Dipeptides containing D‐phenylglycine or D‐p‐hydroxyphenylglycine were attached onto the antihypertensive agent α‐methyldopa to form prodrugs 1a, 1b and 1c. The nonessential amino acids were introduced into the prodrug molecules as tools of chemical delivery to improve the intestinal absorption of the parent drug. Preliminary tests revealed that the prodrugs were stable in phosphate buffer solutions at pH 7.4 (t1/2 > 10 h). These compounds also demonstrated satisfactory stability toward enzymatic degradation in a mucosa preparation isolated from rat intestine, indicating that they might be feasibly formulated as an oral prodrug of α‐methyldopa.
ASJC Scopus subject areas
- 化學 (全部)