GB1123768A - New thebaine and oripavine derivatives and processes for preparing the same - Google Patents

Abstract

Novel compounds of general Formula I <FORM:1123768/C2/1> wherein R1 is H, -CH2-C(R5)=C(R6) R7 wherein R5, R6 and R7 are each, hydrogen, methyl or halogen, a propargyl group, a phenethyl group or a cycloalkylmethyl group; R2 is H, C1- 4 alkyl, or acyl; R3 is H or acyl and R4 is hydrogen or C1- 4 alkyl and pharmaceutically acceptable acid addition salts thereof are prepared by (a) hydrogenation of the corresponding thebaine or oripavine of general formula <FORM:1123768/C2/2> such that only the heterocyclic ring oxygen atom is affected e.g. by metallic sodium in ammonia or (b) by N-substitution of a compound of general Formula I in which R1 is H with a reactant capable of introducing the desired R1 substituent, followed by acylation when necessary. Intermediates isolated are N-cyclobutylcarbonyl-D 6 -dihydronorthebaine from N-cyclobutylcarbonyldihydronorcodeinone (prepared from dihydronorcodeinone and cyclobutyl - carbonyl chloride) and dimethyl sulphate; N-cyclobutylmethyl - D 6 - dihydronorthebaine by reduction of the first-named intermediate; N-3,3-dimethylallyl - dihydronorcodeinone from 1 - bromo - 3 -methyl-2-butene and dihydronorcodeinone; and N - 3,3 - dimethylallyl - D 6 - dihydronorthebaine by methylation of the former named intermediate. Pharmaceutical compositions comprise the compounds I or their acceptable acid addition salts, for example the salicylate salts, mixed with carriers and/or diluents, and may be administered orally or parenterally. They possess analgesic activity and analgesic-antagonistic effects against morphine.