Carbamate analogues of (-)-physostigmine: in vitro inhibition of acetyl- and butyrylcholinesterase.
Reaction of (-)-eseroline (1) with alkyl, aryl and aralkylisocyanates afforded a series of carbamate analogues of (-)-physostigmine (2) which were assayed for inhibition of acetyl- and butyrylcholinesterase (AChE and BChE, respectively) in vitro. Included in this study were two N-alkyl-substituted carbamates 9 and 14 obtained from (-)-eseroline (1) with dialkylcarbamoyl chlorides, and allophanates 12 and 13 obtained as by-products in the reaction of 1 and benzylcarbamoyl eseroline (8) with benzyl isocyanate. Whereas none of the analogues studied was more potent than 2 against electric eel AChE, and carbamates 6, 7 and 8 were all more than 3 times more potent against human plasma BChE than 2.
Yu
Q S
QS
Medicinal Chemistry Section, NIDDK, Bethesda, MD 20892.
Atack
J R
JR
Rapoport
S I
SI
Brossi
A
A
D000110:Acetylcholinesterase; D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood; D002219:Carbamates / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D002800:Cholinesterase Inhibitors; D004593:Electrophorus; D006801:Humans; D007211:Indoles; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000494:pharmacology
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007211:Indoles; D010830:Physostigmine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C022594:eseroline