Semmelweis University Department of Pharmaceutical Chemistry Hungarian Academy of Sciences, Hőgyes E. u. 9., 1092, Budapest, Hungary.
ChemMedChem. 2020 Jul 3;15(13):1102-1110. doi: 10.1002/cmdc.202000164. Epub 2020 Jun 9.
In solution, amphoteric compounds exist in anionic, uncharged, zwitterionic and cationic forms. The importance of zwitterionic drugs is currently under-represented in the literature. Herein, the acid-base parameters, lipophilicity and solubility of such compounds are discussed to deepen the molecular-level understanding of their pharmacokinetic and pharmacodynamic behaviour. Our recent studies show there are many drug molecules, including thyroid hormones and 5-hydroxytryptophan, the precursor of the neurotransmitter serotonin, for which the contribution of the zwitterionic microspecies to the overall lipophilicity exceeds that of the uncharged one, which is of higher individual lipophilicity, but occurs in much lower concentration. The second part of the minireview highlights the most important zwitterionic compounds in therapy, grouped into therapeutic classes. The importance of the charge of the molecules is emphasized in their binding to the target molecules.
在溶液中，两性化合物以阴离子、中性、两性离子和阳离子形式存在。目前，两性药物的重要性在文献中被低估了。本文讨论了这类化合物的酸碱参数、亲脂性和溶解度，以加深对其药代动力学和药效动力学行为的分子水平理解。我们最近的研究表明，有许多药物分子，包括甲状腺激素和 5-羟色氨酸，即神经递质血清素的前体，其中两性离子微种对整体亲脂性的贡献超过了具有更高个体亲脂性但浓度低得多的中性分子。这篇综述的第二部分重点介绍了治疗中最重要的两性化合物，按治疗类别分组。强调了分子电荷在与靶分子结合中的重要性。
