| Literature DB >> 3494849 |
F I Carroll, P Abraham, K Parham, R C Griffith, A Ahmad, M M Richard, F N Padilla, J M Witkin, P K Chiang.
Abstract
The synthesis and antimuscarinic properties of 6-methyl-6-azabicyclo[3.2.1]octan-3 alpha-ol 2,2-diphenylpropionate (1, azaprophen) are described. Azaprophen is 50 times more potent than atropine as an antimuscarinic agent as measured by the inhibition of acetylcholine-induced contraction of guinea pig ileum and is more than 1000 times better than atropine in its ability to block alpha-amylase release from pancreatic acini cells induced by carbachol. In addition, azaprophen is 27 times more potent than atropine as an inhibitor of binding of [N-methyl-3H]scopolamine to muscarinic receptors, with human IMR-30 neuroblastoma cells. The potencies of azaprophen and atropine in altering operant behavior were similar. The structural features of 1 are compared to the standard anticholinergic drugs atropine and quinuclidinyl benzilate by using energy calculations and molecular modelling studies. A modification of the pharmacophore model hypothesis for cholinergic agents is suggested.Entities:
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Year: 1987 PMID： 3494849 DOI： 10.1021/jm00388a010
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446