CARBOSTYRIL DERIVATIVES, PROCEDURES FOR YOUR PRODUCTION AND THESE CONTAINING PHARMACEUTICAL PREPARATIONS.

The invention refers to Carbostyril derivatives of the formula given in the requirement 1 (1) with daselbst indicated meanings of the symbols, on its acid addition salts as well as on procedures for their production and these ents pharmaceutical preparations holding for use as the central nervous system absorbing Mittel.

The connections according to invention exhibit an antihistamine effect and an absorbing effect on the central nervous system, why them as Antihistaminica and o for the absorption of the central nervous system useful sind.

Like it in different articles of the medical and pharmaceutical literature descriptive, for example in Goodman, Gilman is: “Pharmacology” (volume 1); “YAKUBUTSU CHIRYO NO KISO TON of RINSHO” (bases is and clinical the Pharmaeotherapie), pages 781-835 [given change by Hirokawa Shoten CO., (1974)]; “SHIN OYO YAKURIGAKU” (new applied pharmacology) by Hisashi UN, pages 307 to 319 [given change by Nagai Shoten CO., (1970)]; “SHIN'YAKU TONS of RINSHO” (magazine for new cures & hospital), volume 20, No. 11, pages 129-133 (1971); and “KISO TON of RINSHO” (laboratory and hospital), volume I0, No. 10, pages 17-27 (1976), restrains generally an antihistamine means the consequences of a conjugated histamine connection not, which is formed 2s by the antigen antibody reaction of the allergy, but does not restrain the combination (through kompetitiven antagonism) of an active histamine connection with a histamine acceptor, whereby the antihistamine effect results. Therefore are in accordance with Antihistaminica the vorliea0 genden invention effectively as treatment means and preventive means for different allergische illnesses and symptoms, which arise as a result of the combination of histamine and histamine acceptor, like chronic Niessen and/or cold, burning the eyes, nose and 3s the throat, allergische symptoms of the breathing ways, hay cold, Polynosis, acute Urticaria (itch, edemas, swelling and such a thing), vascular edemas, Pruritus, atopische Dermatitis, insect bites, Dermatitis the contact type, like “Urushi Kabure”, Urticaria with serum illness, desert-mix disturbances, allergische Rhinitis, allergisches Conjunctivitis or Corneitis. Beyond that the antihistamine means can serve also as additives for the healing of the general Anaphylaxie, whereby Autacoide, which are different from histamine, can play an important role. Beyond that an antihistamine means can also as Diagnosticum for the measurement of the gastrischen acidity dienen.

In the pharmaceutical literature it was reported that 5 (3-tert. Butylamino-2-hydroxy) propoxy-3,4-dihydroso carbostyrilhydrochlorid the following formula:

with a connection of the formula:

Xt0_A /N-RI3 (26) where R s, A and Q have the before indicated meaning and Xlo means a halogen atom or a group of outlets, umsetzt.

Pharmaceutical preparation for use as the central nervous system absorbing means, characterized by an effective quantity of a Carbostyrilderivates OH CH OCH2CHCH2NHC CH3 CH3 N H a Antihistamiñwirkung in certain extent shows in accordance with requirement 1 as an active component beside pharmazeues (pA2=5,02), [OYO YAKURI (applied pharmacology), table acceptable carriers. Volume 11, No. 4, pages 437-462 (1976)]. Beyond that the DE-OS describes 23 02 027 (those the US-PS 3.910.924 corresponds) (2Hydroxy-3-amin o) propoxy-3,4-dihydro-car641 of 455 bostyril derivatives, the one l-adrenergic blocker effect aufweisen.

Other Dihydrocarbostyrilderivate, in particular such with one [(4-Hydroxylalkyll-piperazinyl) - alkoxy] - Seitenkette in the 7-Stellung, were described in GB-PS 1.212.174 or DE-OS 1.932.384 (Cassella of inking attachments Main cure AG); they can be used as output products for the production of new connections with coronardilatierenden characteristics. Similar Dihydrocarbostyrilderivate indicated as the same Seitenkette as was described above later than antidepressives (US-PS 3.994.900; E.R.

Squibb & Sons, Inc.).

The connection in accordance with the invention with antihistamine effect and absorbing effect on the central nervous system are however so far does not admit geworden.

The absorbing characteristics on that; central nervous system of the connections according to invention are among other things it shown by a strong Hemmwirkung of the aggressiveness of the mouse, yielded of others during a long period isolated is. Compared with diazepam, which admits as connection with strong such activity is, the connections exhibit one would except-accustom-borrow Herumwirkung of the aggressiveness of the mouse, why they are useful against manischdepressive Psychosen in particular as Sedativa, Anxiolytica and means. Beyond that they cause a strong exponentiation of the anaesthesia and the Schlafes, if them assigned in combination with Anästhetica and Hypnotica werden.

The connections according to invention are also for the Präanästhesie and as sleep-inducing Agentien nützlich.

The absorbing characteristics on the central nervous system show up in particular by a muskelrelaxierende effect, Hemmwirkung in relation to the Apomorphinerzeugte vomiting, a ptosis effect, a hypothermische effect, inhibition of the Spontanmotilität, an inhibition of the Hypermotilität of rats, one anti- methamphetaminwirkung, a reduction of the toxicity of the Methanphetamingruppe, a analgetische effect and a anti- Nordrenalinwirkung. However they have only weak Antieholinwirkung, Cardioinhibitorwirkung and kataleptische effect. Therefore the connections according to invention to the absorption of the central nervous system are as as central Muskelrelaxantien, sleep-inducing means, präoperative means, Antìschizophreniemitte! , Sedativa, Anxiolytica, means against manisch depressive Psyehosen, Antipyretica, Analgetica and Depressiva useful, without they show side effects, like thirst feeling, Konstipation, Tachycardie, Parkinsonismus and/or retarded Dyseinesie, those by conventional Steuerungsagentien for the central nervous system shown werden.

The designation “an alkyl group with 1 to 6 carbon flavours” means an alkyl group, which geradkettig or can be branched out and 1 to 6 carbon atoms exhibits, whereby the examples groups of methyls, groups of ethyls, Propylgruppen, Isobutylgruppen, Butylgruppen, Isobutylgruppen, test Butylgruppen, lake. - Butyl pentylgruppen, Hexylgruppen and such a thing umfassen.

The designation “a group of alkenyls with 2 to 4 carbon atoms” means a group of alkenyls, which can exhibit a straight or branched chain, with 2 to 4 carbon atoms, whereby the examples cover a Vinylgruppe, an allyl group, a 2-Butenylgruppe, an l-methyl-allyl group and such a thing. Examples of the designation “a Alkynylgruppe with 2 to 4 carbon atoms” cover Äthynylgruppen, 2-Propynylgruppen, 2-Butynylgruppen, 1-Methyl-2-propynylgruppen and such a thing. The designation “a Phenylalkylgruppe, their group of alkyls of 1 to 4 carbon atoms exhibits” means a Phenylalkylgruppe, which is compound from a Phenylgruppe with a AIkylengruppe, which geradkettig or can be branched out and 1 to 4 carbon atoms exhibits, whereby the examples the benzyle, 2-Phenäthylgruppe, l-Phenäthylgruppe, s 3-Phenylpropylgruppe, 4-Phenylbutylgruppe, 1,1-Dimethyl2-phenäthylgruppe and such a thing to cover. The designation “an alkyl group with I to 4 carbon atoms” means an alkyl group with straight lines or branched chain with I to 4 carbon atoms, whereby the examples l0 for this groups of methyls, groups of ethyls, Propylgruppen, Isopropylgruppen, Butylgruppen, tert Isobutylgruppen. - Butylgruppen and such a thing cover. The examples of the designation “a halogen atom” cover the fluorine, chlorine, Bromund iodine atom. The designation “a Alka 5 noyloxygruppe with 1 to 4 carbon atoms” means a Alkanoyloxygruppe with straight lines or branched chain with 1 to 4 carbon atoms, whereby the examples for this the Formyloxygruppe, which cover Acetyloxygruppe, Propionyloxygruppe, Butyryloxygruppe and such a thing. The Bezeieh o nung “C3 -8 Cycloalkylgruppe” means a Cycloalkylgruppe with 3 to 8 carbon atoms, whereby the examples for this the Cyelopropylgruppe, Cyclopentylgruppe, group of cyclohexyls, Cycloheptylgruppe, Cyclooctylgruppe and such a thing umfassen.

2s the designation “Ct-4Alkoxygruppe” means a geradkettige or branched alkoxy group with 1 to 4 KohIenstoffatomen, whereby the examples the Methoxygruppe, Äthoxygruppe, Propoxygruppe, Isopropoxygruppe, Butoxygruppe, Isobutoxygruppe, test Butoxygruppe and such a thing umfassen.

Concerning the concrete examples of a Phenylgruppe, which can exhibit up to three groups of substituents, those under groups of halogens, C -4Alkylgruppen and C -4Alkoxygruppen selected are mentioned, can the Phenylgruppe, 2-Methoxyphenylgruppe, 4-Methoxyphenylgruppe, 3-Methoxyphenylgruppe, 2-Äthoxyphenylgruppe, 4-Butoxyphenylgruppe, 3,4-Dimethoxyphenylgruppe, 3,4,5-Trimethoxyphenyl, 3-Isopropoxyphenylgruppe, 2-Methylphenyl.g.ruppe, 3-Methylphenylgruppe, 4-Methylphenylgruppe, 2-Athylphenylgruppe, 4-Butylphenylgruppe, 3,4-Diäthylphenylgruppe, 3,4,5-Trimethylphenylgruppe, 2-Chlorphenylgruppe, 3-Bromphenylgruppe, 4-Fluorphenylgruppe, 3-Chlorphenylgruppe, 4-Chlorphenylgruppe, 2-Fluorphenylgruppe, 3,4Dichlorphenylgruppe, 3,4,5-Trichlorphenylgruppe, 4s 4-Chlor-3-methylphenylgruppe, 2-Methoxy-3-chlorphenylgruppe, 4-Bromphenylgruppe, 2-Bromphenylgruppe, 4-Jodphenylgruppe and such a thing werden.

The designation “C -4Alkanoylgruppe” means a geradkettige or branched Alkanoylgruppe with 1 to 4 in such a way Kohlenstoffatomela, whereby the examples for this the Formylgruppe, acetyl group, Propionylgruppe, Butyrylgruppe, Isobutyrylgruppe and such a thing umfassen.

Concrete examples of C -4Alkylgruppe, which covers a group of substituents, as, Phenylgruppe can exhibit the hydroxy group ss or Cl-4Alkanoyloxygruppe, the Hydroxymethylgruppe, 2-Hydroxyäthylgruppe, 3-Hydroxypropylgruppe, 4-Hydroxybutylgruppe, 2-Hydroxypropylgruppe, Acetyloxymethylgruppe, 2-Acetyloxyäthylgruppe, 2-Propionyloxyäthylgruppe, 3-Acetyloxypropylgruppe, 4-Butyloxybutylgruppe, 2-Acetyloxypropylgruppe, group of benzyles, 2-Phenäthylgruppe, l-Phenäthylgruppe, 3-Phenylpropylgruppe, 4-Phenylbutylgruppe, l, l-Dimethyl2-phenãthylgruppe and dergleichen.

Representative examples of the Verbinss are following dungen the invention aforementioned. The designation “3,4Dehydroverbindung”, which is specified in the respective connections, means that the carbon carbon connection between the 3und 4-Stellungen in the Carbostyrilgerüst represents a double bond. For example 5 [2-Hydroxy-3 (4-phenylpiperazinyl) - propoxy] becomes - 3,4-dihydrocarbostyril and 5 [2-Hydroxy-3 (4-phenylpiperazinyl) propoxy] - carbostyril described here as “5 [2Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and its 3,4-Dehydroverbindung”.

6 [2-Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [2-Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrozo carbostyril and their 3,4-Dehydroverbindung 6 [3-Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [4-Hydroxy-5 (4-phenylpiperazinyl) pentyloxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4.dihydro-carbostyril and their 3,4-Dehydroverbindung 1-Athyl-6 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung l-Methyl-7 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l-Methyl-8 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1 (3-Methylbutyl) - 5 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l-Hexyl-6 [2-hydroxy-3 (4-p enylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung l-Allyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1 (2-Butenyl) - 6 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l-Allyl-7 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4.

