Compounds related to pethidine-IV. New general chemical methods of increasing the analgesic activity of pethidine.

A variety of chemical methods are available to increase the analgesic activity of pethidine (I). Replacement of the carbethoxy group (COOC2H,) by propionoxy (OCOC,H,) is one of the known methods.2-6~*~11-13~ 16* 101 201 23-26 Another one is the replacement of N-CH, by selected N-substituents such as aralkyl,2*43 6, 179 18, 2 2 propiophen~ne,~~ lo large alkyl groups,2l morpholinoethy1,lt 73 l4 alkoxyor phenoxyalkyl.s* l6 The available evidence, on the other hand, seems to indicate that activity usually decreases when carbethoxy (COOC,H,) is replaced by carbomethoxy (COOCH,), or when propionoxy (OCOC,H,) is replaced by acetoxy (OCOCH3).2i 4 9 6* 12* 2 3 9 z4* 26 (Also unpublished results.) The purpose of this study is to present new experimental evidence in this field and to arrive at certain tentative generalizations concerning the structure-activity problem of compounds (11) related to pethidine.