3-(1-Substituted-4-piperazinyl)-1H-indazoles, a process for their preparation and their use as medicaments

Claim 2

A compound of the formula I wherein R 1 is hydrogen, lower alkyl, arylloweralkyl, acyl, cycloalkylloweralkylene, or phenylsulfonyl; and R 2 is hydrogen, lower alkyl, hydroxyloweralkyl of the formula -(loweralkylene)-OH, arylloweralkyl, acyl, cycloalkylloweralkylene, where Z is selected from hydrogen, halogen, loweralkoxy, CF 3 , N0 2 , and NH 2 ; where Z is as defined above; where Z is as defined above; where R 3 and R 4 are each independently hydrogen and loweralkyl; where Z is as defined above: where R and R are each independently hydrogen and loweralkyl; X is hydrogen, loweralkyl, hydroxyl, halogen, loweralkoxy, CF 3 , N0 2 and NH 2 ; n is an integer of 1 to 4, with the proviso that R 2 is not loweralkyl when R 1 is hydrogen or acyl and X is chloro; the pharmaceutically acceptable acid addition salts thereof; where applicable the geometric and optical isomers thereof and the racemic mixtures thereof.

Claim 3

A compound as defined in claim 1 wherein R 1 is hydrogen, lower alkyl, acyl or cycloalkyl-loweralkylene and R 2 is hydrogen, lower alkyl hydroxyloweralkyl, or a compound of the formulae where Z is halogen, X is hydrogen, loweralkoxy or halogen, and n is 1.

Claim 4

A compound as defined in claim 2 wherein R 1 is hydrogen, methyl, ethyl, acetyl, benzoyl or cyclopropylmethyl.

Claim 5

The compound as defined in claim 1 which is 3-(4-methyl-1-piperazinyl)-1 H-indazole or a pharmaceutically acceptable acid addition salt thereof.

Claim 6

The compound as defined in claim 1 which is 1-ethyl-3-(4-methyl-1-piperazinyl)-1H-indazole or a pharmaceutically acceptable acid addition salt thereof.

Claim 7

The compound as defined in claim 1 which is 3-(1-piperazinyl)-1H-indazole or a pharmaceutically acceptable acid addition salt thereof.

Claim 8

The compound as defined in claim 1 which is 8-[4-[1-(1 H-indazol-3-yl)-4-piperazinyl]butyl-8-azaspiro[4.5]-decane-7,9-dione or a pharmaceutically acceptable acid addition salt thereof.

Claim 9

The compound as defined in claim 1 which is 3-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-1H-indazole or a pharmaceutically acceptable acid addition salt thereof.

Claim 10

The compound as defined in claim 1 which is 3-[4-[3-(2-methylindole-3-yl)propyl]-1-piperazinyl)-1H-indazole or a pharmaceutically acceptable acid addition salt thereof.

Claim 11

The compound as defined in claim 1 which is 6-fluoro-3-[4-[3-(1,3-dihydro-2-oxo-2H-benzimidazole-1-yl)propyl]-1-piperazinyl]-1 H-indazole or a pharmaceutically acceptable acid addition salt thereof.

Claim 12

A pharmaceutical composition which comprises a compound as defined in claim 1 as the active ingredient and a suitable carrier therefor.

Claim 13

Use of a compound for the preparation of a medicament having analgesic and/or antipsychotic activity.

Claim 14

Use of a compound for the preparation of a medicament having analgesic and/or antipsychotic activity.

Claim 15

A process for the preparation of a compound as defined in claim 1, which comprises a) condensing a compound of the formula VIII wherein R 2 is loweralkyl and X and n are as defined, to form a compound of the formula I, wherein R 1 is phenylsulfonyl and R 2 is loweralkyl, b) optionally reacting a compound of the formula I as obtained in step a) above with a halocyanide to form a compound of the formula I wherein R 2 is CN, and reducing the compound obtained with a metal hydride to form a compound of the formula I, where X and n are as defined and R 1 and R 2 are both hydrogen, or c) optionally reacting a compound of the formula I as obtained in step a) above, with a strong base to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is loweralkyl, d) optionally reacting a compound of the formula I as obtained in step e) with a halocyanide to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is CN, and reducing the compound obtained with a metal hydride to form a compound of the formula I, wherein X and n are as defined and R 1 and R 2 are both hydrogen, e) optionally reacting a compound of the formula I, wherein X and n are as defined, and R 1 and R 2 are both hydrogen, with a compound of the formula R 2 Y, where Y is chloro or bromo and R 2 is hydroxyloweralkyl, loweralkyl, arylloweralkyl, cycloalkylloweralkylene or a radical of the formulae and to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is as defined above, f) optionally reacting a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is loweralkyl, with a compound of the formula where Hal is chloro or bromo and R 8 is loweralkyl or aryl, to form a compound of the formula I, wherein X and n are as defined, R 1 is the group R 8 CO and R 2 is loweralkyl, g) optionally reacting a compound of the formula I where X and n are as defined R 1 is hydrogen and R 2 is loweralkyl, with a compound of the formula R 1 Hal where Hal is chloro or bromo, and R 1 is loweralkyl, arylloweralkyl or cycloalkylloweralkyl to form a compound of the formula I, where X and n are as defined, R 1 is as defined above and R 2 is loweralkyl.

