Verfahren zur Herstellung von die beta-Rezeptoren des Sympaticus hemmenden Verbindungen

• Main Author: JOSEPH MCLOUGHLIN,BERNARD
• Format: Patent
• Language: German
• Published: 24.07.1969
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention comprises compounds of general formula <FORM:0990061/C2/1> wherein R is halogen, X and Y are alkyl or alkoxy radicals (1-6 C) or one may be hydrogen, R1 is hydrogen or alkyl (1-6 C), and R2 is alkyl (2-10 C) optionally substituted by a hydroxy or phenyl radical; and their pharmaceutically acceptable acid addition salts; and their preparation by (1) reacting a compound RXY-Ph-(ethylene oxide) or RXY-Ph-CHOHCH2Z, where Z is halogen, or mixtures thereof, with an amine HNR1R2, (2) reducing a compound RXY-Ph-COCH2NR1R2 or a salt thereof, (3) reacting a compound RXY-Ph-COCH =NOH or RXY-Ph-BCH2NH2 where B is CO or CHOH, under reducing conditions with a compound R3R4CO, where R3 is hydrogen or alkyl and R4 is alkyl optionally substituted by hydroxy or phenyl, or (4) reacting under reducing conditions an amine HNR1R2 or a salt thereof with a compound RXY-Ph-COR5, where R5 is CHO or CH(OR6)OR7, R6 and R7 being hydrogen or alkyl. Glyoxals RXY-Ph-CO-CHO are obtained by selenium dioxide oxidation of acetophenones. Compounds RXY-Ph-(ethylene oxide and RXY-Ph-CHOHCH2Z are obtained by reduction of phenacyl halides with, e.g. sodium borohydride. 2 - Chloro - 4 - methylphenyl hydroxyiminomethyl ketone is obtained from the substituted acetophenone and amyl nitrite. 2 - Chloro - 4 - methylphenyl isopropylmethylaminomethyl ketone is obtained from the substituted phenacyl bromide and N-methylisopropylamine. 2 - Chloro - 4 - ethoxy - acetophenone is obtained from 3-chlorophenetole and acetyl chloride by Friedel-Crafts reaction. Pharmaceutical compositions comprise compounds I and salts of the invention with diluents or carriers. Oral and parenteral administration of tablets, capsules, powders, solutions, suspensions and emulsions is mentioned. The compounds have b -adrenergic blocking activity useful in coronary artery disease.