Drug discovery requirement is to have a highly potent hit that has to be optimized to remove undesirable characteristics such as poor oral bioavailablity, metabolic stability or toxicity. In medicinal chemistry, isosterism, bioisosterism and scaffold hopping are research tools that have been successfully applied for designing new pharmacotherapeutically attractive substances. Isostere are group of atoms that impart similar physical or chemical properties to a molecule while substituents imparting similar biological properties on a compound are termed bioisostere. Bioisosteric replacement allows a medicinal chemist to modulate the physicochemical properties, selectivity, toxicity and pK characteristics of a small molecule while maintaining or improving its primary binding activity. Bioisosterism may alter the metabolism of the lead, and acquire novel intellectual property. The scaffold hopping techniques assist to identify structurally novel compounds by modifying the central core structure of the molecule and yet binding to the same molecular target. This review covers the developments in the fields of isosterism, bioisosterism and scaffold hopping in drug discovery. Various drugs developed or being developed using these strategies, and various software employed in the identification of isosteresc/bioisosters scaffold hopping are included. Moreover, combined bioisosteric replacement in different molecules has bright future in drug discovery. Experts are of the opinion that the knowledge generated in this direction has the potential towards accelerated development of better and effective drugs that could potentially treat the disorder they are researching, particularly to control autoimmune disorders and cardiovascular disorders where limited knowledge is available at present.
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