New Developments in Medicinal Chemistry

Volume: 2

Indexed in: EMBASE, EBSCO.

This e-book series is recommended for readers who are interested in or work with current theoretical and experimental research in medicinal chemistry, with an emphasis on computer aided-drug design ...
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Bioisosteric Replacements in Drug Design

Pp. 213-238 (26)

Vinicius Barreto da Silva, Daniel Fábio Kawano, Ricardo Pereira Rodrigues, Susimaire Pedersoli Mantoani, Jonathan Resende de Almeida, Evandro Pizeta Semighini and Carlos Henrique Tomich de Paula da Silva

Abstract

Bioisosterism is a molecular modification Medicinal Chemistry strategy applied during drug design projects when a lead compound is available. The idea of bioisisterism is centered at the use of chemical diversity in order to optimize pharmaceutical properties of lead compounds and generate active analogs, replacing problematic substructures inside lead compounds by others with similar physicochemical properties that can improve the limitations observed for the original lead compound. Bioisosterism can be a useful strategy in order to optimize lead compounds searching for analogs with better selectivity and synthetic accessibility, decreased toxicity, improved pharmacokinetics, enhanced solubility and metabolic stability. This chapter highlights the computational approaches used to identify potential bioisosters, discusses how bioisosterism can be helpful during the design of molecules with better synthetic accessibility, and reviews the scaffold hopping technique, a novel trend of bioisosterism application intended to identify interchangeable scaffolds among pharmaceutical interesting molecules.

Keywords:

Bioactivity, bioisosteric replacements, bioisosterism, chemoinformatics, drug design, drug metabolism, intermolecular interactions, lead compounds, medicinal chemistry, molecular descriptors, molecular modeling, scaffold hopping, synthetic accessibility, toxicity, virtual screening.

Affiliation:

School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.