dihydrocarbostyril and their 3,4-Dehydroverbindung l (3-Phenylpropyl) - 5 (2-hydroxy-3 [4 (4-methylphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l (4-Phenylbutyl) - 6 [2-hydroxy-3 (4-phenylpiperazinyl) propoxyl-3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l-Benzyl-7 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-8 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-5-brom-6 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Fluor-7 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung l-Benzyl-5-chlor-8 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6,8-Dictilor-5 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Chlor-8-brom-7[2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-5,6-dibrom-8 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l - Methyl-5 (2-hydroxy-3 [4 (2-chlorphenyl) piperazinyl] propoxy)--3,4-di ydrocarbostyril and their 3,4-Dehydroverbin6s dung 6 (2Hydroxy-3 [4 (3-bromophenyl) piperazinyl] propoxy), - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 641,455 7 (2-Hydroxy-3 [4 (4-fluor-phenyl) piperazinyl] propoxy), - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 (2-Hydroxy-3 [4 (2-methylphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung s 1-Benzyl-6 (2-hydroxy-3 [4 (3-methylphenyl) piperazinyl] propoxy)--3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-5 (2-hydroxy-3 [4 (4-äthylphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6 (2-Hydroxy-3 [4 (2-propylphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 (2-Hydroxy-3 [4 (2-methoxyphenyl) piperazinyl] propoxy)-- 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindang 1-Methyl-6 (2-hydroxy-3 [4 (3-methoxyphenyl) piperazinyl] propoxy), - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (2-Hydroxy-3 [4 (4-methoxyphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung zo 6 (2-Hydroxy-3 [4 (2-äthoxyphenyl) piperazinyl] propoxy). - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8-Chlor-5 (2-hydroxy-3 [4 (4-chlorphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 2s 1-Methyl-6-chloro-7 (2-hydroxy-3 [4 (4-chlorphenyl) piperazinyl] propoxy), - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Allyl-6-ehlor-7 (2-hydroxy-3 [4 (4-methoxyphenyl) piperazinyl] propoxy)--3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Chlor-5 (2-hydroxy-3 [4 (4-methylphenyl) piperazinyl] propoxy)--3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6,8-Dibrom-5 (2-hydroxy-3 [4 (4-methylphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 (4-Phenylpiperazinylmethoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 [2 (4-Phenylpiperazinyl) äthoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [2 (4-Phenylpiperazinyl) äthoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8 [2 (4-Phenylpiperazinyl) äthoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6 [7 (4-Phenylpiperazinyl) heptyloxy] - 3,4-dihydrocarbostyril so and their 3,4-Dehydroverbindung 5 [4 (4-Phenylpiperazinyl) propoxy-3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7[4 (4-Phenylpiperazinyl) butoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung ss 6 [5 (4-Phenylpiperazinyl) pentyloxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8 [5 (4-Phenylpiperazinyl) pentyloxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [6 (4-Phenylpiperazinyl) hexyloxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-5 [2 (4-Phenylpiperazinyl) äthoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-6 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l-Hexyl-6 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 641,455 I0 1-Allyl-5 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Allyl-6 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l (l-Methylallyl) - 7 [3 (4-phenylpiperazinyl) propoxy] - 3.4 - “dihydrocarbostyril and their 3,4-Dehydroverbindung 1 (2-Propinyl) - 7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-5 [2 (4-phenylpiperazinyl) äthoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung lo l (2-Phenyläthyl) - 6 [3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1 (4-Phenylbutyl) - 5 [3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrois carbostyril and their 3,4-Dehydroverbindung 5 {3 [4 (2-Methoxyphenyl) piperazinyl] propoxy) '- 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 {3 [4 (3-Methylphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6 {3 [4 (4-Methylphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyriI and their 3,4-Dehydroverbindung 7 {2 [4 (4-Propylphenyl) piperazinyl] äthoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 {3 [4-Chlorphenyl) piperazinyl] propoxy) - 3,4-dihydrocarss bostyril and their 3,4-Dehydroverbindung 6 {3 [4 (4-Brom-phenyl) piperazinyl] propoxy)--3,4-dihydrocarbostyriI and their 3,4-Dehydroverbindung 7 {2 [4 (2-Chlorphenyl) piperazinyl] äthoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-5 {3 [4 (4-chlor-phenyl) piperazinyl] propoxy} - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-6 {2 [4 (2-brom-phenyl) piperazinyl] äthoxy} - 3,4dihydroearbostyril and their 3,4-Dehydroverbindung 1-Allyl-7 {4 [4 (4-brom-phenyl) piperazinyl] butoxy) - 3,4dihydroearbostyril and their 3,4-Dehydroverbindung l-Methyl-6 {3 [4 (4-methylphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-5 {3 [4 (2-methylphenyl) piperazinyl] propoxy} - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-7 {3 [4 (4-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l-Benzyl-5 (3 [4-O-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydroßarbostyríl and their 3,4-Dehydroverbindung 8-Brom-5 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-5-brom-6 [2 (4-phenylpiperazinyl) thoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung ó-Flu or-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Color-5 [2 (4-phenylpiperazinyl) äthoxy] - 3,4-dihydroearbostyñl and their 3,4-Dehydroverbindung 6-Chlor-5 {4 [4 (4-methylphenyl) piperazinyl] - butoxy} 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Allyl-ó-chlor-7 {2 [4 (4-methoxyphenyl) piperazinyl] äthoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6,8-Dichlor-5 [2 (4-phenylpiperazinyl) äthoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung ó-Chlor-8-brom-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4dihydrocarbostyri] and their 3,4-Dehydroverbindung 1-Methyl-5,6-dibrom-8 [2 (4-phenylpiperazinyl) äthoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 8-Chlor-5 {3 [4 (4-chlor-phenyl) piperazinyl] propoxy} - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-ó-ehlor-7 {2 [4 (4-chlor-phenyl) píperazinyl] ïthoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l-Benzyl-6,8-dichlor-5 {2 [4 (2-brom-phenyl) piperazinyl] äthoxy} - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 7 {3 [4 (2-Methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 7 {3 [4 (3-Methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 7 {3 [4 (4-Methoxyphenyl) piperazinyl] propoxy), - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 7 {3 [4 (2-Äthoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-7 {3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 1-Allyle-7 {3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4dihydroearbostyñl and their 3,4-Dehydroverbindurtg 1-Benzyl-7 {3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1 (2-Prõpinyl) - 7 {3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbõstyril and their 3,4-Dehydroverbindung 7 {3 [4 (3,4-Dimethoxyphenyl) piperazinyI) propoxy} - 3,4dihydroearbostyril and their 3,4-Dehydroverbindung 7 {3 [4 (3,4,5-Trimethoxyphenyl) piperazinyl] propoxy} - 3,4dihydroearbostyril and their 3,4-Dehydroverbindung 5 {3 - [4 (3,4-Dimethoxyphenyl) piperazinyl] propoxy)--3,4dihydroearbostyril and their 3,4-Dehydroverbindung 1-Methyl-7 {3 [4 (3,4-dimethoxyphenyI) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1 - Benzyl-7 {3 [4 (3,4-diehl or-phenyl) piperazinyl] propoxy} - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 7 {3 - [4 (3,4-Dimethylphenyl) piperazinyl] propoxy)--3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 5 [2-Methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [2-Methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4-Methyl-6 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [4-Methyl-5 (4-phenylpiperazinyI) pentyloxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [2-Äthyl-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 1-Methyl-7 [2-methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-7 [2-methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyriI and their 3,4-Dehydroverbindung 1-Allyl-7 [2-methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1 (2-Propinyl) - 7 [2-methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 6-Chlor-5 [2-methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Chlor-8-brom-7 [2-methyl-3 (4-phenylpiperazinyl) pross poxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 7 {2-Methyl-3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-5 {2-methyl-4 [4 (4-methylphenyl) - pipera “o zinyl] butoxy} - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 7 {2-Methyl-3 [4 (3,4-dimethoxyphenyl) piperazinyl] propoxy} - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung it 7 [2-Methyl-3 (3-methyl-4-phenylpiperazinyl) propoxy] - 3,4dihydroearbostyril and their 3,4-Dehydroverbindung 5 [2-Acetyloxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 1 - Methyl-6 [2-propionyloxy-3(4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (2-Acetyloxy-3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 {3-Acetyloxy-5 [4 (4-methylphenyl) piperazinyt] pentyloxy), - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1 - benzyle (2-acetyloxy-3 [4 (4-ehlorphen yl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung! - Allyl-8 [2-acetyloxy-3 [2-acetyloxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Chlor-5 [2-acetyloxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydroearbostyri! and their 3,4-Dehydroverbindung l-Äthyl-7 [2-acetyloxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1 (2-Propinyl) - 7 [2-acetyloxy-3 (4-phenylpiperazinyl) propoxyl-3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (2-Isobutyryloxy-3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4 [2-Acetyloxy-3 (4-phenylpiperazinyl) ptopoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4Methyl-7 [2-acetyloxy-3 (4-phenylpiperaziny!)propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4Phenyl-7 [2-acetyloxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung [2 (3,4,5-Trimethoxybenzoyloxy) - 3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1 - Benzyl-6 [2 (3,4,5-trimethoxybenzoyloxy) - 3 (4-pheny! - piperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [2 (3,4,5-Trimethoxybenzoyloxy) - 3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-7 [2 (3,4,5-trimethoxybenzoyloxy) - 3 (4-phenylpiperaziny!)propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 {2 (3,4,5-Trimethoxybenzoyloxy) - 3 [4 (2-methoxyphenyl) piperazinyl] propoxy)--3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1 - Benzyl-7 [2 (3,4,5-Trimethoxybenzoy! oxy) - 3 (4-phenylpiperazinyI) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4-Methyl-7 [2 (3,4,5-trimethoxybenzoyloxy) - 3 (4-pheny! - piperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4Phenyl-8 [2 (3,4,5-trimethoxybenzoyloxy) - 3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Allyl-6-chlor-7 (2 (3,4,5-trimethoxybenzoyloxy) - 3 [4 (3,4dimethoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [2Hydroxy-3 (3-methyl-4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (3-Methyl-4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [3-Methyl-4 (4-chlor-phenyl) piperazinyl] propoxy} - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 - (3 - Methyl-4-phenylpiperazinyl) propoxy] - 3,4-dihydro - carbostyñl and their 3,4-Dehydroverbindung 7 (3 [3-Methyl-4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 11,641,455 8 [3 (3-Äthyl-4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4 [3 (3-Methyl-4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung “1-Methyl [3 (3-methyl-4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl [3 (2-methyl-4-phenylpiper azinyl) propoxy] - 3,4dihydroearbostyril and their 3,4-Dehydroverbindung 4-Methyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrolO carbostyril and their 3,4-Dehydroverbindung 4-Phenyl-7 {3 [4 (2-methoxyphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung is 4-Äthy! - 7 (3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 1,4-Dimethyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Benzyl-4-phenyl-7 (3 [4 (2-chlor-phenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 [2-Hydroxy-3 (4-eyelohexylpiperazinyl) propoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 6 [2-Acetyloxy-3 (4-cycloheptylpiperazinyl) propoxy] - 3,42s dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (4-Cyclohexylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4 [3 (4-Cyclohexylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung a0 1-Methyl-7 [3 (4-Cyelohexylpiperazinyl) propoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung l-Benzyl-7 [2-methyl-3 (4-Cyelohexylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 [3 (4-Cyclohexylpiperazinyl) propoxy] - 3,4-dihydrocarbo3s styril and their 3,4-Dehydroverbindung 4-Methyl-7 [3 (4-Cyclohexylpiperazinyl) propoxy] - 3,4-dihydrocarbostyri! and their 3,4-Dehydroverbindung 4-Phenyl-6 [2-methyl-3 - (4-Cyclohexylpiperazinyl) pr opoxy] - 3,4-dihydrocarbostyri! and their 3,4-Dehydroverbindung 1 (2-Propinyl) - 7 [4 (4-Cyclohexylpiperazinyl) butoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 6,8-Dichlor-5 [3 (4-Cyclohexylpiperazinyl) propoxy] - 3,4dihydrocarbostyrit and their 3,4-Dehydroverbindung 5 [2-Acetyloxy-3 (4-benzylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6 [2-Hydroxy-3 (4-benzylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (4-Benzylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung so 4 [3 (4-Benzylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6 [3 (4-Benzylpiperazittyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-7 [2-methyl-3 (4-benzylpiperazinyl) propoxy] - 3,4ss dihydroearbostyri! and their 3,4-Dehydroverbindung l-Benzy! - 7 [3 (4-benzylpiperazinyl) propoxy] - 3,4-dihydrocarbostyñ! and their 3,4-Dehydroverbindung 4-Methyl-7 [3 (4-benzylpiperazinyl) propoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 4-Phenyl-7 [3 (4-benzylpiperazinyl) propoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung l-Allyl-6 [4-benzylpiperazinyl) butoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l (2-Propinyl) - g [2 (4-benzylpiperazinyl) - äthoxy] - 3,4-dihycc drocarbostyril and their 3,4-Dehydroverbindung 6,8-Dichlor-5 [3 (4-benzylpiperazinyl) propoxy] - 3,4-dihydroearbostyril and their 3,4-Dehydroverbindung 7 [2-Acetoxyloxy-3 (4-benzylpiperazinyl) propoxy] - 3,4-dihy641 455 12 drocarbostyril and their 3,4-Dehydroverbindung 7, (3 [4 (1-Phenyläthyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyñl and their 3,4-Dehydroverbindung 7 (3 [4 (4-Phenylbutyl) piperazinyl] propoxy) -3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 (2-Hydroxy-3 [4 (2-acetyloxyäthyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [4 (2-Acetyloxyethyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8 (2-Methyl-3 [4 (2-acetyloxyethyl) piperazinyl] propoxy) - lo 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 43 [4 (2-Acetyloxyethyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [4 (4-Butyryloxybutyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyñl and their 3,4-Dehydroverbindung is 1-Methyl-7 (3 [4 (2-acetyloxyethyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4-Phenyl-7 (3 [4 (2-acetyloxyethyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (2-Hydroxy-3 [4 (2-acetyloxyethyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 {2-Acetyloxy-3 [4 (2-hydroxyäthyl) piperazinyllpropoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [4 (2-Hydroxyäthyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [4 (4-Hydroxybutyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [4 (1 - Hydroxyäthyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4 (2 [4 (2-Hydroxyäthyl) piperazinyl] propoxy) - 3,4-dihydro39 carbostyril and their 3,4-Dehydroverbindung 4-Methyl-7 (3 [4 (2-hydroxyäthyl) piperazinyl] propoxy) - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 7 `(2-Hydroxy-3 [4 (2-hydroxyäthyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 [3 (4-Benzoylpiperazinyl) propoxyl-3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [2-Acetyloxy-3 (4-benzoylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (4-Benzoylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8 [3 (4-Benzoylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1 - Methyl-7 [3 (4-benzoylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4-Phenyl-7 [3 (4-benzoylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l (2-Propinyl) - 5 [2 (4-benzoylpiperazinyl) ethoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Chlor-5 [4 (4-benzoylpiperazinyl) butoxy] - 3,4-dihydrocarso bostyril and their 3,4-Dehydroverbindung 5 [3 (4-Acetylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (4-Acetylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8 [2-Acetyloxy-3 (4-acetylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung l-Benzyl-7 [3 (4-acetylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4-Methyl-7 [3 (4-acetylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4 [3 (4-Acetylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (4-Butyrylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6s 1 - MethyI [4 (4-propionylpiperazinyl) butoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8-Brom-5 [3(4-acetylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (4-Phenyl-hexahydro-l, 4-diazepin-l-yl) propoxy] - 3,4dihydrocarbostyri] and their 3,4-Dehydroverbindung 6 [3 (4-Phenyl-hexahydro1,4-diazepinI - yl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 5 [3 (4-Phenyl-hexahydro1,4-diazepin1 - yl) propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 4 [4 (4-Phenyl-hexahydro-1,4-diazepin-I - yl) butoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [4 (2-Methoxyphenyl) - hexahydro1,4-diazepin1 - yl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6 `(2 [4 (4-Chlor-phenyl) - hexahydro l, 4-diazepin-1yl] äthoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [3 (4-Benzyl-hexahydro-l, 4-diazepin-l-yl)propoxy] - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung 7 [2-Hydroxy-3 (4-phenyl) - hexadihydro1,4-diazepin1 yl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydtoverbindung 5 [2-Methyl-3 (4-phenyl-hexahydro1,4-diazepin1-yl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1-Methyl-7 [3 (4-phenyl-hexahydro-l, 4-diazepin-l-yl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung I - Benzyl-7 [3 (4-phenyl-hexahydro1,4-diazepin1 - yl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4-Phenyl-7 [3 (4-phenyl-hexahydro-l, 4-diazepin-l-yl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8-Chlor-5 [3 (4-phenyl-hexahydro-l, 4-diazepin-l-yl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (2-Hydroxy-3 [4 (4-chlor-phenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Chlor-7 {2-hydroxy-3 [4 (2-methoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 4-Methyl-7 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6 (3 [4 (2-Methoxyphenyl) piperazinyllpropoxy) - 3,4-dihydrocarbostyñl and their 3,4-Dehydroverbindung 1-Methyl-5 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 {2 [4 (4-Methylphenyl) piperazinyl] äthoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 8 (3 [4 (2-Methoxyphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 `(3 [4 (4-Methylphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 53 [4 (2-Äthoxyphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and of them 3,4-Dehydroverbindung 6-Chlor-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 6-Brom-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [4 (2-Chlor-phenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 {3 [4 (3-Chlor-phenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 (3 [4 (4-Chlor-phenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyri] and their 3,4-Dehydroverbindung 1 - Allyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 1 - Hexyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydrovêrbindung l-Benzyl-5 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 7 {3 [4 (3-Fluor-pbenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 53 [4 (2-Fluor-pbenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 73 [4 (2-Fluor-phenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril and their 3,4-Dehydroverbindung 5 {3 [4 (3-Fluor-pbenyl) piperazinyl] propoxy} - 3,4-dibydro13 641,455 carbostyril and their 3,4-Dehydroverbindung 5, (3 [4 (3,4,5-Trimethoxyphenyl) piperazinyl] propoxy). - 3,4dihydrocarbostyril and their 3,4-Dehydroverbindung.

The connections are manufactured according to invention in the procedures in accordance with requirements 31 to 39; these procedures are given by the following Reaktionsschemen; therein the different symbols have the Bedeutungen.<br indicated above/> Reaction pattern 1 R6 I O (CH2) Z CH (CH2) mXl (x) n åI (2) // (Cri2) qk k + HN N-R5 R4 (3) R6 (CH2) q i/O (CH2) I (CH2) mN! N-R5 4 tI o (la) (X) n R R6 is a hydrogen atom, a hydroxy group or an alkyl group with 1 to 4 carbon atoms and X is a halogen atom or a group of outlets, like a Mesityloxygruppe or a Tosyloxygruppe.

As represented in the reaction pattern I, the connection of the general formula becomes (la) (where R3 another meaning than a Alkanoyloxygruppe with 1 to 4 carbon atoms or a 3,4,5-Trimethoxybenzoyloxygruppe, how it in the general formula (1) was indicated, has) manufactured, by one a HalogenalkoxycarbostyrilDerivat of the general formula (2) with an amine derivative of the general formula (3), that simply and in well-known way, or in way similar to well-known methods to be manufactured can, umsetzt.

The conversion between a connection of the general formula (2) and a connection of the general formula (3) can be preferably terminated in absence or in presence of an inert solvent at ambient temperature up to 200°C, with temperature conditions within the range of to 120°C in the course of several hours up to 24 h. As inert solvents one knows an ether, like Dioxan, Tetrabydrofuran, Äthylenglycol, Dimethyläther and such a thing, an aromatic hydrocarbon, like benzene, toluol, xylene and such a thing, a low alcohol, like methanol, ethanol, isopropanol and such a thing, or a aprotisches polar solvent, like dimethylformamide, Dimethylsulfoxid and such a thing verwenden.

The conversion is preferably accomplished using a basic connection as Dehydrohalogenierungsmittel. The basic connection used during the conversion can be selected from a large multiplicity of well-known basic connections, e.g.

from potassium carbonate, Natriumcarbonat, sodium hydroxide, thus Natriumhydrogencarbonat, sodium amide, sodium hydride, one tert. - Amine, like tri ethyl amine, Tripropylamin, Pyñdin or Chinolin. The conversion can also using an alkali iodide, as potassium iodide or sodium iodide is accomplished as reaction accelerators. The Verss hältnis the quantity of the connection of the general formula (2) to the Ve_. “connection of the general formula (3) during the above conversion is subject to no special restriction and can be selected within a wide range, but generally it is desirably, the latter äquimolar or in the surplus, preferably äquimolar up to the fivefold molecular quantity of the first connection, in particular äquimolar to the 1,2lachen of the molecular quantity of the first connection too verwenden.

