Benzoazacycloalkene

摘要

Novel compounds of formula wherein Ph is an o-phenylene radical which may be substituted by lower alkyl, lower alkoxy, methylenedioxy, halogeno, and/or trifluoromethyl, one of R1 and R2 is a phenyl radical which may be substituted by lower alkyl, lower alkoxy, methylenedioxy, halogeno and/or trifluoromethyl, and the other is hydrogen or lower alkyl, ""alk"" represents an alkylene group having 1-4 carbon atoms and contributing at most 3 carbon atoms to the ring, ""alk1"" represents an alkylene group having 1-7 carbon atoms and contributing 2-4 carbon atoms to the ring, and R5 is hydrogen or lower alkyl, and acid addition salts thereof may be prepared by reacting a nitrile of formula with a diamine of formula H2N-Alk1-NH2 i the presence of a small amount of carbon disulphide. In a resulting compound in which R5 = H the hydrogen may be replaced by lower alkyl. The nitrile starting material may be prepared by converting a corresponding 2-arylbenzocycloalkenone in which the carbonyl group is adjacent to the aryl portion, and the cyclo-alkenone ring has 5-7 ring members, into its homoaza compound by reacting it with hydrazoic acid according to Schmidt or by rearrangenging its hydroxy-imino derivative according to Beckmann, and reducing the cyclic amido compound formed, and heating the momoaza compound with formaldehyde or a reactive derivative thereof in the presence of hydrocyanic acid or a salt thereof, or with a a -halogenoacetonitrile. A 2-phenyl-1,2,3,4-tetrahydronaphthalen - 1 - one used as starting material in this process may be prepared by reacting benzaldehyde with acetophenone, heating the benzal-acetophenone, heating the benzal-acetophenone obtained in acetic acid with potassium cyanide, treating the resulting 2-phenyl - 4 - oxo - 4 - phenylbutyronitrile with concentrated sulphuric acid and methanol, hydrolysing the methyl-2-phenyl-4-oxo-4-phenylbutyrate, and reducing the free acid formed to give 2 - phenyl - 4 - phenylbutyric acid which is reacted with phosphorus pentachloride, or by reacting 4-phenylacetonitrile mixed with dimethylformamide, toluene and sodium hydride, with phenethylbromide, hydrolysing the 2-phenyl - 4 - phenyl - butyronitrile obtained and treating the resulting 2,4-diphenylbutyric acid with thionyl chloride. A 3-phenyl-1,2,3,4-tetrahydroquinoline may be prepared by reacting N-acetylglycine with benzaldehyde, sodium acetate and acetic anhydride, refluxing the 4-benzal - 2 - methyloxazolin - 5 - one obtained with water and acetone, refluxing the resulting a -acetylaminocinnamic acid with hydrochloric acid, reacting the 2-phenylpyruvic acid with isotin in concentrated hydrochloric acid, decarboxylating the 3 - phenylquinoline - 2,4 - dicarboxylic acid and hydrogenating 3-phenylquinoline. Therapeutic compositions having anti-fibrillatory properties, which may be administered enterally or parenterally, contain as active ingredient compounds of Formula I above.