IL40457A - Esters and salts of vincaminic and apovincaminic acid their preparation and pharmaceutical compositions containing them - Google Patents

Abstract

A process for the preparation of pharmaceutically active eburnamine-type alkaloid esters of the general formula (I) of the accompanying drawings, wherein X"-".y represents a =C=CH or CCH^group, and OH R repre eivsa CV6 alko^ycarbonyt orC-s alkenylo^ycarbo-ny! group optionally mbsiiiuted wi h ahydro>.y group or w;tha halogen a om or salt- orrjua ernary dertva";ves ihereof in which a salt of apovincaniinic acid or of vincaminic acid is reacted with a C,-o alkyl halidc and C^o alkenyt hafide, bodi substituted by halogen or hydroxy group, and, if desired, the thus-obtained compounds of the general formula (1) are converted into their acid addition salts or quaternary salts by reacting them wjt(i a mineral or organic acid or with an alkyl halide, respectively. [IN138719]

Claims (2)

1. -22- 40457/3 CLAIMS : l) Eburnamine-type alkaloid esters of the general formula (I) R represents an unsubntitutod olkoxycarbonyl group containing 2 to 6 cnrbon atoms in the n.lkyl rnoy ty; a C2-6 alkoxycarbonyl group substituted with a hydroxy group or with a halogen atom, an alkenyloxycarbonyl group or a phenylalkoxycarbony1 group, or their salts or quaternary derivatives.

2. ) Vincaminic acid ethyl ester* 5) Vincaminic acid allyl ester. ) Vincaminio acid hydroxyethyl ester. 5) Vincaminic acid chloroethyl ester. 6) Vincaminic aoid benzyl ester. 7) Apovincaminic acid ethyl eeter in any of ite optically aotive isomers. 8) (-) -Apovincaminic acid ethyl ester. 9) Apovinoaminic aoid ethyl ester methoiodide. 10) Apovinoaminio aoid butyl ester* 40457/4 2 to 6 carbon atoms in the alkyl moiety; a C2_g alkoxycarbonyl group substituted with a hydroxy group or with a halogen atom, an alkenyloxycarbonyl group or a phenylalkoxycarbonyl group, or salts or quaternary derivatives thereof, in which a) a salt of apovincaminic acid or of vincaminic acid is reacted with a C2_g alkyl halide, C2_g alkyl halide substituted with a halogen or a hydroxy group, alkenyl halide, phenylalkyl halide or with the corresponding sulfates, or b) apovincaminic acid or vincaminic acid is esterified with a corresponding alcohol of the general formula R^-OH, wherein R1 represents an alkyl group containing 2 to 6 carbon atoms , an alkyl group substituted by a halogen atom or a hydroxy group containing 2 to 6 carbon atoms , an alkenyl group or a phenylalkyl group in the presence of one or more catalysts, preferably in the presence of mineral or organic acids or aliphatic or aromatic sulfonic acids, or c) apovincamine or vincamine is reacted with a corresponding alkali metal alcoholate, or d) apovincaminic or vincaminic acid, or, respectively, apovincamine or vincamine is reacted with a corresponding -24- 40457/2 and, if desired, the thus-obtained compounds of the general formula (ί) are converted into their acid addition salts or quaternary salts by reacting them with a mineral or organic acid or with an alk l halide, respectively, finally, if desired, the obtained salts are converted to the free basee, and the free bases are converted into other salts thereof, 12) A process as claimed in claim li1, Method a), in which the reaction is carried out in the presenoe of a solvent, preferably in the presence of ethanol and/or of an excess of the esterifying agent, at the boiling point of the mixture. 13) A process as claimed in claim 11, Method b , in which the reaction is carried out in the presence of a solvent, preferably in benzene, toluene and/or in the excess of the appropriate alcohol or in the mixture of said solvents, at the boiling point of the mixture. 14) A process as claimed in claim 11;, Method . c), in which the reaction is carried out- preferably in an apolar solvent or solvent mixture at the boiling point of the reaction mixture, and preferably sodium alcoholate is used as reagent. 15) !A procesB as claimed in claim 11, Method d), in which the reaction ie carried out in a solvent or solvent mixture^ preferably in an alcohol and/or in the excess of the ester reagent, at the boiling point of the reaction mixture* -25- 40457/2 16) A compound as claimed in any of claims 1 to 10, with special reference to the Examples. 17) A process as claimed in any of claims 11 to 15, with special reference to the Examples. 18) Pharmaceutical products containing at least one compound o the general formula (I) in claim 1 or a salt or quaternary derivative thereof, optionally together with other therapuetically active agent (s) and with a carrier or diluent. 19) A process for the preparation of pharmaceutical products, in which one or more compound(s) of the general formula (I) in claim 1, and/or the corresponding salts and/or the corresponding quaternary derivatives are converted alone, or together with other therapeutically active agent (s) , e.g. combined with reserpine, into pharmaceutical products, using carriers and auxiliary substances usable in the pharmaceutical industry.