| Literature DB >> 6737413 |
W S Saari, W Halczenko, D W Cochran, M R Dobrinska, W C Vincek, D C Titus, S L Gaul, C S Sweet.
Abstract
The (5-methyl-2-oxo-1,3- dioxol -4-yl)methyl and (5-tert-butyl-2-oxo-1, 3- dioxol -4-yl)methyl esters of 3-hydroxy-alpha-methyltyrosine (methyldopa) were prepared and evaluated as progenitors of the amino acid. 1H NMR experiments reveal that the esters are converted cleanly to methyldopa and the corresponding alpha-diketone at pH 7.4, with the 5-methyl derivative undergoing hydrolysis faster than the 5-tert-butyl analogue. Bioavailability studies in dogs show that the esters, particularly the 5-methyl derivative, yield significant plasma levels of methyldopa. Both esters are orally effective antihypertensive agents in spontaneously hypertensive (SH) rats. These studies indicate that (2-oxo-1,3- dioxol -4-yl)methyl esters are viable prodrugs for the latentiation of methyldopa.Entities:
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Year: 1984 PMID： 6737413 DOI： 10.1021/jm00372a002
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446