Synthesis and antihypertensive activity of some ester progenitors of methyldopa

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-p...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1978-08, Vol.21 (8), p.746-753
Main Authors: Saari, Walfred S, Freedman, Mark B, Hartman, Richard D, King, Stella W, Raab, Andrew W, Randall, William C, Engelhardt, Edward L, Hirschmann, Ralph, Rosegay, Avery
Format: Article
Language:English
Subjects:
Animals
Antihypertensive Agents - chemical synthesis
Antihypertensive Agents - therapeutic use
Esters - chemical synthesis
Half-Life
Hydrolysis
Hypertension - drug therapy
Male
Methyldopa - analogs & derivatives
Methyldopa - chemical synthesis
Methyldopa - therapeutic use
Rats
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00206a006