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Mini-Reviews in Medicinal Chemistry

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ISSN (Online): 1875-5607

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Review Article

Exploring the N1 Position of Biginelli Compounds: New Insights and Trends for Chemical Diversity Generation of Bioactive Derivatives

Author(s): Itamar Luís Gonçalves*, Gustavo Machado das Neves, Luciano Porto Kagami, Guilherme Arraché Gonçalves, Leonardo Davi and Vera Lucia Eifler-Lima

Volume 22, Issue 11, 2022

Published on: 18 January, 2022

Page: [1545 - 1558] Pages: 14

DOI: 10.2174/1389557521666211027105534

Price: $65

Abstract

Dihydropyrimidinones (DHPMs) are heterocycles obtained by the multicomponent Biginelli reaction. Recently, new synthetic protocols have allowed us to explore functionalisation at less explored positions of DHPMs, such as the N1 position. In this context, a full literature survey of N1- substituted DHPMs was performed. We analysed 27 papers and identified 379 compounds with substituents at the N1 position, most of them with alkyl groups, and a total of 28% compounds with aromatic substituents attached at the N1 position. N1-substituted DHPMs were explored mainly due to their effects on cancer cell proliferation via numerous targets, such as kinesin Eg5, heat shock protein 70, heat shock protein 90, and the epidermal growth factor receptor. Similarity analyses were performed using the data of 379 DHPMs from different cheminformatic approaches, i.e., chemical property correlations, principal component analysis, similarity networks, and compound clustering.

Keywords: Multicomponent reactions, DHPMs, Biginelli reactions, privileged structure, molecular diversity, bioactive derivatives.

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