Carbamate analogues of (−)‐physostigmine: In vitro inhibition of acetyl‐ and butyrylcholinesterase

FEBS Letters

Brossi, Arnold²  Yu, Qian-Sheng²  Atack, John R.¹  Rapoport, Stanley I.¹ 

[1] Laboratory of Neurosciences, NIA, National Institutes of Health, Bethesda, MD 20892, USA;Medicinal Chemistry Section, Laboratory of Analytical Chemistry, NIDDK Bethesda, MD 20892, USA

关键词: Carbamate analogue;    Enzyme inhibition;    Acetylcholinesterase;    Butyrylcholinesterase;   

DOI  :  10.1016/0014-5793(88)81317-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown