A Concise Synthesis of Pyrrole-Based Drug Candidates from α-Hydroxyketones, 3-Oxobutanenitrile, and Anilines

Abstract

A simple and concise three-component synthesis of a key pyrrole framework was developed from the reaction between α-hydroxyketones, oxoacetonitriles, and anilines. The synthesis was used to obtain several pyrrole-based drug candidates, including COX-2 selective NSAID, antituberculosis lead candidates BM212, BM521, and BM533, as well as several analogues. This route has potential to obtain diverse libraries of these pyrrole candidates in a concise manner to develop optimum lead compounds.

Sustainable Synthesis of Indole-Substituted Densely Functionalized Pyrrole

“…Pyrrole is one of the most important structural attribute in porphyrins, alkaloids, vitamins, heterocyclic compounds of pharmaceuticals and new organic materials, , and building blocks for optical materials . Pyrrole skeletons are present in different molecules displaying antibacterial, antiviral, antitumor, anti-inflammatory, and antioxidant activities. , Among different synthetic approaches for the synthesis of pyrroles, the Paal–Knorr cyclization reaction between a 1,4-dicarbonyl compound and a primary amine under acidic conditions has been the most frequently investigated one . Since the first report of Paal–Knorr synthesis, many variations of the reaction condition have been developed by using various acidic reagents such as Bronsted acids (e.g., H 2 SO 4 , HCl, p- toluenesulfonic acid) and Lewis acids [e.g., Sc­(SO 3 CF 3 ) 3 , Bi­(NO 3 ) 3 · 5H 2 O, RuCl 3 , InCl 3 , SnCl 2 · 2H 2 O] to promote the condensations.…”