A connection of the general formula (1 c) (where R3 manufactured in 6s of the general formula (1) a Alkanoyloxygruppe with 1 to 4 Koblenstoffatomen or a 3,4,5-Tdmethoxybenzoyloxygruppe is), by a procedure, that by the following reaction pattern 2 shown wird.

64I 455 14 reaction pattern 2 OH I o (OH2) toe (CH2) mN (x) n aI/(OH2)! '\. , I _/I R4 (lb) (lb) + RTX2 (4) N-R5 or (R7) 20 (5) OR7 (CH2) 0 (CH2) î " CH (CH2) mN i N-R5 blank xç '1 'o (in R (le) X2 a halogen atom and a R7 a Alkaloyloxygruppe with I to 4 Kohlenstofîatomen or a 3,4,5-Trimethoxybenzoylgruppe.<br means/> One places thus a connection of the general formula (1 c) in accordance with the invention ago, by one a Hydroxyalkoxyearbostyril derivative of the general formula (lb) with a Säurehalogenid or a Säureanhydrid of the general 4s formulas (4) or (5) umsetzt.

The conversion of a connection of the general formula (lb) with a connection of the general formulas (4) or (5) can take place in present or in absence of a suitable solvent and in present or in absence of a in such a way suitable basic connection. Preferably dimethylformamide and such a thing to be used. As basic connection can during the conversion mentioned above tert. - Amine, like Triäthylamín or Pyridin, sodium hydroxide, potassium hydroxide or sodium hydride and such a thing uses werden.

The relationship of the quantity of a connection of of the general formulas (4) or (5) to a connection of of the general formula (lb) can be like that the first in a at least äquimolaren quantity of the latters is preferably used, in a äquimolaren quantity of the latters molecular up to the 5fach. The above reaction becomes at a temperature between ambient temperature to 150°C, preferably in the range between ambient temperature and 100°C mehwird the conversion to presence of a basic Verbinrere hours, up to 15 hours, durchgeführt.

dung durchgef'úhrt. AusgangsAls solvent used with the available invention can with the above reaction aromaterial is a connection of the general formula (2) and matischer hydrocarbon, like benzene, toluol or xylene, ss closes well-known connections (US-PS 4,072,683) or a Halogenkohlenwasserstoff, like chloroform or Methyneue connections in and can be manufactured after the following Reaklenchlorid, acetone, Pyridin, Dimethylsulfoxid, tionsschemata 3 and 4 in simple way:

OH (6) R2 I! R reaction pattern 3 OR8 R2 (8) 641,455 Halogenierungsmittel Halogenierungsmitte! OH R2 (X) n, (7) n' means 1 or 2, R-S means an alkyl group with 1 to 4 carbon atoms or a Alkanoylgruppe with 1 to 4 Kohlenstoffatomen.

In the reaction pattern 3 one receives a connection of the general formula (7) by shifting of a Hydrocarbostyrils of the general formula (6) with a Halogenierungsmittel or by hydrolysis of a connection of the general formula (9), which by shifting of a Alkoxyoder Alkanoyloxycarbostyrils of the general formula (8) with a halo genius rank means one manufactures. The above-mentioned Halogenierungsreaktion can take place using well-known Halogenierungsmittel. Examples of such Halogenierungsmittel are fluorine, chlorine, bromine, iodine, Xenondifluorid, Sulfurylchlorid, sodium hypochlorite, hypochlorous acid, unterbromige acid, bleaching powder, iodine chloride and such a thing. The quantity of the Halogenierungsmittels is selected in such a way within a broad range, as the portions of the halogen atoms, which into the connections (6) or (8) to be introduced are, it require. If a halogen atom is to be introduced, the Halogenierungsmittel is preferably used generally äquimolar or in the surplus, in a 1bis 1,5fachen molecular quantity of the parent compound. If 2 halogen atoms are introduced, then the Halogenierungsmittel is preferably used in a 2fach molecular quantity to za a large surplus, in a 2bis 3lachen molecular quantity of the respective parent compound. The Halogenierungsreaktion is accomplished generally in a suitable solvent, like water, methanol, ethanol, chloroform, carbon tetrachloride, acetic acid or a mixture of it. The reaction temperature is subject to no special restriction and can be selected within a wide range, however it is appropriate for n, IR generally with approximately -20 to OR8 R2 (X)! 0 (9) 100°C, preferably O°C to ambient temperature. The reaction runs within a time of 30 minutes to 20 h vollständig.

The hydrolysis reaction of a connection of the general formula (9) varied depending upon the kind of R8 in the formula (9).

If R8 is e.g. a Alkanoylgruppe with 1 to 4 carbon flavours, then the hydrolysis under conditions of a usual hydrolysis reaction of an ester becomes durchgeführt.

said 4s of details, the hydrolysis can be accomplished in presence of a basic connection, like sodium hydroxide, potassium hydroxide, barium hydroxide, Natriumcarbonat, potassium hydrogencarbonate, a mineral acid, like sulfuric acid or hydrochloric acid, an organic acid, like acetic acid, as an aromatic sulfone acid in a solvent, as water, methanol, ethanol, acetone, Dioxan, tetrahydrofurane or benzene. The reaction temperature is generally between ambient temperature and 150°C, preferably about 50 to 100°C. After 1 to 12 h those ran sports club reaction completely. If on the other hand R8 is an alkyl group with I to 4 carbon atoms, then the hydrolysis reaction on the usual hydrolysis conditions for an ether can be accomplished. More exactly said, the conversion can be accomplished using aluminum chloride, boron tri fluoride, boron tri bromide, hydrobromic acid or Trimethylsilylchlorid than catalyst and in a solvent, like water, methanol, ethanol, benzene, dichloromethane or chloroform, at a temperature within the range of 0 to 200°C, vorzugses wise between ambient temperature and 120°C during several bs to 12 hours. With both hydrolysis reactions the quantity of the used catalyst is not subject to special restrictions, and the catalyst becomes 641,455 16 general in a surplus amount, in, in relation to the connection which can be hydrolyzed (9) eingesetzt.

Reaction pattern 4 OH R2 (x) n g 1 R6 l X3 (CH2) /CH (CH2) taxi > (11) R6 I x1 0 (CH2) zCH (CH2) m (10) in the reaction pattern 4 the conversion of a connection of of the general formula (10) with a connection of of the general formula (11) becomes preferably using a basic connection as Dehydrohalogenierungsmittel in a suitable solvent at ambient temperature to 200°C, preferably 50 to 150°C, during meh2s red to 15 h accomplished. Examples of suitable solvents are accomplished low alcohols, like methanol, ethanol or isopropanol, a Keton, like acetone or methylethylketone, an ether, like Dioxan, Diäthylenglykoldimethyläther, an aromatic hydrocarbon, like toluol or xylene, dimethylformamide, Dimethylsnlfoxid or Hexamethylphosphoryltriamid. Examples of basic connections, which can be used as Dehydrohalogenierungsmittel, are sodium hydroxide, potassium hydroxide, Natriumearbonat, potassium carbonate, Natrias ummethoxid, Natriumäthoxid, Kaliumäthoxid, sodium hydride, metallic potassium, metallic sodium, tert. - Amine, like Pyridin, Chinolin, tri ethyl amine or Tripropylamin. With the above reaction an alkali iodide can as reaction accelerator, as potassium iodide or sodium iodide is used. The relationship of the connection of of the general formula (10) to the connection of of the general formula (11) during the conversion mentioned above it is not limited particularly but it is desirable that the latter in a äquimolaren a quantity or more means, in the allge4s in a 1 - to 1,5lachen and preferably 1bis 1,2fachen molecular quantity, related to which first is used. One receives so a connection of the general formula (2), which is used with the available invention as raw material. s0 in the Reaktionsschemen 3 and 4 close the verb in 'dungen the general formulas (6), (8) and (10), which are used as raw materials in the reactions, such, which have substituted groups, where g 1 an alkyl (2) with 2 to 4 carbon atoms, a Alkynylgruppe with 2 to 4 carbon atoms or a Phenylalkylgruppe with an alkyl group with 1 to 4 Koblenstoffatomen means, new connections. This connections can simply manufactured using well-known Hydroxycarbostyrils, with which g 1 hydrogen atom is, when raw material and shifting with an alkyl halide, an alkenyl halide, a Alkynylhalogenid or a Phenylalkylhalogenid in presence of of a basic connection, like an alkali metal, a e.g. metallic sodium or a metallic potassium, an alkali amide, like sodium amide or potassium amide or sodium hydride in a suitable solvent, like benzene, tetrahydrofurane, Dioxan, Dimethylsulfoxid, dimethylformamide, Hexamethylphosphoryltriamid, and at a temperature from 0 to 70°C, preferably 0°C to ambient temperature, whereby the conversion runs in 30 minutes to 12 h, on which one hydrolisiert then in such a way formed connection under similar conditions, as with the hydrolysis of one Connection of the general formula (9), with which the alkyl group has 1 to 4 carbon atoms and like this in the Reaktionssehema 3 was shown. With the above reaction the relationship of the quantity of the basic connection, the alkyl halide, alkenyl halide, alkyl halide or Phenylalkylhaiogenids to the raw material can be selected within a wide range, however the quantity is generally with the 2bis 10fachen molecular quantity, vorzngsweise 2bis 4lachen molecular quantity, the Ausgangsverbindung.

One knows so the connection of the general formula (1) herstellen.

Under the connections of the general formula (1) a connection of the general formula (1 d), where 1 and m means I in each case and R3 a hydroxy group is, becomes after folgruppe with 1 to 6 carbon atoms, a group of alkenyls ss towards that reaction pattern 5 hergestellt.

Reaction pattern OH R2 cE2 cR-cH2 x4 (! 2)° (X) n R “(IO) '(13) 17,641,455 I R4 (3) N-R5 iH/(CH2) I degrees of 2C CH2N “I /N-R5 RI! (x) n Ri] _ 0” (. - OD) therein means X4 a halogen atom, Y places the group of OH/°! - I - CH-CH2 or - CHCH2 X4 dar.

With the reaction pattern 5 the conversion of a Hydrocarbostyrilderivates of of the general formula (10) with an epihalogenohydrin of of the general formula (12) can in presence of a suitable basic connection, like beizs spielsweise of an inorganic basic compound, like sodium hydroxide, potassium hydroxide, Natriumcarbonat, Kaliumearbonat, Natriummethoxid, Natriumäthoxid, sodium hydride, metallic sodium, metallic potassium, sodium amide, or an organic basic compound, like Piperidin, Pyridin, tri ethyl amine, in absence or in presence of a solvent, e.g. a low alcohol, like methanol, ethanol or isopropanol, a Keton, like acetone or methylethylketone, an ether, like ether, Dioxan, Diäthylenglycolmethyläther, an aromatic hydrocarbon, like benzene, toluol, Xylene, or by water to be accomplished. With this reaction the quantity of the connection within a wide range, indicated by the general formula (12), is selected, however it lies above it generally with a äquimolaren quantity or, preferably with the 5bis 10fachen molecular quantity by the general formula (10) Verbindung.<br beschriebeìaen/> The conversion runs at a temperature between 0 and 150°C, preferably between 50 and 100°C. During the above conversion a Epihalogenhydrid of the general 4s formula (12) with a hydroxy group of the connection of the general formula (10) and one receives connections, which have (2,3-Epoxy) reacts a propoxygruppe or a 3-Halogeno-2-hydroxypropoxygruppe. Generally the reaction products are received as mixture of these connections, sports club in such a way received reaction product can with an amine of the formula (3), like that as it is, without previous separation or cleaning, to be converted. Further the reaction product with an amine of the formula (3) can to be converted, after the product was cleaned by usual separation, ss Umkristallisieren.oder Säulenchromatografie, whereby one a cleaned product with a 2,3-Epoxypropoxygruppe or a 3-Halogeno-2-hydroxypropoxygruppe erhält.

The conversion of a connection of the general formula (13) with a connection of the general formula (3) solvent can do at ambient temperature to 200°C, preferably 60 to 120°C, to be accomplished in Abweseneheit or in presence of an inert, usually used, and the conversion runs within a time of several 6s hours to 24 h. During the above conversion examples of inert solvents ethers, like Dioxan, are tetrahydrofurane, Äthylenglycol and Dimethyläther, aromatic Kohis lenwasserstoffe, like benzene, toluol and xylene, low alcohols, like methanol, ethanol, isopropanol, polar solvents, like dimethylformamide or Dimethylsulfoxid.

Further one can add a basic connection during the above conversion. Examples of basic connections are tert inorganic, basic compounds, like Caliumcarbonat, Natriumcarbonat, sodium hydroxide, Natriumhydrogencarbonat and sodium amide, and. - Amines, like tri ethyl amine, Tripropylamin, Pyridin and Chinolin. The relationship of the quantities converted of the connections of in each case can lie within a wide range, but generally it is desirable that the connection of of the general formula (3) in a äquimolaren quantity or in a surplus quantity, preferably in a ãquimolaren quantity up to the 5fach molecular quantity and in particular the 1bis 1,2fach molecular quantity of the connection of of the general formula (13) vorliegt.

Under the connections of the general formula (1) becomes a connection of the general formula (1 f), in soft R an alkyl group with 1 to 6 carbon atoms, a group of alkenyls with 2 to 4 carbon atoms, a Phenylalkylgruppe, at which the group of alkyls 1 to 4 carbon atoms has meant, by shifting of a connection in which R a hydrogen atom means, with a halogen connection of the general formula (I 4) manufactured, how in the following reaction pattern (6) is shown:

Reaction pattern 6 R3 I/O (CH2) £CH (CH2) mN (H 0 (CH2) q f/(le) N-R5/Rgx5 (! 4) 641,455 R3 i/O (OH2) OH (CH2) mN R2 0 (z (If) HO 18 I/l R4 N-- R5 1 {9 is an alkyl group with 1 to 6 carbon atoms, a Alkenylgrnppe with 2 to 4 carbon atoms, a Alkynylgruppe with 2 to 4 carbon atoms, a Phenylalkylgruppe, into more softly the group of alkyls of 1 to 4 charring material atoms has, and X5 is a Halogenatom.

During the conversion of a connection of the general formula (le) with a connection of the general formula (1 4) the latter appropriately in a äquimolaren quantity up to a 3 to laugh molecular quantity in relation to the o first, preferably in äquimolarer quantity opposite the first, one uses. Díe gleíchen Reaktíonsbedingungen for the conversion of a connection (in which g 1, like in the general formulas (6), (8) or (10) indicated, meant a hydrogen atom) with an alkyl halide, one is alkenyl halide, a Alkynylhalogenid or a PhenyIalkylhalogenid can applied werden.

The connections according to invention of the general formula (1) also according to the reaction pattern 7 are manufactured, by one a connection of the general formula (1 0) with a connection of the general formula (1 5) umsetzt.

R2 reaction pattern 7 I (x) n (10) I RI O R6 I/X6 (CH2) £CH (CH2) mN R6 I O (CH2) CH (CH2) mN I1 o (X) n R (CH2) J R4 N-R5 (CH2). , 7 N-R5 '! 4 (ia) X is a halogen atom or a group of outlets, like a 6s Mesityloxyoder a Toxyloxygruppe. If I = 1 know, then X6 and RA by means of the oxygen atom a Epoxyring bilden.

The connection of the general formula (15) can be received in well-known procedures or in analogy procedures. For execution the reaction of a connection of of the general formula (10) with a connection of the allge19 641,455 can the reaction conditions, which during the conversion of a connection of the general, mean formula (15) formula (10) with a connection of the general formula (I 1) with the reaction pattern 4 were shown, to be also used. Also at the time of the execution of the reaction of a connection of the general formula (15), in which X6 and R3 with the oxygen atom a Epoxygruppe form, with a connection of the general formula (10) the reaction conditions, how them in the reaction pattern 5 for the conversion of a connection of of the general formula (10) with a connection of of the general formula (12) was shown, can be used. In these cases becomes a verse a connection of the general form] (15) in at least äquimolarer quantity a connection of the general formula (! 0), preferably in a äquimolaren quantity of the latters molecular to 3fach, angewendet.