Claim 16

A process for the preparation of a compound of the formula I wherein R 1 is hydrogen, lower alkyl, arylloweralkyl, acyl, cycloalkylloweralkylene, or phenylsulfonyl; and R 2 is hydrogen, lower alkyl, hydroxyloweralkyl of the formula -(loweralkylene)-OH, arylloweralkyl, acyl, cycloalkylloweralkylene, where Z is selected from hydrogen, halogen, loweralkoxy, CF 3 , N0 2 , and NH 2 ; where Z is as defined above; where Z is as defined above; where R 3 and R 4 are each independently hydrogen and loweralkyl; where Z is as defined above; where R and R are each independently hydrogen and loweralkyl; X is hydrogen, loweralkyl, hydroxyl, halogen, loweralkoxy, CF 3 , N0 2 and NH 2 ; n is an integer of 1 to 4, with the proviso that R 2 is not loweralkyl when R, is hydrogen or acyl and X is chloro; the pharmaceutically acceptable acid addition salts thereof; where applicable the geometric and optical isomers thereof and the racemic mixtures thereof, which comprises a) condensing a compound of the formula VIII wherein R 2 is loweralkyl and X and n are as defined, to form a compound of the formula I, wherein R 1 is phenylsulfonyl and R 2 is loweralkyl, b) optionally reacting a compound of the formula I as obtained in step a) above with a halocyanide to form a compound of the formula I wherein R 2 is CN, and reducing the compound obtained with a metal hydride to form a compound of the formula I, where X and n are as defined and R 1 and R 2 are both hydrogen, or c) optionally reacting a compound of the formula I as obtained in step a) above, with a strong base to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is loweralkyl, d) optionally reacting a compound of the formula I as obtained in step c) with a halocyanide to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is CN, and reducing the compound obtained with a metal hydride to form a compound of the formula I, wherein X and n are as defined and R 1 and R 2 are both hydrogen, e) optionally reacting a compound of the formula I, wherein X and n are as defined, and R 1 and R 2 are both hydrogen, with a compound of the formula R 2 Y, where Y is chloro or bromo and R 2 is hydroxyloweralkyl, loweralkyl, arylloweralkyl, cycloalkylloweralkylene or a radical of the formulae and to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is as defined above, f) optionally reacting a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is loweralkyl, with a compound of the formula where Hal is chloro or bromo and R s is loweralkyl or aryl, to form a compound of the formula I, wherein X and n are as defined, R 1 is the group R 8 CO and R 2 is loweralkyl, g) optionally reacting a compound of the formula I where X and n are as defined, R 1 is hydrogen and R 2 is loweralkyl, with a compound of the formula R 1 Hal where Hal is chloro or bromo, and R 1 is loweralkyl, arylloweralkyl or cycloalkylloweralkyl to form a compound of the formula I, where X and n are as defined, R 1 is as defined above and R 2 is loweralkyl.

