Combinatorial Chemistry-Methods and Application in Pharmaceutical Industry

About author
P. V. Sapkale*, M. A. Chaudhari, N.B. Chaudhari, Megha Sahu, Atul R. Bendale, Anil G. Jadhav
Department of Chemistry SES, Arunamai College of pharmacy, Jalgaon, India
Department of Chemistry ICMR, Pune, India
Smt. B. N. B. Swaminarayan Pharmacy College, Salvav (Vapi), Gujarat
E-mail: [email protected] , [email protected]

Abstract
In olden days active compounds used in drug discovery programs have been natural products, isolated from plant, animal or fermentation sources. Combinatorial chemistry is one of the important techniques developed by researchers in the pharmaceutical industry to minimize the time and costs associated with producing effective and competitive new drugs. Combinatorial chemistry has become established. It has changed drug discovery. It’s a mainstream tool many drug companies would not want to do without. Many compounds discovered combinatorially, including a couple mentioned in this article, have at least entered preclinical or clinical trials. That’s some proof of the value of combinatorial chemistry. But the bottom line is that many researchers in academia, industry, and government already recognize it as an integral component of the drug discovery repertoire.
Key words: Development of combi-chem, Combinatorial Chemistry in pharmaceuticals, Combinatorial Chemistry methods and applications.
Introduction
Combinatorial chemistry is a novel method of synthesizing various different compound quickly and at the single time. A part from the time-consuming and labor useful methods of traditional chemistry where compounds are synthesized individually, one at a time. While at first used by organic chemists who are seeking new drugs, chemists are also now applying combinatorial chemistry to other fields such as semiconductors, superconductors, catalysts and polymers. Combi Chem is used to synthesize big number of chemical compounds by combining sets of building blocks. Each freshly synthesized compound’s composition is slightly different from the last one. A traditional chemist can synthesize 300-400compounds per year. A combinatorial system can produce in a year 1,000 or 10,000 compounds which can be tested for potential drug candidates in a high-throughput screening process. In the last few years, the Combi Chem has emerged as an exciting new and novel method for the drug discovery. In a short time the topic has become a considerable scientific interest and research efforts. Combi Chem is currently applied, in addition to natural product synthesis and drug discovery, to Agri. chemistry, biochemistry, catalyst discovery and material science. Gene sequences for targets that have been identified by genomics approaches are cloned and shown as target proteins that are suitable for screening with probe library of small, drug like chemical compounds. These compounds are screened to find active hits using a quantitative, universal binding assay.
Initial hits or quantitative structural activity data that obtained from binding assay are analyzed and used to formulate a selection strategy for the synthesis of more compounds with improved properties. These compounds are choice from a computer database of synthetically accessible analogs of the initial probe library, synthesized by parallel synthesis methods and tested to explain the structure activity profile of the target under observation and to refine the selection criteria for further rounds of chemical synthesis and biological testing. In each reaction priority is assigned to the synthetic candidates using a multi objective optimization process that is designed to ensure that compounds are not only optimized for target binding affinity, but also have drug like characteristics that will allow them to be used directly as tool compounds in biological.