1-Indolylalkyl-4-(substituted-pyridinyl)piperazines

Claim 2

A compound of Formula I and the pharmaceutically acceptable acid addition salts thereof, wherein R' and R 2 are independently selected from lower, meaning C 1-4 , alkyl or hydrogen; R 3 , R 4 , R 8 and R 9 are independently selected from hydrogen, lower alkyl, lower alkoxy, carbamide, halogen, trifluoromethyl and thio-lower alkyl, with the proviso that R 8 and R 9 cannot both be hydrogen at the same time; A is a C 5-7 cycloalkanyl or cycloalkenyl ring, or A is wherein n is an integer from 1 to 3 and R 5 is the same as R 1 ; and R 6 and R 7 are independently selected from hydrogen, methyl or R 6 and R 7 can be taken together as a methylene bridge.

Claim 3

The compound of claim 1 wherein A is a C 5-7 cycloalkanyl or cycloalkenyl ring.

Claim 4

The compound of claim 1 wherein A is

Claim 5

The compound of claim 1 wherein R 6 and R 7 are selected from hydrogen or methyl.

Claim 6

The compound of claim 1 wherein R 6 and R 7 are taken together as a methylene bridge.

Claim 7

The compounds of claim 1: 1-[2-(1 H-indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[2-(1H-indol-3-yl)ethyl]-4-(3-trifluoromethyl-2-pyridinyl)piperazine ; 1-[2-(1H-indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)-2-methylpiperazine ; 1-[2-(1 H-mdol-3-yl)ethyl]-5-(3-methoxy-2-pyridinyl)-(1 R,4R)-2,5-diazabicyclo[2.2.1 ]heptane ; 1-[2-(1H-indol-3-yl)ethyl]-4-(6-chloro-2-pyridinyl)piperazine ; 1-[2-(1H-indol-3-yl)ethyl]-4-(6-methoxy-2-pyridinyl)piperazine ; 1-[2-(1 H-indol-3-yl)ethyl]-5-(3-methoxy-2-pyridinyl)-(1 S,4S)-2,5-diazabicyclo[2.2.1 ]heptane ; 1-[3-(1 H-indol-3-yl)propyl]-4-(3-methoxy-2-pyridinyl)piperazme ; 1-[3-(1 H-indol-3-yl)propyl]-4-(6-chloro-2-pyridinyl)piperazine ; 1-[4-(1H-indol-3-yl)butyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[2-(1H-indol-3-yl)ethyl]-4-(6-trifluoromethyl-2-pyridinyl)piperazine , 2-[2-(1 H-indol-3-yl)ethyl]-5-(6-chloro-2-pyridinyl)-(1 S,4S)-2,5-diazabicyclo[2.2.1 ] heptane ; 2-[2-(1 H-indol-3-yl)ethyl]-5-(6-chloro-2-pyridinyl)-(1 R,4R)-2,5-diazabicyclo[2.2.1 ] heptane ; 1-[3-(1H-indol-3-yl)propyl]-4-(6-trifluoromethyl-2-pyridinyl)piperazine ; 1-[4-(1 H-indol-3-yl)butyl]-4-(6-chloro-2-pyridinyl)piperazine ; 1-[4-(1 H-indol-3-yl)butyl]-4-(6-trifluoromethyl-2-pyridinyl)piperazine ; 1-[3-(1 H-indol-3-yl)propyl]-4-(4-trifluoromethyl-2-pyridinyl)piperazine; 2-[3-(1 H-indol-3-yl)propyl]-5-(3-methoxy-2-pyridinyl)-(1 S,4S)-2,5-diazabicyclo[2.2.1 ] heptane ; 2-[3-(1 H-indol-3-yl)propyl]-5-(3-methoxy-2-pyridinyl)-(1 R,4R)-2,5-diazabicyclo[2.2.1 heptane; 1-[2-(1 H-indol-3-yl)ethyl]-4-(6-chloro-2-pyridinyl)-2-methylpiperazine ; 1-[2-(1H-indol-3-yl)ethyl]-4-(4-trifluoromethyl-2-pyridinyl)piperazine ; 1-[2-(5-methoxy-1H-indol-3-yl)-ethyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[2-(5-fluoro-1H-indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[2-(5-methoxy-1H-indol-3-yl)ethyl]-4-(6-chloro-2-pyridinyl)piperazine ; 1-[2-(5-fluoro-1H-indol-3-yl)ethyl]-4-(6-chloro-2-pyridinyl)piperazine ; 1-[2-(1H-indol-3-yl)-ethyl]-4-(3-chloro-2-pyridinyl)piperazine ; 1-[2-(5-fluoro-1H-indol-3-yl)ethyl]-4-(6-trifluoromethyl-2-pyridinyl)piperazine ; 1-[2-(5-methoxy-1 H-indol-3-yl)ethyl]-4-(6-trifluoromethyl-2-pyridinyl)piperazine ; 3-[4-[4-(6-chloro-2-pyridinyl)-1-piperazinyl]-1-cyclohexen-1-yl]-5-methoxyindole ; 3-[4-[4-(6-chbro-2-pyridinyl)-1 -piperazinyl]-1-cyclohexen-1-yl]-1 H-indole; 3-[4-[4-(6-chloro-2-pyridinyl)-1-piperazinyl]-1-cyclohexen-1-yl]-1H-indole-5-carboxamide ; 1-[2-(N-methyl-1H-indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[2-(5,6-dimeth ox y-1 H-indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[2-(5,6-dimethoxy-1 H -indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[3-(N-methyl-1H-ind o l-3-yl)propyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[3-( N -methyl-1 H -indol-3-yl)propyl]-4-(6-chloro-2-pyridinyl)piperazine ; 1-[3-(5-fluoro-1H-indol-3-yt)propyl]-4-(6-chloro-2-pyridinyl)piperazine ; 1-[3-(5-fluoro-1 H -indol-3-yl)propyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[2-(1H-indol-3 - yl)ethyl]-4-(5-chloro-2-pyridinyl)piperazine ; 1-[2-[N-methyl-1 H-indol-3-yl)ethyl]-4-(6-chloro-2-pyridinyl)piperazine; 1-[2-( 5 -chloro-1H - indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)piperazine ; 1-[2-(5-chloro-1 H -indol-3-yl)ethyl]-4-(6-chloro-2-pyridinyl)piperazine ; 1-[2-(5-chloro-1 H -indol-3-yl)ethyl]-4-(6-trifluoromethyl-2-pyridinyl)piperazine ; 1-[2-(1H-indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)-2-methyl-piperazine ; 4-(6-chloro-2-pyridinyl)-1-[2-(6-methoxy-1 H-indol-3-yl)ethyl]-piperazine ; 1-[2-6-methoxy-1H-indol-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)-piperazine ; 1-[3-(1H-indol-3-yl)-3-methylpropyl]-4-(6-chloro-2-pyridinyl)-piperazine ; 1-[3-(1 H-indol-3-yl)-3-methylpropyl]-4-(3-methoxy-2-pyridinyl)-piperazine ; 1-[2-(5,6-dimethoxy-1 H-indol-3-yl)ethyl]-4-(6-trifluoromethyl-2-pyridinyl)piperazine ; 3-(4-[4-(6-chloro-2-pyridinyl)-1-piperazinyl]-1-cyclohexen-1-yl]-5-fluoro-1H-indole ; 4-(5-chloro-3-methoxy-2-pyridinyl)-1-[3-(1 H-indol-3-yl)propyl]-piperazine hydrochloride ; 4-(6-chloro-2-pyridinyl)-1-[3-(1 H-indol-3-yl)propyl]-2-methyl-piperazine ;

