(2,6-Methano-3-benzazocin-11.beta.-yl)alkanones. 1. Alkylalkanones: a new series of N-methyl derivatives with novel opiate activity profiles

• Published in: Journal of medicinal chemistry Vol. 22; no. 10; pp. 1158 - 1163
• Main Authors: Michne, William F, Lewis, Thomas R, Michalec, Stephen J, Pierson, Anne K, Rosenberg, Franklin J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-10-1979
• Subjects: Analgesics, Opioid - chemical synthesis; Animals; Azocines - chemical synthesis; Azocines - pharmacology; Chemical Phenomena; Chemistry; Drug Interactions; Ketones - chemical synthesis; Ketones - pharmacology; Mice; Narcotic Antagonists - pharmacology; Rats; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00196a002

A general stereospecific synthesis of (N-methyl-2,6-methano-3-benzazocin-11 beta-yl)alkanones is described and applied to the preparation of a series of alkyl ketones wherein the alkyl group is a straight or terminally branched chain containing from one to six carbon atoms. Several compounds with methoxy groups in the aromatic ring are in the morphine range of potency; they are uniformly inactive as phenazocine antagonists. Phenolic analogues range up to 100 times as potent as morphine. Those containing five or six carbon atoms in the alkyl group exhibit phenazocine antagonist activity, in one case equivalent to naloxone. This compound (3e) is selective for phenazocine in its antagonist action.