Synthesis and anticholinesterase activity of (-)-N1-norphysostigmine, (-)-eseramine, and other N(1)-substituted analogues of (-)-physostigmine.
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Yu QS, Atack JR, Rapoport SI, Brossi A
Synthesis and anticholinesterase activity of (-)-N1-norphysostigmine, (-)-eseramine, and other N(1)-substituted analogues of (-)-physostigmine.
J Med Chem. 1988 Dec;31(12):2297-300.
- PubMed ID
- 3193422 [ View in PubMed]
- Abstract
(-)-N1-Benzylnorphysostigmine (4), prepared from synthetic (-)-O-methyl-N1-noreseroline (1) by N-benzylation, ether cleavage, and reaction of (-)-N1-benzylnoreseroline (3) with methyl isocyanate, was the intermediate used to prepare the title compounds. Catalytic debenzylation of 4 afforded (-)-N1-norphysostigmine (5), and (-)-eseramine (6) was obtained by reaction of 5 with methyl isocyanate. Reductive N-methylation of 5 gave (-)-physostigmine (9) while reaction of 5 with allyl bromide and phenethyl bromide afforded carbamates 7 and 8, respectively. Data on the in vitro potencies (IC50) and activities of certain of these compounds (4-8) as inhibitors of electric eel acetyl cholinesterase are reported. (-)-N1-Norphysostigmine (5) was found to be similarly potent against AChE as (-)-physostigmine (9).
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Isoflurophate Acetylcholinesterase IC 50 (nM) 480 N/A N/A Details Physostigmine Acetylcholinesterase IC 50 (nM) 61 N/A N/A Details