4-,5-,6-and 7-indole derivatives useful for the treatment of CNS disorders

A compound selected from the group consisting of

• 5-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(5-indolyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-phenylpiperazin-1-yl]methyl]-1H-indole;
• 6-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-indole;
• 6-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(2-chlorophenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(2,3-dichlorophenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(3,4-dichlorophenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(4-bromophenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(4-iodophenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(4-hydroxyphenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(3-methoxyphenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(3,4-dimethoxyphenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(4-methylphenyl)piperazin-1-yl]methyl]-1H-indole;
• 6-[[4-(4-methylphenyl)piperazin-1-yl]methyl]-1H-indole;
• 5-[[4-(4-Chlorophenyl)piperazin-1-yl]methyl]-1-methyl-1H-indole;
• 6-[[4-(4-Chlorophenyl)piperazin-1-yl]methyl]-1-methyl-1H-indole;
• and
• 5-[[(4-Benzo[1,3]dioxol-5-yl-)piperazin-1-yl]methyl]-1H-indole;
• or a pharmaceutically acceptable salt thereof.

A method of treating the positive symptoms of schizophrenia comprising administering a therapeutically effective amount of a compound of formula I or pharmaceutically acceptable salt thereof, wherein formula I is

• wherein R is phenyl or phenyl substituted one or more times with a substituent selected from halogen, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C1-6-alkoxy, C1-6-alkylthio, hydroxy, hydroxy-C1-6-alkyl, trifluoromethyl, trifluoromethylsulfonyl, C1-6-alkylsulfonyl, amino, C1-6-alkylamino, di-(C1-6-alkyl)amino, acyl, aminocarbonyl and a methylene dioxy group;
• X is N;
• R1 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, aryl, aryl-C1-6-alkyl, acyl, thioacyl, C1-6-alkylsulfonyl, trifluoromethylsulfonyl or arylsulfonyl;
• and
• R2 and R3 are independently selected from hydrogen, halogen, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C1-6-alkoxy, C1-6-alkylthio, hydroxy, hydroxy-C1-6-alkyl, trifluoromethyl, trifluoromethylsulfonyl, C1-6-alkylsulfonyl, amino, C1-6-alkylamino, di-(C1-6-alkyl)amino, acyl and aminocarbonyl.

A method of treating psychoses comprising administering a therapeutically effective amount of a compound of formula I or pharmaceutically acceptable salt thereof, wherein formula I is:

• wherein
• R is phenyl or phenyl substituted one or more times with a substituent selected from halogen, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C1-6-alkoxy, C1-6-alkylthio, hydroxy, hydroxy-C1-6-alkyl, trifluoromethyl, trifluoromethylsulfonyl, C1-6-alkylsulfonyl, amino, C1-6-alkylamino, di-(C1-6-alkyl)amino, acyl, aminocarbonyl and a methylene dioxy group;
• X is N;
• R1 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, aryl, aryl-C1-6-alkyl, acyl, thioacyl, C1-6-alkylsulfonyl, trifluoromethylsulfonyl or arylsulfonyl;
• and
• R2 and R3 are independently selected from hydrogen, halogen, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C1-6-alkoxy, C1-6-alkylthio, hydroxy, hydroxy-C1-6-alkyl, trifluoromethyl, trifluoromethylsulfonyl, C1-6-alkylsulfonyl, amino, C1-6-alkylamino, di-(C1-6-alkyl)amino, acyl and aminocarbonyl.

A 4-, 5-, 6- or 7-methylene substituted indolyl derivative of formula I

• wherein
• R is indole or indole substituted with one or more substituent selected independently from the group consisting of halogen, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C1-6-alkoxy, C1-6-alkylthio, hydroxy, hydroxy-C1-6-alkyl, trifluoromethyl, trifluoromethylsulfonyl, C1-6-alkylsulfonyl, amino, C1-6-alkylamino, di-(C1-6-alkyl)amino, acyl, aminocarbonyl and methylene dioxy group;
• X is N;
• R1 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, aryl, aryl-C1-6-alkyl, acyl, thioacyl, C1-6-alkylsulfonyl, trifluoromethylsulfonyl or arylsulfonyl;
• and
• R2 and R3 are independently selected from hydrogen, halogen, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C1-6-alkoxy, C1-6-alkylthio, hydroxy, hydroxy-C1-6-alkyl, trifluoromethyl, trifluoromethylsulfonyl, C1-6-alkylsulfonyl, amino, C1-6-alkylamino, di-(C1-6-alkyl)amino, acyl and aminocarbonyl;
• or a pharmaceutically acceptable salt thereof.