Centre for the Control and Evaluation of Medicines, Chemical Medicines Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.
Molecules. 2023 Sep 8;28(18):6518. doi: 10.3390/molecules28186518.
Isoxazoline is a nitrogen- and oxygen-containing five-membered heterocyclic scaffold with diverse biological profiles such as antimicrobial, fungicidal, anticancer, antiviral, analgesic and anti-inflammatory activity. Accordingly, the use of this peculiar structural framework in drug discovery is a successful strategy for the development of new drug candidates. Here, a chiral saccharin/isoxazoline hybrid was considered to investigate the tendency of the imine moiety of the heterocyclic ring to tautomerize to the enamine form in the presence of a basic catalyst. The pseudo-first-order rate constants for the base-catalyzed tautomerization process were measured in different solvents and at different temperatures by off-column kinetic experiments based on the amylose (3,5-dimethylphenylcarbamate)-type chiral stationary phase. The kinetic results obtained in this study may be a useful aid in the perspective of designing experimental conditions to control the stereointegrity of these types of pharmacologically active compounds and drive their synthesis toward the preferred, imine or enamine, tautomer.
异恶唑啉是一种含氮和氧的五元杂环骨架，具有多种生物学特性，如抗菌、杀菌、抗癌、抗病毒、镇痛和抗炎活性。因此，在药物发现中使用这种特殊的结构框架是开发新候选药物的成功策略。在这里，考虑了一种手性磺酰亚胺/异恶唑啉杂合体，以研究杂环环的亚胺部分在碱性催化剂存在下向烯胺形式互变异构的趋势。通过基于直链淀粉（3,5-二甲基苯基氨基甲酸酯）型手性固定相的柱外动力学实验，在不同溶剂和不同温度下测量了碱催化互变异构过程的假一级速率常数。本研究中获得的动力学结果可能有助于设计实验条件，以控制这些类型的具有药理活性的化合物的立体完整性，并促使它们的合成朝着优选的亚胺或烯胺互变异构体进行。
