Abstract
A new series of atropine analogs, in which an asymmetric center was introduced onto the N-atom in addition to that existing in the ester moiety, was prepared. The anti-muscarinic potency of the drugs was evaluated in the guinea-pig ileum test and compared to that of atropine itself. All the drugs tested inhibited competitively the acetylcholine-induced contractions. KD values were calculated for the various isomers and their racemates. The order of activity was found to be RR > RS ≈ SR > SS. In addition, the acetates of the N-Cabc-substituted analogs were also found to possess a weak anti-muscarinic activity. These results are discussed in terms of the contribution of both the nitrogen and ester sites to the recognition process of the muscarinic pharmacophore.
ACKNOWLEDGMENTS Valuable discussions with Prof. H. Weinstein are appreciated. Thanks are due to Miss T. Lessen and Mrs. E. Kerbis for their assistance with the syntheses.
- Copyright © 1978 by Academic Press, Inc.
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