Synthesis and analgesic activity of N-arylakyl-N [2- [1-pyrrolidinyl] cyclohexyl] propanamides

ABSTRACT

The objective of this study was investigate further the presence of structural or functional analogies between the arylacetamide U50488 [1] and fentanyl [3]. The synthesis and in vitro analgesic activity [hot-plate test] of N-benzyl, N-[2-phenylethyl], and N-[3-phenylpropyl] derivatives of trans-[ +/- ] -N-[2-[1-pyrrolidinyl] cyclohexyl] propanamide [5-7, respectively] were discussed. Attempts to synthesize N-phenyl derivative 4 were also discussed. The lack of significant analgesic activity of 5-7 indicated the stringent structural requirement for the N-methyl-N-arylacetamide group of the k-selective opioid trans-[ +/- ]-2-[3, 4-dichlorophenyl]-N-methyl- N-[2- [1-pyrrolidinyl] cyclohexyl] acetamide [U50488][1]