seja de origem natural ou sintética, foram testados com sucesso em determinadas doenças, incluindo a inflamação (LEHUÉDÉ et al, 1999;DEMIR et al, 2002;RANU E DEY, 2003;MINETTO et al, 2004;BIAVA et al, 2005;DEMIR, EMRULLAHOGLU, 2005;BIAVA et al, 2007;ATTANASI et. al., 2008;DAVIS, et.…”