Synthesis and pharmacological evaluation of 4,4-disubstituted piperidines.
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.
Colapret
J A
JA
Anaquest Pharmaceuticals, BOC Technical Center, Murray Hill, New Jersey 07974.
Diamantidis
G
G
Spencer
H K
HK
Spaulding
T C
TC
Rudo
F G
FG
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
D000700:Analgesics; D000777:Anesthetics; D010880:Piperidines