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神奇的甲基及其在药物研发中的作用

The Magic Methyl and Its Tricks in Drug Discovery and Development.

作者信息

Pinheiro Pedro de Sena Murteira, Franco Lucas Silva, Fraga Carlos Alberto Manssour

机构信息

Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.

Instituto Nacional de Ciência e Tecnologia de Fármacos e Medicamentos (INCT-INOFAR), CCS, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro 21941-902, RJ, Brazil.

出版信息

Pharmaceuticals (Basel). 2023 Aug 15;16(8):1157. doi: 10.3390/ph16081157.

DOI:10.3390/ph16081157
PMID:37631072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10457765/
Abstract

One of the key scientific aspects of small-molecule drug discovery and development is the analysis of the relationship between its chemical structure and biological activity. Understanding the effects that lead to significant changes in biological activity is of paramount importance for the rational design and optimization of bioactive molecules. The "methylation effect", or the "magic methyl" effect, is a factor that stands out due to the number of examples that demonstrate profound changes in either pharmacodynamic or pharmacokinetic properties. In many cases, this has been carried out rationally, but in others it has been the product of serendipitous observations. This paper summarizes recent examples that provide an overview of the current state of the art and contribute to a better understanding of the methylation effect in bioactive small-molecule drug candidates.

摘要

小分子药物发现与开发的关键科学问题之一是分析其化学结构与生物活性之间的关系。了解导致生物活性发生显著变化的影响因素对于合理设计和优化生物活性分子至关重要。“甲基化效应”，即“神奇甲基”效应，因其有大量实例表明其能使药效学或药代动力学性质发生深刻变化而备受关注。在许多情况下，这是经过合理设计实现的，但在其他情况下则是偶然观察的结果。本文总结了近期的实例，这些实例概述了当前的技术水平，并有助于更好地理解生物活性小分子候选药物中的甲基化效应。

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