RT Journal Article
SR Electronic
T1 Structure-Activity Relationship in a New Series of Atropine Analogs
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 781
OP 786
VO 14
IS 5
A1 S. CHERKEZ
A1 H. YELLIN
A1 Y. KASHMAN
A1 B. YAAVETZ
A1 M. SOKOLOVSKY
YR 1978
UL http://molpharm.aspetjournals.org/content/14/5/781.abstract
AB 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.