Derivatives of condensed polycyclic heterocyclic compounds and method of production thereof

 

(57) Abstract:

The invention relates to novel condensed polycyclic heterocyclic compounds of the formula I and the way they are received. The compounds of formula I are of low toxicity and high antitumor activity and can be used in the pharmaceutical industry. The compounds correspond to the General structural formula I, in which the ring And indicates benzene, optionally substituted by oxo, or disilicate condensed ring, where at least one of the rings is an aromatic ring and selected from the group including: 1) naphthalene, optionally hydrogenated in a single ring and/or optionally substituted with halogen, hydroxy, lower alkyl, optionally containing a hydroxy group, lower alkoxy, nitro, amino, lower acyl, oxo, cyano, benzosulfimide, substituted lower alkyl, and lower acylamino; 2) inden, optional hydrogenated in a single ring and/or optionally substituted oxo; 3) benzofuran, optionally hydrogenated in a single ring and/or optionally substituted by hydroxy or oxo in the heterocyclic ring; 4) isobenzofuran, optionally hydrogenated and/or optional timesbaseline substituted by oxo; 7) benzodioxol; and 8) quinoline and isoquinoline, optionally hydrogenated in the heterocyclic ring and/or optionally substituted by oxo or lower alkyl; ring means pyrrole, 4H-1,4-oxazin, 4H-1,4-thiazin or 4(1H)-pyridone, the ring denotes a monocyclic or disilicate aromatic ring selected from: 1) phenyl, optionally substituted with halogen, hydroxy, lower alkoxy, lower alkyl, nitro or amino; 2) naphthyl, and (3) chinoline, Y denotes the group represented by the formula-e-f where e denotes the lowest alkylen and f denotes a lower alkylamino, di-lower alkylamino, pyrrolidinyl, N-(dimethylamino)ethyl-N-methylamino and N-(hydroxyethyl)-N-methylamino; or their pharmacologically acceptable salts. The compounds of formula I or their pharmacologically acceptable salt is produced by interaction of the compounds of formula II, where the rings AA and Sa are shown for a and C, in which the substituents may be protected, ring VA means 4H-1,4-thiazin, 4H-1,4-oxazin, 4(1H)-pyridone, fa is f values specified above, e has the values specified above, with a compound of formula III, where D and are the same or different and are removable protective group or groups, if any, of the thus obtained product.

Tricyclic compound amonafide [5-amino-2-[2-(dimethylamino)ethyl]-1H-Benz[de] isoquinoline-1,3-(2H)-dione] is the most well-known condensed polycyclic heterocyclic antitumor compound having in its molecule cyclic imido part, However, it was reported that amonafide found a strong toxicity to bone marrow and low efficiency in clinical tests done so far [Drugs Fut. , 17, 832 (1992)]. As tetracyclic compounds was described ozonated [2-[2'- (dimethylamino)ethyl] -1,2-dihydro-3H-dibenz(deh)isoquinoline - 1,3-dione] , obtained by transformation aminonaphthalene part amonafide in anthracene to gain through this antitumor activity in preclinical tests (WO9200281).

As condensed, tetracyclic heterocyclic antitumor substances having in the molecule structure of uracil, cyclic imido-part of which was introduced to the nitrogen atom, have been known 2-[2-(dimethylamino)ethyl] pyrimido[5,6,1-de]acridine - 1,3,7-Trion [Farmaco, 47 1035 (1992)] and 2,3-dihydro-2-[2- (dimethylamino)ethyl]-1H,7H-naphthylidine[3,2,1-ij] -hinzelin-1,3,7 (2H)-Trion [J. Med. Chem., 37, 593 (1994)]. However, each of these compounds was found only subtilisin condensed heterocyclic antitumor substances of this type.

This invention has as its purpose the provision of new compounds or new derivatives of condensed Pyh and exactlyonce heterocyclic compounds with low toxicity and high antitumor activity. The purpose of this invention is the provision of a method of obtaining these compounds and pharmaceutical compositions containing these compounds as active ingredient.

Description of the invention

To achieve the above objectives, the inventors have conducted intensive studies to develop a highly effective anti-tumor substances. As a result, they have found that the new condensed Pyh and exactlyonce heterocyclic compounds having oralloy structure in their molecule, have high antitumor activity and low toxicity, which is the completion of the present invention.

Thus, this invention relates to a compound represented by the following General formula (I) or its pharmaceutically acceptable salt:

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where ring A denotes optionally substituted monocyclic aromatic ring or disilicate con which includes pyrrole, 4H-1,4-oxazin, 4H-1,4-thiazin or 4(1H)-pyridone; ring C represents optionally substituted, monocyclic or disilicate condensed aromatic ring; and Y represents a group represented by the formula-e-f (where e denotes the lowest alkylen and f denotes amidino, guanidino or amino, optionally substituted optional gidroksilirovanii or optional lower alkylaminocarbonyl lower alkyl;

provided that the excluded cases, when rings A and B both represent an optionally substituted monocyclic aromatic ring.

Further, this invention relates to medicinal compositions containing condensed polycyclic heterocyclic compound as described above is derived in a pharmacologically effective dose or its pharmacologically acceptable salt and pharmaceutically acceptable carriers.

Further, this invention relates to a method of preventing or treating tumors by injecting the patient-derived condensed polycyclic heterocyclic compounds described above, in a pharmacologically effective dose.

In the definition of ring A in the above formula (I), the term "monoc what about the at least one oxygen atom or sulfur. The term "disilicate condensed ring, where at least one of the rings is aromatic ring" means disilicate condensed ring in which each of the rings is a 5 - to 8-membered ring, optionally containing at least one nitrogen atom, oxygen or sulfur, and at least one of the rings is an aromatic ring. There may be one or three of the substituents on these rings.

Examples of the ring include A benzene, pyridine, pyrazin, pyrimidine, pyridazine, furan, thiophene, pyrrole, thiazole and other dziklicska condensed structures, which may be partially gidrirovanie and oxidized at the sulfur atom, if it is contained in them. These rings can be kondensirovannye the ring for an arbitrary admissible chemically position.

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Each of the above rings may have 1 to 3 substituent. In the case of the include hydroxy, oxo, cyano, halogen, nitro, optionally gidroksilirovanii or lower alkylaminocarbonyl lower alkyl, lower alkoxy, lower acyl, optionally lower - alkilirovanny carbarnoyl and optional low - alkilirovanny, low - acylated, arylsulphonyl or lower alkylsulphonyl amino.

The term "monocyclic or disilicate condensed aromatic ring" as used in the definition of ring C denotes a monocyclic or disilicate aromatic hydrocarbon or aromatic heterocycle containing one or two nitrogen atom. May contain 1 to 3 substituent on the ring (rings).

Examples of the ring C include benzene, pyridine, pyrimidine, naphthalene, quinoline, izochynolyn indole and hinzelin. These rings may be condensed with ring B at arbitrary chemically permissible position.

Each of the above rings may have 1 to 3 substituent. In case two or more substituents, these substituents may be the same or different. Examples of substituents include halogen, hydroxy, lower alkyl, lower alkoxy, nitro, and optionally lower - alkilirovanny or lower - acylated amino.

The term is use of General formula (I), denotes a linear or branched C1-6is an alkyl group. The examples include methyl groups, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl (amyl), isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1,2-dimethylpropyl, n-hexyl, isohexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methyl-propyl. Among these groups, methyl, ethyl, n-propyl and isopropyl are preferred, and the most desirable of all groups are methyl and ethyl.

The term "lower alkylene" used in the definition of e in Y denotes a residue obtained by excluding one hydrogen atom from the lower alkyl groups described above. In the case of substitution of two amino lower - alkyl groups in the definition of the substituents, it is not necessarily located on the rings A and C, and f in Y, these alkyl groups can be linked together with the formation of 5 - or 6-membered ring.

Group, a lower alkoxy in the definition of the substituents, it is not necessarily located on the rings A and C, denotes GRX, n-butoxy, isobutoxy and tert-butoxy. Among these lower - alkoxygroup most preferred are methoxy and ethoxypropan. Examples of the halogen atom are fluorine, chlorine and bromine.

Examples of the lower acyl groups include groups having 1-6 carbon atoms, such as formyl, acetyl, propionyl, butyryl, isobutyryl and valeryl.

The term "arylsulphonyl or lower alkylsulphonyl amino" as used in the definition of substituent optionally located on the ring A, denotes, for example, amino group, optionally n-toluensulfonate, methylsulfonylamino or ethylsulfonylimidazo.

Derivatives of condensed polycyclic heterocyclic compounds represented by the above formula (I), sometimes form salts with acids. Salts of these compounds (I) are also included in the scope of this invention. Examples of salts with acids include inorganic salts such as hydrochloride, hydrobromide, sulfate, etc. and organic acid salts such as acetate, lactate, succinate, fumarate, maleate, citrate, benzoate, methanesulfonate, p-toluensulfonate etc.

Not to mention the fact that this invention also includes hydrates strong antitumor activity, compounds which exhibit antitumor activity when they metabolize, for example, oxidized, restored, hydrolyzed or conjugated in vivo, are also included in this invention. In addition, the invention includes compounds capable of forming the compounds of this invention when they metabolize, for example, oxidation, restoring or hydrolysis in vivo.

The compound (I) of this invention can be obtained in various ways. Next will be described the typical examples of such methods of obtaining.

1) Compound of General formula (I) can be obtained by the interaction of the compounds represented by the following General formula (II):

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where rings Aa and Ca respectively denote optional protected rings A and C; ring Ba denotes 4H-1,4-oxazin, 4H-1,4-thiazin, 4(1H)-pyridone, or pyrrole; fa denotes optional protected f; and e has the above meanings, with a compound represented by the following General formula (III):

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where D and E are the same or different and each denotes a group to delete.

This reaction is typically performed by dissolving the compound (II) in an aprotic solvent such as dimethylformamide, tetrach">

Examples of compound (III) include phosgene, ethylchloride and N,N'-carbonyldiimidazole. This reaction is conducted usually within a temperature range from -50oC to 150oC.

When the thus obtained product is protected at the amino - or hydroxyl group, and so on, the protective group can be removed by conventional means such as treatment with acid or alkali or catalyst recovery, obtaining the target compound (I).

2) Compound (I) can be obtained by the interaction of the compounds represented by the General formula (IV):

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where the ring Ab denotes disilicate condensed ring, where at least one of the rings is an aromatic ring and which has a lower acyl or oxoprop, optional with optional protected by a Deputy (deputies); ring Bb denotes pyrrole, 4H-1,4-oxazin or 4H-1,4-thiazin; ring Cb denotes a monocyclic aromatic ring optionally having protected Deputy (deputies); and Y has the above meaning, with a carbonyl-regenerating agent.

The recovery may be carried out using the method commonly used to restore carboncalculator, such as palladium on charcoal, and the restoration of borane/pyridine complex or berciano-hydride sodium.

Next will be described the method of obtaining the starting compounds (II) used in this invention. Starting compound (II) include known compounds and new compounds. New connections can be obtained with the use or combination of methods of synthesis of known compounds that have already been reported in the literature.

The method of obtaining the 1 presented at the end of

Compounds represented by the General formula (IX) can be obtained using, for example, the method of Fisher for the synthesis of indole and how Borse for the synthesis of tetrahydrocarbazole [Org. Syn. IV, 884 (1963]. Namely, it can be obtained by heating the cyclic ketone represented by the formula (VII), and o-gidrodinamicheskoi carboxylic acid in acetic acid or in a neutral solvent such as ethanol, in the presence of an acid catalyst such as hydrochloric acid, sulfuric acid or zinc chloride. When the ring as in compound (IX) represents an optionally substituted decillions condensed structure in which one of the rings is aromatic to which the target compound (IIa). The compound (X) can be obtained partial or complete dehydration of non-aromatic rings in the compound (IX) dehydrating agent. As the dehydrating agent can be used, for example, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, chloranil or palladium on coal. The reaction is usually carried out at room temperature or when heated. If the ring Ac is dziklicska condensed structure in which both rings are non-aromatic rings, can also be selectively degidrirovanii one of these rings by appropriate selection of the type and amount of reagent, reaction conditions, etc. of the Target compound (IIa) can be obtained by condensation of the thus obtained compound (X) with compound (VI). The condensation can be carried out, for example, the acid chloride method, the method with active ether complex or the method of mixed anhydrides of carboxylic acids, or by using a condensing agent such as 1,3-dicyclohexylcarbodiimide, N, N'-carbonyldiimidazole or diphenylphosphoryl.

The method of obtaining 2 is provided at the end of the description.

