title: Synthesis and pharmacological evaluation of 4,4-disubstituted piperidines.
abstract: A new class of piperidine derivatives is added to the increasing family of compounds related to fentanyl and carfentanil. Herein, we describe the synthesis and pharmacology of a number of 1-(arylethyl)-4-(acylamino)-4-[(acyloxy)-methyl]piperidines such as 9, 15, and 23. As expected, many of these congeners of fentanyl are extremely potent narcotic agonists. The aim of the study was to identify short-acting analgesic agents (i.e. less than 6 min in the mouse hot-plate assay) for possible use in the surgical theater. Many of the drugs proved to be of intermediate and long duration (i.e. 6-15 min and greater than 15 min, respectively). In addition to analgesic activity, many of the compounds exhibited anesthetic properties as well. The structure-activity relationship for these entities is presented and discussed.
authors.affiliation: Anaquest Pharmaceuticals, BOC Technical Center, Murray Hill, New Jersey 07974.
authors.forename: J A
authors.initials: JA
authors.lastname: Colapret
authors.forename: G
authors.initials: G
authors.lastname: Diamantidis
authors.forename: H K
authors.initials: HK
authors.lastname: Spencer
authors.forename: T C
authors.initials: TC
authors.lastname: Spaulding
authors.forename: F G
authors.initials: FG
authors.lastname: Rudo
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D008297:Male; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000777:Anesthetics; D010880:Piperidines