Saari W S, Freedman M B, Hartman R D, King S W, Raab A W, Randall W C, Engelhardt E L, Hirschmann R, Rosegay A, Ludden C T, Scriabine A
J Med Chem. 1978 Aug;21(8):746-53. doi: 10.1021/jm00206a006.
A variety of esters of methyldopa was synthesized with the objective of obtaining derivatives that would be more efficiently absorbed from the gastrointestinal tract than the free amino acid and would undergo conversion to methyldopa readily in the blood or target tissues. Two of the esters, alpha-pivaloyloxyethyl (4u) and alpha-succinimidoethyl (4w), were found to be more potent antihypertensive agents than methyldopa in animal models and were selected for further study in man. The amino esters were prepared by three different methods, including direct esterification of methyldopa without the use of N- or O-protecting groups.
合成了多种甲基多巴酯，目的是获得比游离氨基酸更易从胃肠道吸收且能在血液或靶组织中迅速转化为甲基多巴的衍生物。在动物模型中发现其中两种酯，α-特戊酰氧基乙酯（4u）和α-琥珀酰亚胺基乙酯（4w），作为抗高血压药比甲基多巴更有效，并被选用于人体进一步研究。氨基酯通过三种不同方法制备，包括不使用N-或O-保护基团直接酯化甲基多巴。
