The Application of Microwaves in Combinatorial and High‐Throughput Synthesis as New Synthetic Procedure in Drug Discovery

Abstract

Heterocyclic compounds hold a special place among pharmaceutically important natural and synthetic materials. The remarkable ability of heterocyclic nuclei to serve both as biomimetics and reactive pharmacophores has largely contributed to their unique value as traditional key elements of numerous drugs. In both lead identification and optimization processes there is an acute need for new organic small molecules. Traditional methods of organic synthesis are orders of magnitude too slow to satisfy the demand for these compounds; so, the fields of combinatorial and automated medicinal chemistry have been developed to meet the increasing requirement of new compounds for drug discovery; within these fields, speed is of the essence. The efficiency of microwave 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. We believe that the time saved by using focused microwaves is potentially important in traditional organic synthesis but could be of even greater importance in high‐speed combinatorial and medicinal chemistry.

Microwave assisted synthesis of some novel Flurbiprofen hydrazide hydrazones as anti-HCV NS5B and anticancer agents

“…All computations were carried out on a Dell Precision 470n dual processor with the Linux OS (Red Hat Enterprise WS 4.0). The structures of compounds 3a-u were confirmed by elemental analyses and spectrometry techniques such as UV, IR, 1 H NMR, 13 C NMR (only 3l) and EI-mass (only 3s) and single crystal X-ray analysis (only 3s).…”

“…Further, this method requires much less solvent to generate compounds, thus making this green chemistry technique more environmentally friendly. Given the advantages of microwave assisted synthesis of compounds, the application of this technology in medicinal chemistry has the potential to rapidly generate chemical libraries for the purpose of screening molecules for drug discovery (13).…”

Microwave‐induced enhancement of the dissolution rate of poorly water‐soluble tibolone from poly(ethylene glycol) solid dispersions

“…Microwave-assisted organic chemistry has received considerable attention during the last decade, and nowadays more and more research chemists are applying microwave technology to organic reactions, especially for drug synthesis on a small or kilolab scale and for polymer synthesis. [1][2][3][4][5] Microwaves can be directly converted into heat inside the material. Therefore, it is possible to achieve rapid and uniform heating even in materials exhibiting low heat conductivity, such as polymers, because the transfer of energy does not rely on heat diffusion.…”

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

“…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.…”