New heteroaryl derivatives of fentanyl

Abstract

The preparation of analogues of fentanyl with N-phenyl replaced with a heterocyclic aromatic ring, and with N-alkyl/arylalkyl N-acyl substituents is reported. Only those compounds carrying an N-phenylethyl substituent were active in the rat tail-withdrawal test. Fentanyl (1) is the prototype of the 4-anilido-piperidine class of opioid analgesics (Casy & Parfitt 1986). Several recent publications (Casy & Huckstep 1988; Bagley et al 1989) on this series have dealt with heterocyclic and aromatic modifications of the fentanyl molecule. Although the antinociceptive potency of most novel derivatives was greater than that of morphine, they had reduced activity when compared with fentanyl itself. To acquire further information on the structure-reactivity relationships of the series, new heteroaryl derivatives have been prepared and tested for antinociceptive activity.