The connection represented by the General formula (XIII) can be obtained by the interaction of the compounds of the General formula, accordingly, the nitro-group and halogen. The reaction can be conducted by heating these compounds, optionally in the presence of a base, such as triethylamine, sodium acetate or sodium hydroxide. The target compound (IIb) can be obtained by hydrolysis of ester compound (XIII) with alkali to compound (XIV) with subsequent condensation of this compound with the formation of compound (VI) according to the method described in production method of (I).

When using the compounds of this invention as a drug can be administered orally or parenterally. Although the dose is not specifically limited and varies depending on the severity of the symptom, age, sex, body weight and sensitivity of the patient, the manner, time and intervals of administration, properties, type, and specific active ingredients of a medicinal product, and so on, usually it can be administered to an adult patient in a daily dose of from 1 to 3000 mg, preferably from 10 to 2000 mg, and more preferably from 20 to 1000 mg 1-3 servings a day.

For preparing a solid preparation for oral administration, the active agent is mixed with fillers and, if necessary, binders, dezinfeciruyuhimi obtained mixture is formed into tablets, tablet coatings, pellets, finely divided particles, powders, capsules, etc. by using common methods.

As fillers can be used, for example, lactose, corn starch, sucrose, glucose, sorbitol, crystalline cellulose and silicon dioxide. As binders can be used, for example, polyvinyl alcohol, ethylcellulose, methylcellulose, Arabian gum, hydroxypropylcellulose and hypromellose. As a lubricating means can be used, for example, magnesium stearate, talc and silicon dioxide. As dyes can be used pharmaceutically acceptable dyes. As corrigentov can be used, for example, cocoa powder, aromatic acid, eucalyptus oil, camphor of Borneo and powdered bark brown wood, not to mention the fact that these tablets and granules may be coated, if necessary, sugar, gelatin, etc.

For the preparation of injectable active ingredient is mixed, if necessary, regulating pH agents, buffers, suspendresume agents, solubilizers agents, stabilizers, isotherwise agents, preservatives, etc. and from the floor of the AMI. Then these drugs can be dried in a conventional manner, if necessary.

As suspendida agents can be used, for example, methylcellulose, Polysorbate 80, hydroxyethyl cellulose, Arabic gum, powdered tragakant, carboxymethylcelluose sodium and monolaurin of polyoxyethylenesorbitan.

As solubilizing agents can be used, for example, curing polyoxyethylene castor oil, Polysorbate 80, nicotinamide, monolaurin of polyoxyethylenesorbitan, macrogol and ethyl esters of fatty acids of castor oil.

As stabilizers can be used, for example, sodium sulfite and metasulfite sodium. As preservatives can be used, for example, methyl parahydroxybenzoate, metilparagidroksibenzoat, sorbic acid, phenol, cresol and chlorocresol.

Next, you will be given pharmacological experimental examples to illustrate the action of the compounds of this invention.

Experimental example 1

Antitumor test in vitro on P388 cells (leukemic cells of mice)

The P388 cells suspended in RPMI1640 medium (produced by Sanko Junyaku) containing 10% fetal calf saw the Ali in 96-well U-bottom microplate with respect 1,25103cells (0.1 ml) per well and incubated in an incubator containing 5% carbon dioxide at 37oC for one day.

The compound of this invention was dissolved in dimethyl sulfoxide to obtain a concentration of 10-2M and then diluted with 10% fetal calf serum culture medium RPMI1640 with obtaining a concentration of 10-4or 10-5M Taking this concentration as the maximum level was performed three times serial dilution of the culture medium RPMI1640 containing 10% fetal calf serum. Then, the resulting dilution was added to the incubation tablet with P388 described above, when the ratio of 0.1 ml per well, followed by incubation in an incubator containing 5% carbon dioxide at 37oC for 3 days.

After incubation were added 0.05 ml per well of a solution of 3.3 mg/ml MTT [bromide 3-(4,5-dimethylthiazol-2-yl)-2,5 - diphenyltetrazolium] and incubation continued for another 2 hours. The microplate was centrifuged and the supernatant was aspirated from each well. Then formed in this way formazan was dissolved in 0.1 ml of DMSO, and the absorption measured at 540 nm in a microplate reader, was taken as an indicator was determined by giving 50% inhibition concentration (IC50) test the connection:

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where T denotes the absorption wells containing test compound, and C denotes the absorption wells, nestorgames test connection.

Table 1 summarizes the resulting data IC50.

Experimental example 2

Antitumor test in vivo in M5076 (reticulocytosis sarcoma mice)

M5076 cells (1106cells per animal) subcutaneously transplanted into the lateral part of each mouse BDF1 (females aged 6 to 7 weeks). The compound of this invention was dissolved in 5% glucose solution. From the next day after transplantation solution of the compound was administered intraperitoneally to the animals once a day in accordance with each scheme's introduction. On the other hand, the control group was injected with 5% glucose solution. The control group consisted of 10 animals, whereas each test group consisted of 5 animals.

On day 21 after transplantation, tumors were removed and weighed. Factor inhibiting the multiplication of tumor in each test group relative to the control group was determined in accordance with the following formula:

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where T denotes the average tumor weight of the test group and C represents the average weight of tumors con the capacity example 3

Protivoopujolevy in vivo test on MX-1 (breast cancer man)

Pieces of the tumor MX-1 (approximately 1 mm3) subcutaneously transplanted into the lateral part of each "Nude" mice (BALB/Cnu/nu, female aged 6 to 7 weeks). The compound of this invention was dissolved in 5% glucose solution. When tumor volume reached 50 mm3(approximately the 10th day after transplantation), a solution of the compound was administered intraperitoneally to the animals once a day in accordance with each scheme's introduction. On the other hand, the control group was injected with 5% glucose solution. The control group consisted of 10 animals, whereas each test group consisted of 5 animals.

On the 22nd day after the transplantation of the tumor were removed and weighed. Factor inhibiting the multiplication of tumor each test group relative to the control group was determined in accordance with the following formula:

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where T denotes the average tumor weight of the test group and C represents the average weight of tumors in the control group.

Table 3 shows the results of this experiment.

As clearly show these experimental data, the compounds of this invention have excellent antitumor de will be presented Examples of the preparation, showing the receipt of the original compounds used in this invention, and Examples related to specific examples of the compounds of the present invention. However, it should be clear that the invention is not limited to only these examples.

Example obtain 1

5,6-Dihydro-7H-benzo[C]carbazole-8-carboxylic acid:

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A solution of 5.00 g (a 34.2 mmol) -tetralone in acetic acid (10 ml) was added in drops to a suspension 7,05 g (or 37.4 mmol) of the hydrochloride of 2-hydrazinobenzene acid in acetic acid (40 ml) at 80oC and the resulting mixture was heated under reflux for 3 hours and 45 minutes. After returning to room temperature was added water and the resulting thus precipitate was collected by filtration, washed with water, dried and recrystallized from ethanol to obtain 5.2 g of the compound indicated in the title of the example.

1H-NMR (DMSO-d6) (M. D.): 2,91 - of 3.06 (m, 4H), 7,03 (t, J = 7,6 Hz, 1H), 7,17 (t, J= 7,6 Hz, 1H), 7,20-7,27 (m, 2H), 7,72 (d, J= 7,6 Hz, 1H), 7,76 (d, J=7,6 Hz, 1H), 8,19 (d, J=7,6 Hz, 1H), of 11.29 (s, 1H).

Example of getting 2

7H-Benzo [C] carbazole-8-carboxylic acid:

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3,29 g (of 14.3 mmol) of 2,3-dichloro-5,6-dicyano-1,4 - benzoquinone was added to a suspension of 2.97 g (11.3 mmol) of the compound Prim is then heated under reflux for 3 hours and 20 minutes. After returning to room temperature thus obtained precipitate was collected by filtration and recrystallized from ethanol to obtain 2.76 g of the compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.): 7,39 (t, J = 7,3 Hz, 1H), of 7.48 (t, J= 7,3 Hz, 1H), of 7.70 (t, J=7,3 Hz, 1H), to 7.93 (d, J=8.7 Hz, 1H), 8,00-8,07 (m, 3H), 8,79 (d, J=7,3 Hz, 1H), 8,87 (d, J=7,3 Hz, 1H), 11,82 (s, 1H), 13,22 (Shir. s, 1H).

Example of getting 3

N-[2-(Dimethylamino)ethyl]-7H-benzo[C]carbazole-8-carboxamide:

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2,52 g (of 15.5 mmol) of N,N'-carbonyldiimidazole was added to a solution of 1.89 g (of 7.25 mmol) of the compound of Example getting 2 in dimethylformamide (60 ml) at room temperature and the resulting mixture was stirred for 45 minutes. Then thereto was added 5.0 ml (to 45.5 mmol) of N,N'-dimethylethylenediamine and the resulting mixture was stirred for 2 hours and 40 minutes. After concentration, it was extracted by adding water and ethyl acetate. The organic layer was collected, washed with water, dried over sodium sulfate and concentrated to dryness to obtain 2,47 g of compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.): of 2.33 (s, 6H), 2,60 (t, J = 5.7 Hz, 2H), 3,63 (K, J=5.7 Hz, 2H), 7,16 (Shir. s, 1H), 7,38 (t, J=7.5 Hz, 1H), 7,46 is 7.50 (m, 1H), 7,65-7,73 (m, 3H), 7,89 (d, J=9.0 Hz, 1H), 8,01 (d, J=8,2 Hz, 1H), 8,69 (d, J=7.5 G islote:

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1,17 g (12.4 mmol) of acetic anhydride was added to a suspension of 5.1 g (38 mmol) of aluminium chloride in dichloromethane (300 ml) at 0oC and the resulting mixture was stirred for 20 minutes. Then thereto was added 2.16 g (of 8.28 mmol) of the compound of Example getting 2 and the resulting mixture was stirred at the same temperature for 4 hours and 30 minutes. Then the reaction mixture was poured into ice water and was extracted with a mixture of chloroform-ethanol. The organic layer was collected and concentrated. The residue was purified column chromatography on silica gel to obtain 1.45 g of the compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.): 2,72 (s, 3H), 7,44 (t, J = 7,6 Hz, 1H), 8,07 (d, J= 7,6 Hz, 1H), 8,11 (d, J=9.1 Hz, 1H), 8,14 (d, J= 9.1 Hz, 1H), 8,18 (DD, J= 9,8;8 Hz, 1H), 8,79 (d, J=1.9 Hz, 1H), 8,87 (d, J=8,8 Hz, 1H), 8,91 (d, J=7,6 Hz, 1H), 12,01 (s, 1H)

Example of getting 5

3-Acetyl-N-[2-(dimethylamino)ethyl]-7H-benzo[C]carbazole-8-carboxamide:

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291 mg (1,80 mmol) of N,N'-carbonyldiimidazole was added to a solution of 247 mg (0,815 mmol) of the compound of Example 4 in dimethylformamide (7 ml) under cooling with ice. After returning to room temperature the resulting mixture was stirred for approximately 2 hours. Then it was added to 0.45 ml (4.1 mmol) of N, N'-dimethylethylenediamine and is approximately 12 hours. After extraction by adding water and chloroform, the organic layer was collected, dried over sodium sulfate and concentrated to dryness. Then the residue was purified column chromatography on silica gel to obtain 140 mg of the compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.):to 2.29 (s, 6H), 2,53-2,61 (m, 2H), 2,74 (s, 3H), 3,52 (K, J = 5,9 Hz, 2H), 7,43 (t, J=7,1 Hz, 1H), of 7.97 (d, J=7,1 Hz, 1H), 8,10 (d, J=8.7 Hz, 1H), 8,14 (d, J=8.7 Hz, 1H), to 8.20 (DD, J=1,8; 8.5 Hz, 1H), 8,72 (t, J=5,9 Hz, 1H), 8,79-8,83 (m, 2H), 8,88 (d, J=8.5 Hz, 1H), 12,17 (s, 1H)

An example of obtaining 6

3,4,5,8-Tetrahydronaphthalene-1,6(2H,7H)-dione:

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6.8 g (38,2 mmol) 1,2,3,4,5,8-hexahydro-1-oxo - 6-methoxynaphthalene was dissolved in 50 ml of tetrahydrofuran and added to a solution of 5 ml of 1 N. hydrochloric acid. After stirring at room temperature for 1 hour to the solution was added ethyl acetate. Then the reaction mixture was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After concentration was added a small amount of the mixture n-hexane-ethyl acetate (1:1) and the resulting mixture was cooled in a bath with a mixture of dry ice-ether. Thus obtained precipitate was removed by filtration and washed with a small amount of n-hexane to obtain 4.8 g of the compound indicated in the title is

Example of getting 7

4-Oxo-1,2,3,4-tetrahydro-7H-benzo[C]carbazole-8-carboxylic acid:

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to 5.4 g (28.6 mmol) of the hydrochloride of 2-hydrazinobenzene acid and 4.7 g (to 34.3 mmol) of zinc chloride were added to 300 ml of glacial acetic acid. Under stirring at ~ 85oC was added 4.7 g (28.6 mmol) of the compound of Example, get 6 for ~ 5 minutes. Then the resulting mixture was stirred at the same temperature for about 2 hours, returned to room temperature and the precipitate was removed by filtration. After concentration of the filtrate were added water and the thus obtained precipitate was removed by filtration. These sediments were combined, dried and then dissolved in 500 ml of dimethylformamide. Under stirring at room temperature was added a solution of 6.6 g (28.6 mmol) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in tetrahydrofuran (20 ml) and the resulting mixture was stirred for approximately 30 minutes. After concentration was added about 50 ml of ethanol, and the thus obtained precipitate was removed by filtration to obtain 3.4 g of the compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.): 2,17-to 2.29 (m, 2H), 2,63-2,70 (m, 2H), 3,55 (t, J = 6.0 Hz, 2H), was 7.36 (t, J=7,6 Hz, 1H), 7,73 (d, J=8,8 Hz, 1H), 8,03 (diamino)ethyl] -4-oxo-1,2,3,4-tetrahydro-7H-benzo[C] carbazole-8-carboxamide;

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3.4 g (12.2 mmol) of the compound of Example obtaining 7 was added to 120 ml of dimethylformamide and stirred. Then to the mixture was added a solution of 3.0 g (18.5 mmol) of N, N'-carbonyldiimidazole in dimethylformamide (30 ml). After stirring at room temperature for 1 hour was added 3.2 g (36,3 mmol) of N,N'-dimethylethylenediamine. After stirring at the same temperature for 1 hour the reaction mixture was concentrated and added to it the ethyl acetate. Then it was washed successively with diluted aqueous ammonia and an aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated to dryness to obtain 4.3 g of the compound indicated in the title of the example.

