| 摘要 |
<p>944,443. Indolyl-alkyl-piperazines and -homopiperazines. STERLING DRUG Inc. Sept. 22, 1960 [Sept. 25, 1959], No. 32569/60. Heading C2C. The invention comprises compounds of the general formula: wherein R 1 is a hydrogen atom or one or more halogen, lower-alkyl, lower-alkoxy, hydroxy, methylenedioxy, ethylenedioxy, lower-alkylmercapto, lower-alkyl-sulphinyl, lower-alkyl-sulphonyl, trifluoromethyl, monocarbocyclic aryl-lower-alkoxy, or lower-alkanoyloxy substituents; R 2 is a hydrogen atom or a lower-alkyl, hydroxy-lower-alkyl, monocarbocyclic aryl, monocarbocyclic aryl-loweralkyl, bis (monocarbocyclic aryl)-lower-alkyl, monocarbocyclic aryl-lower-alkenyl or heteromonocyclic radical; R 3 is a hydrogen atom or a lower-alkyl or monocarbocyclic aryl radical; R4 is a hydrogen atom or a lower-alkyl, monocarbocyclic aryl, monocarbocyclic aryl-lower-alkyl or monocarbocyclic aryl-lower-alkenyl radical; R 5 is a hydrogen atom or lower-alkyl radical; R 6 is a hydrogen atom or lower-alkyl radical; m is 1 or 2; and Y is an alkylene radical having 1-7 carbon atoms affixed at one open bond to the 1-, 2- or 3-position of the indole ring and when affixed at the 1- or 2-position replacing the atom or radical R 3 or R 4 respectively and when affixed to the 3-position optionally having a hydroxy group affixed to the carbon atom vicinal to the 3-carbon atom of the indole ring, said hydroxy group being at least two carbon atoms removed from the 1-nitrogen atom of the piperazine ring and Y having at least two carbon atoms when affixed to the N-indole atom: and their acid addition and quaternary ammonium salts: and their preparation (1) (X is hydrogen, n is one to seven) by reducing with an alkali metal aluminium hydride a corresponding 1-[(1-, 2- or 3-indolyl)-α-keto-lower-alkyl]-piperazine or -homopiperazine, which may itself be prepared by condensing a mixed anhydride of a lower-alkanoic acid and a 2- or 3-indole carboxylic acid with an N-substituted-piperazine or -homopiperazine at -20‹C. to +20‹C., (2) for those compounds of the sort: (X is hydrogen or hydroxy, n is two) by reducing with an alkali metal aluminium hydride at 0‹C. to 65‹C. in an inert organic solvent a 1-[(3-indolyl)-glyoxalyl]-4-substituted-piperazine orhomopiperazine, which may itself be prepared by condensing a 3-(indolyl)-glyoxalyl halide with an N- substituted-piperazine or -homopiperazine at -5‹C. to 65‹C. in the presence of an acid-acceptor, (3) for those compounds of the sort: X is hydrogen): by reacting a (1-, 2- or 3-indolyl)-lower alkyl halide with an N-substituted-piperazine or -homopiperazine at 50‹C. to 150‹C. in the presence of an acid-acceptor, (4) for compounds of formula 1a above by reacting a [#-(3-indolyl)-#-keto-lower-alkyl]-4-substituted-piperazine or -homopiperazine with an alkali metal aluminium hydride or an alkali metal borohydride, a compound wherein X is hydroxy necessarily being produced with an alkali metal aluminium hydride when R 4 is other than hydrogen, (5) for compounds of formula 1a above (X is hydrogen, n is one) by reacting an indole with formaldehyde and a 1-substituted-piperazine or -homopiperazine at 50‹C. to 150‹C., and (6) catalytically hydrogenating a compound produced as above wherein R 2 is a benzyl, benzhydryl or cinnamyl radical to produce a compound wherein R 2 is hydrogen. Starting materials which may be obtained and processes described in the Specification are shown in the following reaction schemes. Certain modified processes are also referred to. Pharmaceutical compositions comprise a compound or salt of the invention with a pharmaceutical carrier. Forms for parenteral (solutions) and oral (tablets, capsules, solutions, emulsions) administration are mentioned. They have hypotensive, antinauscant, antipyretic, sedative, tranquilising and muscle relaxing properties.</p> |
