58780-60-2Relevant academic research and scientific papers
Synthesis of α-Methyldopa Prodrugs Containing Dipeptide Moieties as Tools for Intestinal Delivery
Wang, Hui-Po,Cheng, Chih-Yuan,Ma, Jin-Ran,Lee, Jia-Shuai
, p. 561 - 568 (2007/10/02)
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.Key Words α-Methyldopa prodrugs; Dipeptides as tools for intestinal delivery.
Synthesis and antihypertensive activity of some ester progenitors of methyldopa
Saari,Freedman,Hartman,King,Raab,Randall,Engelhardt,Hirschmann,Rosegay,Ludden,Scriabine
, p. 746 - 753 (2007/10/06)
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, α-pivaloyloxyethyl and α-succinimidoethyl, 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.
Esterification process
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, (2008/06/13)
Esters are formed by reacting an amino carboxylic acid with an alkylating agent in an aprotic solvent.