FAB mass spectrometry m/z: 350 ([M+H]+).

1H-NMR (CDCl3): (M. D.): 2,30-2,40 (m+s, 2H+6H), 2,62 (t, J = 6.0 Hz, 2H), 2,74-and 2.79 (m, 2H), 3,56-3,66 (m, 4H), 7,21 (Shir. s, 1H), 7,32 (t, J=8.0 Hz, 1H), 7,41 (d, J=8,4 Hz, 1H), of 7.70 (DD, J= 0,8; 8.0 Hz, 1H), 8,25 (d, J= 8,4 Hz, 1H), with 8.33 (DD, J= 0,8; 8.0 Hz, 1H), 10,91 (Shir. s, 1H)

Example of getting 9

2,3-Dihydro-3-oxo-1H,6H-cyclopent[C]carbazole-7-carboxylic acid

< / BR>
The connection specified in the title of the example was obtained by reaction 2,3,4,7-tetrahydro-1H-inden-1,5(6H)-dione, which was synthesized from 2,3,4,7-tetrahydro-5-methoxy-1H-inden-1-it according to the ptx2">

FAB mass spectrometry m/z: 266 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.): 2,70-2,82 (m, 2H), 3,52-3,62 (m, 2H), 7,41 (t, J=7,6 Hz, 1H), of 7.70 (d, J=8,4 Hz, 1H), 7,81 (d, J=8,4 Hz, 1H), 8,09 (DD, J=0,8;and 7.6 Hz, 1H), 8,39 (d, J=7,6 Hz, 1H), 11,95 (s, 1H), 13,37 (Shir. s, 1H)

Example 10

2,3-Dihydro-N-[2-dimethylamino)ethyl]-3-oxo-1H, 6H-cyclopent[C]carbazole-7-carboxamid:

< / BR>
The connection specified in the title of the example was obtained from the compound of Example obtaining 9, in the same way as described in the method of Example receipt 8.

FAB mass spectrometry m/z:336 ([M+H]+).

1H-NMR (CDCl3): (M. D.): was 2.34 (s, 6H), 2,61 (t, J=6.0 Hz, 2H), 2,85-only 2.91 (m, 2H), to 3.58-3,66 (m, 4H), 7,18 (Shir. s, 1H), was 7.36 (t, J=7,6 Hz, 1H), 7,49 (d, J=8,4 Hz, 1H), 7,71 (d, J=7,6 Hz, 1H), 7,88 (d, J=8,4 Hz, 1H), they were 8.22 (d, J=7,6 Hz, 1H), 10,95 (Shir. s, 1H)

Example of getting 11

Methyl 5,6,7,8-tetrahydro-9H-carbazole-1-carboxylate:

< / BR>
A solution of 28 ml (0,270 mol) of cyclohexanone in acetic acid (100 ml) was added in drops to a suspension of 52 g (0.276 mol) of the hydrochloride of 2-hydrazinobenzene acid in acetic acid (500 ml) at 100oC and the resulting mixture was heated under reflux for 6 hours. After returning to room temperature, to the mixture was added 1 l of water and the thus obtained precipitate was collected by filtration, washed the (0,602 mol) under the conditions and 41.4 g (0,300 mol) of anhydrous potassium carbonate, the reaction mixture was heated under reflux for 2 hours. After returning to room temperature, insoluble substances were filtered off. After concentration of the filtrate was added water and the thus obtained precipitate was removed by filtration receipt of 45.7 g of compound indicated in the title of the example.

1H-NMR (CDCl3); (M. D.): 1,85-of 1.97 (m, 4H), 2,70-to 2.74 (m, 2H), was 2.76 is 2.80 (m, 2H), of 3.97 (s, 3H), to 7.09 (t, J=7,6 Hz, 1H), 7,65-to 7.68 (m, 1H), 7,79 (DD, 1,1; 7,6 Hz, 1H), 9,39 (Shir. s, 1H)

Example 12

Methyl 5-oxo-5,6,7,8-tetrahydro-9H-carbazole-1-carboxylate:

< / BR>
of 45.7 g (0,199 mol) of the compound of Example, receiving 11 was dissolved in a mixture of tetrahydrofuran (500 ml) with water (50 ml). In the resulting solution was added dropwise a solution of the 90.8 g (0.400 mol) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in tetrahydrofuran (200 ml) under nitrogen atmosphere under ice cooling. After stirring at room temperature for 3 hours the solution was added to 1 l of an aqueous solution of potassium carbonate followed by extraction with ethyl acetate. Then the organic layer was collected, washed with water, dried over magnesium sulfate and concentrated. The residue was recrystallized from ethanol to obtain and 39.7 g of compound indicated in the title of the example.

1H-NMR (DMSO-d6); (M. D.): 2,10-2,17 (m, 2H), 2,44-2,48 (m, 2H), of 3.07 (t, J= 6.2 Hz, 2H), 3.96 points, hydroxy-9H-carbazole-1-carboxylate:

< / BR>
39,1 g (0,161 mol) of the compound of Example 12 suspended in diphenyl ether (150 ml). After adding 10 g of 10% palladium on coal obtained mixture was heated under reflux in nitrogen atmosphere for 3 hours. After cooling, the precipitated crystals and palladium on coal was removed by filtration and washed with hexane. Then the extracted mixture was dissolved in hot tetrahydrofuran and palladium on coal was filtered. After concentration the residue was recrystallized from ethanol with the receipt of 34.7 g of compound indicated in the title of the example.

1H-NMR (CDCl3): (M. D. ): a 4.03 (s, 3H), 5,54 (s, 1H), 6,62 (DD, J= 0,6,7,9 Hz, 1H), 7,10 (DD, J= 0,6; 7.9 Hz, 1H), 7,27 (t, J=7.9 Hz, 1H), 7,30 (t, J= 7.9 Hz, 1H), with 8.05 (DD, J=1,2; 7.9 Hz, 1H), 8,46-of 8.50 (m, 1H), to 9.93 (Shir. s, 1H)

Example of getting 14

[1-Methoxycarbonyl-9H-carbazole-5-yl]oxiana acid:

< / BR>
34.8 g (0.144 mol) of the compound of Example obtaining 13 was dissolved in acetone (550 ml). After adding to the solution 68,5 ml (0,432 mol) of benzylbromide, to 64.8 g (0,432 mol) of sodium iodide and 29.8 g (0,216 mol) of anhydrous potassium carbonate the mixture was heated under reflux for 60 hours. After conditioning for cooling the thus obtained residue was filtered with posleduushie, washed with water, dried over magnesium sulfate and concentrated. To the obtained residue were added n-hexane to curing. Then it was recovered by filtration and recrystallized from ethanol to obtain 40,7 g benzyl ester compounds of the header. This product is suspended in a mixture of tetrahydrofuran (600 ml) - methanol (500 ml). Then, to the suspension was added 12 g of 10% palladium on coal and the product was first made at atmospheric pressure at ordinary temperature with the receipt of 29.4 g of compound indicated in the title of the example.

1H-NMR (CD3OD): (M. D.): was 4.02 (s, 3H), of 4.90 (s, 2H), to 6.67 (DD, J= 0,6; 8.0 Hz, 1H), 7.23 percent (t, J=7.7 Hz, 1H), 7,26 (DD, J= 0,6; 8.0 Hz, 1H), 7,35 (t, J= 8.0 Hz, 1H), 8,02 (DD, J= 1,1; and 7.7 Hz, 1H), 8,63 (DD, J=1,1; and 7.7 Hz, 1H), 10,87 (Shir. s, 1H)

Example get 15

2,3-Dihydro-3-oxo-6H-furo[3,2-C]carbazole-7-carboxylic acid:

< / BR>
of 29.4 g (0,098 mol) of the compound of Example obtaining 14 suspended in toluene (500 ml). After adding 36 ml (0,494 mol) of thionyl chloride the mixture was heated under reflux until the mixture became homogeneous. After concentration was dissolved by adding thereto 500 ml of dichloromethane and added portions of 32.1 g (0,240 mol) of ammonium chloride with stirring under ice cooling. Then the mixture was returned to the Institute with ice. After stirring at room temperature the solution was concentrated and added to it with diluted hydrochloric acid. The precipitate was recovered by filtration, washed successively with water and ethanol and dried to obtain 26.5 g of powder. All the powder was dissolved in a mixture of tetrahydrofuran (350 ml) - methanol (250 ml) and then added to a solution of 750 ml of degassed solution of sodium hydroxide in a nitrogen atmosphere. After hydrolysis of ester at 50oC to the solution was added 20 ml of concentrated hydrochloric acid. Then it was extracted with a mixture of ethyl acetate with tetrahydrofuran and the organic layer was collected, washed with water, dried over magnesium sulfate and concentrated. The residue was purified column chromatography on silica gel to obtain 11.4 g of the compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.): 5,00 (s, 2H), 7,41 (t, J=7.7 Hz, 1H), 7,56 (d, J= 8.5 Hz, 1H), 7,63 (d, J=8.5 Hz, 1H), 8,07 (DD, J=1,3; and 7.7 Hz, 1H), 8,29-8,32 (m, 1H), 12,10 (Shir. s, 1H)

Example of 16

N-[2-(Allylmethylamine)ethyl]-4-oxo-1,2,3,4-tetrahydro-7H - benzo[C]carbazole-8-carboxamide:

< / BR>
Using 0.5 g (1,79 mmol) of the compound of Example obtaining 7 and of 0.53 g (7,15 mmol) of N-methylethylenediamine received of 0.49 g of N-[2-(methylamino)ethyl]-4-oxo-1,2,3,4-tetrahydro is oduct, 0.25 g (1,74 mmol) allylbromide and 0.23 g (1.78 mmol) of N,N-diisopropylethylamine was dissolved in tetrahydrofuran (30 ml) and stirred at 55oC for about 5 hours. After cooling, the solution was diluted with ethyl acetate, washed successively with sodium chloride, dried over magnesium sulfate and concentrated. The residue was purified preparative thin-layer chromatography to obtain 0.24 g of the compound indicated in the title of the example.

1H-NMR (CDCl3): (M. D.): 2,28-2,40 (m+, 2H+3H), 2,70 (t, J=6.0 Hz, 2H), 2,73 is 2.80 (m, 2H), 3,11-3,17 (m, 2H), 3,56-3,68 (m, 4H), 5,17-of 5.29 (m, 2H), of 5.82-5,97 (m, 1H), 7,24 (Shir. s, 1H), 7,33 (t, J=7,6 Hz, 1H), 7,42 (d, J= 8,4 Hz, 1H), to 7.67 (DD, J=0,8; and 7.6 Hz, 1H), 8,25 (d, J=8,4 Hz, 1H), with 8.33 (DD, J= 0,8; and 7.6 Hz, 1H), 10,88 (Shir. s, 1H)

Example of getting 17

5-[1-(Allylmethylamine)ethyl]-12,13-dihydro-4H-benzo[C]pyrimido [5,6,1-jk] carbazole-4,6,10(5H,11H)-Trion:

< / BR>
Using 0.24 g (0.64 mmol) of the compound of Example 16, to 0.23 g of compound of the title was obtained according to the method described in Example 2, except for the procedures related to hydrochloride.

