Design, synthesis and biological evaluation of L-dopa amide derivatives as potential prodrugs for the treatment of Parkinson's disease.
A range of amide derivatives of L-dopa were synthesized and investigated for their pharmacological activity and their ability to be converted to L-dopa using the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat, as an experimental model of Parkinson's disease. The diacetyl derivative of L-dopa amide (11b) was found to be more active than L-dopa after its oral administration and generated plasma levels of L-dopa in the therapeutic range for an antiparkinsonian effect in man.
Zhou
Tao
T
School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310035, PR China.
Hider
Robert C
RC
Jenner
Peter
P
Campbell
Bruce
B
Hobbs
Christopher J
CJ
Rose
Sarah
S
Jairaj
Mark
M
Tayarani-Binazir
Kayhan A
KA
Syme
Alexander
A
D000577:Amides / Q000737:chemistry*; D000818:Animals; D015195:Drug Design; D007980:Levodopa / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000577:Amides; D011355:Prodrugs; D007980:Levodopa; D016627:Oxidopamine