What, This "Base" Is Not a Base? Common Misconceptions about Aqueous Ionization That May Hinder Drug Discovery and Development.

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-10-01 DOI:10.1021/acs.jmedchem.5c01783

Robert Fraczkiewicz

引用次数: 0

Abstract

The challenges of modern medicinal chemistry increase with the complexity of the chemical compounds studied. Often these compounds are multiprotic with both acidic and basic functional groups. Since ionization patterns of such compounds are overly complex, the traditional concepts applied to apparent ionization constants (pKa) such as group "assignment", "acid", and "base" are woefully inadequate and may hamper drug discovery and development. We highlight this inadequacy and its consequences so that the medicinal chemistry community fully understands the critical issues at stake.

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什么，这个“基地”不是基地吗？关于水电离的常见误解可能阻碍药物的发现和开发。

现代药物化学的挑战随着所研究的化合物的复杂性而增加。这些化合物通常是多质子的，同时具有酸性和碱性官能团。由于这类化合物的电离模式过于复杂，应用于表观电离常数（pKa）的传统概念，如基团“分配”、“酸”和“碱”，严重不足，可能阻碍药物的发现和开发。我们强调这种不足及其后果，以便药物化学界充分理解危在其中的关键问题。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.