1H-NMR (CDCl3): (M. D.): 2,23-2,42 (m+, 2H+3H), 2,73-2,84 (m, 4H), 3,10-3,15 (m, 2H), 3,53 (t, J=6.4 Hz, 2H), 4,35 (t, J=7.2 Hz, 2H), 5,08-5,22 (m, 2H), 5,74-5,90 (m, 1H), 7,63 (t, J=7,6 Hz, 1H), 8,19 (DD, J=0,8; and 7.6 Hz, 1H), 8,32 (DD, J=0,8; and 7.6 Hz, 1H), 8,35 (d, J=8,4 Hz, 1H), 8,51 (d, J=8,4 Hz, 1H)

PDA 2-hydrazinobenzene acid in acetic acid (20 ml) was slowly heated with stirring was added dropwise 1.2 ml (9.8 mmol) of 4-methylcyclohexanone series. The resulting mixture was heated under reflux for 8 hours and then allowed it to cool. After adding water thus obtained precipitate was recovered by filtration, washed with water and dried to obtain a 1.96 g of 6-methyl-5,6,7,8-tetrahydro-9H-carbazole-1-carboxylic acid. This product was dissolved in acetone (50 ml) was added to a solution of 2.1 ml (34 mmol) under the conditions and 2.35 g (17 mmol) of anhydrous potassium carbonate. The reaction mixture was heated under reflux with stirring for 2 hours, then allowed it to cool and was extracted with water and ethyl acetate. The organic layer was collected, washed with water, dried over magnesium sulfate and concentrated to dryness. Thus, we have obtained 1,49 g of methyl 6-methyl-5,6,7,8-Tetra hydro-9H-carbazole-1-carboxylate. This product is suspended in diphenyl ether (10 ml) and to the suspension was added to 890 mg of 10% palladium on coal. The resulting mixture was heated under reflux with stirring in nitrogen atmosphere for 1 hour.

After conditioning for cooling, the product was dissolved by addition of tetrahydrofuran. Then the catalyst was filtered and the filtrate was concentrated. After adding n-hexane thus obtained crystals were extracted filtrov (s, 3H), as 4.02 (s, 3H), 7,22 (t, J=7.8 Hz, 1H), 7,27-7,31 (m, 1H), 7,41 (d, J=8,2 Hz, 1H), 7,87-of 7.90 (m, 1H), with 8.05 (DD, J=1,1; 7.8 Hz, 1H), 8,21-of 8.25 (m, 1H), 9,82 (Shir. s, 1H)

Example of getting 19

Methyl 6-formyl-9H-carbazole-1-carboxylate:

< / BR>
1.8 g (10 mmol) of N-bromosuccinimide and 220 mg (1.3 mmol), azobisisobutyronitrile was added to a solution of 1.2 g (5 mmol) of the compound of Example getting 18 in carbon tetrachloride (100 ml) and the resulting mixture was heated under reflux with stirring for 1 hour. After cooling, the mixture was concentrated and the residue was purified column chromatography on silica gel to obtain 1.13 g of the compound indicated in the title of the example.

1H-NMR (CDCl3): (M. D.): of 4.05 (s, 3H), of 7.36 (t, J=7.8 Hz, 1H), 7.62mm (d, J= 8,4 Hz, 1H), 8,03 (DD, J=1,6; and 8.4 Hz, 1H), 8,14 (DD, J=1,2; 7,8 Hz, 1H), 8,32-at 8.36 (m, 1H), 8,62-8,64 (m, 1H), 10,12 (s, 1H), 10,23 (Shir. s, 1H)

Example of getting 20

Methyl 1,2-dihydro-1-oxo-7H-pyrido[4,3-C]carbazole-8 - carboxylate:

< / BR>
2.6 g (25 mmol) of malonic acid and 0.3 ml of piperidine was added to a solution of 2.0 g (7.9 mmol) of the compound of Example getting 19 in pyridine (80 ml) and the resulting mixture was stirred in a bath at 80oC for 1 hour. Then thereto was added 2.6 g (25 mmol) of malonic acid by heating and stirring for 1 hour and the resulting mixture negreiros hydrochloric acid with ice and the so formed precipitate was removed by filtration, washed with water and dried to obtain 1.8 g of 3-(1-methoxycarbonyl-9H-carbazole-6-yl) acrylic acid. The compound obtained was dissolved in acetone (70 ml) was added to a solution of 2 ml of triethylamine. While cooling with ice and stirring was added dropwise of 0.64 ml (6.7 mmol) of ethylchloride and then the reaction mixture was stirred at the same temperature for 1 hour. Then it was added dropwise a solution of 870 mg (12 mmol) of sodium azide (90%) in 20 ml of water under ice cooling and stirring. The reaction mixture was stirred at the same temperature for 1 hour and then poured into ice. The so formed precipitate was removed by filtration. This precipitate was added with 3 ml of tributylamine to diphenyl ether (20 ml) and was heated to 260oC. After cooling, hexane was added and the thus obtained precipitate was removed by filtration and washed successively with n-hexane and ethanol to obtain 1.39 g of the connection header.

1H-NMR (DMSO-d6): (M. D. ): 4,01 (s, 3H), 6.73 x (d, J=7,0 Hz, 1H), 7.18 in-7,24 (m,1H), 7,31 (t, J=7.9 Hz, 1H), to 7.77 (d, J=8.5 Hz, 1H), 8,08 (DD, J= 1,3; 7.9 Hz, 1H), they were 8.22 (d, J=8.5 Hz, 1H), 10,13 (DD, J=1,3; 7.9 Hz, 1H), 11,36-11,42 (m, 1H), 11,93 (Shir. s, 1H)

Example of getting a 21

Methyl 7H-pyrido[4,3-C]carbazole-8-carboxylate:

< / BR>
10 E. reflux. After 3 hours the reaction mixture was poured into ice and neutralized with sodium bicarbonate. Then it was extracted with dichloromethane. The organic layer was collected, washed with water, dried over magnesium sulfate and concentrated. The residue was purified column chromatography on silica gel to obtain 390 mg of methyl 1-chloro-7H-pyrido[4,3-C]carbazole-8-carboxylate. This product was dissolved in a mixture of tetrahydrofuran-methanol and added to a solution of 1 ml of triethylamine. Then carried out the hydrogenation in the presence of palladium on coal at atmospheric pressure at ordinary temperature to obtain 300 mg of the compound indicated in the title of the example.

1H-NMR (DMSO-d6)): (M. D.): Android 4.04 (s, 3H), of 7.48 (t, J=7.7 Hz, 1H), 8,00 (d, J=5.4 Hz, 1H), 8,02 (d, J=8,8 Hz, 1H), 8,14 (d, J=7.7 Hz, 1H), 8,28 (d, J= 8,8 Hz, 1H), 8,58 (d, J= 5.4 Hz, 1H), 9,06 (d, J=7.7 Hz, 1H), 10,22 (s, 1H), 12,11 (Shir. s, 1H)

Example of getting 22

10-Nitro-7H-benzo[C]phenothiazines-8-carboxylic acid:

< / BR>
5 ml of 2 N. aqueous sodium hydroxide solution was added to a solution of 1.7 g (9.73 mmol) of 2-amino-1-naphthalenedione in ethanol (30 ml) and the resulting mixture was heated under reflux. To this mixture was added to 2.54 g (9,76 mmol) of methyl 2-chloro-3,5-dinitrobenzoate and the resulting mixture was heated under reflux for 1 hour. To Embratel refrigerator for up to 10 hours. Then the mixture was allowed to cool to room temperature and concentrated. After adding water to the mixture was slowly added 1 N. hydrochloric acid with stirring to bring the pH to about 1. The precipitate was removed by filtration and washed successively with ethanol and methanol with getting to 1.14 g of compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.):? 7.04 baby mortality (d, J=8,4 Hz, 1H), 7,40 (t, J=8,4 Hz, 1H), 7,55 (t, J=8,4 Hz, 1H), to 7.64 (d, J=8,4 Hz, 1H), 7,68 (d, J=8,4 Hz, 1H), 7,82 (d, J=8,4 Hz, 1H), of 7.90 (s, 1H), 7,68 (d, J=8,4 Hz, 1H), of 7.82 (d, J=8,4 Hz, 1H), of 7.90 (s, 1H), 8,35 (s, 1H), 11,37 (Shir. s, 1H)

An example of retrieving 23

N-[2-(Dimethylamino)ethyl]-10-nitro-7H-benzo[C]phenothiazines-8-carboxamide:

< / BR>
10 ml of trichloride phosphorus and 2 ml of dimethylformamide was sequentially added to a suspension 1,82 g (5,39 mmol) of the compound of Example getting 22 in chloroform (60 ml) at 0oC. Then the mixture was let to cool down slowly to room temperature and stirred her during the night. After complete removal of the solvent from the mixture under reduced pressure, to the residue was added 30 ml of dichloromethane. Under stirring atoC to the mixture was added dropwise a solution of 5 ml of N, N-dimethylethylenediamine in dichloromethane (30 ml). Then the reaction mixture was let to cool down slowly to room tdny solution of sodium bicarbonate and the resulting mixture was stirred and filtered through celite to remove insoluble substances. The organic layer was extracted, washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, concentrated to dryness and recrystallized from ethanol to obtain 956 mg of the compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.):2,20 (s, 6H), of 2.45 (t, J=6.0 Hz, 2H), 3,37 (t, J= 6.0 Hz, H), 7,06 (d, J=8,4 Hz, 1H), 7,41 (t, J=8,4 Hz, 1H), 7,56 (t, J= 8,4 Hz, 1H), 7,66 (t, J=8,4 Hz, 1H), 7,69 (d, J=8,4 Hz, 1H), 7,83 (d, J= 8,4 Hz, 1H), 7,93 (Shir. s, 1H), 8,39 (d, J=2,9 Hz, 1H), 9,50 (Shir. s, 1H)

Example of getting 24

3-(4-Methylbenzenesulfonamide)-7H-benzo[C]carbazole-8-carboxylic acid:

< / BR>
The connection header was obtained by reaction of 5,6-dihydro-3- (4-methylbenzenesulfonamide)-7H-benzo[C]carbazole-8-carboxylic acid, which was obtained by heating under reflux for 6-(4-methylbenzenesulfonamide)-2-tetralone hydrochloride and 2-hydrazinobenzene acid in xylene according to the method described in Example getting 2.

1H-NMR (DMSO-d6): (M. D.): and 2.26 (s, 3H), 7,29 (t, J=8.0 Hz, 2H), 7,35 (dt, J= 2,0; and 7.6 Hz, 1H), 7,46 (d, J=8,8 Hz, 1H), 7,66 (d, J=6,8 Hz, 2H), 7,71 (s, 1H), 7,79 (d, J=9,2 Hz, 1H), of 7.96 (DD, J= 2,0; and 9.2 Hz, 1H), 8,01 (d, J=8,8 Hz, 1H), 8,66 (d, J=8,8 Hz, 1H), 8,79 (d, J=8.0 Hz, 1H), 10,33 (s, 1H), 11,76 (s, 1H)

Example of getting 25

Ethyl 13H-benzo[6,7]indolo[2,3-C]Hina the ml) slowly boiled and with stirring was added dropwise a solution of 3.4 g (to 20.6 mmol) of 2-nitrophenylacetonitrile in acetic acid (15 ml). After completion of adding dropwise the mixture was heated under reflux for 1 hour. Then added 20 ml of a mixture of 1 N. hydrochloric acid with acetic acid and the resulting mixture was heated under reflux for 1 hour. After removal of the solvent the residue was dissolved by adding ethyl acetate. The organic layer was washed sequentially with an aqueous solution of sodium bicarbonate, water and saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After removal of the solvent the residue was purified column chromatography on silica gel with getting 1,91 g (yield 32%) of 7-(2-nitrophenyl)benzo[g]-indole. Then the obtained product was dissolved in ethyl acetate (60 ml) and was added 200 mg of platinum oxide (IV). Then spent catalytic reduction at atmospheric pressure in an atmosphere of hydrogen at room temperature to obtain 1.7 g (yield 99%) 7-(2-AMINOPHENYL)benzo[g]indole.

