GB1069067A - Novel phenanthrene derivatives and the manufacture thereof - Google Patents

Abstract

Novel phenanthrene derivatives of formula <FORM:1069067/C2/1> wherein R1 represents hydrogen, a saturated or unsaturated aliphatic hydrocarbon group having 1-5 carbon atoms, or an acyl group, and R2 represents an alkyl group having 1-4 carbon atoms, and acid addition salts thereof, are prepared (a) by reducing the carbonyl group of a compound of formula <FORM:1069067/C2/2> wherein R1 has the significance above and R2 is absent, to the methylene group using an alkali-metal aluminium halide; (b) by reacting an amine of formula <FORM:1069067/C2/3> wherein R1 has the above meaning, with a halide of formula <FORM:1069067/C2/4> where R2 is as defined above and Hal is a halogen atom: and (c) by cyclising an isoquinoline compound of formula <FORM:1069067/C2/5> wherein R1 and R2 are as defined above, and one of the symbols R3 represents a hydroxyl group and the other a hydrogen atom, or where the symbols together represent a double bond, by heating in the presence of an acid and, when required, converting the product to an acid addition salt. Compounds of the second formula above are prepared by reacting a compound of the third formula above wherein R1 is as previously defined with a halide of pivalic acid in a solvent free from hydroxyl groups. Isoquinoline compounds of the fifth formula above are prepared from the corresponding octahydro-isoquinolines which are unsubstituted at the nitrogen atom either by reaction with the appropriate acid halide and subsequent reduction with lithium aluminium hydride or directly by reaction with the appropriate alkyl halide. (-) - 3 - Methoxy - N - pivaloyl - morphinan is prepared by reaction of the corresponding 3-hydroxy compound with dimethyl sulphate. (-) - 3 - Allyloxy - N - pivaloyl - morphinan is prepared by reaction of the corresponding 3-hydroxy compound with allyl bromide. The d-tartrate thereof is mentioned. (-) - 3 - Acetoxy - N - pivaloyl - morphinan hydrochloride is prepared by heating the corresponding 3-hydroxy compound with acetic anhydride.ALSO:Pharmaceutical compositions having analgesic and morphine antagonistic activity and which may be administered orally or parenterally in the form of tablets, dragees, suppositories, capsules, solutions, suspensions or emulsions, contain morphinan compounds of the formula <FORM:1069067/A5-A6/1> and/or acid addition salts thereof, wherein R1 represents hydrogen, a saturated or unsaturated aliphatic hydrocarbon group having 1-5 carbon atoms, or an acyl group derived from a lower alkane carbocylic acid, and R2 represents an alkyl group having 1-4 carbon atoms, as the active ingredient, and may also contain other therapeutically active substances and the usual pharmaceutical carriers.