Reaction pattern 8 R6 (Cri2) \ ith o (CH2) £CH (CH2) mN/NH \ I., i E4 RIIx8 or' (RII) 20 (16) k 0 (18) (19) (ç RIOx7 I} OH2) @ \ 1 (17) O (CH2) £CH (CH2) mN [- \ /N R/R6 Y-- I/(CH9) ₜ I' 9 R4 ““\ N RI0 RO (OH2) zCH (CH2) rnN I” I R4 -- (X) n RI1 0 (ih)/I o f X'n RI (RI2) A, x9 - (industrial union) “(20) R6 (R12) a' I/(CH2) c1 \ _ O (CH2) £CH (CH2) mN 1/N ./v (X) n R (left) x7, x8 and X9 is in each case a halogen atom; Rlo is substituted substituted with a Phenylgruppe or a C. - 4-Alkylgruppe, a C, - - alkyl group, with a Phenylgrnppe or a Ct-4-AIkanoyloxygruppe, or a C3-s-Cycloalkylgruppe; R' is a C -4-Alkanoylgruppe or a Benzoylgruppe; R'2 is a halogen atom, a Ct-4-Alkylgruppe or a C -4-Alkoxygruppe; q' means 0, 1 or 2nd R o means however no phenyl (c1 - C4) alkyl group, if RZ 6 represents “a Phenylgruppe. With the reaction pattern 8 one can keep the parent compound of of the general formula (16) easy, by one a connection (those the general formula (3) correspond, in which R5 a Wasser641455 is material atom) with a connection of the general formula (2) as with the reaction pattern 1 converts. Further a connection of the general formula (16) can be made by katalytísche reduction and Debenzylierung of a connection according to the general formula (1), into soft R5 a group of benzyles bedeutet.

The Debenzylierungsreaktion can be accomplished under similar conditions as with a usual katatytischen reduction. So the conversion in an inert solvent can be made. Examples of lo suitable solvents are water, a low alcohol such as methanol, ethanol or isopropanol, ethyl acetate, acetic acid, Tolnol, xylene or such a thing. Examples of catalysts usable with this reaction are palladium on coal, palladium-black, platinum, Raney nickel and deris resemble. The Debenzylierung is preferably accomplished with a pressure between 1 to 30 atmospheres, 1 to 3 atmospheres, at ambient temperature to 100°C, preferably at ambient temperatures to 60°C, during 30 minutes to 6 h. During the conversion of a connection allgezo formula (16) with a well-known connection of the general formula (17) can the same reaction conditions mean be used, as during the conversion of a connection of the general formula (2) with a connection of the general formula (3). Further the same reaction conditions can be used as with the reaction of a connection of the general formula (lb) with a connection of the general formula during the 2s conversion of a connection of the general formula (16) with a connection of the general formula (18) (4) or (5), like this shown in the Reaktionssehema 2 wird.

The conversion of a connection of the general formula (16) with a connection of the general formula (20) is taken in absence or in presence of a basic condensation means in a suitable inert solvent voras. Examples of such inert solvents are aromatic hydrocarbons, like benzene, toluol or xylene and such a thing; Low alcohols such as methanol, ethanol, Propanol, butanol and such a thing; Pyridin, acetone, Dimethylsulfoxid, dimethylformamide or Hexamethylphosphoryltriamid and such a thing. Examples of basic condensing means are Natriumcarbonat, potassium carbonate, Natrinmhydrogencarbonat, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, sodium hydride, Kaliumhydrid, tri ethyl amine and such a thing. 4s the quantity of a connection of the general formula (20) becomes in at least a äqnimolaren quantity a connection of the general formula (16), preferably in the äquimolaren quantity of the latters molecular to 3fach, verwendet.

The conversion can at ambient temperature to 180°C, preferably with 100 to 150°C during 3 to 30 h made werden.

Halogenierungsmittel or s sulphonation means reaction pattern 9 R6, n (CH2) q-°E O (CH2) zCH (CH2) m A-OH Iz (X) n A (21) (x) R6 9r 1/(CE”) A-x O (CH2) zCH (CH2) mN A_X9! /- z-o (22) n. b. E2 N-R13 (23) R6 I 0 (CH2) zCH (CH2) rnN I R'. j ï! o (X) n R (left) (CH2)/\ N_RI3 A is a group of ethylens, which can carry a Ci-as0 alkyl group as substituents; X9 " is a halogen atom or a group of outlets, like a Mesityloder Tosylgruppe; G 1 is a C3 - Cycloalkylgruppe, a Phenylgruppe, which can have 1 to 3 substituent, selected consisting of the group of a halogen atom, C -4-AlkyIgruppe and Ct-4ss alkoxy group, or is a C -4-Alkylgruppe with a Ct-4 - Alkanoyloxygruppe or a Phenylgruppe as Substituent.

R'3 means however no phenyl (Ct-C4) - alkyl group, if R2 for Phenyl steht.

As one shows is the case for the reaction pattern 9, a connection of the general formula (22) is made by shifting of a connection of the general formula (21) with a Halogenierungsmittel or a sulfonierten ester means and by conversion of a connection of the general formula (2) with a connection of the general ós formula (24). A connection of of the general formula (21) manufactured by shifting of a connection of of the general formula (2) with a connection of of the general formula (25) 21 where q and The before indicated meaning to have. The s conversion of a connection of of the general formula (2) with a connection of of the general formulas (24) or (25), which in well-known or similar way are manufactured, can be accomplished under the same conditions as the Umsetznng of a connection of the general formula (2) with lo a connection of the general formula (3).

The conversion of a connection of the general formula (21) with an H alogenierungsmittel is accomplished in a suitable inert solvent. Examples of such solvents are ethers, like Dioxan or Tetrahyis drofuran, halogenierte hydrocarbons, like chloroform or dichloromethane. Examples of Halogenierungsmittel are N, N-Diäthyi-l, 2.2, - trichlorvinylformamid, phosphorus pentachloride, Phosphorpentabromid, Phosphoroxychlorid and dergleichen.

The quantity of Halogenierungsmittel amounts to at least the 2fache molecular quantity of the connection of the general formula (21) and generally in a surplus quantity is used. The conversion becomes at ambient temperature to 100°C, preferably with 40 to 70°C, during 1 to 2s 6 h durchgeführt.

The conversion of a connection of the general formula (21) with a sulfonierten ester means is accomplished in presence of a basic condensation means in a suitable inert solvent. Examples of s0 inert solvents are aromatic hydrocarbons, like benzene, toluol and such a thing, ethers, like Dioxan, tetrahydrofurane and such a thing, Pyridin, Dimethylsul641455 foxid, dimethylformamide or Hexamethylphosphoryltriamid. Examples of sulfonierte ester center [are alkyl sulphonyl halides, like Mesitylchlorid, Mesitylbromid, and Tosylchlorid and dergleichen.

Examples of condensing means are tert. - Amines, like tri ethyl amine, Pyridin or N, N-Dimethylanilin, Natriumhydrogencarbonat, potassium hydrogencarbonate, Natriumcarbonat odr Kaliumcarbonat.

The quantity of the sulfonierten ester means is preferably used in at least the 2fach molecular quantity of a connection of the formula (21), the 2bis 4fachen molecular quantity. The conversion becomes with -30 to 100°C, preferably with 0 to 50°C during 1 to 15 h durchgeführt.

The conversion of a connection of the general formula (22) with a connection of the general formula (23) is accomplished in present or in absence of a basic condensing means in a suitable inert solvent. Examples of such inert solvents are a low alcohol, e.g. a methanol, an ethanol, an isopropanol, a butanol or such a thing; aromatic hydrocarbons, like benzene, toluol, xylene and such a thing, acetic acid, ethyl acetate, Dimethylsulfoxid, dimethylformamide, Hexamethylphosphoryltriamid and such a thing. Examples of basic condensation means are Natriumcarbonat, potassium carbonate, Natriumhydrogencarbonat, sodium hydroxide, potassium hydroxide, Natriummethylat, Natriumäthylat, Pyridin or Triäthy [amin.

The connection of the general formula (23) is used with advantage in at least a äquimolaren quantity of a connection of the formula (22), preferably a äquimolaren quantity of the latters molecular to 5fach. The conversion becomes with 40 to 120°C, preferably with 70 to 100°C, during 1 to 15 h durchgeführt.

Reaction pattern R6 I O (CH2) £CH (CH2) mNH2 (X) n jR1 0 R6 [/(CH2) e 1 O (CH2) £CH (CH2) mN. , NR \ k “R2 R4 (26) (X) n R [1 t) (25) (l j) Xl° is a halogen atom or a group of outlets, like a Mesityloxyoder Tosyloxygruppe.

The connections of the formulas (25), used as raw material, and (26) can in well-known procedures or in analogy procedures manufactured werden.

During the conversion of a connection of the general formula (25) with a connection of the general formula (26) the reaction conditions can be used in such a way as during the conversion of a connection of the general formula (22) with a connection of the general formula (23), as shown in the reaction pattern 9 wurde.

If necessary the connections of the general formulas (la) can, (lg), (LH), (left) and (left), which according to the reaction patterns 7 to 10 will receive, in which entspres5 chenden ester transferred, by one it alkanoyliert or by being shown a connection, with which R6 a hydroxy group is, in accordance with a procedure, like it in the reaction pattern 2, 3,4,5-trimethoxybenzoyliert.

Of the Carbostyril connections of the general óo formula (1) of the available invention a connection, in which the carbon carbon connection is into the 3und 4-Stellung in the Carbostyrilgerüst a single bond, knows 6s converted in a connection with a carbon carbon double bond by the dehydrogenation werden.

Alternatively Carbostyril connections of the connections according to invention of the general formula (1), with which the carbon carbon connection is in the 3und 641,455 22 4-Stellung in the Carbostyrilgerüst a double bond, can into a connection to be transferred, in which the carbon carbon connection is into the 3und 4-Stellung a Einfachbíndung and no halogen atoms, AIkylgruppen or contains groups of alkenyls, by one the first catalytically hydriert.

Connections of the general formula (l) can be transferred easily into the acid addition salts by conversion with pharmaceutical acceptable acids. Examples of such acids are inorganic acids, like Chlorwasserx0 material acid, sulfuric acid, phosphoric acid, hydrobromic acid and such a thing; organic acids, like oxalic acid, maleic acid, Furmarsäure, malic acid, tartaric acid, citric acid, benzoic acid and such a thing. The connections manufactured after the different Reaktionsschemen xs know präparative Dünnschichtchromatografie by usual procedures, like solvent extraction, solvent dilution, recrystallizing, Säulenchromatografie, in an isolated manner and cleaned werden.

The connections according to invention close also optical isomers ein.

As Antihistaminica and means for the absorption of the central nervous system the connections of the formula (1) in the form of pharmaceutical preparations as well as other pharmaceutical acceptable carriers ver2s can turns become. The used carriers depend on the kind of the pharmaceutical composition and close Excipientien, fillers, diluents, bonding agents, Befeuehtungsmittel, decay means, surface-active materials and lubricants ein.

Regarding the administration units no special restrictions and the connections exist can in each desired unit form be used and typical single dosage forms are tablets, pills, powder, liquid preparations, suspensions, emulsions, ss granulates, caps, Suppositorien, injections (solutions and suspensions), and ointments. For the shaping to tablets carriers, how they are common in this area, can be used, e.g. Excipientien, like lactose, Rohrzucker, sodium chloride, solutions of glucose, urea, strength, calcium carbonate, Caolin, crystalline cellulose, silicic acid; Bonding agent, like water, ethanol, Propanol, simple syrups, glucose, starch solutions, gel solutions, Carboxymethylcellulose, Schellak, methyl cellulose, Caleiumphosphat and Polyvinylpyrrolidon; Zerfall4s means, like dry strength, Natriumalginat, agar agar powder, Laminalien powder, Natriumhydrogencarbonat, calcium carbonate, Tweens (registered registered trade mark for fatty acid esters of Polyoxyäthylensorbitan, manufacturer: Atlas Powder CO., Ltd., the USA), Natriumlaurylsulfat, Monoglycerid so oil hydrogenated by stearic acid, strength, lactose, decay inhibitors, like Rohrzucker, Stearin, coconut butter; AbsorpUonsbesch [euniger, like quaternäre ammonium bases, Natriumlaurylsulfat; Humidification means, like GIycerin or strength; Absorbent, like strength, lactose, ss Caolin, Bentonit, colloidale silicic acid; Lubricant, like cleaned talc, stearic acid salt, boric acid powder, Macrogol (registered registered trade mark for a PL glycol, manufacturer: Shinetsu Chemical Industry CO., Ltd., Japan) and firm Polyäthylenglycol. 6 for deformation to pills can do those for this admitted carrier to be used, e.g. Excipientien such as glucose, lactose, strength, coconut butter, hydrogenated vegetable oils, Caolin and talc; Bindemíttel, like powdered rubber arabicum, powdered Tragacanth, gel and ethanol; Decay means, like Laminañen and agar agar. Tablets can with usual Überzugsmaterialien, how sugars, gel coats are manufactured or with enterischen coatings, and the tablets can also with simple, double or multilayered coats provides sein.

Suppositorien manufactured using on this s area admitted to carriers, e.g. Polyäthylenglycol, coconut butter, higher alcohols, Estero of higher alcohols, gel and halfsynthetic Glyceriden.

Inject-cash preparations, solutions and suspensions are sterilized and are preferably isotonisch to Blut.

During the production of injected preparations all know carriers to be used, e.g. water, ethyl alcohol, Propylenglycol, äthoxylierter Isostearylalkohol, Polyoxyäthylensorbit or Sorbitanester for such preparations admitted. In this case appropriate quantities of sodium chloride, glucose or Glycerin the desired preparations can, in order to make these isotonisch, to be added. In addition can the ûblichen solvents, buffer, Analgesierungsmittel, preservatives and just as means, odoriferous substances, taste material, sweet means also colorgiving and other drugs the desired preparations if required added werden.

For the production of pastes or creams for this area admitted diluents used, like white Vasiline, paraffin, Glycerin, cellulose derivatives, Polyäthylenglycol, silicones and Bentonit.

The quantity of the connection of the general formula (1) or their acid addition salts, which is contained in the Antihistaminica or in the means for the absorption of the central Nervensysterns, particularly and preferably amounts to I to 70 Gew is not limited. - %, related to the entire Zusammensetzung.

The mentioned antihistamine means and means to the Dämplung of the central nervous system can be used without restriction for the respective purpose in the different forms. E.G. one can give tablets, pills, solutions, suspensions, emulsions, granulates and caps orally and injectable preparations become intravenously separately or with physiologically compatible solutions, like glucose solutions and amino acid solutions, given and if necessary can the injection preparations intramuskulär, intrakutan, subkutan or intraperitoneal be given. Suppositorien will become rektal given and ointments by laying on verabreicht.

The dosage of the available Antihistaminica and means for the absorption of the central nervous system is selected depending upon the use, the purpose and the conditions and symptoms, whereby generally pharmaceutical compositions the 40 gg to 2 mg/kg • day of the connection of the general formula (l) or their acid addition salts three to four times daily gives werden.

Example for the production of tablets (1) 7 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril. Dihydrochlorid 5 mg 6s corn strength 132 mg magnesium stearate 18 mg lactose 45 mg entirely 200 mg example of a preparation of tablets (2) 23 7 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril. Dihydrochlorid 10 mg corn strength 130mg s magnesium stearate 18 mg lactose 42 mg entirely 200 mg the tablets become from the above formulations in usual procedures hergestellt.

The results of pharmakologischen examinations of the connections according to invention become following gezeigt.

6 7 8 9 RST 11 is 12 13 14 16 2s 17 18 19 21 (I) antihistamine activity examination Zllr determination of the antihistamine activity of a connection in vitro a procedure is used, with a cut out oleum of a guinea pig used wird.

A male sea pig with 300 to 500 g body weight is killed by Ausbluten. A Ileum of a length of 15 cm is cut out from the ileozäkalen region and in Tyrode's solution (made of 0,8 g NaC1, 0.2 g KCI, 0.2 g CaCh, 1.0 g glucose, 1.0 g NaHCO3, 0.065 g NaH2PO 2H2 0 and 0.2135 g MgCh. 6H2 0 and water up to a total quantity of 1000 mi) dipped. Then the Ileumgewebe is cut to lengths from 2,5 to 30 cm and suspended in an organ bath, which is filled with 30 valley Tyrode's solution. The organ bath is held at a temperature of 36°C and blown by the bath a Dowson gas from 5% CO2 and 95% 02. One admits 10-aM histamine to 10 minutes after injecting to the bath, in order to measure the sensitivity of the fabric, and one receives a reaction curve (control) regarding the dosage from histamine. As soon as 3s 22 becomes constant the dosage of the Hystaminreaktionskurve (control), one gives 10-tg/mi to the connection 23 to the bath, which can be examined, and further one admits 5 minutes late histamines, around a dosage reaction curve to 24 received. The Retraktion of the Ileum is aufgezeiehnet by means of a Schreibcrs at a isotonischen transfer equipment (TD112S, manufactured of Nihon Koden). The antihistamine activity of the examined connection becomes as pA2 - value after 26 “Van Rossam” - method (J.M. Van Rossam: Arch. 27 Inst. Pharmacodyn., 143.299 (1963)) expressed so that the maximum Retraktion of the Ileums, as she is caused by 28 histamine is in the control curve 100%. The results become in table 1 gezeigt.