Then 20 ml of ethanol was added to 540 mg (2.1 mmol) of 7-(2-AMINOPHENYL)benzo[g] indole and 260 mg (2.5 mmol) of acylglycerol (polymer) and the mixture was heated under reflux for 8 hours. After removal of the solvent the residue was purified column chromatography on silica: (m D.): 1,64 (t, J=7,1 Hz, 3H), 4,74 (K, J=7,1 Hz, 2H), 7,63-to 7.77 (m, 3H), 7,79 (d, J=8.6 Hz, 1H), 7,70-a 7.85 (m, 1H), of 8.06 (DD, J= 1,3; and 7.7 Hz, 1H), 8,35 (DD, J=0,7; 8,1 Hz, 1H), 8,45 (DD, J=1,3; and 8.4 Hz, 1H), 8,54 (d, J=8.6 Hz, 1H), 8,79 (DD, J=1,1; 8,2 Hz, 1H), 10,98 (Shir. s, 1H)

Example 1

Hydrochloride 5-[2-(dimethylamino)ethyl] -4H-benzo[C] pyrimido[5,6,1-jk] carbazole-4,6(5H)-dione:

< / BR>
457 mg (10.5 mmol) of sodium hydride (55% in oil) was added to a solution of 1.44 g of the compound of Example for the preparation of 3 in dimethylformamide (50 ml) at room temperature and the resulting mixture was stirred for 50 minutes. Then added 1 ml (10.5 mmol) of ethylchloride at 0oC and the resulting mixture was stirred at the same temperature for 2 hours and then at room temperature for 6 hours. After adding water the precipitate was recovered by filtration, washed with water and dried. Then it was dissolved in a mixture of dichloromethane-methanol, and insoluble substances were filtered off. After concentration was sequentially added ethanol and concentrated hydrochloric acid. Formed in this way hydrochloride was removed by filtration and recrystallized from ethanol to obtain 1.24 g of the compound indicated in the title of the example.

Melting point: 254-255oC (recrystallization from ethanol).

FAB-mass-Spa is a 5.5 Hz, 2H), to 7.67 (t, J=8.0 Hz, 1H), 7,78 (t, J=8.0 Hz, 1H), 7,83 (t, J=8.0 Hz, 1H), 8,14 (d, J=8.0 Hz, 1H), 8,19 (d, J=8.0 Hz, 1H), 8,23 (d, J=8,8 Hz, 1H), to 8.62 (d, J=8.0 Hz, 1H), 8,86 (d, J=8.0 Hz, 1H), of 9.02 (d, J=8.0 Hz, 1H), 9,70 (Shir. s, 1H)

Elemental analysis: as C22H19N3O2H2O

calculated: C 64,15; H 5,38; N 10,20;

found: C 64,38; H of 5.05; N 10,22.

Example 2

Hydrochloride of 11-acetyl-5-[2-(dimethylamino)ethyl] -4H-benzo[C] pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
13.2 mg (0,549 mmol) of sodium hydride was added to a solution of 105 mg (0,282 mmol) of the compound of Example, get 5 in dimethylformamide (2.5 ml) at 0oC and the resulting mixture was stirred at the same temperature for 1 hour and 10 minutes and then at room temperature for 1 hour. Then added 53,6 ál (0,564 mmol) ethylchloride at 0oC and the resulting mixture was stirred at the same temperature for 1 hour and 20 minutes. After extraction by adding water and chloroform, the organic layer was extracted, dried over sodium sulfate and concentrated. The residue was purified column chromatography on silica gel and converted into the hydrochloride with 1 N. hydrochloric acid (ethanol) to give 106 mg of the compound indicated in the title of the example.

Melting point: painted from p is 0 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.):2,78 (s, 3H), 2,92 (s, H), 3,48-of 3.54 (m, 2H), of 4.44 (t, J=5.6 Hz, 2H), 7,80 (t, J=7.5 Hz, 1H), 8,16 (d, J=7.5 Hz, 1H), 8,24 (DD, J= 2,3; and 9.4 Hz, 1 H), 8,40 (d, J=8,9 Hz, 1H), 8,68 (d, J=8,9 Hz, 1H), 8,87-8,91 (m, 2H), 9,01 (d, J=7.5 Hz, 1H), 9,88 (Shir. s, 1H)

Elemental analysis: as C24H21N3O3HCl2H2O

calculated: C 63,50; H 5,33; N 9,26,

found: C 63,42; H 5,04; N 9,16.

Example 3 Hydrochloride

5-[2-(dimethylamino)ethyl] -11-(1-hydroxyethyl)-4H-benzo[C] pyrimido[5,6,1-jk] carbazole-4,6(5H)-dione:

< / BR>
21 μl (has 0.168 mmol) of the complex, borane/pyridine (~ 8 M) was added to a suspension of 84 mg (0,211 mmol) of the compound obtained by converting the compound of Example 2 in its free base in acetic acid (1.5 ml) and the resulting mixture was stirred at 70oC for 3 hours. Then it was acidified by adding 1 n hydrochloric acid at room temperature, was stirred for 1 min and neutralized with saturated aqueous sodium bicarbonate solution. Then it was extracted by adding thereto a mixture of dichloromethane ethanol. The organic layer was collected, washed with water, dried over sodium sulfate and concentrated. The residue was purified preparative thin-layer chromatography and converted into the hydrochloride by means of 1 N. chlorotoluron>oC (decomposition) (recrystallization from ethanol).

FAB mass spectrometry m/z: 402 ([M+ H]+).

1H-NMR (DMSO-d6): (M. D.): 1,50 (d, J=5.0 Hz, 3H), of 2.92 (s, 6H), 3,49 (t, J=5.7 Hz, 2H), 4,43 (t, J=5.7 Hz, 2H), 4.95 points-of 5.05 (m, 1H), the 5.45 (d, J=4,2 Hz, 1H), to 7.77 (t, J=8,4 Hz, 1H), to 7.84 (t, J=8,4 Hz, 1H), 8,08-of 8.15 (m, 2H), 8,21 (d, J= 8,4 Hz, 1H), 8,59 (DD, J=1,4; and 8.4 Hz, 1H), 8,81 (d, J=8,4 Hz, 1H), 8,99 (d, J=7,6 Hz, 1H), 9,90 (Shir. s, 1H)

Elemental analysis: as C24H24N3O3Cl

calculated: C 65,82; H 5,52; N 9,60;

found: 65,49; H of 5.53; N 9,49.

Example 4

Hydrochloride 12,13-dihydro-5-[2-(dimethylamino) ethyl]-4H-benzo[C]pyrimido[5,6,1-jk]carbazole-4,6,10(5H,11h)-trione:

< / BR>
A solution of 4.9 g (14 mmol) of the compound of Example obtaining 8 in dimethylformamide (70 ml) was added dropwise to a suspension of 0.9 g (37.5 mmol) of sodium hydride in dimethylformamide (30 ml) at room temperature and the resulting mixture was stirred at the same temperature for 2 hours. Then added 2.5 g (23 mmol) of ethylchloride while cooling with ice and stirring. After 15 minutes was added ethyl acetate and the resulting mixture was washed successively with diluted aqueous ammonia and an aqueous solution of sodium chloride and dried over magnesium sulfate. After concentration was added methanol and the crystals were removed filtro under stirring. After stirring at room temperature, and concentration) was added ethanol and the precipitate was removed by filtration to obtain 4.3 g of the compound indicated in the title of the example.

Melting point: painted from approximately 250oC, gradually decomposes from about 260oC and it decomposes at approximately 273-275oC.

FAB mass spectrometry m/z: 376 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.): 2,22-of 2.36 (m, 2H), 2,72 is 2.80 (m, 2H), 2,92 (s, 6H), 3,44-of 3.54 (m, 2H), 3,54-of 3.60 (m, 2H), to 4.38-to 4.46 (m, 2H), of 7.75 (t, J= 7,6 Hz, 1H), 8,17 (DD, J=0,8; and 7.6 Hz, 1H), 8,25 (d, J=8,8 Hz, 1H), to 8.41 (d, J=8,8 Hz, 1H), 8,61 (DD, J=0,8; and 7.6 Hz, 1H), 9,52 (Shir. s, 1H)

Elemental analysis: as C22H21N3O3HCl1H2O

calculated: C 61,47; H 5,63; N 9,77;

found: C 61,47; H to 5.57; N 9,77.

Example 5

5-[2-(Dimethylamino)ethyl]-10-hydroxy-10,11,12,13-tetrahydro-4H-benzo [C] pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
0.5 g (1.2 mmol) of the compound of Example 4 was dissolved in a mixture of water (50 ml) with methanol (25 ml) was added 1.2 ml of 1 N. hydrochloric acid. Then carried out the hydrogenation in the presence of palladium on coal in an atmosphere of hydrogen at a pressure of approximately 4.5 kg/cm2. After confirming completion of the reaction thin-I 50 ml of water and 5 ml of concentrated aqueous ammonia, the mixture was extracted with ethyl acetate. The organic layer was extracted, washed with an aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated. The residue was purified column chromatography on silica gel to obtain 0.35 g of the compound indicated in the title of the example.

FAB mass spectrometry m/z: 378 ([M+H]+).

1H-NMR (CDCl3) (M. D.): 1,92-of 2.30 (m, 4H), is 2.37(s, 6H), 2,70 (t, J=6,8 Hz, 2H), 3,06-of 3.32 (m, 2H), 4,32 (t, J=6,8 Hz, 2H), 4.95 points (Shir. t, J=4,8 Hz, 1H), 7,52 (t, J=7,6 Hz, 1H), to 7.67 (d, J=8,4 Hz, 1H), 8,09 (DD, J=0,8; and 7.6 Hz, 1H), 8,15 (DD, J=0,8; and 7.6 Hz, 1H), with 8.33 (d, J=8,4 Hz, 1H).

Elemental analysis: as C22H23N3O31H2O

calculated: C 66,82; H 6,37; N 10,63;

found: C 67,10; H 6,03; N 10,34.

Example 6

(+)-5-[2-(Dimethylamino)ethyl]-10-hydroxy-10,11,12,13-tetrahydro-

4H-benzo[C]pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The compound of Example 5 were separated on a column for separating optical stereoisomers [Chiralcel OD, conducted by Daicel; elwira a mixture of n-hexane/2-propanol(7: 3 - 6:4)]. Faction eluroomus earlier, was concentrated to dryness to obtain the connection header.

Melting point: ~ 160-162oC

FAB mass spectrometry m/z: 378 ([M+H]+).

1H-NMR (CDCl3): (M. D.): 1,90-of 2.30 (m, 4H), 2,43 (s, 6H), 2,77 (t, J= 6.4 Hz, 2H), 3.04 from-and 3.31 (m, 2H), 4,34 (t, J=6,8 Hz, 2H is emanny analysis: as C22H23N3O30,75 H2O

calculated: C 67,59; H 6,32; N 10,75;

found: C 67,34; H to 5.93; N 10,48.

The angle of rotation []2D7:9,8(C=1,0, CHCl3).

Example 7

Hydrochloride 11,12-dihydro-5-[2-(dimethylamino)ethyl]-4H,10H of cyclopent[C] pyrimido[5,6,1-jk]carbazole-4,6,10(5H)-trione:

< / BR>
The named compound was obtained from the compound of example 10 according to the method described in Example 2.

Melting point: painted approximately 255oC and gradually decomposes from about 265oC.

FAB mass spectrometry m/z: 362 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.): 2,83-to 2.94 (m, 8H), 3.45 points (Shir. s, 2H), 3,64 (Shir. t, J=6.0 Hz, 2H), 4,42 (Shir. t, J=6.0 Hz, 2H), 7,79 (t, J=7,6 Hz, 1H), of 7.97 (d, J= 8,4 Hz, 1H), 8,19 (DD, J=0,8; and 7.6 Hz, 1H), 8,49 (d, J=8,4 Hz, 1H), 8,55 (DD, J=0,8; and 7.6 Hz, 1H), 9,44 (Shir. s, 1H).

Elemental analysis: as C21H19N3O3HCl0,75H2O

calculated: C 61,31; H 5,27; N OF 10.21;

found: C 61,17; H 5,04; N 10,16.

