Journal of Medicinal and Pharmaceutical Chemistry VOL. 2, No. 1 (1960)
CompoundsRelated to PethidineIV. New General Chemical Methods of Increasing the Analgesic Activity of Pethidine PAULA . J. JANSSEN, Research Laboratories Dr. 0.Janssen, Beerse (Turnhozlt), Belgium and
NATHAN B. EDDY,National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland
Introduction 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 16* 101201 23-26 Another one is the known methods.2-6~*~11-13~ replacement of N-CH, by selected N-substituents such as aralkyl,2*436,179 18, 2 2 propiophen~ne,~~ lo large alkyl groups,2l morpholinoethy1,lt l 4 alkoxy- or 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is replaced by carbomethoxy (COOCH,), or when propionoxy (OCOC,H,) is replaced by acetoxy (OCOCH3).2i 6*12* z4*26 (Also unpublished results.)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. 73
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