29 examined connections (connections according to invention (No. 1-39) VerbinNameder connections dung 1 2 3 4 31 ss 32 33 5 [2-Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3.434 dihydrocarbostyril. Mono hydrochloride 7 [2-Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril. Mono hydrochloride 8-Chlor-5 (2-hydroxy-3 [4 (4-chlorophenyl) - pipera36 zinyl] propoxy) - 3,4-dihydrocarbostyril • Monohy37 drochlorid it 38 6,8Dichlor-5 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril • Monohy39 drochlorid 641455 5 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril. Dihydrochlorid 7 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril. Dihydrochlorid 1-Methyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril. Mono hydrochloride 1-Benzyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril • mono hydrochloride 1-Methyl-5 [3 (4-phenylpiperazinyl) propoxyl-3,4dihydrocarbostyril. Mono hydrochloride 5 (4 [4 (4-Methylphenyl) piperazinyl] butoxy} - 3,4dihydrocarbostyril 1-AUyl-5 {2-hydroxy-3 [4 (4-methylphenyl) piperazinyl] propoxy)--3,4-dihydr ocarbostyril 1-Benzyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril 4-Methyl-7 [3 (4-phenylpiperazinyl) propoxy] - carbostyril 7 [3 (4-Benzylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril 7 {3 [4 (4-Methylphenyl) piperazinyl] propoxy) - 3,4dihydrocarbostyril 7 (3 [4 (4-Chlor-phenyl) piperazinyl] propoxy) - 3,4dihydrocarbostyril 7 (3 [4 (2-Methoxyphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril 7. (3 [3-Methyl-4 (4-chlor-phenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril. Dihydrochlorid 8 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril 5 [2-Acetyloxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril 5 [2 (3,4,5-Trimethoxybenzoyloxy) - 3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril 7 (3 [4 (2-Methoxyphenyl) piperazinyl] propoxy} - carbostyril. Dihydrochlorid i (2-Propyl) - 7 [3 (4-phenylpiperazinyl) propoxy] - 3,4dihydroearbostyril. Dihydrochlorid 7 {3 [4 (3-Fluorophenyl) piperazinyl] propoxy) - 3,4dihydrocarbostyril 7 [2-Methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril 4 [3 (4-Phenylpiperazinyl) propoxy] carbostyril 4-Phenyl-7 [3 (4-phenylpiperazinyl) propoxy] carbostyril 6Chlor-8-brom-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril • Dihydrochlorid 7 (3 [4 (3,4,5-Trito ethoxyphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril • Dihydrochlorid 5 [3 (4-Cyclohexylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril 5 [3 (4-Phenylhomopiperazinyl) propoxy] 3,4-dihydrocarbostyril 7 (3 [4 (2-Acetyloxyäthyl) piperazinyl] propoxy} - 3,4dihydrocarbostyril 7 (3 [4 (2-Hydroxyäthyl) piperazinyl] propoxy)--3,4dihydrocarbostyril 7th [3 (4-Acetylpiper azinyl) propoxy] - 3,4-dihydrocarbostyril 7 [3 (4-Benzoylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril 6 [3 (4-Phenylpiperazinyl) propoxy] carbostyril 7 [3 (4-Phenylpiperazinyl) propoxy] carbostyril 1-Hexyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril. Dihydrochloride 7 {3 [4 (3-Chlorphenyl) piperazinyl] propoxy} - 3,4dihydrocarbostyril 641,455 table I tested connection pAz tested connection pA2 No. Nr.

1 8.08 21 9.04 2 7.75 22 7.93 3 8.31 23 9.23 4 8.95 24 9.59 8.87 25 9.21 6 9.34 26 8.66 7 9.88 27 9.01 8 10.80 28 9.64 9 10.58 29 8.57 8.90 30 7.35 I 1 9.21 31 9.58 I2 8.21 32 7.52 13 9.39 33 7.02 14 9.10 34 7.24 9.48 35 8.58 16 9.63 36 7.99 17 9.06 37 9.53 18 8.66 38 8.93 19 7.99 39 9.74 8.91 (II) Anästhesieund sehlaferhöhende activity (A) Halothananästhesie increasing activity it male mice with a weight were used by 20 g of the DDY trunk. An experimental group consisted of 10 mice. An aqueous rubber arabikum suspension of the connection which can be examined (80 GM one connection which can be examined and 1 g rubber arabicum/100 ml physiological NaC1-Lösung) is orally given with each mouse in a dose by 80 mg of the Prüfverbindung/kg body weight. 1 h after the administration is given each mouse containing into a Gasrespirationskammer (13 x 13 x 24 cm) and to oxygen gas, 4% Haloth (2-Brom-2-Chlor-l, l, l-trifluoräthan) into the chamber during 3 minutes in a quantity of 2 l/Minute on blown. The anästhesierte mouse is taken from the chamber and the time between the introduction of the anaesthesia up to waking up is measured. The mice of the control group kept arabicum an aqueous physiological solution in a dose oral to 24 3 l%-ige rubber from 0,1 ml/10 g body weight (reference: M.J.

Turn bulletin and J.W. Watkins: Br. J. Pharmac., 58, 27-35 (1976)).

The results become in table 2 gezeigt.

Table 2 (dose: 8 mg/kg) tested time (minutes) tested time (minutes) connection No. connection Nr.

1,9.3 _+ 4.9 21 8, I +_3,9 2 11.7 _+ 5.6 22 10.4 + _ 4.1 3 7.9 _+ 3.4 23 7.6 + 4.2 4 7.4 + - 2.7 24 11.6 _+ 6.7 16.9 _+ 7.9 25 7.8 + - 3.3 6 16.8 + - 6.2 26 8.5 ± 3.7 7 8.9 ± 2.4 27 7.8 ± 3.2 8 7.5 + - 3.3 28 10.2 + _ 5.8 9 9.5 _+ 3.2 29 9.3 _+ 4.4 l0 7.9 + _ 3.7 30 7.9 _+ 3.7 11 6,8_+2,2 31 8,2+,3.9 12 7.5 _+ 3.5 32 7.9 + - 3.1 13 8.1 + _ 2.7 33 7.4 + _ 2.6 14 7.5 + 4.3 34 7.8 + 3.4 12,7+,3.5 35 8,2__+3,7 16 11.4+ 5.6 36 15.3 + _ 3.1 17 13,6+_ 5.2 37 13.1 + _ 6.0 18 8.4+2.5 39 5,0-/-2.9 19 9.3+3.5 9.8 + _ 3.7 (B) halo-Thana-branch-they-increasing activity the same procedure as under (II) - (A) is described applied with the exception that the quantity of the orally given connection auf4 dosage stages which can be examined is divided of 0,5 mg/kg, 1 mg/kg, 2 mg/kg and 4 mg/kg, and the relationship between the dose and the degree of the strength of the anaesthesia increasing activity measured wird.

The results become in table 3 gezeigt.

Table 3 anaesthesia-increasing activity (minutes) tested connection 0 mg/kg 0.5 mg/kg 1 mg/kg 2 mg/kg 4 mg/kg reference example Haloperidol 5.6 + _ 3.1,5.3 + _ 2.9,5.1 + _ 2.5,9.3 + _ 3.1 10.2 ± 3.7 PentobarbitaI 5.1 _+ 3.5,5.3 + _ 2.6,4.9 + - 3.5,6.3 + - 2.3 8, l ± 3, I connection according to invention connection No. 5,4.9 + 2.5 connection No. 6,5.5 + 2.1 connection No. 7,4.8 + 3.1 connection No. 29,5.1 + _ 2.6 5,2+_2,1 8,5±3,5 9,6±4, I 12,7±3,9 8,2±2,6 10,3+_3,3 I2,1±4,2 16,6±5,1 5,3±2,5 7,4±3,1 9,5±3,8 13,7±4,7 5,6±2,8 6,6±3,1 8,3±3,7 13,6±4,9 (C) Hexobarbital schlaferhöhende activity male mice of the DDY trunk with a body weight of 20bis 25 g 24 h chamfered left. A group consisted of 10 mice. An aqueous Gurnmi arabicum suspension of the connection which can be examined (0.05 g of the connection which can be examined and 1 g rubber arabicum/100 mi physiological NaC1-Lösung) is given orally in the dose mentioned in table 4. 1 h after the administration 0.7% of Hexobarbital become. Well salt intraperitoneal in a dose of 70 mg/kg body weight gives. Ss the time between the sleep introduction up to awaking is measured, whereby the putting up reflex is used” as index (reference: A.M. t-ljort, De E.J. Beer and D.W. Fassett; J.

Pharmac. Exptl. Ther., 63.421 (1963)).

641,455 table 4 examined Verbindnng dose sleep time (minutes) (mg/kg) (means + SD) invention according to invention physiological saline solution - 36.52+ 10.15 connection 6,0.5 43.76 + 6.09 connection 6,1.0 51.24 + 11.75 connection 6,2.0 54.11 + 7.80 connection 6,4.0 65.13 + 11.59 connection 6,8.0 85.83 + 12.24 physiological saline solution - 32.14 + 6.25 connection 17 0.125 39.51 _+8,45 connection 17 0.25 45.57 + 10.05 connection 17,0.5 51.77+6.60 connection 17,1.0 56.92 + 6.13 acquaintance comparison connection physiological Kochsal71ösung - 35.07+4.98 Haloperidol 4 43.01 + 19.22 Haloperidol 8 46.83 + 13.94 Haloperidol 16 66.81 + 14.32 Lösung/10 g body weight intraperitineal injects. With the mice, to which orally the comparison connection (Haloperidol) had been given, the injection is given 110 minutes after the administration. The amount of the stuff mungen after 10 minutes 10 minutes are noted, and the EDs0 - values of the respective connections are compared compared with the number of curvatures with the control group (reference: R., M. Anderson and E.I. Debber costs: Fed. Proc., 18.412, (1959)).

lo the results become in table 6 gezeigt.

Table ó examined connection connection according to invention No. 6 connection No. 37 connection No. 31 acquaintance comparison connection Haloperidol (II1) activity regarding the combat desire of a mouse, the long time isolates separately war.

Particulars, male mice of the DDY trunk with 15 to g body weight were kept 1 month separate in cages. A group of tests consisted in each case of 10 pairs of mice. Each member of a pair of mice was in such a way selected that, if a mouse were given to others to the cage or two these fought over 30 seconds constantly. EDs0 - Values were computed, by giving the 3s respective test connection of each group of the mice. The activity for the Inhibierung of the combat desire of the test connections is called positive, if the mouse continues a fighting only within 5 seconds in one minute. If the mouse fights longer than 5 seconds, then they were again separated, in order a smaller number of injured mice too received (reference: C.Y. Yen, R.L.

Stanger and N. Millman: Arch. Int. Pharmacodyn., 123, 1979 (1959)).

The results become in table 5 gezeigt.

Table EDso (mg/kg) 1.28 (0,63-2,72) 0.70 (0,51-1,12) 1.52 (0,78-3,53) 0.78 (0,22-1,38) 0.96 (0,52-2,31) 0.92 (0,38-1,59) 7.29 (4,04-18,6) examined connection connection according to invention connection 6 connection 9 connection 37 connection 39 connection 17 comparison connection:

Diazepam EDs (mg/kg) 2.31 (1,53-3,46) 1.52 (0,71-3,15) 1.92 (1,28-4,31) 2.31 (1,26-5,31) (V) of acutes toxicity (LDs0) mice of the DDY trunk with 20 to 22 g body weight were used. A group of tests consisted of 10 Mäusen.

Oral administration:

(IV) Analgeti activity mãnnliche mice were used by the DDY trunk with a weight from 15 to 23 g body weight. A group of tests consisted of 10 mice. The connections which can be examined became oral after in (II) described procedures given. 50 minutes after the administration are suspended 0.1 ml a 0,6%-igen acetic acid, the aqueous connection which can be examined in l%iger rubber arabicum physiological NaCl solution (water), intravenous administration: The connection which can be examined is solved in 50%iger of aqueous Propylenglycol solution. The results become in table 7 gezeigt.

Examined connection table of 7 (LDso) male mice female mice oral intravenous oral intravenous (mg/kg) (mg/kg) (mg/kg) (mg/kg) connection according to invention No. 6,920,240,890,250 connection No. 7 1600 424 1650 432 4s connection No. 39 1206 310 1100 293 connection No. 17,898,218,860,216 connection No. 31,870,256,923,248 acquaintance connection diazepam - 59 58 LD 0-Werte (oral administration) of the available connections, which were not the connections 6, 7, 17, 31 and 39, became also over 800 mg/kg when using male Måusen of the DDY trunk bestimmt.

In the following some reference examples are indicated for the production of the connections, those as raw material for the production of the desired connections of the invention dienen.

Reference example 1 20.5 g 5-Acetyloxy-3,4-dihydrocarbostyril are dissolved in 200 valley acetic acid. This solution will become under cooling with water agitated and it 60 valley acetic acid solution, which contains 16 g bromine, drop by drop during 30 minutes in addition-given, whereby the reaction is accomplished during 2 h at the same temperature. The reaction mixture is poured in 300 ml water and during 3 h to stand leave/> The failed crystals become by filtration abge641 455, 26 separate and from methanol under receipt of 21 g 8-Brom-5-acetyloxy-3,4-dihydrocarbostyril in form of colorless, needle-like crystals with a fusion point of 237-239°C umkristallisiert.

The thereby received 21 g 8-Brom-5-aeetyloxy-3,4-dihys drocarbostyril are dispersed in 150 valley 8n hydrochloric acid. The dispersion is heated up on return flow conditions during 3 h and cooled down then. The thereby formed insolublenesses is separated by filtration, washed and dried with water and from z0 methanol water under receipt from 14 g 8-Brom-5-hydroxy3,4-dihydrocarbostyril in form of colorless, needle-like crystals with a fusion point from 212-213°C umkristallisiert.

Reference example 2 s 16.4 g 5-Hydroxy-3,4-dìhydrocarbostyril are dissolved in 300 valley acetic acid. This solution will become at ambient temperature agitated and it 50 valley acetic acid solution, yields 7 g chlorine contains, drop by drop in addition-given, whereby the reaction is accomplished during 3 h under agitating. The reaction mixture is poured in 500 ml water and let during 1 h stand, whereby the thereby formed precipitation is separated by filtration, washed with water and dried then. By recrystallization from ethanol water 13.5 become g 6-Chlor-5-hydroxy-3,42s dihydrocarbostyril in form of colorless, needle-like crystals with a Sehmelzpunkt of 209-210°C erhalten.

Reference example 3 16.4 g 5-Hydroxy-3,4-dihydrocarbostyril are dissolved in 300 valley acetic acid. This solution will become at ambient temperature agitated and it 80 valley acetic acid solution, which contains 16.4 g chlorine, drop by drop in addition-given, whereby the reaction during 3 h under agitating accomplished wird.

To the procedure of the reference example 2 as the raw crystals become similar from methanol under receipt of 16 g 6,8-Dichlor-5-hydroxy-3,4-dihydrocarbostyril in the form of colorless, needle-like crystals with a fusion point of 259-250°C umkristallisiert.

Reference example 4 35.4 g 7-Methoxy-3,4-dihydrocarbostyril are dissolved in 300 mi acetic acid. This solution is agitated under ice cooling, whereby 100 valley acetic acid solution, which 27 g Sulforylchlorid contains, is drop by drop in addition-given and of 43 over night stand is let. The reaction mixture is then poured in 1 1 ice water and the thereby formed precipitation by filtration is separated, washed and dried with water. By recrystallizing from methanol 30 g 6-Chlor-7-methoxy-3,4-dihydroearbostyril in s0 become form of colorless, needle-shaped crystals with a Sehmelzpunkt of 212°C erhalten.

The thereby received 30 g 6-Chlor-7-methoxy-3,4dihydrocarbostyril are dispersed in 300 ml 47%iger of aqueous hydrobromic acid solution and heated up during 4 h ss on return flow conditions. After cooling of the reaction mixture the insoluble is separated by filtration, washed and getroeknet with water. By recrystallizing from methanol chloroform 25 g 6-Chlor-7-hydroxy-3,4-dihydrocarbostyril in form of colorless, needle-like crystals with a fusion point of 264-266°C become erhalten.

Reference example g 8-Methoxy-3,4-dihydroearbostyril are dissolved in 200 mi acetic acid. This solution will become under cooling agitated and it 100 ml acetic acid solution, which contains 16 g chlorine, in addition-given, and it is let stand over night. The reaction mixture is poured in 1 1 water and the thereby formed precipitation is then separated by filtration, washed and getroeknet with water. By recrystallizing from chloroform 42 g 5,6-Diehlor-8-methoxy-3,4-dihydrocarbostyril in form of weakly red, needle-like crystals with a fusion point of 201-202°C become erhalten.