Example 8

Hydrochloride 8-[2-(dimethylamino)ethyl] -7H-furo[3,2-C] pyrimido[5,6,1-jk] carbazole-3,7,9(2H,8H)-trione:

< / BR>
590 mg (2.2 mmol) of the compound of Example receive 15 was dissolved in dimethylformamide (20 ml). After adding 720 mg (4.4 mmol) of N,N'-Carbo is ulali of 0.97 ml (8,8 mmol) of N,N-dimethylethylenediamine and the resulting mixture was stirred overnight, followed by concentration. To the residue was added water and the resulting mixture was extracted with a mixture of ethyl acetate-tetrahydrofuran. The organic layer was extracted, washed sequentially with saturated aqueous sodium bicarbonate solution and water and dried over magnesium sulfate. After concentration the residue was purified column chromatography on silica gel to obtain 250 mg of 2,3-dihydro-N-[2-(dimethylamino) ethyl]-3-oxo-6H-furo[3,2-C]carbazole-7-carboxamide. This product was dissolved in dimethylformamide (10 ml). After adding 60 mg (1.5 mmol) of sodium hydride (60% in oil) and the mixture was stirred in nitrogen atmosphere for 30 minutes. After adding 0,145 ml (1.5 mmol) of ethylchloride with ice cooling the resulting mixture was stirred for 30 minutes and then acidified by the addition thereto of 1 N. hydrochloric acid. After concentration was added saturated aqueous sodium bicarbonate solution and the resulting mixture was extracted with a mixture of ethyl acetate-tetrahydrofuran. The organic layer was extracted, washed with water, dried over magnesium sulfate, concentrated and purified column chromatography on silica gel. The product is then suspended in ethanol (20 ml). After adding 1 ml of 1 N. hydrochloric acid and stirring the crystals were removed by filtration with poluchenii 240oC and decomposes at approximately 270 - 273oC.

FAB mass spectrometry m/z: 364 ([M+H]+).

1H-NMR (DMSO-d6): (M. D. ): 2,89 (Shir. s, 6H), 3,42-to 3.50 (m, 2H), 4,39 is 4.45 (m, 2H), 5,14 (s, 2H), 7,78 (t, J=7.7 Hz, 1H), 7,95 (d, J=8,4 Hz, 1H), 8,17 (DD, J=0,8; and 7.7 Hz, 1H), they were 8.22 (d, J=8,4 Hz, 1H), 8,43 (DD, J=0,8; and 7.7 Hz, 1H), 9,62 (Shir. s, 1H).

Elemental analysis: as C20H17N3O4HCl0,15H2O

calculated: C 59,68; H 4,58; N 10,44;

found: C 59,64; H 4,49; N 10,33.

Example 9

2,3-Dihydro-8-[2-(dimethylamino)ethyl]-3-hydroxy-7H-furo[3,2-C] pyrimido[5,6,1-jk]carbazole-7,9(8H)-dione

< / BR>
105,5 mg (0.29 mmol) of the compound of Example 8 was dissolved in acetic acid (1 ml). Then add 36 ál of 8 M complex, borane/pyridine with stirring at room temperature. The resulting mixture was stirred for 4.5 hours. After adding 30 μl of 8 M complex Bourne/pyridine the mixture continued to stir overnight and then concentrated. Then it was extracted with water, saturated aqueous sodium bicarbonate solution and chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified column chromatography on silica gel. Thus obtained product was recrystallized from the>H-NMR (DMSO-d6): (M. D.):2,24 (s, 6H), of 2.56 (t, J=6,8 Hz,2H), 4,15 (t, J=6,8 Hz, 2H), 4,56 (DD, J=2,8; 10,0 Hz, 1H), 4,84 (DD, J=6,8; 10,0 Hz, 1H), 5,43-5,49 (m, 1H), 5,80 (d, J= 5.6 Hz, 1H), to 7.61-to 7.67 (m, 2H), of 7.97 (d, J= 8,4 Hz, 1H), 8,02 (DD, J=0,8: 7,6 Hz, 1H), they were 8.22 (DD, J=0,8; and 7.6 Hz, 1H)

Example 10

Hydrochloride 12,13-dihydro-5-[2-(methylamino)ethyl] -4H-benzo[C] pyrimido[5,6,1-jk] carbazole-4,6,10(5H,11H)-trione:

< / BR>
to 0.23 g (or 0.57 mmol) of the compound of Example obtaining 17 and 95 mg (0.1 mmol) of Tris (triphenylphosphine) radioid was dissolved in 20 ml of a mixture of acetonitrile with water (84: 16). Then the obtained mixture was heated in a nitrogen atmosphere for removal of the solvent, adding at the same time a mixture of acetonitrile with water (84:16) to maintain the constant volume of the mixture. After continuing this operation for ~ 3 hours, the disappearance of the parent compounds was confirmed by thin-layer chromatography. Then the reaction mixture was concentrated to approximately 1/4 and were extracted with ethyl acetate. The organic layer was collected, washed successively with diluted aqueous ammonia and an aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated. The residue was purified preparative thin-layer chromatography and then converted into its hydrochloride according to the method described in Example 4 to obtain 0.1 g of soy is C, gradually decomposes from about 260oC and it decomposes at ~ 267 - 269oC.

FAB mass spectrometry m/z: 362 ([M+H]+).

1H-NMR (DMSO-d6D2O): (M. D.): 2,24-of 2.34 (m, 2H), 2,59 (s, 3H), was 2.76 (Shir. t, J=6.0 Hz, 2H), 3,31 (Shir. t, J=5,2 Hz, 2H), 3,56 (Shir. t, J=6.0 Hz, 2H), 4,36 (Shir. t, J=5,2 Hz, 2H), of 7.75 (t, J=8.0 Hz, 1H), 8,16 (d, J=8.0 Hz, 1H), 8,24 (d, J=8,8 Hz, 1H). 8,39 (d, J=8,8 Hz, 1H), 8,59 (d, J=8.0 Hz, 1H)

Elemental analysis: as C21H19N3O3HCl0,2H2O

Calculated: C 62,83; H 5,12; N 10,47;

found: C 62,78; H 5,09; N 10,36.

Example 11

Hydrochloride 12,13-dihydro-5-[2-(1-pyrrolidinyl)ethyl] -4H-benzo[c] pyrimido[5,6,1-jk]carbazole-4,6,10(5H,11H)-trione:

< / BR>
The connection header was obtained by reaction of the compound of Example obtaining 7 with 1-(2-amino-ethyl) pyrrolidine according to the methods described in Example receiving 8 and Example 4.

Melting point: painted from approximately 235oC and gradually decomposes from about 260oC.

FAB mass spectrometry m/z: 402 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.) : 1,86 (Shir. s, 2H), 2,01 (Shir. s, 2H), 2,23 of - 2.32 (m, 2H), 2.71 to and 2.79 (m, 2H), 3.15 in (Shir. s, 2H), 3.46 in-3,74 (Shir. t+m, J= 6.0 Hz, 4H+2H), and 4.40 (Shir. t, J=5,2 Hz, 2H), 7,73 (t, J=8.0 Hz, 1H), 8,15 (d, J=8.0 Hz, 1H), 8,23 (d, J=8,8 Hz, 1H), 8,39 (d, J=8,8 Hz, 1H), to 8.57 (d, J=8.0 Hz, 1H), 10, is: C 62,00; H OF 5.85; N 9,04;

found: C 62,27; H 5,49; N 9,03.

Example 12

Hydrochloride 5-[2-(1-pyrrolidinyl)ethyl] -4H-benzo[C] pyrimido [5,6,1-jk] carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained by reaction of the compound of Example getting 2 with 1-(2-amino-ethyl)pyrrolidine according to the methods described in the Example of a 3 and Example 1.

FAB mass spectrometry m/z: 384 ([M+H]+).

1H-NMR (DMSO-d6): (M. D. ): 1,78-of 1.92 (m, 2H), 1,94-2, 06 (m, 2H), is 3.08-up 3.22 (m, 2H), of 3.56 (t, J=5.6 Hz, 2H), 3,60-3,70 (m, 2H), to 4.41 (t, J=5.6 Hz, 2H), 7,66 (t, J=7,6 Hz, 1H), of 7.75 (t, J=8.0 Hz, 1H), 7,81 (t, J=8.0 Hz, 1H), 8,11 (d, J=7,6 Hz, 1H), 8,18(d, J=8.0 Hz, 1H), 8,21 (d, J=9,2 Hz, 1H), at 8.60 (d, J= 9,2 Hz, 1H), 8,83 (d, J=8.0 Hz, 1H), 8,98 (d, J=7,6 Hz, 1H), 10,29 (Shir. s, 1H).

Elemental analysis: as C24H21N3O3HClH2O

calculated: C 65,83; H 5,52; N 9,60;

found: C 66,04; H to 5.57; N at 9.53.

Example 13

Hydrochloride of 2-[2-(dimethylamino)ethyl] -5-nitro-1H-benzo[C] pyrimido [5,6,1-kl]phenothiazines-1,3(2H)-dione:

< / BR>
A solution of 200 mg (0.49 mmol) of the compound of Example getting 23 in tetrahydrofuran (15 ml) was stirred at room temperature was added sequentially with 0.5 ml of triethylamine and 200 ál (2,09 mmol) ethylchloride. After stirring at room temperature overnight, the reaction mixture koncentrere. The organic layer was washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated to dryness. The residue was recrystallized from ethanol to obtain 104 mg of the free base compound of the title. Then this product is suspended in methanol and was added concentrated hydrochloric acid with stirring. Then the mixture was concentrated to dryness to obtain the connection specified by name.

1H-NMR (DMSO-d6): (M. D.):2,90 (s, 6H), 3,49 (Shir. s, 2H). to 4.38 (t, J= 5.6 Hz, 2H), 7,66 (t, J=7,6 Hz, 1H), 7,73 (t, J=7,6 Hz, 1H), 7,82 (d, J=9,2 Hz, 1H), of 7.96 (t, J=8,8 Hz, 1H), 8,03 (d, J=8.0 Hz, 1H), of 8.09 (d, J=8,4 Hz, 1H), 8,49-charged 8.52 (m, 1H), 8,59-to 8.62 (m, 1H), 9,72 (Shir. t, 1H)

Example 14

Hydrochloride of 2-[2-(dimethylamino)ethyl]-1H-pyrimido[5,6,1-jk]-thieno [3,2-a] carbazole-1,3(2H)-dione:

< / BR>
The named compound was obtained using 4-oxo-4,5,6,7-tetrahydro-benzo[b]thiophene hydrochloride and 2-hydrazinobenzene acid as starting compounds and repeating the procedures of Examples of the preparation of 1,2 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D. ): 2,92 (Shir. s, 6H), 3,44 is 3.57 (m, 2H), of 4.44-4,51 (m, 2H), 7,74 (t, J=7,6 Hz, 1H), 7,98 (d, J=5.6 Hz, 1H), 8,13 (DD, J= 0,8; and 7.6 Hz, 1H), compared to 8.26 (d, J=8,4 Hz, 1H), at 8.36 (d, J=8,4 Hz, 1H), 8,65 (DD, J=0 is sooner[3,2-C] pyrimido[5,6,1-jk]carbazole-4,8,10(9H)-trione:

< / BR>
The named compound was obtained according to the procedure described in Example 2.

FAB mass spectrometry m/z: 378 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.): is 2.88 (s, 6H), to 2.99 (t, J=6.4 Hz, 2H), 3.46 in (lat. s, 2H), 4,40 (Shir. t, J=5.6 Hz, 2H), 4,89 (t, J=6.4 Hz, 2H), 7,73 (t, J= 7,6 Hz, 1H), of 8.06 (d, J=8,4 Hz, 1H), of 8.09 (d, J=8,4 Hz, 1H), 8,12 (d, J= 7,6 Hz, 1H), 8,42 (d, J=7,6 Hz, 1H), 9,68 (Shir. s, 1H)

Elemental analysis: as C21H19N3O4HCl1,25H2O

calculated: C 57,80; H 5,20; N 9,63;

found: C 57,99; H 5,07; N RS 9.69.

Example 16

The hydrochloride of 9-[2-(dimethylamino)ethyl] -4H, 8H-pyrano[3,2-C] pyrimido [5,6,1-jk]carbazole-4,8,10(9H)-trione:

< / BR>
The named compound was obtained using the procedures of Example 2.

