Microwave Assisted Synthesis: A New Technology in Drug Discovery

Abstract

The interest in the microwave assisted organic synthesis has been growing during the recent years. It results from an increasing knowledge of fundamentals of the dielectric heating theory, availability of an equipment designed especially for the laboratory use as well as the discovery of the special techniques of the microwave syntheses. The efficiency of microwave flash-heating chemistry in dramatically reducing reaction times (reduced from days and hours to minutes and seconds) has recently been proven in several different fields of organic chemistry and this aspect is of great importance in high-speed combinatorial and medicinal chemistry. In this contribution, the current state of the art is summarized providing examples of the most recent applications in the field of microwave assisted synthesis of biologically active compounds both in heterocyclic and in peptide and peptidomimetic optimization.

Microwave-assisted synthesis of N-heterocycles in medicinal chemistry

“…The core structure was synthesised under MW irradiation; previously prepared 5--(trifluoromethyl)--1,3,4--thiadiazol--2--amine and multi--substituted α--haloaryl ketones were irradiated at 600 W for 10 15 min (Scheme 5). The 2--(trifluoromethyl)--6--arylimidazo [2,1--b] [1,3,4]--thiadiazoles were formylated at position 5 via the Vilsmeier Haack reaction and then subjected to Knoevenagel condensation which gave the desired products. All the reactions were carried out under both conventional and dielectric heating and results showed that MW irradiation dramatically cut down the reaction time to a few minutes.…”

“…Some products showed potential antibacterial activity, but no antiviral action was observed. Coumarin and quinazoline rings were combined in a single scaffold in a new group of molecules designed by Rajitha et al 41 The appropriate previously prepared substituted 2--(2-- [1,3]oxazin--4--ones were either functionalised with o--phenylenediamine or with benzo[c][1,2,5] thiadiazole--4,5--diamine to form the desired products. The reactions were carried out under conventional conditions and dielectric heating; the results were compared and cellulose sulphuric acid was used as a green catalyst.…”

Microwave Assisted Reactions in Organic Chemistry: A Review of Recent Advances

“…(Mingos et al, 1997). The research areas that rely on the development of large libraries of compounds, such as combinatorial chemistry (Pon-On et al, 2007;Pande et al, 2009;Nuchter et al, 2001) and drug discovery (Sekhon et al, 2010;Santagada et al, 2009) have been motivated due to the ability of microwave heating process in reducing the reaction time.…”

“…The ability to reduce reaction time from days and hours to minutes using microwave assisted reactions has promoted advent of microwave technology in combinatorial chemistry (Santagada et al, 2004;Kappe, 2004) and drug discovery (Sekhon et al, 2010;Santagada et al, 2009) as there is reliance on generation of large number of compounds whose production has been diversified as well as enhanced due to MAOS as there is increased production of cleaner reactions and more pure products (Bogadal et al, 2003;Mosely et al, 2007). This importance given to microwave assisted reactions in organic chemistry has resulted in a number of reviews on this subject.…”

Microwave-assisted synthesis of thermo- and pH-responsive antitumor drug carrier through reversible addition–fragmentation chain transfer polymerization

“…Microwave irradiation appears to be an attractive synthetic tool for solving these drawbacks because of several advantages such as reduced reaction times, increased product yields, limited generation of byproducts, and environmentally benign preparation. Microwave-assisted organic synthesis has been widely applied in the medicinal chemistry over the last decade [4]. For example, Imatinib (Gleevec), a marketed anticancer drug, can be produced through microwave heating in five steps with shorter reaction times and higher yields than what can be obtained through traditional heating methods [5].…”