Sulfur-containing isoquinoline derivatives, process for the preparation thereof and pharmaceutical compositions containing them

Abstract

Isoquinolines are disclosed of the formula (I) ##STR1## wherein R independently represents hydrogen, hydroxyl or alkoxy having 1 to 4 carbon atoms, R 1 is hydrogen, alkyl having 1 to 4 carbon atoms and optionally substituted with phenyl, phenyl optionally substituted with one or more halogen or alkoxy group, cyano or carbomoyl, R 2 is phenyl optionally substituted with one or more halogen, alkoxy or carboxyl, or a group of the general formula A ##STR2## wherein R 3 is hydrogen, a straight or branched chained alkyl having 1 to 4 carbon atoms or phenyl, m and n independently represent 0, 1 or 2, with the proviso that m+n is at least 1, R 4 is hydrogen, phenyl, hydroxyl, acyloxy, carboxyl, alkoxycarbonyl having 1 to 6 carbon atoms, carbamoyl, carbazoyl or dialkylamino containing 1 to 6 carbon atoms in the alkyl moiety, or R 2 is a straight or branched chained alkylene group having 1 to 6 carbon atoms, and the dotted line stands for a further carbon-carbon bond or hydrogen atoms in the 3- and 4-positions of the ring, or salts thereof. The new compounds are potent diuretic agents.

We claim: 
     
       1. A compound of the formula (I) ##STR10## wherein R is hydrogen, hydroxyl or C 1  to C 4  alkoxy; R 1  is hydrogen, C 1  to C 4  alkyl, phenyl-C 1  to C 4  alkyl, phenyl, halo-phenyl or C 1  to C 4  alkoxy-phenyl .Iadd.or R 1  is cyano or carbamoyl.Iaddend.;   R 2  is allyl, phenyl, halo-phenyl, C 1  to C 4  alkoxy-phenyl, carboxy-phenyl, or a group of the formula (A): ##STR11## wherein R 3  is hydrogen, C 1  to C 4  straight or branched chain alkyl, or phenyl;   m and n are each 0, 1 or 2 and m+n is at least 1; and   R 4  is hydrogen, phenyl, hydroxyl, acetoxy, carboxyl, C 1  to C 6  alkoxycarbonyl, carbamoyl, carbazoyl, or dialkylamino having 1 to 6 carbon atoms in each alkyl moiety; and   the dotted line stands for a further carbon-carbon bond or a hydrogen atom.[.s.]. in each of the 3- and 4-positions of the ring, or a pharmaceutically effective salt thereof.   
     
     
       2. α-(Ethyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       3. α-(Allyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       4. α-(2-Hydroxy-ethyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       5. α-(3-Hydroxy-propyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       6. α-(Carboxy-methyl-mercapto)-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       7. α-(Carboxy-methyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       8. α-(2-Carboxy-ethyl-mercapto)-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       9. .alpha.-(2-Carboxy-ethyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       10. α-(2-Carboxy-ethyl-mercapto)-6,7-diethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       11. .alpha.-(1-Carboxy-ethyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       12. α-(2-Diethylamino-ethyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitril-hydrochloride as defined in claim 1. 
     
     
       13. α-(2-Dimethylamino-ethyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitril-hydrochloride as defined in claim 1. 
     
     
       14. α-(2-Carboxy-phenyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       15. .alpha.-(Ethoxycarbonyl-methyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       16. α-(2-Butoxycarbonyl-methyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       17. α-[2-(2-Butoxycarbonyl)-ethyl-mercapto]-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       18. α-[2-(3-Methyl-1-butoxycarbonyl)-ethyl-mercapto]-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       19. α-(Carbazoyl-methyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       20. α-(2-Acetoxy-ethyl-mercapto)-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       21. α-Phenyl-mercapto-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       22. .alpha.-Phenyl-mercapto-6,7-diethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       23. α-(Carboxamido-methyl)-mercapto-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       24. α-(1-Ethoxycarbonyl-1-ethyl)-mercapto-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       25. α-(4-Chlorophenyl)-mercapto-6,7-dimethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       26. α-(4-Chlorophenyl)-mercapto-6,7-diethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       27. α-(2-Hydroxyethyl)-mercapto-6,7-diethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1. 
     
     
       28. α-(3-Hydroxy-propyl-mercapto)-6,7-diethoxy-3,4-dihydro-1-isoquinolyl-acetonitrile as defined in claim 1.