The thereby received 42 g 5,6-Dichlor-8-methoxy-3,4dihydrocarbostyril are dispersed in 500 valley 47%iger of aqueous hydrobromic acid solution and heated up during 4 h on return flow conditions. After cooling of the reaction mixture the insoluble is separated by filtration, washed and dried with water. The thereby received raw crystals become from methanol under receipt of 29 g 5,6-Dichlor-8-hydroxy-3,4-dihydrocarbostyril in form of colorless, needle-like crystals with a fusion point of 233-235°C umkristallisiert.

Reference example 6 something similar to a procedure in accordance with reference example will 8-Brom-5-hydroxycarbostyril in form of colorless, needle-like crystals received (recrystallization solvent methanol). Fusion point 266-267°C (decomposition).

Reference example 7 22.7 g 8-Brom-5-meth0xy-3,4-dihydrocarbostyñl and 25 g copper (I) chloride are mixed with 100 mi Dimethylsulfoxid and heated up with 135 to 140°C during 4 h under agitating. After completion of the reaction the reaction mixture is mixed with 200 g ice and 50 valley of konzentñerter hydrochloric acid and agitated at ambient temperature during 1 h. The crystals thereby failed are separated by filtration, washed first with diluted hydrochloric acid and then with water and getroeknet.

The thereby received raw crystals are umkristallisíert from LigroinBenzol under receipt by 13 g 8-Chlor-5-methoxy-3,4-dihydrocarbostyril in form of weakly orange, needle-like crystals with a fusion point by 165°C. The thereby received 13 g 8-ChIor-5-methoxy-3,4dihydrocarbostyril and 35 g aluminum chloride are dispersed in valley benzene and heated up during 2 h on return flow conditions. The reaction mixture is separated in ice water gegosen and the thereby formed precipitation by filtration, washed with water and getrocknet.

Umkñstallisation from isopropanol resulted in 8 g 8-Chlor-5hydroxy-3,4-dihydrocarbostyril in the form of colorless, needle-like crystals with a fusion point of 206-207°C.

Reference example 8 20.0 g 8-Chlor-5-hydroxy-3,4-dihydroearbostyril and 18 g potassium carbonate are suspended in 160 ml isopropyl alcohol, then 40 ml Epichlorhydñn are admitted and the reaction mixture is held with 70 to 80°C during 6 h. The Reaktionsgemiseh is concentrated under reduced pressure and the thereby received arrears are agitated with 100 mi 2n sodium hydroxide on cooling conditions. The insoluble is separated by filtration, washed and dried in water. The raw crystals become from isopropanol under receipt of 18,5 g 8-Chlor-5 (2,3-epoxypropoxy) - 3,4-dihydrocarbostyril in form of colorless, needle-like crystals with a fusion point of 161-165°C umkristallisiert.

Reference example 9 20.0 g 6-Chlor-7-hydroxy-3,4-dihydrocarbostyril and 3.7 g sodium hydroxide are mixed with I00 valley methanol and agitated during 3 h. Then 150 valley is in addition-given to epichlorohydrin and it is heated up during 5 h on return flow conditions. After completion of the reaction the reaction mixture under reduced pressure is concentrated to dry ones. The thereby received arrears are mixed with 100 valley 2n Natñumhydroxid and well gerührt.

The insoluble is separated by filtration, washed and dried in water 27,641,455. The thereby received raw crystals become from methanol ethanol under receipt of 19,7 g 6-Chlor-7 (2,3-epoxypropoxy) - 3,4-dihydrocarbostyril in form of colorless crystals with a fusion point of s 190-192°C umkristallisiert.

Reference examples 10 to 13 something similar za the procedure of the reference examples 8 to 9 are received as follows the connections:

Reference example connection crystalline form (Umkristallisieruugsmittel) fusion point °C 11 12 13 6-Chlor-5 (2,3-epoxypropoxy) - 3,4-dihydrocarbostyril 6,8-Dichlor-5 (2,3-epoxypropoxy) - 3,4-dihydrocarbostyril 8-Brom-5 (2,3-epoxypropoxy) - 3,4-dihydrocarbostyril 5,6-Dichlor-8 (2,3-epoxypropoxy) - 3,4-dihydrocarbostyril colorless crystals (isopropanol) of 218-221 colorless crystals (methanol) of 117-178 colorless, needle-like crystals (methanol) of 220-222 colorless crystals (methanol) 183-184 Bezugsbeispie114 24.3 g 8-Brom-5-hydroxy-3,4-dihydroxy-carbostyril and 9 g potassium hydroxide are mixed with 150 valley isopropanol and with 70 to 80°C during 30 minutes gerührt.

Then 25 g 1,3-Bromchlorpropan are in addition-given and heated up during 6 h on return flow conditions. After completion of the reaction the reaction mixture in 200 valley aqueous sodium hydroxide solution is cast in and then the insoluble, which is thereby formed, is separated by filtration, washed in water and getrocknet.

The thereby received raw crystals become from ethanol under receipt of 21,5 g 8-Brom-5 (3-chlorpropoxy) - 3,4-dihydrocarbostyril in form of colorless, needle-like crystals with a fusion point of 184-185°C umkristallisiert.

Reference example g 6-Color-8-brom-7-hydroxy-3,4-dihydrocarbostyril and 2s 3 g sodium hydroxide are mixed with 120 ml isopropanol and agitated with 50 to 60°C during 1 h. Then 10 valley is in addition-given to 3-Boom-I-chlorpropan and it is agitated during 6 h with 70 to 80°C. The reaction mixture is concentrated under reduced pressure to dry ones and the thereby received arrears with chloroform are extracted. The chloroform layer is washed and dried with water. Then the chloroform is removed for 3,4-dihydrocarbostyril in form of colorless, needle-like crystals with a fusion point by distillation and the thereby formed arrears from ethanol under receipt from 6,2 g 6-Chlor-8-brom-7 (33s chlorpropoxy) - from 87-88°C umkristallisiert.

Reference examples 16 to 19 something similar to the procedure in accordance with reference example 15 the connections are received as follows:

Reference example connection Kristallîorm (recrystallization means) Sehmelzpunkt °C 16 17 18 19 4-Methyl-6 (3-chlorpropoxy) carbostyril 4-Methyl-7 (3-chlorpropoxy) carbostyril 5 (2-Methyl-3-chlorpropoxy) - 3,4-dihydrocarbostyril 7 (Methyl-3-chlorpropoxy) - 3,4-dihydrocarbostyril colorless, needle-like crystals (ethanol) of 183 colorless, needle-like crystals (ethanol) of 169-170 colorless, needle-like crystals (ethanol) of 139-140 colorless, needle-like crystals 75-76 (ethanol water) Bezugsbeispie120 18.3 g 3,4,5-Trimethoxyanilin and 31.2 g to ([3-bromäthyl) - amino monohydrobromid with 170 mi methanol are mixed and held under heating up under a nitrogen gas flow during 10 h at the return flow. After cooling of the reaction mixture 5.3 g water-free Natriumcarbonat are then in addition-given to the mixture and by heating up during further 10 h at the return flow gehalten.

Under reduced pressure about 70 valley methanol is removed by distillation and the mixture is left at ambient temperature cooling. The crystals thereby failed are collected by filtration and washed with a small ethanol quantity. By recrystallization from ethanol 38 g become 4 (3,4,5-Trimethoxyphenyl) piperazin monohydrobromid, panel-like crystals with a fusion point of 227-228°C, colorless in form, erhalten.

Then this connection in 20%-iger of aqueous sodium hydroxide solution is dissolved and extracted with chloroform. The chloroform layer is three times washed with satisfied fool ISO umchloridlösung, dried then and removed the chloroform by distillation. The free form of 4 (3,4,5-Trimethoxyphenyl) piperazin is received as only substance in form of a colorless, viscous, oily material. The chemical structure of this connection becomes ss by NMRund IR method identifiziert.

Example 1,4.4 g 5 (2,3-Epoxypropoxy) - 3,4-dihydrocarbostyril and 3.4 g 4-Phenylpiperazin are dispersed in 60 ml methanol and converted with 50 to 60°C during 3 h. After completion of the reaction the reaction mixture under reduced pressure is concentrated. The thereby received arrears 5 will become ml concentrated hydrochloric acid and 30 ml ethanol the even Auflõsung of the arrears in addition-given and it far 200 valley acetone in addition-given. The failed crystals are collected and dried by filtration. By recrystallizing from water 6.5 g become 5 [2-Hydroxy-3 (4-phe641455 28 nylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril-monohydroclalorid in form of colorless, needle-like crystals with a fusion point of 239-241 °C erhalten.

Example 2,4.4 g 6 (2,3-Epoxypropoxy) - 3,4-dihydrocarbostyril and 3.4 g 4-Phenylpiperazin are dissolved in 80 valley isopropanol and converted with 50 to 60°C during 3 h on agitating conditions. Then 5 is in addition-given to valley concentrated hydrochloric acid and concentrated under reduced pressure to dry ones. The thereby received arrears become from hot water under receipt of 6,1 g 6 [2Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril-monohydrochlorid. 1/2 water in form of colorless, needle-like crystals with a fusion point of 223-224°C umkristallisiert.

Example 3,2.9 g 1 (3-Methylbutyl) - 5 (2,3-epoxy-propoxy) - 3,4-dihyIR ([nfrarotabsorptionsspektrum) 3400 cm-l (OH), 1680 cm-j (- CO) NMR*: 8 = 6.8 - 7.3 ppm (aromatic proton BH) = 0.92 ppm (methyl proton, 6H) s (* the NMR measurements with d6-DMSO were accomplished) the thereby received connection according to usual method neutralized and the raw crystals will become out lo ethanol under receipt of 1 - (3-Methylbutyl) - 5 [hydroxy-3 (4phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril in form colorless, prism-like Kñstalle with a fusion point of 156-157°C umkñstallisiert.

Example 4 3,4g 1 (3-Phenylpropyl) - 5 (2,3-epoxypropoxy) - 3,4-dihydrocarbostyril and 2.0 g 4 (4-Methylphenyl) piperazin drocarbostyril and 1.7 g 4-Phenylpiperazin are mixed with 50 valley 2o with 50 valley methanol and by a methanol mixed and with 50 to 60°C during 3 h umgefahren converted, which bury similarly to the managing. The reaction mixture becomes under reduced pressure of play 3 was. The thereby received raw crystals are concentrated and the thereby received arrears in 50 ml from methanol ether under receipt of 4,2 g 1 (3-PhenylAceton dissolved. Into this solution will 20 valley of a Acepropyl) - 5 (2-hydroxy-3 [4 (4-methylpbenyl) piperazinyl] protonlõsung, which contains 1.1 g oxalic acid, in addition-given, then 2s poxy} - 3,4-dihydrocarbostyril-monooxalat in form more colorless becomes the thereby formed precipitation by filtration of crystals umkristallisiert.

separated, washed with acetone and dried. By recrystallization from ethanol ether 2.1 g 1 (3-Methylbutyl) become - 5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril-monooxalat in form of colorless crystals receive. This product is confirmed as individual connection by silicagel Dünnschichtchromatografie (development solvents:

Elementary analysis: C34 H41 OTN3 30Ber. (%): C 67,64; H 6,85; N 6.96 gel. (°B): C 67,85; H 6,52; N 6.81 Chloform: Methanol = 9: 1) elementary analysis C29 H39 OTN3 Ber. (%): C 64,30; H 7,26; Gel'. (%): C 64,52; H 7,10; N 7.76 N 7.48 [R (infrared absorption spectrum) 3480 cm (OH) 1675 cm (C=O) NMR **: 8 = 6.6 - 7.4 ppm (aromatic protons, 12H) -- 2,30 ppm (methyl protons, 3H) (** the NMR measurements became with d6. DMSO accomplished.) Examples 5 to 23 by methodologies, which were similar to those of the examples I to 4, were received as follows connections:

Example connection crystalline form (Umkristallísierungsmíttel) Sehmelzpunkt °C 6 8 9 11 12 8 [2-Hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 6 (2-Hydroxy-3 [4 (4-chlor-phenyl) - piperazinyl] - propoxy) - 3,4-dihydrocarbostyril monohydrochlorìdeV2 of hydrates 7 (2-Hydroxy-3 [4 (4-chlor phenyl) - piperazinyl] propoxy} - 3,4-dihydrocarbostyril mono hydrochloride. Mono hydrate 8-Brom-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 8-Chlor-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril mono hydrochloride. 3/2 hydrate 8-Chlor-5 (2-hydroxy-3 [4 (4-chlor phenyl) - piperazinyl] propoxy} - 3,4-dihydrocarbostyril mono hydrochloride 6-Chlor-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril dihydrochlorid. Mono hydrate 6,8-Dichlor-5 [2-hydroxy-3 (4-phenylpiperanzinyl) - propoxy] - 3,4-dihydrocarbostyril mono hydrochloride colorless crystals (methanol ethers) of 263 colorless, needle-like crystals of 212-214 (ethanol) colorless, needle-like crystals of 66-70 (isopropanol) colorless crystals (methanol) colorless Kñstalle (methanol ether) colorless, needle-like crystals (methanol ether) colorless, needle-like crystals (methanol ether) colorless crystals (water) 174-176 226-228 228-230 218-225 251-253 example connection 13 14 16 17 18 19 21 22 23 29 8-Chlor-5 (2-hydroxy-3 [4 (2-chlor phenyl) - piperazinyl] propoxy) - 3,4-dihydrocarbostyril 8-Brom-5 (2-hydroxy-3 [4 (2-methoxyphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyñldihydrochlorid 6-Chlor-7 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy]- 3,4-dihydrocarbostyril 6-Chlor-7 (2-hydroxy-3 [4 (2-methoxyphenyl) - piperazinyl] - propoxy) - 3,4-dihydrocarbostyril 1-Methyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 1-Äthyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril • mono oxalate 1-Allyl-5 {2-hydroxy-3 [4 (4-methylphenyl) - piperazinyl] propoxy) - 3,4-dihydrocarbostyril 1-Benzyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 6 [2-Hydroxy-3 (4-phenylpiperazinyl) - propoxy] - carbostyril. 1/2 hydrate 8-Brom-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] carbostyril 6,8-Dichlor-5 (2-hydroxy-3 [4 (4-chlorophenyl) - piperazinyl] propoxy) - 3,4-dihydrocarbostyril • mono hydrochloride. I/2 hydrate crystalline form (recrystallization means) colorless crystals (ethanol) colorless crystals (methanol ether) colorless, needle-like crystals (methanol water) colorless crystals (ethanol) colorless, needle-like crystals (n-hexane benzene) colorless crystals (ethanol ether) colorless, needle-like crystals (Ligroin benzene) colorless, needle-like Kñstalle (petroleum ether ether) colorless crystals (methanol) colorless, plättehenartige crystals (methanol) colorless, puderförmige crystals (methanol) 641,455 fusion point °C 156-158 226-228 171-173 183-184 143-145 201-203 123-124 148-150 218-219 179-182 158-161 example 24,2.4 g 4-Methyl-7 (2,3-epoxypropoxy) - carbostyril and 1.8 g 4-Phenylpiperazin are mixed with 30 valley ethanol and heated up during 3 h on return flow conditions. After cooling of the reaction mixture the crystals thereby failed are collected by filtration and with ether gewaschen.

The thereby received raw crystals are dissolved in 50 valley methanol and 3 ml concentrated hydrochloric acid and the mixture is then evaporated under reduced pressure to dry ones. The thereby received arrears become from ethanol ether under receipt of 2,7 g (yield 63%) 4-Methyl-7 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] carbostyril monohydrochlorid in form of colorless crystals with a fusion point of 190-191 °C umkristallisiert.

Example something similar to the procedure of the example 24 becomes 4-Methyl6 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] carbostyril 1/2-hydrate in form of colorless crystals (recrystallized from ethanol) with a fusion point of 212-213°C erhalten.

Example 26,4.8 g 5 (3-Chlorpropoxy) - 3,4-dihydrocarbostyril and 4 g 1-Phenylpiperazin are mixed with 40 ml toluol and heated up during 24 h on return flow conditions. Then the reaction mixture under decreased pressure is concentrated to dry ones. The thereby received arrears are dissolved in 80 valley chloroform and the chloroform layer is washed twice with 5,0% of aqueous sodium hydrogencarbonate solution, removed then twice washed with water, with water-free sodium sulfate dried and the chloroform by distillation. To the thereby received arrears hexane is in addition-given and the insoluble material is collected by filtration, the insoluble material in 30 valley 5% HC1-Methanollösung is so then dissolved and concentrated under reduced pressure to dry ones. The thereby received arrears become from methanol ether under receipt of 3,2 g 5 [3 (4-Phenyl-piperazinyl) propoxy] - 3,4-dihydrocarbostyril-monohydrochlorid in as form of colorless crystals with a Sehmelzpunkt of 262°C (decomposition) umkristallisiert.

