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非经典两性离子作为一种设计原则，可在不影响渗透性的情况下降低亲脂性。

Nonclassical Zwitterions as a Design Principle to Reduce Lipophilicity without Impacting Permeability.

作者信息

Möbitz Henrik, Dittrich Birger, Rodde Stephane, Strang Ross

机构信息

Novartis BioMedical Research, 4002 Basel, Switzerland.

出版信息

J Med Chem. 2024 Jun 13;67(11):9485-9494. doi: 10.1021/acs.jmedchem.4c00596. Epub 2024 May 15.

DOI:10.1021/acs.jmedchem.4c00596
PMID:38747896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11292855/
Abstract

The ionization of bioactive molecules impacts many ADME-relevant physicochemical properties, in particular, solubility, lipophilicity, and permeability. Ampholytes contain both acidic and basic groups and are distinguished as ordinary ampholytes and zwitterions. An influential review states that zwitterions only exist if the acidic p is significantly lower than the basic p. Through concordance of measured and calculated p and log , we show that the zwitterionic behavior of several marketed drugs and natural products occurs despite a low or negative Δp. These nonclassical zwitterions are characterized by a weak acidic and basic p and conjugation through an extended aromatic system, often including pseudorings via intramolecular hydrogen bonds. In contrast to most classical zwitterions, nonclassical zwitterions can exhibit excellent permeability. As permeability and lipophilicity are typically correlated, the combination of low lipophilicity and high permeability makes nonclassical zwitterions an attractive design principle in medicinal chemistry.

摘要

生物活性分子的离子化会影响许多与药物吸收、分布、代谢和排泄（ADME）相关的物理化学性质，特别是溶解度、亲脂性和渗透性。两性电解质同时含有酸性和碱性基团，可分为普通两性电解质和两性离子。一篇有影响力的综述指出，只有当酸性p显著低于碱性p时，两性离子才会存在。通过测量和计算的p以及log的一致性，我们表明，尽管Δp较低或为负，但几种市售药物和天然产物仍会出现两性离子行为。这些非经典两性离子的特征是具有较弱的酸性和碱性p，并通过扩展的芳香体系共轭，通常包括通过分子内氢键形成的假环。与大多数经典两性离子不同，非经典两性离子可表现出优异的渗透性。由于渗透性和亲脂性通常相关，低亲脂性和高渗透性的结合使非经典两性离子成为药物化学中一种有吸引力的设计原则。

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2
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10
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