3-(Omega-substituted alkyl)-indoles

Abstract

3-(OMEGA-SUBSTITUTED ALKYL)-INDOLES ARE DISCLOSED WHICH ARE USEFUL IN AMELIORATING THE TREMORS OF Parkinsonism. The compounds are prepared by metal hydride reduction of the precursor indole glyoxyloyl compounds.

What is claimed and desired to be secured by U.S. Letters Patents is: 
     
       1. A member selected from the group consisting of compounds having the formula: ##SPC2## and pharmaceutically acceptable acid addition salts thereof, wherein;   R 1  is selected from the group consisting of hydrogen and lower alkyl;   R 1  is selected from the group consisting of hydrogen, lower alkyl and phenyl;   R 2  is selected from the group consisting of hydrogen, fluoro, chloro, bromo, lower-alkyl and lower-alkoxy; and   R 4  is selected from the group consisting of benzyl, phenyl and mono-substituted phenyl in which the substituent is selected from the group consisting of fluoro, chloro, bromo, lower-alkyl and trifluoromethyl.   
     
     
       2. A compound selected from the group consisting of a free base and its pharmaceutically acceptable acid addition and quaternary ammonium salts, the free base having the structural formula: ##SPC3## wherein:   R is selected from the group consisting of hydrogen, lower-alkyl, lower-alkanoyl, benzoyl, benzyl, and cycloalkyl containing three to nine carbon atoms inclusive;   R 1  is selected from the group consisting of hydrogen, lower-alkyl, and phenyl;   R 2  is selected from the group consisting of hydrogen, halogen of atomic weight less than 80, trifluoromethyl, hydroxyl, lower-alkyl, lower-alkoxy, and benzyloxy;   n is an integer from zero to four inclusive;   Sub is a member selected from the group consisting of ##SPC4## wherein;     A is selected from the group consisting of hydrogen, 3,4,5-trimethoxybenzoyl, 3,4,5-trimethoxyphenylcarbamoyl, p-methoxycarbamyol, and 2-methoxyphenyl;   R 5  is a member selected from the group consisting of benzyl, phenyl and monosubstituted phenyl in which the substituent is selected from the group consisting of lower-alkyl, trifluoromethyl, and halogen of atomic weight less than 80, and   R 6  is selected from the group consisting of trifluoromethyl and halogen of atomic weight less than 80.   
     
     
       3. A compound of claim 2 which is 3-[2-(3-hydroxypyrrolidinyl)ethyl]indole. 
     
     
       4. A compound of claim 2 which is 2-methyl-3-{2-[3-(3,4,5-trimethyoxybenzoyloxy)pyrrolidinyl]ethyl]}indole. 
     
     
       5. A compound of claim 2 which is 2-methyl-3-[2-(3-hydroxypyrrolidinyl)ethyl]indole hydrochloride. 
     
     
       6. A compound of claim 2 which is 3-{2-[3-(3,4,5-trimethoxybenzoyloxy)pyrrolidinyl]ethylene]}indole. 
     
     
       7. A compound of claim 2 which is 3-{2-[3-(3,4,5-trimethoxyphenylcarbamoyloxy)pyrrolidinyl] ethyl]}indole. 
     
     
       8. A compound of claim 2 which is 5,6-dimethoxy-3-[2-(3-hydroxypyrrolidinyl)ethyl]indole hydrochloride. 
     
     
       9. A compound of claim 2 which is 3-{2-[3-(o-methoxyphenoxy)pyrrolidinyl]ethyl]}indole hydrochloride. 
     
     
       10. A compound of claim 2 which is 3-{2-[3-(4-methoxyphenylcarbamoyloxy)pyrrolidinyl]ethyl]}indole. 
     
     
       11. A compound of claim 2 which is 3-[2-(4-hydroxy-4-phenylpiperidinyl)ethyl]indole. 
     
     
       12. .[.A compound of claim 2 which is.]. 3-[2-(4-phenyl-3,4-dehydropiperidinyl)ethyl]indole. 
     
     
       13. .[.A compound of claim 2 which is.]. 2-methyl-3[2-(4-phenyl-3,4-dehydropiperidinyl)ethyl]indole. 
     
     
       14. .[.A compound of claim 2 which is.]. 2-methyl-5,6-dimethoxy-3-[2-(4-phenyl-3,4-dehydropiperidinyl)ethyl]indole. 
     
     
       15. .[.A compound of claim 2 which is.]. 5-chloro-3[2-(4-phenyl-3,4-dehydropiperidinyl)ethyl]indole. 
     
     
       16. A compound of claim 2 which is 5-benzyloxy-3-[2-(4-hydroxy-4-phenylpiperidinyl)ethyl]indole hydrochloride. 
     
     
       17. A compound of claim 2 which is 5-hydroxy-3-[2-(4-hydroxy-4-phenylpiperidinyl)ethyl]indole. 
     
     
       18. .[.A compound of claim 2 which is.]. 5,6-dimethoxy-3-[2-(4-phenyl-3,4-dehydropiperidinyl)ethyl]indole. 
     
     
       19. .[.A compound of claim 2 which is.]. 2,5-dimethyl-3-[2-(4-phenyl-3,4-dehydropiperidinyl)ethyl]indole. 
     
     
       20. A compound of claim 2 which is 3-[2-(4-hydroxy-4-m-trifluoromethylphenylpiperidinyl)ethyl]indole hydrochloride. 
     
     
       21. A compound of claim 2 which is 3-[2-(4-m-trifluoromethylphenyl-3,4-dehydropiperidinyl)ethyl]indole. 
     
     
       22. .[.A compound of claim 2 which is.]. 1-methyl-3-[2-(4-phenyl-3,4-dehydropiperidinyl)ethyl]indol 
     
     
       23. A compound of claim 2 which is 3-[2-(4-p-fluorophenyl-3,4-dehydropiperidinyl)ethyl]indole. 
     
     
       24. A compound selected from the group having the formula: ##SPC5## wherein;   R is selected from the group consisting of hydrogen, lower-alkyl, benzyl, and cycloalkyl containing three to nine carbon atoms inclusive;   R 1  is selected from the group consisting of hydrogen, lower-alkyl and phenyl;   R 2  is selected from the group consisting of hydrogen, halogen of atomic weight less than 80, trifluoromethyl, hydroxyl, lower-alkyl, lower-alkoxy and benzyloxy;   n is an integer from zero to four inclusive; Sub is a member selected from the group consisting of ##SPC6##   wherein;     R 5  is a member selected from the group consisting of benzyl, phenyl and monosubstituted phenyl in which the substituent is selected from the group consisting of lower-alkyl, trifluoromethyl, and halogen of atomic weight less than 80, and   R 6  is selected from the group consisting of trifluoromethyl and halogen of atomic weight less than 80.