Recent methodologies toward the synthesis of valdecoxib: A potential 3,4-diarylisoxazolyl COX-II inhibitor

Abstract

Non-steroidal anti-inflammatory drugs are widely used therapeutic agents in the treatment of inflammation, pain and fever. Cyclooxygenase catalyzes the initial step of biotransformation of arachidonic acid to prostanoids, and exist as three distinct isozymes; COX-I, COX-II and COX-III. Selective COX-II inhibitors are a class of potential anti-inflammatory, analgesic, and antipyretic drugs with reduced gastrointestinal (GI) side effects compared to nonselective inhibitors. 3,4-diarylisoxazole scaffold is recurrently found in a wide variety of NSAIDs, protein kinase inhibitors, hypertensive agents, and estrogen receptor (ER) modulators. In the present review, we document on the recent synthetic strategies of 3,4-diarylisoxazolyl scaffolds of valdecoxib and its relevant structural analogues.

Synthesis of novel isoxazolines and isoxazoles of N-substituted pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives through [3+2] cycloaddition

“…Also they showed, anti-tubercular (Rakesh et al, 2009), antifungal (Basappa et al, 2003) and anti-influenza effects (Kai et al, 2001). In the other hand, isoxazole structural motif is found in the COX II inhibitors, bextra and parecoxib because of its capability to exhibit a wide range of bioactivities, including the antiinflammatory and antimicrobial activities (Dadiboyena and Nefzi, 2010;Sobenina et al, 2005). For these reasons the synthesis of this family of heterocycles continues to attract the attention of synthetic organic and medicinal chemists.…”

Design, Synthesis, and Anti‐Inflammatory Evaluation of Novel Diphenylthiazole–Thiazolidinone Hybrids

“…Celecoxib, rofecoxib, and valedoxib are the most familiar examples of NSAIDs incorporating different diphenylheterocyles as main building blocks in their structures [6]. Meanwhile, a series of diarylthiazole derivatives (1) was reported as anti-inflammatory agents that showed high affinity for COX enzymes [10], preferentially for COX-2 isoform (Fig.…”

“…Cyclooxygenases (COXs) were found to be the key enzymes that catalyze the rate-limiting step in the biotransformation of arachidonic acid into prostaglandins, biologically active materials that are responsible for various physiological processes and pathological conditions (such as inflammation) as well [4,5]. Currently, COX enzymes exist in three different isoforms: mainly COX-1 and COX-2 isoforms and recently, COX-3 [6]. COX-1 is a constitutive isoform and is basically involved in the biosynthesis of cytoprotective prostaglandins in GIT and thromboxane which stimulates platelet aggregation.…”

One pot spiropyrazoline synthesis via intramolecular cyclization/methylation

“…3,4 Furthermore, as the syntheses of isoxazoles and pyrazoles flourished, 5,6 the corresponding synthetic methodologies targeting spiroisoxazolines and spiropyrazolines were also developing. 7,8 While the major structural feature of a number of biologically active bromotyrosine derived heterocyclic marine natural products is the spiroisoxazoline, 1,2,7 spiropyrazolines have an extra nitrogen, in place of isoxazoline oxygen, and offer the feasibility to construct structurally relevant analogues for the exploration of potential biological activity.…”