作者
Rafik Karaman, Hiba Ghareeb, Khuloud Kamal Dajani, Laura Scrano, Hussein Hallak, Saleh Abu-Lafi, Gennaro Mecca, Sabino A Bufo
发表日期
2013/7
期刊
Journal of computer-aided molecular design
卷号
27
页码范围
615-635
出版商
Springer Netherlands
简介
Abstract
Based on density functional theory (DFT) calculations for the acid-catalyzed hydrolysis of several maleamic acid amide derivatives four tranexamic acid prodrugs were designed. The DFT results on the acid catalyzed hydrolysis revealed that the reaction rate-limiting step is determined on the nature of the amine leaving group. When the amine leaving group was a primary amine or tranexamic acid moiety, the tetrahedral intermediate collapse was the rate-limiting step, whereas in the cases by which the amine leaving group was aciclovir or cefuroxime the rate-limiting step was the tetrahedral intermediate formation. The linear correlation between the calculated DFT and experimental rates for N-methylmaleamic acids 1–7 provided a credible basis for designing tranexamic acid prodrugs that have the potential to release the parent drug in a sustained release fashion. For example, based on …
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R Karaman, H Ghareeb, KK Dajani, L Scrano, H Hallak… - Journal of computer-aided molecular design, 2013