Synthesis and analgesic activity of N-aryl/arylalkyl-N-[2-(1-pyrrolidinyl)cyclohexyl]propanamides.

The synthesis and in vivo 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) are discussed. Attempts to synthesize the N-phenyl derivative 4 are also discussed. The lack of significant analgesic activity of 5-7 indicated the stringent structural requirement for the N-methyl-N-arylacetamido group of the chi-selective opioid trans-(+/-)-2-(3,4-dichlorophenyl)- N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]acetamide (U50488) (1).