Incorporation of an Isohexide Subunit Improves the Drug-like Properties of Bioactive Compounds

被引：2
|
作者：
Knapp, Spencer [1 ]
Dresel, Mark J. [1 ]
Sidduri, Achyutharao [1 ,2 ]
机构：
[1] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA
[2] Aunova Medchem LLC, West Orange, NJ 07052 USA
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2023年 / 14卷 / 02期
基金：
美国国家卫生研究院;
关键词：
Isosorbide; isoidide; Mitsunobu; solubility; permeability; EGFR; alpha4; integrin; isosteres; DIANHYDROHEXITOLE-BASED BENZAMIDINES; BIOLOGICAL EVALUATION; MITSUNOBU REACTION; ISOSORBIDE; DERIVATIVES; INHIBITORS; DESIGN; IDENTIFICATION; POTENT; POLYMERIZATION;
D O I：
10.1021/acsmedchemlett.2c00476
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
An enhanced ability to pre-engineer favorable drug-likeness qualities into bioactive molecules would focus and streamline the drug development process. We find that phenols, carboxylic acids, and a purine react with isosorbide ("GRAS" designated) under Mitsunobu coupling conditions to deliver the isoidide conjugates selectively and efficiently. Such conjugates show improved solubility and permeability properties compared with the bare scaffold compounds themselves, and the purine adduct may have applications as a 2 '-deoxyadenosine isostere. We anticipate additional benefits, implied by their structures, in metabolic stability and reduced toxicity of the isoidide conjugates as well.
引用
收藏
页码：176 / 182
页数：7
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