FAB mass spectrometry m/z: 376 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.): 2,89 (s, 6H), 3.46 in (lat. s, 2H), 4,43 (Shir. t, J= 5.6 Hz, 2H), 6,55 (d, J=6.0 Hz, 1H), 7,83 (t, J=7,6 Hz, 1H), 8,23 (DD, J=0,8 and 7.6 Hz, 1H), 8.34 per (d, J=8,8 Hz, 1H), 8,48 (d, J=8,8 Hz, 1H), 8,54 (d, J=6.0 Hz, 1H), 8,65 (DD, J=0,8; and 7.6 Hz, 1H), 9,52 (Shir. s, 1H)

Example 17

The hydrochloride of 9-[2-(dimethylamino)ethyl] -1H-furo[3,2-a]pyrimido [5,6,1-jk] carbazole-1,3(2H)-dione:

< / BR>
The connection header received with use of 4-oxo-4,5,6,7-tetrahydrobenzo[b] furan hydrochloride and 2-hydrazinobenzene acid and repeating the procedures of Example the 72 (t, J=7,6 Hz, 1H), 7,83 (d, J=2.0 Hz, 1H), 7,88 (d, J=8,4 Hz, 1H), of 8.09 (d, J=7,6 Hz, 1H), to 8.20 (d, J=2.0 Hz, 1H), 8,32 (d, J=8,4 Hz, 1H), 8,61 (d, J=7,6 Hz, 1H), 9,46 (Shir. s, 1H)

Example 18

Hydrochloride of 2-[2-(dimethylamino)ethyl] -1H-benzo[a] pyrimido[5,6,1-jk] carbazole-1,3(2H)-dione:

< / BR>
The connection header has been using as starting compounds-tetralone hydrochloride and 2-hydrazinobenzene acid and repeating the procedures of Examples of getting 1, 2 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D.): 2,89 (s, 6H), 4,49 (Shir. s, 2H), 4,49 (t, J= 5.5 Hz, 2H), of 7.64-7,71 (m, 2H), 7,74 (t, J=8.0 Hz, 1H), 8,11-8,18 (m, 3H), 8,44 (d, J= 8,3 Hz, 1H), 8,66 (d, J=8.0 Hz, 1H), 9,59 (Shir. s, 1H), 9,76 (d, J=8,3 Hz, 1H)

Elemental analysis: as C22H19N3O2HCl0,2H2O

calculated: C 66,48; H 5,17; N 10,57;

found: C 66,47; H 5,20; N 10,51

Example 19

Hydrochloride 5-[3-(dimethylamino)propyl] -4H-benzo[C] pyrimido[5,6,1-jk] carbazole-4,6(5H)-dione:

< / BR>
The connection header was obtained by reaction of the compound of Example getting 2 with N, N-dimethyl-1,3-propandiamine according to the procedure described in Example getting 3 and Example 1.

FAB mass spectrometry m/z: 372 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.): 2,03-to 2.13 (m, 2H), 2, 74 (s, 6H), 3,19 (t, J= 8.0 Hz, 2H), 4,12 (t, J=6.0 Hz, 2H), 7,65 (t, J=7.2 Hz, 1H), of 7.75 (t, J= 8.0 Hz, 1H), 7,81 (t, J=7,6 Hz, 1H), 8, is entry analysis: as C23H21N3O2HCl0,3H2O

calculated: C 66,84; H 5,51; N 10,17;

found: C 66,75; H the 5.45; N there is a 10.03.

Example 20

Hydrochloride of 2-[2-(dimethylamino)ethyl] -1H, 11H-indeno[1',2': 4,5] pyrrolo[3,2,1-ij]hinzelin-1,3(2H)-dione:

< / BR>
The connection header received with use of 2 - indanone hydrochloride and 2-hydrazinobenzene acid and repeating the procedures of Examples of getting 1 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D.):to 3.02 (s,6H), 3,53 (t, J=5.8 Hz, 2H), 4,10 (s, 2H), 4,50 (t, J=5.8 Hz, 2H), 7,28 (dt, J=1,2; and 7.6 Hz, 1H), 7,41 (dt, J= 1,0; and 7.6 Hz, 1H), 7,56-to 7.59 (m, 1H), 7.62mm (t, J=7.7 Hz, 1H), 7,76-7,79 (m, 1H), 8,02 (DD, J=0,8; and 7.7 Hz, 1H), 8,25 (DD, J=0,8; and 7.7 Hz, 1H)

Example 21

The hydrochloride of 7-[2-(dimethylamino)ethyl] -6H,14H-benzo[a]pyrimido[5,6,1-de] acridine-6,8,14(7H)-trione:

< / BR>
The named compound was obtained according to the procedure described in Example 2.

1H-NMR (DMSO-d6): (M. D.): 2.91 in (lat. s, 6H), 3,50 of 3.56 (m, 2H), 4,49 (t, J=5.7 Hz, 2H), of 7.64-of 7.69 (m, 1H), to 7.77-of 7.82 (m, 1H), 7,87-a 7.92 (m, 1H), 7,98-8,03 (m, 1H), of 8.37-to 8.40 (m, 1H), 8,43-8,46 (m, 1H), 8,63 (DD, J=0,5; 8,8 Hz, 1H), 9,26 (s, 1H), 9,81 (DD, J=0.7 and 8.6 Hz, 1H), 10,04 (Shir. s, 1H)

Example 22

Hydrochloride 5-[2-(dimethylamino)ethyl] -11-methoxy-4H-benzo- [C] pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained using 6-methoxy - a-tetralone hydrochloride and 2-d is (DMSO-d6): (M. D.): at 2.93 (d, J=4,6 Hz, 6H), 3,47-of 3.54 (m, 2H), of 3.94 (s, 3H), 4,39 is 4.45 (m, 2H), 7,46 (DD, J=2,2; 9,0 Hz, 1H), 7.62mm (d, J= 2.2 Hz, 1H), 7,78 (t, J=8,4 Hz, 1H), 8,14 (d, J=8,4 Hz, 1H), 8,16 (d, J=9.0 Hz, 1H), 8,59 (d, J=9.0 Hz, 1H), 8,78 (d, J=9.0 Hz, 1H), 9,01 (d, J=8,4 Hz, 1H), 9,16 (Shir. s, 1H)

Elemental analysis: as C23H21N3O3HCl1,5H2O

calculated: C 61,26; H 5,59; N TO 9.32;

found: C 61,08; H 5,46; N 9,40.

Example 23

Hydrochloride 5-[2-(dimethylamino)ethyl] -10-methoxy-4H-benzo-[C] pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained using 5-methoxy - a-tetralone hydrochloride and 2-hydrazinobenzene acid and repeating the procedures of Examples of getting 1, 2 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D.): 2,89 (s, 6H), 3,44-3,51 (m, 2H), Android 4.04 (s, 3H), and 4.40 (t, J=6.2 Hz, 2H), 7,12 (d, J=8,2 Hz, 1H), 7,72 (t, J=8.5 Hz, 1H), 7,73 (dt, J= 3,4; 8,2 Hz, 1H), of 8.09 (d, J=8.5 Hz, 1H), 8,32 (d, J=8.5 Hz, 1H), to 8.41 (d, J=8.5 Hz, 1H), charged 8.52 (DD, J=1,0; and 8.5 Hz, 1H), 8,88 (d, J=8.5 Hz, 1H), to 9.93 (Shir. s, 1H)

Elemental analysis: as C23H21N3O3HCl1,3H2O

calculated: C 61,76; H 5,54; N 9,40;

found: C 61,89; H 5,32; N 9,45.

Example 24

The dihydrochloride of 2-[2-(dimethylamino)ethyl]-1H-benzo[b]pyrimido-[1,6,5-lm]-4 - azucarbol-1,3(2H)-dione:

< / BR>
The named compound was obtained according to the method described in Example 2.

1H), 10,41 (Shir. s, 1H)

Example 25

Hydrochloride 1,2-dihydro-9-[2-(dimethylamino)ethyl] -4H, 8H-pyrano[3,4-C] pyrimido[5,6,1-jk]carbazole-4,8,10(9H)-trione:

< / BR>
The named compound was obtained according to the method described in Example 2.

1H-NMR (DMSO-d6): (M. D.): 2,89 (s, 6H), 3,47 (t, J=6.0 Hz, 2H), to 3.64 (t, J=6.0 Hz, 2H), to 4.38 (t, J=6.0 Hz, 2H), and 4.68 (t, J=6.0 Hz, 2H), 7,73 (t, J= 7,6 Hz, 1H), 8,15 (t, J=7,6 Hz, 1H), 8,27 (d, J=8,8 Hz, 1H), 8,44 (d, J= 8,8 Hz, 1H), 8,55 (d, J=7,6 Hz, 1H), 9,82 (Shir. s, 1H)

Example 26

Hydrochloride 5-[2-(dimethylamino)ethyl] -12-methoxy-4H-benzo-[C] pyrimido [5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained using 7-methoxy - a-tetralone hydrochloride and 2-hydrazinobenzene acid and repeating the procedures of Examples 1, 2 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D.):2,85 (Shir. s, 6H), 3,35-of 3.46 (m, 2H), 4,08 (s, 3H), 4,39 (Shir. s, 2H), 7,32 (DD, J=2,2; 8,8 Hz, 1H), 7,79 (t, J=7.8 Hz, 1H), to 7.99 (d, J=1.7 Hz, 1H), 8,09-8,19 (m, 3H), 8,48 (d, J=8,8 Hz, 1H), 8,97 (d, J=7.8 Hz, 1H), 9,25 (Shir. s, 1H)

Example 27

Hydrochloride of 2-[2-(dimethylamino)ethyl] -5-nitro-1H-benzo-[b] pyrimido [5,6,1-jk]phenoxazin-1,3(2H)-dione:

< / BR>
304 mg (1,91 mmol) 3-amino-2-naphthol, 477 mg (1,81 mmol) of methyl 2-chloro-3,5-dinitrobenzoate and 178 mg (2,17 mmol) of sodium acetate suspended in a mixture of water (5 ml) with ethanol (10 ml) and was heated with reverse hoodiabuy under reflux for 2.5 hours and then allowed it to cool to room temperature. After adding 10 ml of 1 N. hydrochloric acid thus obtained precipitate was removed by filtration and washed successively with water, 1 N. hydrochloric acid and ethanol to obtain 430 mg of 3-nitro-12H-benzo[b] phenoxazine-1 carboxylic acid. Then this product was treated according to the methods described in Example getting 23 and Example 13, to obtain the compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.): 2,89 (s, 6H), of 3.45 (t, J=5,2 Hz, 2H), and 4.40 (t, J=5,2 Hz, 2H), 7,47 (t, J=8.0 Hz, 1H), 7,52 (t, J=8.0 Hz, 1H), 7,69 (s, 1H), 7,86 (d, J=6,8 Hz, 1H), 7,88 (d, J=8.0 Hz, 1H), 8,19 (d, J=2.4 Hz, 1H), 8.34 per (d, J=2.4 Hz, 1H), 9,05 (s, 1H), 9,82 (Shir. s, 1H)

Example 28

Hydrochloride of 2-chloro-5-[2-(dimethylamino)ethyl] -4H-benzo[C] pyrimido [5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained using as starting compounds-tetralone hydrochloride and 5-chloro-2-hydrazinobenzene acid and repeating the procedures of Examples of the preparation of 1,2 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D.): 2,89 (s, 6H), 3,39-of 3.53 (m, 2H), to 4.38-4,48 (m, 2H), 7.68 per to 7.75 (m, 1H), 7,81-7,89 (m, 1H), 8,13 (d, J=1.6 Hz, 1H), they were 8.22 (d, J=8,4 Hz, 1H), 8,31 (d, J= 8,8 Hz, 1H), 8,63 (d, J=8,8 Hz, 1H), to 8.94 (d, J=8,4 Hz, 1H), 9,14 (d, J=1.6 Hz, 1H), 9,46 (Shir. s, 1H)

Elemental analysis: as C22H18N3O2ClHCl1,75H2O

calculated: C 5 ° [4,3-C]pyrimido [5,6,1-jk] carbazole-1,8,10(2H,9H)-trione:

< / BR>
The named compound was obtained by saponification of ester compounds of Example get 20 and then by repeating the procedures of Example for the preparation of 3 and Example 2.

1H-NMR (DMSO-d6): (M. D. ): 2,90 (Shir. s, 6H), 3.43 points-of 3.53 (m, 2H), 4,40-to 4.46 (m, 2H), 6,80-6,83 (m, 1H), 7,34-7,38 (m, 1H), 7,73 (t, J=7.9 Hz, 1H), 8,01 (d, J=8,9 Hz, 1H), 8,18 (DD, J=0,9, 7.9 Hz, 1H), 8,89 (d, J=8,9 Hz, 1H), 9,52 (Shir. s, 1H), to 9.91 (DD, J=0,9; 7.9 Hz, 1H), 11,67-11,71 (m, 1H)

Elemental analysis: as C21H18N4O3HCl1,3H2O

calculated: C 58,08; H 5,01; N 12,90;

found: C 57,94; H 4,78; N 12,72.

Example 30

Hydrochloride 5-[2-(dimethylamino)ethyl] -4H-Hino[4', 3', -4,5] pyrrolo[3,2,1-ij]hinzelin-4,6(5H)-dione:

< / BR>
The named compound was obtained according to the method described in Example getting 2.

FAB mass spectrometry m/z: 359 ([M+H]+)+]/

1H-NMR (DMSO-d6+D2O): (M. D.): to 2.94 (s, 6H), 3,54 (Shir. t, J=5.6 Hz, 2H), 4,47 (Shir. t, J=5.6 Hz, 2H), 7,89 (t, J=7,6 Hz, 1H), to $ 7.91-to 7.99 (m, 2H), 8,30-of 8.37 (m, 2H), 8,89-8,95 (m, 1H), 9,16 (d, J=7,6 Hz, 1H), becomes 9.97 (s, 1H)

Elemental analysis: as C21H18N4O22HCl0,5H2O

calculated: C 57,28; H to 4.81; N 12,72;

found: C 57,28; H equal to 4.97; N 12,60.

