The xanthene-9-spiro-4'-piperidine nucleus as a probe for opiate activity

• Published in: Journal of medicinal chemistry Vol. 32; no. 10; pp. 2357 - 2362
• Main Authors: Galt, Ronald H. B, Horbury, John, Matusiak, Zbigniew S, Pearce, Robert J, Shaw, John S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.10.1989
• Subjects: Analgesics, Opioid - chemical synthesis; Animals; Chemistry; Exact sciences and technology; Guinea Pigs; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Ileum - physiology; In Vitro Techniques; Mice; Molecular Structure; Muscle Contraction - drug effects; Muscle, Smooth - physiology; Organic chemistry; Pain - physiopathology; Piperidines - chemical synthesis; Piperidines - pharmacology; Preparations and properties; Structure-Activity Relationship; Xanthines - chemical synthesis; Xanthines - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00130a022

A series of novel 1'-methylxanthene-9-spiro-4'-piperidines has been prepared in the search for opiate analgesics with improved pharmacological properties. It has been found that introduction of a hydroxyl group into the 4-position of the xanthenespiropiperidine nucleus produces a potent mu-opiate agonist. The structure-activity relationship of the series has been explored by use of isosteric replacements of the phenolic hydroxyl group. Moreover, the effect of altering the conformation of the piperidine ring has been studied. It was interesting to note that, in compounds lacking the phenolic hydroxyl group, opiate activity could be produced by introduction of the (phenylamino)ethyl group instead of methyl at the 1'-position.