Syntheses and Evaluation of the Analgesic Activity of Some 4-Acetyl- 4-phenylpiperidine and 4-Hydroxy-4-phenylpiperidine Derivatives

Z a fa r S aeed Saify3, K halid M oham m ed K hanb, Syed M oazzam H a id e r3, Z e e sh a n b, Syed T asad aq u e A li S hahb, M uham m ad S aeedc, M oham m ed Saleh S h ek h an id, and W olfgang V o e lte rc a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi b International Center for Chemical Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan. Fax: 0092-21-4963373, 4963124. E-mail: [email protected] c Abteilung für Physikalische Biochemie, Physiologisch-chemisches Institut der Universität Tübingen, Hoppe-Seyler-Straße 4, D-72076 Tübingen, Germany. Fax: (+49) 7071-293348. E-mail: [email protected] d Ophidian Pharmaceuticals, Inc. 5445 E. Cheryl Parkway Madison, WI 53711 U SA * Reprint request to Prof. Dr. Zafar Saeed Saify or Prof. Dr. Dr. h. c. Wolfgang Voelter Z. Naturforsch. 54b, 1327-1336 (1999); received June 24, 1999 4-Acetyl-4-phenylpiperidine, 4-Hydroxy-4-phenylpiperidine, Analgesic Activity Synthesis and analgesic activity of 4-phenylpiperidine derivatives is a topic of high actual­ ity. A s part of a programme towards obtaining new potential analgesics, ten derivatives of 4acetyl-4-phenylpiperidine and ten derivatives of 4-hydroxy-4-phenylpiperidine were synthe­ sised and characterized through spectroscopic techniques. All derivatives along with the par­ ent compounds were evaluated for analgesic activity in the acetic acid-induced writhing assay and tail-flick test in mice. All derivatives of 4-acetyl-4-phenylpiperidine except one com ­ pound exhibited more or less protection against mice writhing, whereas all the compounds proved to be inactive in the tail-flick test at doses of 50 and 100 mg/kg body weight.