Synthesis and Pharmacochemistry of New Pleiotropic Pyrrolyl Derivatives

Abstract

Within the framework of our attempts to synthesize pleiotropic anti-inflammatory agents, we have synthesized some chalcones and their corresponding 3,4-pyrrolyl derivatives. Chalcones constitute a class of compounds with high biological impact. They are known for a number of biological activities, including anti-inflammatory and free radical scavenging activities. They inhibit several enzymes implicated in the inflammatory process, such as lipoxygenase, cyclooxygenase (COX) and lysozymes. The synthesized pyrroles have been studied for: (1) their in vitro inhibition of lipoxygenase; (2) their in vitro inhibition of COX; (3) their in vitro inhibition of lipid peroxidation; (4) their interaction with the stable, N-centered, free radical, 2,2-diphenyl-1-picrylhydrazyl (DPPH); (5) their inhibition on interleukin-6 (IL-6); (6) their anti-proteolytic activity; and (7) their in vivo anti-inflammatory activity using carrageenan-induced rat paw edema. Their physicochemical properties were determined to explain the biological results. Lipophilicity was experimentally determined. 2i and 2v were found to be promising multifunctional molecules with high antiproteolytic and anti-inflammatory activities in combination with anti-interleukin-6 activity.

Pyrazoles and Pyrazolines as Anti-Inflammatory Agents

“…The synthesis of the pyrazolines and pyrazole derivatives was accomplished via the condensation of the appropriate substituted aldehydes, suitable chalcones and hydrazine hydrate in absolute ethanol in the presence of drops of glacial acetic acid, as presented in Scheme 1 [ 34 ]. Chalcones as starting materials were successfully synthesized via Claisen–Italics Schmidt condensation using 15% KOH from the corresponding aldehydes with acetophenone in methanol ( Scheme 1 ) [ 35 ].…”

“…A Claisen–Schmidt condensation was performed between acetophenone and the suitable substituted aryl aldehyde at a molar ratio of 1:1 in methanol [ 35 ]. Five milliliters (3 mL) of aqueous KOH (15%) was added and the mixture was stirred at room temperature for 24 h. Reaction completion was monitored by TLC.…”

“…All the synthesized chalcones have been already reported in the literature [ 35 , 55 , 56 ] except the following ones:…”

Indolylvinyl Ketones: Building Blocks for the Synthesis of Natural Products and Bioactive Compounds

“…The same transformation of 3-(1H-indol-5-yl)-1-phenylprop-2-en-1-one gave indol-5-ylpyrrole 63, which demonstrated anti-inflammatory activity (Scheme 34). 42…”

Recent Strides in the Transition Metal-Free Cross-Coupling of Haloacetylenes with Electron-Rich Heterocycles in Solid Media

“…Functionalized five-membered aromatic heterocycles represent a frequent structural motif of bioactive natural products and pharmaceuticals [1][2][3][4][5][6][7][8][9][10][11][12]. Among them, of particular interest are the compounds bearing acetylenic moieties [13][14][15].…”