GB980898A - 6-methyl- and 1,6-dimethylergoline i derivatives - Google Patents

Abstract

The invention comprises 6-methyl- and 1,6-dimethyl - 8 - (a - hydroxy - alkyl) - ergoline-I derivatives of the general formula <FORM:0980898/C2/1> where R represents a hydrogen atom or a methyl radical, R1 represents a methyl or ethyl radical X represents <FORM:0980898/C2/2> and R11 represents a hydrogen atom or a radical of an aliphatic-, cycloaliphatic-, or aromatic-carboxylic acid having from 1 to 10 carbon atoms or of nicotinic acid, and the preparation thereof by reducing the corresponding 8-acyl-ergoline-I with a reducing agent capable of reducing a keto group to a secondary alcohol group to an 8 - (a - hydroxy - alkyl) - ergoline - I which, where necessary, is separated into the two C17 stereoisomers "Rectus" and "Sinister" and/or acylated with the anhydride or chloride of the appropriate carboxylic acid. The reduction of the 8-acyl-ergoline is preferably performed with lithium aluminium hydride in an inert solvent, e.g. an ether, generally at room temperature but preferably completed warm. The acylation may be carried out with the anhydride or chloride of the appropriate carboxylic acid, optionally in the presence of a tertiary amine. The stereoisomers may be separated prior to or after acylation by fractional crystallization or chromatography. 1,6-Dimethyl - 8 - (a - hydroxy - ethyl) - ergoline - I R (and S) N-ethylcarbamate are prepared by the reaction of 1,6 - dimethyl - 8 - (a - hydroxy-ethyl) -ergoline-I R (and S) with ethyl isocyanate in the presence of pyridine. 6 - Methyl - and 1,6 - dimethyl - 8 - acyl - ergolines-I may be prepared by reacting dihydrolysergamide and 1-methyl dihydrolysergamide with an alkyl magnesium bromide. Therapeutic compositions with oxytocic, antienteraminic, adrenolytic, hypotensive and sedative properties comprise compounds of the formula given above together with a therapeutically acceptable diluent or carrier.