STRUCTURE-ACTIVITY RELATIONS IN ANALGESICS BASED ON 4-ANILINOPIPERIDINE

The synthesis of some 1‐alkyl and l‐aralkyl‐4‐(N‐phenylpropion‐amido)piperidines and related derivatives is described and the hot‐plate activities in mice of these compounds reported. Activity variations among 1‐methyl, 1‐benzyl, and 1‐phenethyl derivatives resemble those of corresponding open‐chain anilide rather than 4‐phenyl‐piperidine analgesics. Infrared and nmr data show the two nitrogen atoms of the 4‐anilinopiperidine derivatives to be further apart than those of open‐chain anilides in their respective preferred conformations; these results, together with the extreme potency difference between the N‐phenethyl derivatives diampromide and fentanyl, show that the two classes are best regarded as mutually distinct types of analgesic. 1969 Royal Pharmaceutical Society of Great Britain