GB1178187A - Bis(tetrahydroisoquinolines) and compositions thereof - Google Patents

Abstract

1,178,187. Alkylene bis - (1,2,3,4 - tetrahydroiso-quinolines). ENDO LABORATORIES Inc 2 Aug., 1967 [9 Aug., 1966], No. 35489/67 Heading C2C. Novel alkylene bis-(1,2,3,4-tetrahydro-iso quinolines) of formula wherein R 1 , R 2 , R 3 and R 4 are hydrogen or C 1 to C 6 alkyl, and R<SP>1</SP> 5 , R<SP>11</SP> 5 , R<SP>111</SP> 5 , R<SP>1</SP> 6 , R<SP>11</SP> 6 and R<SP>111</SP> 6 are hydrogen, alkyl, halogen, hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkenoxy, C 1 -C 6 alkynoxy, C 1 -C 6 acyloxy, aryloxy, phenyl C 1 -C 6 alkoxy, amino, C 1 -C 6 alkylamino, C 1 -C 6 acylamino, or nitro, with the proviso that R 5 (i.e. any of R<SP>1</SP> 5 , R<SP>11</SP> 5 and R<SP>111</SP> 5 ) and R 6 (i.e. any of R<SP>1</SP> 6 , R<SP>11</SP> 6 and R<SP>111</SP> 6 ) are not simultaneously hydroxyl groups, and two substituents on one or both aromatic rings may be linked to form C-C 4 alkylenedioxy, and "alk" is a straight or branched C 1 -C 15 alkylene group, are prepared by dehydration of an appropriately substituted alkylene bis-(phenethylamide) to effect cyclization to an alkylene bis-(3,4-dihydro-isoquinoline), which is then reduced to the corresponding alkylene bis- (1,2,3,4 - tetrahydro - isoquinoline). The bis-(phenethylamide) starting material may be produced by reacting a phenylethylamine with a dicarboxyalkane. The hydrochloride salts of 1,1<SP>1</SP>-tetramethylenebis- and 1,1<SP>1</SP> - hexamethylenebis - (1,2,3,4 - tetrahydro-iso-quinoline) are separated into two isomers by fractional crystallization. 1,1<SP>1</SP>-Tetramethylenebis - (1,2,3,4 - tetrahydro - 6,7 - dimethoxy-iso-quinoline) is separated into isomeric forms via the tartrate salt, the various isomers then being converted into other salts. Pharmaceutical compositions having fibrinolytic activity, comprise the inventive compounds or their salts together with a pharmaceutically acceptable carrier.