Deepali M. Jagdale

  Examination of nature’s favorite molecules revealed that nucleic acids, proteins and polysaccharides are condensation polymers of small subunits stitched together by carbon ± heteroatom bonds. Taking clue from the natures approach, a set of powerful, highly reliable and selective reactions were developed for the rapid synthesis of useful new compounds, an approach called as “click reactions”.  Thus click chemistry is a modular synthetic approach that utilizes the most practical and reliable chemical transformations. Its applications are increasingly found in all aspects of drug discovery, ranging from lead finding through combinatorial chemistry and target-template in situ chemistry, to proteomics and DNA research, using bioconjugation reactions. One of the reactions of click chemistry i.e. copper (I)-catalyzed 1, 2, 3-triazole forming reaction has become the gold standard of click chemistry due to its reliability, specificity and biocompatibility of the reactants. The triazole products are more than just passive linkers; they readily associate with biological targets, through hydrogen bonding and dipole interactions. This review gives a brief overview about some of the advances and applications of these click reactions.

  Bioisosteres are atoms or group of molecules that fit the broadest definition for isosteres. They have chemical and physical similarities thus producing broadly similar biological properties. Many heterocycles, when appropriately substituted exhibits bioisosterism. Bioisosterism represents an approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. It has significant value in drug design and lead optimization process as it may enhance the desired biological or physical properties of a compound, reduce toxicity and also alter the metabolism of the lead. Bioisosteric replacement is not simple replacement with another isostere but they are firstly analyzed by structural, solubility and electronic parameters to obtain molecules having similar biological activity. Few of the popular examples of the successful use of bioisosteres have been included. The objective of this review is to provide an overview of bioisosteric replacements which can be used for advance drug development.