Synthesis of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine as potential prodrug of L-dopa.
The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described. Prodrug 9 possesses a good lipophilicity (log P = 2.153 +/- 0.017), is stable in aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it is turned into L-Dopa.
Cingolani
G M
GM
Dipartimento di Scienze Chimiche, Università di Camerino, Italy. giemmeci@camserv.unicam.it
Di Stefano
A
A
Mosciatti
B
B
Napolitani
F
F
Giorgioni
G
G
Ricciutelli
M
M
Claudi
F
F
D000818:Animals; D000978:Antiparkinson Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000737:chemistry*; D009025:Morpholines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats
C415648:3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine; D000978:Antiparkinson Agents; D009025:Morpholines; D011355:Prodrugs; D007980:Levodopa