Example 2 7 4.5 g6 (2-Chloräthoxy) - 3,4-dihydrocarbostyril and 3.3 g sodium iodide are mixed with 50 ml acetone and heated up during 5 h on return flow conditions. Then 4Ò valley dimethylformamide to the reaction mixture hinzuge4s to give and the acetone is removed for distillative with 40 to 45°C under decreased pressure. 3.8 g l-Phenylpiperazin are in addition-continued to give to the reaction mixture and the reaction is accomplished with 60 to 70°C during 7 h on agitating conditions. The reaction mixture is concentrated under verso ringertem pressure to dry ones and the thereby received arrears are dissolved in 80 ml chloroform. The chloroform layer is washed twice with aqueous 5% sodium hydrogencarbonate solution and then twice with water. After drying ss the chloroform layer the chloroform is removed by distillation. The thereby received arrears become by silicagel Säulenchromatografie (silicagel: Wako gel C-200, registered trade mark, manufactured and drove out by Wako Chemical CO., Ltd. ; Elutionslösungsmittel chloroform: Meaa thanol = 20: 1), and the desired connection is übergeffihrt into the hydrochloride using ethanol, which is with hydrogen chloride-satisfied, whereby ethanol is removed by distillation under reduced pressure. The thereby received arrears become from Meas thanol ether under receipt of 3,8 g 6 [2 (4-Phenylpiperazinyl) äthoxy] - 3,4-dihydrocarbostyril-monohydrochlorid. Mono hydrate in form of colorless crystals with a fusion point of 196-198°C umkristallisiert.

641,455 examples 28 to 72 something similar to the methodology of the examples 26 to 27 are received as follows connections:

Example connection crystalline form (Umkristallisierungsmiuel) fusion point °C 28 29 31 32 33 34 36 37 38 39 41 42 43 44 46 47 48 49 51 52 53 54 56 57 58 5 [2 (4-Phenylpiperazinyl) äthoxy] - 3,4-dihydrocarbostyril dihydrochlorid 6 {3 [4 (2-Methoxyphenyl) piperazinyl] - propoxy} carbostyril dihydrochlorid 7 [2 (4-Phenylpiperazinyl) äthoxy] - 3,4-dihydrocarbostyril 7 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril dihydrochlorid. 3/4 hydrate 8 [2 (4-Phenyl-piperazinyl) äthoxy] - 3,4-dihydrocarbostyril dihydrochlorid, lA hydrate 1-Methyl-5 [3 (4-phenylpiperazinyl) - propoxy] - 3,4dihydrocarbostyril dihydrochlorid, lA hydrate 8-Brom-5 {3 [4 (4-methylphenyl) - piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 5 {4 [4 (4-Methylphenyl) piperazinyl] - butoxy} - 3,4-dihydrocarbostyril 5 {5 [4 (2-Methoxyphenyl) piperazinyl] - pentyloxy} - 3,4-dihydrocarbostyril 5 {2 [4 (4-Methylphenyl) piperazinyl] - äthoxy} - 3,4-dihydrocarbostyril 6 [3 (4-Phenylpiperazinyl) propoxy] - carbostyril 8 (3 [4 (2-Methoxyphenyl) piperazinyl] - propoxy} - carbostyril. Dihydrochlorid 7 [3 (4-Phenylpiperazinyl) propoxy] carbostyril 8-Brom-5 [3 (4-phenylpiperazinyl) - propoxy] - carbostyril, dihydrochlorid. Mono hydrate 7 {3 [4 (4-Methylphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril 5 {3 [4 (2-Äthoxyphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 7 {3 [4 (2-Äthoxyphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 6-Chlor-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril. dihydrochloñd. Mono hydrate 6-Brom-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril • Dihydrochlorid 7 {3 [4 (2-Chlorphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 7 {3 [4 (3-Chlorphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 7 {3 [4 (4-Chlorphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 7 {3 [4 (2-Methoxyphenyl) piperazinyl] - propoxy} - 3,4dihydrocarbostyril 7 {3 [4 (4-Methoxyphenyl) piperazinyl] - propoxy} - 3,4dihydrocarbostyril 6 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril 8 [3 (4-Phenylpiperazinyl) propoxy] - 3,4-dihyd rocarbostyril 7 [4 (4-Phenylpiperazinyl) butoxy] - 3,4-dihydrocarbostyril 5 - (3 [4 (2-Methoxyphenyl) piperaNnyl] - propoxy} - 3.4 dihydrocarbostyril 7 {3 [4 (2-Methoxyphenyl) piperazinyl] - propoxy} carbostyril 1 - Benzyl-7 [3 (4-phenylpiperazinyl) - pr Œ Epoxy] - 3,4-dihydrocarbostyril 1-Allyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril • Dihydrochlorid colorless, shed-like crystals (methanol ether) colorless crystals (methanol) colorless, needle-like crystals (ethanol) colorless, needle-like crystals (methanol ether) colorless crystals (methanol ether) colorless crystals (ethanol ether) weakly yellow, needle-like crystals (Ligroin benzene) colorless, panel-like crystals (methanol) colorless, needle-like crystals (ethanol) colorless, panel-like crystals (Ethanol) colorless, shed-like crystals (methanol) - colorless, needle-like crystals (ether) yellowish, needle-like crystals (methanol) colorless, needle-like crystals (methanol) yellowish, needle-like crystals (ethanol) colorless, needle-like crystals (ethanol) colorless, needle-like crystals (ethanol) colorless, needle-like crystals (methanol ether) colorless, needle-like crystals (methanol ether) weakly yellowish, prismaförmige crystals (ethanol) colorless, needle-like crystals (ethanol) weakly yellowish, primsaförmige crystals (ethanol) colorless, pulvrige crystals (ethanol) colorless, needle-like crystals (ethanol) colorless, plättehenförmig œ e of crystals (Athanol) colorless, plate-like crystals (ethanol) colorless, needle-like crystals (isopropanol) colorless, prismaförmige crystals (methanol) colorless, powdery crystals (ethanol) weakly yellowish, needle-like crystals (Athanol) colorless crystals (ethanol) 270 (decomposition) 241-242 (decomposition) 171-175 213-215 255 (decomposition) 226-228 181-182 170-172 154-156 179-182 226-227 242-245 (CPU etzung) 237-238 206 149-150 155-156 140-142 280 (decomposition) 255-258 146-147 156-158 200-202 134-137 146-149 184-185 112-114 123-124 194-196 229-232 125-127 189-192 example 59 61 62 63 64 66 67 68 69 71 72 31 641,455 connection crystalline form (UmkristallMerungsmittel) fusion point °C 1-Propargyl-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4dihydrocarbostyril. Dihydrochlorid l-Hexyl-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril • Dihydrochlorid l (3-Phenylpropyl) - 7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril, mono hydrochloride 1-Benzyl-5 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril l-Äthyl-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril. Dihydrochlorid 1 - Methyl-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril. Dihydrochlorid 4-Methyl-7 [3 (4-phenylpiperzinyl) - propoxy] - 3,4-dihydrocarbostyril dihydrochlorid. Dihydrate 5 [3 (4-Acetylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril 5 [3 (4-Benzoylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril • hydrochloride 5 {3 [4 (2-Acetyloxyethyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril 5 {3 [4 (2-Hydroxy-Äthyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 4-Phenyl-7 [3 (4-phenylpiperazinyl) - propoxy] - carbostyril 4Phenyl-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 4-Phenyl-7 {3 [4 (2-methoxyphenyl) piperazinyI [propoxy} carbostyril weakly brownish, needle-like crystals of 215-216 (methanol) colorless crystals (ethanol acetone ethers) of 176-181 colorless, shed-like crystals of 201-202 (ethanol) weakly yellowish, needle-like crystals 113 (Ligroin) colorless Crystals (ethanol) of 222-224 colorless crystals (ethanol) of 204-207 colorless crystals (methanol ethers) of 260-265 colorless, needle-like crystals (ethanol) of 143-145 colorless, plate-like crystals 240 (methanol ether) (decomposition) colorless, needle-like crystals of 131-132 (isopropanol) colorless, shed-like crystals of 158-159 (water) colorless, needle-like crystals (methanol) of 198-199 colorless, needle-like crystals (ether hexane) colorless, needle-like crystals (isopropanol water) 138-140 161-162 example 73,4.8 g 7 (3-Chlorpropoxy) - 3,4-dihydrocarbostyril and 3.5 g sodium iodide are mixed with 50 ml acetone and heated up during 3 h on return flow conditions. Then ml dimethylformamide are in addition-given and driven out the acetone by distillation with 40 to 45°C under reduced pressure. Further 4.0 g are in addition-given to 4 (3-Fluorphenyl) - piperazin and 3.0 g tri ethyl amine, whereby the reaction is accomplished with 70 to 80°C during 27 h under agitating. The reaction mixture is concentrated under reduced pressure to dry ones. To the thereby received arrears 60 is in addition-given ml to a wässñgen 5% sodium hydrogencarbonate solution and it is extracted with chloroform. The chloroform layer is extracted and getroeknet twice with water and removed then the chloroform by distillation. To thereby the erhals0 tenon arrears are in addition-given ethers, whereby the insoluble material is collected and dried by filtration. By recrystallization from methanol 6.2 g become 7 {3 [4 (3-Flnorphenyl) piperazinyl] propoxy} - 3,4-dihydrocarbostyril in form weakly yellowish, needle-like Kriss 3s stable with a fusion point of 174-176°C erhalten.

Example 74 12.4 g 7 (3-Chlorpropoxy) - 3,4-dihydrocarbostyril, 1 g Pyridin and 2.6 g 4 (3,4,5-Trimethoxyphenyl) piperazin are mixed in 20 valley Dimethylsulfoxid and agitated then with 80-90°C during 5 h. The reaction mixture in valley 3%ige aqueous sodium-hydrogencarbonate-RST-sang poured and extracted the organic layer with chloroform. The chloroform layer is washed, dried with water and the chloroform by distillation entfernt.

The thereby received arrears are dissolved in 30 valley ethanol and dry hydrogen chloride gas is injected into the ÄthanoIlösung. The crystals thereby failed are collected by filtration and from MethanoI ethanol under receipt of 3,2 g (yield 61%) 7 (3 - [4 (3,4,5-Trimethoxyphenyl) piperazinyl] propoxy) - 3,4-dihydrocarbostyril-dihydrochlorid in form of colorless, needle-like crystals with a fusion point of 225-227°C umkristallisiert.

Examples 75-80 something similar to the procedures of the example 74 are received as follows connections:

Example No. connection crystalline form (recrystallization means) fusion point °C 76 77 5 {3 [4 (- 2-Fluorphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 7 {3 [4 (2-Fluorphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril 5 {3 [4 (3-Fluorphenyl) piperazinyl] - propoxy} - 3,4-dihydrocarbostyril colorless, needle-like crystals (methanol) of 175-178 colorless, needle-like crystals (methanol) of 154-156 colorless, needle-like crystals (methanol) 178-180 641,455 32 something similar to the procedures of the example 74 are received as follows connections:

Example No. connection crystalline form (recrystallization means) fusion point °C 78 79 5 {3 [4 (3,4,5-Trimethoxyphenyl) - piperazinyl] - propoxy} - 3,4-dihydrocarbostyril-dihydrochlorid 5 {3 [4 (3,4-Dimethoxyphenyl) - piperazinyl] - propoxy) - 3,4-dihydroearbostyril 7 - {3 - [4 (3,4-Dimethoxyphenyl) - piperazinyl] - propoxy} - 3,4-dihydrocarbostyñl colorless crystals 205-208 (methanol ether) (decomposition) weakly yellowish, needle well-behaved 190-192 Kñstalle (ethanol) weakly brownish, needle-like crystals 146-147 example 81,2.5 g 7 (3-Chlor-2-methylpropoxy) - 3,4-dihydrocarbostyril and 1.8 g sodium iodide are mixed with 30 valley acetone and agitated at ambient temperature over night. Then 20 is in addition-given ml dimethylformamide and the acetone is removed by distillation under decreased pressure. 1.5 g tri ethyl amine and 1.8 g are in addition-continued to give to l-Phenylpiperazin and the reaction is accomplished with 70 to 80°C during 6 h under agitating. The reaction mixture is poured in 70 valley of a 2%igen aqueous sodium hydrogencarbonate solution and the organic layer is then extracted with chloroform. The chloroform layer is washed with water and getrocknet.

Then the chloroform distillative is removed and the thereby received arrears with petroleum ether gewaschen.

By recrystallizing from methanol water 2.8 g (yield 74%) become 7 [2-Methyl-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril in form of colorless, flöckchenartiger crystals with a fusion point of 146-.147°C erhalten.

Example 82 something similar to methodology described in example 81 become 5 [2-Methyl-3 (4-phenyl-piperazinyl) propoxy] - 3,4dihydrocarbostyril in form of colorless, needle-like crystals (recrystallization center: Ethanol) with a fusion point of 167-169°C erhalten.

natlösung to the effectuation of the crystallization of the product in addition-given and the formed precipitation by filtration collected, with water washed, with isopropanol Is washed, continued to wash and dried with ether. The thereby received raw crystals are dispersed in 80 ml methanol and solved by addition from 5 valley of concentrated hydrochloric acid, according to which under reduced pressure to dry one is concentrated. The thereby received arrears become from methanol ether under receipt of 3,6 g (yield 80%) 4-Methyl-7 [3 (4-phenylpiperazinyl) propoxy] earbostyñl dihydrochlorid in form of colorless Kñstalle with a fusion point of 253-254°C (decomposition) umkñstallisiert.

2s example 84 something similar to the procedure in accordance with example 83 becomes 4-Methyl-6 [3 (4-phenyl-piperazinyl) propoxy] carbostyril. Dihydrochloridtrihydrat in form of weakly brownish crystals (from Äthnaol) with a fusion point of 285-290°C (decomposition) erhalten.

Example 83,2.7 g 4-Methyl-7 (3-chlorpropoxy) - carbostyril and 1.8 g sodium iodide are mixed with 50 ml acetone and heated up during 3 h on return flow conditions. Then ml dimethylformamide are in addition-given and the acetone is removed distillative under reduced pressure. Then 4s 1.5 g are in addition-given to tri ethyl amine and 1.8 g 1-Phenylpiperazin and it is agitated during 3 h with 80 to 90°C, whereby dimethylformamide is then removed by distillation under reduced pressure. The thereby received arrears a 5% aqueous Natriumhydrogencarboso example becomes 2.4 g 5 (3-Chlorpropoxy) - 3,4-dihydrocarbostyril and 1.7 g sodium iodide are mixed with 30 valley acetone and heated up during 3 h on return flow conditions. Then ml dimethylformamide to the reaction mixture are in addition-given and removed the acetone by distillation under reduced pressure. Next 1.5 g are in addition-given to tri ethyl amine, 1.8 g 4-Phenylhomopiperazin and it is heated up on 60 to 70°C during 5 h under agitating. The reaction mixture is poured in 80 mi of a 3%igen aqueous sodium hydrogencarbonate solution and the organic layer is extracted with chloroform. The chloroform layer is washed, dried with water and removed the chloroform by distillation. The thereby received arrears become from Ligroin Be.nzol under receipt of 3,2 g (yield 83%) 5 [3 (4-Phenylhomopiperazinyl) propoxy] - 3,4-dihydrocarbostyril in form of colorless, sehuppenartiger crystals with a fusion point of 122-125°C umkristallisiert.

Examples 86 to 88 something similar to the procedure in accordance with example 85 connections are received as follows:

Example connection crystalline form (recrystallization means) fusion point °C 86 7 [3 (4-Phenylhomopiperazinyl) propoxy] - weakly yellowish shed-like 72-74 3,4-dihydrocarbostyril of crystals (petroleum ether) 87 5 [3 (4-Cyclohexylpiperazinyl) propoxy] - colorless, needle-like crystals (ethanol) 173-176 3,4-dihydrocarbostyril 88 7 [3 (4-Cyclohexylpiperazinyl) propoxy] - colorless, needle-like crystals 115-125 3,4-dihydrocarbostyril (Ligroin benzene) example 89 rend 3 h on return flow conditions heats up. Then 24 g become 5 (3-Chlorpropoxy) - 3,4-dihydrocarbostyril and 17 g 300 ml dimethylformamide, 12 g tri methyl amine and 18 g sodium iodide are mixed with 300 ml acetone and removed for wäh4-Benzylpiperazin in addition-given and the reaction with 33,641,455 to 70°C during 7 h on agitating conditions durchgeroform by distillation. The thereby received leads. The Reaktiõnsgemiseh is washed to 3,4-dihydrocarbostyril in form color drug carbonate solution under reduced pressure arrears with ether and from methanol under receipt of a viscous liquid concentrated and in addition-given it recrystallized, whereby 32 g (yield 84%) 5 [3 (4-Benzylwerden then 300 valley of a 3%igen aqueous Natriumhypiperazinyl) propoxy] -. The organic layer s of loose, needle-like crystals with a fusion point of is extracted with chloroform and washed with water. 157-159°C receive werden.

