Design and synthesis of a novel L-dopa-entacapone codrug.
A novel codrug, in which L-Dopa and entacapone are linked via a biodegradable carbamate spacer to form a single chemical entity, was synthesized and studied kinetically. This carbamate codrug provides adequate stability [t(1/2) = 12.1 h (pH 1.2); 1.4 h (pH 5.0); 1.1 h (pH 7.4)] against chemical hydrolysis but rapidly hydrolyzes to L-Dopa and entacapone in liver homogenate (t(1/2) = 7 min; pH 7.4) at 37 degrees C. The therapeutical potential of this novel codrug is discussed.
Leppänen
Jukka
J
Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, 70211, Kuopio, Finland, and Finncovery Ltd., Kuopio, Finland. jukka.leppanan@uku.fi
Huuskonen
Juhani
J
Nevalainen
Tapio
T
Gynther
Jukka
J
Taipale
Hannu
H
Järvinen
Tomi
T
D000818:Animals; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry; D002396:Catechols / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007980:Levodopa / Q000737:chemistry*; D009570:Nitriles; D011817:Rabbits
D000978:Antiparkinson Agents; D002219:Carbamates; D002396:Catechols; D009570:Nitriles; D007980:Levodopa; C071192:entacapone