Claim 17

A process for the preparation of a compound of the formula I wherein R 1 is hydrogen, lower alkyl, arylloweralkyl, acyl, cycloalkylloweralkylene, or phenylsulfonyl; and R 2 is hydrogen, lower alkyl, hydroxyloweralkyl of the formula -(loweralkylene)-OH, arylloweralkyl, acyl, cycloalkylloweralkylene, where Z is selected from hydrogen, halogen, loweralkoxy, CF 3 , N0 2 , and NH 2 ; where Z is as defined above; where Z is as defined above; where R 3 and R 4 are each independently hydrogen and loweralkyl; where Z is as defined above; where R and R are each independently hydrogen and loweralkyl; X is hydrogen, loweralkyl, hydroxyl, halogen, loweralkoxy, CF 3 , N0 2 and NH 2 ; n is an integer of 1 to 4, with the proviso that R 2 is not loweralkyl when R, is hydrogen or acyl and X is chloro; the pharmaceutically acceptable acid addition salts thereof; where applicable the geometric and optical isomers thereof and the racemic mixtures thereof, which comprises a) condensing a compound of the formula VIII wherein R 2 is loweralkyl and X and n are as defined, to form a compound of the formula I, wherein R 1 is phenylsulfonyl and R 2 is loweralkyl, b) optionally reacting a compound of the formula I as obtained in step a) above with a halocyanide to form a compound of the formula I wherein R 2 is CN, and reducing the compound obtained with a metal hydride to form a compound of the formula I, where X and n are as defined and R 1 and R 2 are both hydrogen, or c) optionally reacting a compound of the formula I as obtained in step a) above, with a strong base to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is loweralkyl, d) optionally reacting a compound of the formula I as obtained in step c) with a halocyanide to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is CN, and reducing the compound obtained with a metal hydride to form a compound of the formula I, wherein X and n are as defined and R 1 and R 2 are both hydrogen, e) optionally reacting a compound of the formula I, wherein X and n are as defined, and R 1 and R 2 are both hydrogen, with a compound of the formula R 2 Y, where Y is chloro or bromo and R 2 is hydroxyloweralkyl, loweralkyl, arylloweralkyl, cycloalkylloweralkylene or a radical of the formulae and to form a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is as defined above, f) optionally reacting a compound of the formula I wherein X and n are as defined, R 1 is hydrogen and R 2 is loweralkyl, with a compound of the formula where Hal is chloro or bromo and R s is loweralkyl or aryl, to form a compound of the formula I, wherein X and n are as defined, R 1 is the group R 8 CO and R 2 is loweralkyl, g) optionally reacting a compound of the formula I where X and n are as defined, R 1 is hydrogen and R 2 is loweralkyl, with a compound of the formula R 1 Hal where Hal is chloro or bromo, and R 1 is loweralkyl, arylloweralkyl or cycloalkylloweralkyl to form a compound of the formula I, where X and n are as defined, R 1 is as defined above and R 2 is loweralkyl.

Claim 18

A process as defined in claim 1 wherein R 1 is hydrogen, lower alkyl, acyl or cycloalkyl-loweralkylene and R 2 is hydrogen, lower alkyl hydroxyloweralkyl, or a compound of the formulae where Z is halogen, or X is hydrogen, loweralkoxy or halogen, and n is 1.

Claim 19

A process as defined in claim 2 wherein R 1 is hydrogen, methyl, ethyl, acetyl, benzoyl or cyclopropylmethyl.

Claim 20

The process as defined in claim 1 wherein 3-(4-methyl-1-piperazinyl)-1H-indazole or a pharmaceutically acceptable acid addition salt thereof is prepared..

Claim 21

The process as defined in claim 1 wherein 1-ethyl-3-(4-methyl-1-piperazinyl)-1 H-indazole or a pharmaceutically acceptable acid addition salt thereof is prepared.

Claim 22

The process as defined in claim 1 wherein 3-(1-piperazinyl)-1 H-indazole or a pharmaceutically acceptable acid addition salt thereof is prepared..

Claim 23

The process as defined in claim 1 wherein 8-[4-[1-(1H-indazol-3-yl)-4-piperazinyl]butyl-8-azaspiro[4.5]-decane-7,9-dione or a pharmaceutically acceptable acid addition salt thereof is prepared.

Claim 24

The process as defined in claim 1 wherein 3-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-1H-indazole or a pharmaceutically acceptable acid addition salt thereof is prepared..

Claim 25

The process as defined in claim 1 wherein 3-[4-[3-(2-methylindole-3-yl)propyl]-1-piperazinyl)-1H-indazole or a pharmaceutically acceptable acid addition salt thereof is prepared.

Claim 26

The process as defined in claim 1 wherein 6-fluoro-3-[4-[3-(1,3-dihydro-2-oxo-2H-benzimidazole-1-yl)-propyl]-1-piperazinyl]-1 H-indazole or a pharmaceutically acceptable acid addition salt thereof is prepared.

Claim 27

Use of a compound for the preparation of a medicament having analgesic and/or antipsychotic activity.

Claim 28

Use of a compound for the preparation of a medicament having analgesic and/or antipsychotic activity.