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使用血红蛋白A-H₂O₂对1,4-二氢吡啶和吡唑啉进行氧化芳构化:一种提供候选药物代谢物的高效仿生催化体系。

Oxidative aromatization of 1,4-dihydropyridines and pyrazolines using HbA-H(2)O(2): An efficient biomimetic catalyst system providing metabolites of drug candidates.

作者信息

Kumar Atul, Maurya Ram Awatar, Sharma Siddharth

机构信息

Medicinal and Process Chemistry Division, Central Drug Research Institute(dagger), Lucknow 226001, India.

出版信息

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4432-6. doi: 10.1016/j.bmcl.2009.05.056. Epub 2009 May 19.

Abstract

Human hemoglobin (HbA) efficiently catalyses the oxidative aromatization of 1,4-dihydropyridines (1,4-DHPs) and pyrazolines with hydrogen peroxide in phosphate buffer. The results of the study reveal that the rates of oxidative aromatization of 1,4-DHPs are substituent dependent. Thus, the present study is very useful in understanding the metabolism of 1,4-DHP drugs in liver by cytochrome P450 and designing novel drugs as well as modifying the existing drugs for better pharmacokinetic profile.

摘要

人血红蛋白(HbA)在磷酸盐缓冲液中能有效催化1,4 - 二氢吡啶(1,4 - DHPs)和吡唑啉用过氧化氢进行氧化芳构化反应。研究结果表明,1,4 - DHPs的氧化芳构化速率取决于取代基。因此,本研究对于理解细胞色素P450在肝脏中对1,4 - DHP药物的代谢、设计新型药物以及改进现有药物以获得更好的药代动力学特性非常有用。

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