Design and Synthesis of New Non-Steroidal Anti-inflammatory Agents with Expected Selectivity toward Cyclooxygenase-2 Inhibition

Nadeem A Abdul Razzak,Ahlam J Qaseer,Samera F.Hussan

doi:10.31351/vol19iss1pp6-13

Abstract

This study includes design and synthesis of new non-steroidal anti-inflammatory agents (NSAIDs) with expected cyclooxygenase-2 (COX-2) selective inhibition to achieve better activity and low gastric side effects. Two series of compounds have been designed and synthesized as potential NSAIDs,these are: Salicylamide derivatives (compounds 3,4,5 ) and Diflunisal derivatives (compounds 10&11). In vivo acute anti-inflammatory effect of one of the synthesized agents (compound 3) was evaluated in the rat using egg-white induced paw edema model of inflammation. Preliminary pharmacological study revealed that compound 3 exhibited less anti-inflammatory effect compared to that of aspirin after 120 and 210 minutes, which encourage the continuation of the search to demonstrate or identify the preliminary pharmacological activity for the synthesized compounds and to identify their selectivity toward COX-2 isoenzymes. Keywords:nonsteriodal anti-inflammatory drugs(NSAID),aspirin derivatives ,diflunisal, Cyclooxygenase -1(cox-1),cyclooxygenase-2(cox-2)

Highlights

Inflammation defined as a complexSelective COX-2 inhibitors have chemical series of tissue changes that result in pain and fever (1); or it is a normal, protective response structure with rigid side extension that binds in this side pocket. .NSAIDs have three major to tissue injury caused by physical trauma, pharmacological desirable actions, all of noxious, chemical, or microbiologic agents.which result mainly from the inhibition of Inflammation is the body's effect to inactivateCOX-2 in inflammatory cells and the resultant or destroy invading organisms, remove irritation, and set the stage of tissue repair(2) .decrease in prostanoid synthesis; these are: anti-inflammatory action,antipyretic effect and Inflammation can be divided into three phases; acute, chronic and immune response (3).There are two cyclooxygenase (COX) enzymes, analgesic effect
COX-1 and COX-2 chemical classes with different physical properties (6).They are frequently prescribed for muscloskeletal complications and are often have similar structures, there are slight taken without prescription for minor aches and differences that affect the drug binding and lead to different actions (5)
The designed compounds have been synthesized successfully as shown in scheme (1) & (2) and their structures were confirmed, using elemental microanalysis (CHN), infrared spectroscopy (IR spectra) and their purity was confirmed by their physical data.The conversion of carboxylic acid group of aspirin and diflunisal to corboxamide group by conjugating the selected moiety of heterocyclic compound may produce new non-steroidal anti-inflammatory agents with expected selectivity toward COX2 inhibition and less gastric irritation

Summary

Introduction

Inflammation defined as a complexSelective COX-2 inhibitors have chemical series of tissue changes that result in pain and fever (1); or it is a normal, protective response structure with rigid side extension that binds in this side pocket. .NSAIDs have three major to tissue injury caused by physical trauma, pharmacological desirable actions, all of noxious, chemical, or microbiologic agents.which result mainly from the inhibition of Inflammation is the body's effect to inactivateCOX-2 in inflammatory cells and the resultant or destroy invading organisms, remove irritation, and set the stage of tissue repair(2) .decrease in prostanoid synthesis; these are: anti-inflammatory action,antipyretic effect and Inflammation can be divided into three phases; acute, chronic and immune response (3).There are two cyclooxygenase (COX) enzymes, analgesic effect. Selective COX-2 inhibitors have chemical series of tissue changes that result in pain and fever (1); or it is a normal, protective response structure with rigid side extension that binds in this side pocket. COX-2 is induced in inflammatory cells and aromatics or aliphatics They include different produces the prostanoid mediators of inflammation. COX-1 and COX-2 chemical classes with different physical properties (6).They are frequently prescribed for muscloskeletal complications and are often have similar structures, there are slight taken without prescription for minor aches and differences that affect the drug binding and lead to different actions (5). There are new many different NSAIDs on the market and non of these is ideal in a long narrow channel into which arachidonic acid enters and be converted into PGs, with controlling or modifying the sign and symptoms of inflammation (7)

Methods

Findings

Conclusion