After drying the chloroform layer the ChloBeispiele will become 90 and 91 something similar the procedure in accordance with example 89 connections to receive as follows:

Example connection crystalline form (Umkristallisiernngsmittel) fusion point °C 90 6 [3 (4-Benzyl-piperazinyl) - propoxy] - colorless, needle-like crystals 114-116 3,4-dihydrocarbostyril (isopropanol) 91 7 [3 (4-Benzyl-piperazinyl) - propoxy] - colorless, needle-like crystals 126-127 3,4-dihydrocarbostyril (ethyl acetate ether) example 92,2.4 g 7 (3-Chlorpropoxy) - 3,4-dihydrocarbostyril and 1.8 g sodium iodide are mixed with 30 valley acetone and agitated with to 60°C during 3 h. Then 30 valley is in addition-given to dimethylformamide. After distance of the acetone by distillation under reduced pressure 1.5 g become tri ethyl amine and 2.3 g 4 (4-Chlorphenyl) - 3-methylpiperazin thereby mixes and with 70 to 80°C during 7 h gerührt.

The reaction mixture will become under reduced pressure concentrated and it 50 ml an aqueous 3%igen Natriumhydrogencarbõnatlösung the thereby received viscous arrears admitted and the organic layer with chloroform is extracted. The chloroform layer is washed, dried with water and removed the chloroform distillative. To the thereby received arrears 50 mi methanol and 5 valley concentrated chlorine water material acid in addition-given, whereby the mixture under reduced pressure is evaporated to dry ones. The arrears become from ethanol under receipt of 3,1 (yield 75%) 7-3 [3-Methyl-4 (4-chlorphenyl) piperazinyl] propoxy-3,4dihydrocarbostyril. Dihydrochlorid in form of colorless crystals with a fusion point of 235-242°C umkristallisiert.

Examples 93 and 94 something similar to the procedure in accordance with example 92 are received as follows connections:

Example connection crystalline form (recrystallization means) Schmelzpnnkt °C 93 8-Brom-ó-chlor-7 [3 (4-phenylpiperazinyl) propoxy] - colorless, needle-like crystals 229-232 3 A-dihydrooarbostyril-dihydrochlorid (ethanol) (decomposition) 3.7 g (yield 67%) of 4 [3 (4-Phenylpiperazinyl) - propoxy] - carbostyril 94 colorless, shed-like crystals 206-208 (ethanol) example 95,5.1 g 7 (3-Chlor-2-hydroxypropoxy) - 3,4-dihydrocarbostyril and 8 g 4-Phenylpiperazin are mixed with 50 ml dimethylformamide and converted with 50 to 60°C during 5 h on agitating conditions. The reaction mixture is restricted under reduced pressure to dry ones and the thereby received arrears are dissolved in 80 ml chloroform. Then the chloroform layer is washed three times with 5% aqueous sodium hydrogencarbonate solution and dried afterwards three times with water nachgewasehen and with water-free sodium sulfate. The chloroform is removed by distillation under decreased pressure and the thereby received arrears by Kieselgelchromatografie (silicagel: Wako C-200, extraction solvent: Chloroform: Methanol = 30:1 (v/v)) gereinigt.

Then the extracted product into its hydrochloride using ethanol, contains is removed for hydrogen chloride, transferred and ethanol by distillation under reduced pressure. The thereby received arrears become from water under receipt of 5,6 g 7 [2-Hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril. Monohydroehlorid. 1/2 hydrate in form of colorless crystals with a fusion point of 122°C (decomposition) amkristallisiert.

Examples 96 to 115 something similar to methodology in accordance with example 95 connections are received as follows:

Example No. connection Krista! lform (Umkrista! lisierungsmittel) 96 97 5 [2-Hydroxy-3 (4-phenyl) propoxy] - 3,4-dihydrocarbostyril. Mono hydrochloride 6 [2-Hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril. mono hydrochlorides. 1/2 hydrate colorless, needle-like crystals (water) colorless, needle-like crystals (water) fusion point °C 239-241 223-224 641,455 34 example No. connection crystalline form (Umkristallisierungsmitlel) fusion point °C 98 8-Chlor-5 [2-hydroxy-3 (4-phenylpiperazinyl) - colorless, needle-like crystals 226-228 propoxy] - 3,4-dihydrocarbostyril, mono (methanol ethanol) hydrochloride. 3/2 hydrate 8-Chlor-5 (2-hydroxy-3 [of 4 (4-chlor-phenyl) - colorless, needle-like crystals piperazinyl] propoxy} - 3,4-dihydrocarbostyril. (Methanol ether) mono hydrochloride 6-Chlor-5 [2-hydroxy-3 (4-phenylpiperazinyl) - colorless, needle-like crystals propoxy] - 3,4-dihydrocarbostyril, dihydrochlorid (methanol ether) mono hydrate 6,8-Dichlor-5 [2-hydroxy-3 (4-phenylpiperazinyl) - colorless crystals (water) propoxy] - 3,4-dihydrocarbostyril.

Monohyd rochlorid 8 [2-Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril • mono hydrochloride 6 {2-Hydroxy-3 [4 (4-Chlor-phenyl) - piperazinyl] - propoxy} - 3,4-dihydrocarbostyril. Monohydrochlorid.

1/2 hydrate 7 {2-Hydroxy-3 [4 (4-Chlor-phenyl) - piperazinyl] propoxy} - 3,4-dihydrocarbostyril • mono hydrochloride 8-Brom-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 8-Brom-5 (2-hydroxy-3 [4 (2-methoxyphenyl) - piperazinyl] - propoxy} - 3,4-dihydrocarbostyril.

Dihydrochlorid 6-Chlor-7 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 6-Chlor-7 (2-hydroxy-3 [4 (2-methoxyphenyl) - piperazinyl] propoxy} - 3,4-dihydroearbostyril 1 - Methyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril l-Äthyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril • mono oxalate 8-Chlor-5 {2-hydroxy-3 [4 (2-chlorophenyl) - piperazinyl] propoxy} - 3,4-dihydroearbostyril l-Allyl-5 (2-hydroxy-3 [4 (4-methylphenyl) - piperazinyl] propoxy} - 3,4-dihydroearbostyril 1-Benzyl-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 6 [2-hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyrilV2 hydrate 8-Brom-5 [2-hydroxy-3 (4-phenylpiperazinyl) - propoxy] carbostyril 99,100,101,102,103 104,105,106,107,108,109,110,111,112,113,114,115 228-230 218-225 251-253 colorless crystals (methanol ether) colorless, needle-like crystals (ethanol) colorless, needle-like crystals (isopropanol) colorless crystals (methanol) colorless crystals (methanol ethers) of 263 212-214 66174-176 226-228 colorless, needle-like crystals (methanol water) colorless crystals (ethanol) of 171-173 183-184 colorless, needle-like crystals (n-hexane benzene) colorless crystals (ethanol ether) colorless crystals (ethanol) colorless, needle-like crystals (Ligroin benzene) colorless, needle-like crystals (petroleum ether) colorless, needle-like crystals (methanol) of 218-219 143-145 201-203 (decomposition) 156-158 123-124 148-150 colorless, panel-like crystals (methanol) 179-182 example 11 ó 0.55 g Natñumhydñd (about 50% in oil) will become washed with petroleum ether and then 30 ml dimethylformamide and 36 g 7 [3 (4-Phenylpiperazinyl) propoxy] - in addition-given 3,4-dihydrocarbostyril, whereby at ambient temperature with 1 h one agitates. To the reaction mixture 1.2 g Äthylss are in addition-given gromid and it is agitated at ambient temperature during 3 h. The Reaktionsgemiseh is poured in 150 valley water and the organic layer with chloroform is extracted. The chloroform layer is twice washed with water, dried with water-free sodium sulfate and driven out the chloroform distillative. To the thereby received arrears a small quantity ethanol is in addition-given for the precipitation by crystals. The crystals are collected by filtration and in 70 valley methanol and 3 valley of concentrated hydrochloric acid dissolved, it according to which under reduced Dru. .ck to dry ones restricted. The arrears become from Athanol under receipt of 4,1 g (yield 88%) l-Äthyl-7 [3 (4-phenylpiperazinyl) propoxy] - in such a way 3,4-dihydrocarbostyril-dihydrochlorid in form of colorless crystals with a fusion point of 222-224°C umkristãllisiers.

Example 117,0.3 g Natriummetall in 80 ml ethanol dissolved and this solution 3.6 g 5 [3 (4-Phenylpiperazinyl) propoxy] will become - and then 1.5 g benzyle chloride given 3,4-dihydrocarbostyril, whereby during 5 h on return flow conditions one heats up. The reaction mixture is concentrated under reduced pressure to dry ones. To the thereby received arrears water is in addition-given and the unsolvable subject by filtration is collected, washed and dried these with water. The raw crystals become from Ligroin under receipt of 3,9 g (yield 86%) l-Benzyl-5 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril in form of weakly yellowish, needle-like crystals with a fusion point of 113°C umkristallisiert.

Examples 118 to I23 something similar to the procedure of the example 117 are received as follows connections:

Example connection crystalline form (recrystallization means) 641,455 fusion point °C 118,119,120,121,122,123 1 - Benzyl-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 1-Methyl-7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril 1-Allyl-7 [3 (4-phenylpipêrazinyl) propoxy] - 3,4-dihydrocarbostydl. Dihydrochlorid 1-Propargyl-7 [3 (4-p enylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril. Dihydrochlorid 1-Hexyl-7 [3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril • Dihydrochlorid 1 (3-Phenylpropyl) - 7 [3 (4-phenylpiperazinyl) - propoxy] - 3,4-dihydrocarbostyril. Mono hydrochloride weakly yellowish crystals (ethanol) colorless crystals (ethanol) colorless crystals (ethanol) weakly yellowish crystals (methanol) of 125-127 204-207 189-192 215-216 colorless crystals (ethanol acetone ethers) of 176-181 colorless, shed-like crystals 201-202 ('g, thanol) example 124,1.0 g 4-Methyl-7 [3 (4-phenylpiperazinyl) propoxy] carbostyriI dihydrochlorid and 0.3 g palladium-black in 200 valley ethanol is dispersed and maintained a hydrogen printing of 2 atmospheres at ambient temperature, whereby the catalytic reduction is accomplished with 70-80°C during 8 h. After cooling of the reaction mixture palladium-black by filtration is removed and the mother liquor to dry ones is concentrated. The arrears become from a mixture methanol ether under receipt of 0,6 g (yield 60%) 4-Methyl-7 [3 (4-phenylpiperazinyl) prcpoxy] - 3,4-dihydrocarbostyril. Dihydrochlorid. Dihydrate in form of colorless crystals with a fusion point of 260-265°C umkristallisiert.

Example 125 2 g 5 [2-Hydroxy-3 (4-phenylpiperazinyl) - propoxy] - 3,4dihydrocarbostyril will become mixed with 30 valley acetone and it far 12 mi acetyl chloride in addition-given, according to which during 10 h on return flow conditions heats up wird.

After cooling of the reaction mixture the failed product is collected by filtration and washed with acetone. The thereby received raw crystals are dissolved in 80 valley water, made basic with ammonia liquor and extracted, dried then with chloroform and the chloroform by distillation entfernt.

The arrears become by Kieselgelchromatografie under receipt of 0,5 g 5 [2-Acetyloxy-3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril in form of colorless crystals with a fusion point of 159-161 °C gereinigt.

Example 12ó something similar to the procedure of the example 125 7 [2Acetyloxy-3 (4-pheny becomes! - piperazinyl) propoxy] - 3,4-dihydrocarbostyril in form of colorless crystals with a fusion point of 130-132°C erhalten.

Example 127,1.9 g 5 [2-Hydroxy-3 (4-phenylpiperazinyl) propoxy] - 3,4dihydrocarbostyril and 0.24 g sodium hydride are dispersed in ml xylene and heated up during 1 h on return flow conditions. Subsequently, the temperature of the bath will become lowered on 130°C and it 1.40 g 3,4,5-Trimethoxybenzoylchlorid gradually in addition-given, whereby during 8 h on return flow conditions one heats up. The xylene is removed from the Reaktionsgêmisch distillative, that is then poured arrears in 80 valley water and extracted with chloroform. The chloroform layer becomes with water: o washed, dried and the chloroform by distillation removes. The arrears become from ethanol under receipt of 1,5 g 5 [2 (3,4,5-Tñmethoxybenzoyloxy) - 3 (4-phenylpiperazinyl) propoxy] - 3,4-dihydrocarbostyril in form of colorless crystals with a fusion point of 125-127°C 2s umkristallisiert.

Example 128,2.0 g 5 (3-Piperazinylpropoxy) - 3,4-dihydrocarbostyñl are mixed with 15 valley acetic anhydrid and 10 valley Essigsãure o and 5 h on return flow conditions are heated up. The reaction mixture is concentrated under reduced pressure to dry ones. The arrears become from ethanol under receipt of 5 [3 (4-Acetylpiperazinyl) propoxy] - 3,4-dihydroxycarbostyril in form more colorless nadelarss tiger of crystals with a fusion point of 143-145°C umkristallisiert.

Example 129,2.0 g 5 (3-Piperazinylpropoxy) - 3,4-dihydrocarbostyril and 1.5 g Benzoylchlorid are mixed with 20 valley Pyridin and agitated with 50 to 60°C during 3 h. The reaction mixture becomes dry one under reduced pressure konzentriert.

The arrears are transferred of colorless, panel-like crystals with a fusion point of 240°C (decomposition) into a hydrogen chloride salt and afterwards from methanol under receipt of 5 [3 (4Benzoylpiperazinyl) propoxy] - 3,4-dihydrocarbosty ril hydrochloride in form umkristallisiert.

so example 130,2.0 g 5 (3-Piperazinylpropoxy) - 3,4-dihydrocarbostyril and 3 valley Äthyl-2-bromacetat and 1.5 ml tri ethyl amine are mixed with valley dimethylformamide with 50 to 60°C during 8 h under agitating. The Reaktionsgemiseh will become under verrins5 gertem pressure concentrated and the thereby received viscous arrears 30 valley of an aqueous 2%igen sodium hydrogencarbonate solution in addition-given and from this with chloroform one extracts. The chloroform layer is washed, dried with water and removed the chloroform distillative. The arrears are cleaned by Kieselgelchromatografie and from isopropanol under receipt of 5 (3 [4 (2-Acetyloxyäthyl) piperazinyl] propoxy)-- 3,4-dihydrocarbostyril in form of colorless, needle-like crystals with a fusion point of 131-132°C of umkristallies siert.

Example 131 61.6 g Natñumjodid into 2 litres acetonitrile aufge641 455 36 solves is admitted, to the solution 65 g 6-Brom-5-chlorpropoxycarbostyñl and heated up on that the reaction mixture during 6 hours at the return flow. A mixture of 45,6 g Phenylpiperazin and 43 is admitted to the reaction mixture ml tri ethyl amine and the whole mixture during 51/2 is heated up hours at the return flow. After conclusion of the reaction the materials separated from the reaction mixture are collected by filtering off, washed with water and ether in the indicated order and dried then for the production of the arrears. 12 g arrears are dissolved into 1,4 litres methanol and 40 valley of concentrated hydrochloric acid, the solution is treated with activated charcoal and according to it over night stand let. The crystals separated from the solution will become by filtering off gesammi) shifted and at the return flow heated up and it 23.3 valley of a 2-normalen sodium hydroxide solution admitted. When the mixture cooled down, the separated crystals will be kept collected by Abfíltrieren, whereby s 8.55 g 6-Brom-5 [3 (4-phenyl-l-piperazinyl) propoxy] carbostyril in the form of colorless panel-similar crystals; Sehmelzpunkt: 177-178°C.

Example 132 after the same function as in the examples is described 26 and 27, the 73 [4 (2,3-Dimethylphenyl) - 1 - piperazinyl] propoxy) carbostyril monohydrochloridmonohydrat in the form of colorless needlelike crystals of the fusion point 262-263°C (from methanol) melt, with a mixture of methanol and water (400 mi15 received.