(2-exo-3-endo)-2-Aryltropane-3-carboxylic esters, a new class of narcotic antagonists.
Tropanes 4 bearing an exo aromatic group on carbon-2, an endo-carbomethoxy group on carbon-3, and either a methyl group or a hydrogen on the nitrogen were found to be narcotic antagonists which were devoid of demonstrable analgesic activity. The activity resided in the 1S enantiomer. Compound 4 (R = m-hydroxyphenyl) showed an AD50 of 0.37 mg/kg sc and 1.8 mg/kg po (rats) as an antagonist in the Harris-Pierson modification of the D'Amour-Smith test. The tropane esters for this study were prepared by a Grignard reaction which gave essentially complete 1,4-addition in the absence of copper salts. Nearly equal quantities of esters epimeric at carbon-3 were formed.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000701:Analgesics, Opioid / Q000138:chemical synthesis; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors; D051379:Mice; D008968:Molecular Conformation; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D011809:Quinones / Q000037:antagonists & inhibitors; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000494:pharmacology
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011809:Quinones; D014326:Tropanes; D000109:Acetylcholine; D001920:Bradykinin