Claim 8

A process for preparing the compounds of claims 1 to 6 characterized in that A) a compound of the general formula II: is reacted with a compound of the general formula R S- M, wherein M represents a metalloid species, to obtain a compound of the general formula VI: a compound of the general formula VI is reacted with a reagent Y-X, wherein X is a leaving group and Y is a hydrogen atom or a counter ion, to obtain a compound of the general formula V: a compound of the general formula V is reacted with a compound of the general formula III: to obtain a compound of the general formula la B) a compound of the general formula II or an active equivalent thereof is reacted with a compound of the general formula III to obtain a compound of the general formula IV: a compound of the general formula IV is reacted with R 5- M, wherein R 5 is defined as above, to obtain a compound of the general formula la, or C) a compound of the general formula III is reductively alkylated with a compound of the general formula X wherein f and g are integers from 0 to 5 with the proviso that f + g must be equal to 3, 4 or 5, to give a compound of the general formula IX: a compound of the general formula IX is deprotected to produce a compound of the general formula VIII a compound of the general formula VIII is condensed with a compound of the general formula VII to give a compound of the general formula Ib and, if desired, a compound of the general formula Ib is reduced to a compound of the general formula Ic: or D) a compound of the general formula VIII is condensed with a compound of the general formula X to give a compound of the general formula XII a compound of the general formula XII is reduced and deketalized to a compound of the general formula XI: a compound of the general formula XI is condensed with a compound of the general formula III to give a compound of the general formula lc, the symbols R' through R 9 and n being defined as in claim 1, and if desired, a so obtained compound of formula I is converted to a pharmaceutically acceptable acid addition salt thereof.

Claim 9

A pharmaceutical composition comprising at least one compound of claim 1 to 6, optionally together with a pharmaceutical carrier and/or adjuvant.

Claim 10

A pharmaceutical composition of claim 8 in dosage unit form suitable for systemic administration to a mammalian host comprising a pharmaceutical carrier and from about 1 to 500 mg of at least one compound of claims 1 to 6.

Claim 11

A process for preparing the pharmaceutical compositions of claims 8 or 9 which comprises providing at least one compound of claims 1 to 6 in a form suitable for systemic administration, preferably in dosage unit form, and optionally incorporated into a pharmaceutical carrier.

Claim 12

The use of at least one compound of claims 1 to 6 for preparing a pharmaceutical composition for ameliorating an undesirable state of depression in a mammal.