Example 31

Hydrochloride 5-amino-2-[2-(dimethylamino)ethyl] -1H-benzo[b] pyrimido [5,6,1-kl]phenoxazin-1,3(2H)-dione:

< / BR>
268 lady on coal. Then spent catalytic reduction at room temperature under nitrogen atmosphere. After filtering off the palladium on coal through celite, the filtrate was concentrated. Then, thereto were added water and saturated aqueous sodium bicarbonate solution and the resulting mixture was stirred at room temperature. The precipitate was recovered by filtration, washed with water and suspended in methanol. After adding concentrated hydrochloric acid the mixture was stirred at room temperature. So it turned into a homogeneous solution and then precipitate formed. This precipitate was recovered by filtration to obtain 179 mg of the compound indicated in the title of the example.

1H-NMR (DMSO-d6): (M. D.): 2,89 (s, 6H), 3.43 points (t, J=5.6 Hz, 2H), 4,34 (t, J= 5.6 Hz, 2H), 6,76 (s, 1H), of 6.96 (s, 1H), 7,38-of 7.48 (m, 2H), to 7.59 (s, 1H), 7,79 (d, J= 8.0 Hz, 1H), 7,81 (d, J=8.0 Hz, 1H), 9.15, with (s, 1H), 9,65 (Shir. s, 1H)

Example 32

Hydrochloride 5-[2-(dimethylamino)ethyl] -13-methoxy-4H-benzo[C] pyrimido [5,6,1-jk]carbazole-4,6(5H)-dione;

< / BR>
The named compound was obtained using 8-methoxy - a-tetralone hydrochloride and 2-hydrazinobenzene acid as starting compounds and repeating the procedures of Examples of the preparation of 1,2 and 3 and Example 2.

1H-NMR (DM) - Rev.,15 (d, J=8.0 Hz, 1H), to 8.20 (d, J=8,8 Hz, 1H), 8,82 (d, J=8,8 Hz, 1H), which is 9.09 (d, J=8.0 Hz, 1H), 9,35 (Shir. s, 1H)

Elemental analysis: as C23H21N3O3HCl0,65H2O

calculated: C 63,42; H 5,39; N 9,65;

found: C 63,31; H 5,14; N 9,68.

Example 33

The dihydrochloride 9-[2-(dimethylamino)ethyl] -8H-pyrido[4,3 -] pyrimido[5,6,1-jk]carbazole-8,10(9H)-dione;

< / BR>
300 mg (1.1 mmol) of the compound of Example obtaining 21 was dissolved in a mixture of tetrahydrofuran (10 ml) - methanol (10 ml). After adding 5 ml of 1 n sodium hydroxide the mixture was heated under reflux for 1 hour. Then, 7H-pyrido[4,3-C] carbazole-8-carboxylic acid, selected conventional way, was dissolved in dimethylformamide (40 ml) was added to a solution of 360 mg (2.2 mmol) of N,N'-carbonyldiimidazole. After stirring at room temperature for 30 minutes was added to 0.48 ml (4.4 mmol) of N, N-dimethylethylenediamine and the resulting mixture was stirred over night. After concentration, it was extracted by adding water and ethyl acetate. The organic layer was collected, washed successively with saturated aqueous sodium bicarbonate solution and water and dried over anhydrous magnesium sulfate. After concentration the residue was purified column chromatography on silica gel with reaction and process, as described in Example 2, to obtain 110 mg of the compound indicated in the title of the example.

Melting point: painted from approximately 270oC and decomposes at 279oC.

1H-NMR (DMSO-d6): (M. D.): 2,89-of 2.93 (m, 6H), 3,49-of 3.54 (m, 2H), 4,46 (t, J=6.0 Hz, 2H), 7,85 (t, J=7,6 Hz, 1H), 8,25 (d, J=7,6 Hz, 1H), 8,40-8,44 (m, 2H), 8,79 (d, J=6,4 Hz, 1H), 9,04 (d, J=9,2 Hz, 1H), 9,23 (d, J=7,6 Hz, 1H), 10,10 (Shir. s, 1H), 10,44 (s, 1H)

Elemental analysis: C21H18N4O22HCl2H2O

calculated: C 53,97; H 5,18; N 11,99;

found: C 54,11; H 4,99; N 11,99

Example 34 Hydrochloride

5-[4-(dimethylamino)butyl] -4H-benzo[C] pyrimido-[5,6,1-jk] carbazole-4,6 (5H)-dione:

< / BR>
The connection header was obtained by reaction of the compound of Example getting 2 with N, N-dimethyl-1,4-butanediamine according to the methods described in the Example of a 3 and Example 1.

FAB mass spectrometry m/z: 386 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.): 1,68-of 1.85 (m, 4H), to 2.74 (s, 6H), 3,09 (Shir. t, J= 6.4 Hz, 2H), 4,10 (Shir. t, J=6.4 Hz, 2H), of 7.64-of 7.70 (m, 1H), of 7.75 (t, J=7,6 Hz, 1H), 7,79-a 7.85 (m, 1H), 8,11 (d, J=7,6 Hz, 1H), 8,16-8,24 (m, 2H), to 8.62 (d, J=8,8 Hz, 1H), 8,83 (d, J=8,4 Hz, 1H), 8,97 (d, J=7,6 Hz, 1H), 9,99 (Shir. s, 1H)

Elemental analysis: C24H23N3O2HCl0,5H2O

calculated: C 66,89; H of 5.85; N 9,75;

found: C 66,54; H 5,71; N 9,66.

BR> The named compound was obtained according to the method described in Example 2.

1H-NMR (DMSO-d6): (M. D.): at 2.93 (s, 6H), 3,48-3,55 (m, 2H), 4,46 (t, J= 5.6 Hz, 2H), 7,83 (t, J=8,2 Hz, 1H), 8,10 (DD, J=1,3, and 8.9 Hz, 1H), 8,21 (d, J= 8,2 Hz, 1H), scored 8.38 (d, J=8,9 Hz, 1H), 8,79 (d, J=8,9 Hz, 1H), 8,88 (d, J= 1.3 Hz, 1H), 9,04 (d, J=8,9 Hz, 1H), 9,10 (d, J=8,2 Hz, 1H)

Example 36

The dihydrochloride 9-[2-(dimethylamino)ethyl] -8H-pyrido[2,3-C] pyrimido [5,6,1-jk]carbazole-8,10(9H)-dione:

< / BR>
The named compound was obtained as described in Example 2.

1H-NMR (DMSO-d6): (M. D.): 2,92 (s, 3H), of 2.93 (s, 3H), 3.46 in-to 3.58 (m, 2H), to 4.41-4,51 (m, 2H), 7,82 (t, J=8.0 Hz, 1H), 7,92 (DD, J=4,8; and 8.4 Hz, 1H), 8,21 (d, J=8.0 Hz, 1H), 8,40 (d, J=9,2 Hz, 1H), of 8.92 (d, J=9,2 Hz, 1H), 9,10 (d, J=8.0 Hz, 1H), 9,14 (DD, J=0,8; and 4.8 Hz, 1H), for 9.47 (DD, J=0,8; and 8.4 Hz, 1H), 9,86 (Shir. s, 1H)

Elemental analysis: C21H18N4O22HCl0,75H2O

calculated: C 56,70; H to 4.87; N 12,59;

found: C, 56.78 has; H 4,82; N 12,36.

Example 37

Hydrochloride 5-[2-(dimethylamino)ethyl] -2-nitro-4H-benzo[C] pyrimido [5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained with the use of a-tetralone and 5-nitro-2-hydrazinobenzene acid as starting materials and by repeating the procedures of Examples of the preparation of 1,2 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D.): 2,89 (s, 6H), 3,44-to 3.52 (m, 2H), 4,45 (t, J= 5,2 Hz, 2H), 7,73 (t, J=8,), 9,75 (Shir. s, 1H)

Example 38

Hydrochloride 5-[2-(dimethylamino) ethyl] -2-methyl-4H-benzo[C] pyrimido [5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained with the use of a-tetralone hydrochloride and 2-hydrazino-5-methylbenzoic acid and repeating the procedures of Examples of the preparation of 1,2 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D.): a 2.71 (s, 3H), 2,90 (Shir. s, 6H), 3,38-3,55 (m, 2H), 4,39-to 4.46 (m, 2H), 7,66-7,72 (m, 1H), 7,81-7,88 (m, 1H), 7,97-of 8.00 (m, 1H), 8,18-8,23 (m, 1H), they were 8.22-of 8.27 (m, 1H), 8,63 (d, J=9,2 Hz, 1H), 8,88-8,95 (m, 2H)

Elemental analysis: C23H21N3O2HCl1,5H2O

calculated: C 63,52; H 5,79; N 9,66;

found: C 63,63; H 5,48; N 9,70.

Example 39

Hydrochloride 1,2-dihydro-9-[2-(dimethylamino)ethyl] -8H-pyrido [3,4-C]pyrimido[5,6,1-jk]carbazole-4,8,10(3H,9H)-trione:

< / BR>
The named compound was obtained as described in Example 2.

1H-NMR (DMSO-d6): (M. D. ): 2,88 (Shir. s, 6H), 3,37-to 3.52 (m, 2H), 3,50-to 3.64 (m, 4H), 4,36-of 4.44 (m, 2H), 7,73 (t, J=7,6 Hz, 1H), 8,11 (Shir. s, 1H), 8,15 (DD, J=0,8; and 7.6 Hz, 1H), they were 8.22 (d, J=8,4 Hz, 1H), 8,40 (d, J=8,4 Hz, 1H), to 8.57 (DD, J=0,8; and 7.6 Hz, 1H)

Elemental analysis: C21H20N4O3HClH2O

calculated: C 58,54; H 5,38; N 13,00;

found: C 58,50; H 5,49; N 12,77.

Example 40

Hydrochloride 8-[2-(dimethylamino) ethyl] -7H-1,3-dioxolo[4,5-C] pyrimido [5UP>H-NMR (DMSO-d6): (M. D. ): 2,90 (Shir. s, 6H), 3,42-to 3.49 (m, 2H), 4,36 was 4.42 (m, 2H), 6.35mm (s, 2H), 7,29 (d, J=8,4 Hz, 1H), 7,68 (t, J=7.7 Hz, 1H), 7,89 (d, J=8,4 Hz, 1H), 8,10 (DD, J=0,8; and 7.7 Hz, 1H), 8,27 (DD, J=0,8; and 7.7 Hz, 1H), 9,35 (Shir. c, 1H)

Example 41

Hydrochloride 11-bromo-5-[2-(dimethylamino)ethyl] -4H-benzo[C] pyrimido [5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained using 6-bromo - tetralone hydrochloride and 2-hydrazinobenzene acid and repeating the procedures of Examples of getting 1, 2 and 3 and Example 2.

FAB mass spectrometry m/z: 436 ([M+H]+), 438 ([M+2+H]+).

1H-NMR (DMSO-d6): (M. D.): 2,90 (s, 6H), 3,48 (Shir. s, 2H), 4,42 (t, J= 5.6 Hz, 2H), to 7.77 (t, J=7,6 Hz, 1H), 7,89 (DD, J = 2,0; 8,8 Hz, 1H), 8,14 (d, J=7.2 Hz, 1H), to 8.20 (d, J=8,8 Hz, 1H), of 8.47 (d, J=2.0 Hz, 1H), 8,63 (d, J=8,8 Hz, 1H), 8,79 (d, J=9,2 Hz, 1H), 8,97 (d, J=8.0 Hz, 1H), 9,74 (Shir. s, 1H)

Elemental analysis: C22H18N3O2BrHCl0,6H2O

calculated: C 54,64; H 4,21; N 8,69;

found: C 54,36; H 3,94; N 8,56.

Example 42

Hydrochloride of 2-[2-(dimethylamino)ethyl] -1H-benzo[b] pyrimido[5,6,1-jk] carbazole-1,3(2H)-dione:.

< / BR>
The named compound was obtained as described in Example 2.

FAB mass spectrometry m/z: 358 ([M+H]+).

1H-NMR (DMSO-d6): (M. D. ): 2,90 (Shir. s, 6H), 3,39-of 3.53 (m, 2H), 4,37-4,48 (m, 2H), 7,60-of 7.70 (m, 2H), 7,73 (t, J=7,6 >2H19N3O2HCl

calculated: C 67,09; H 5,12; N 10,67;

found: C 66,94; H 5,22; N 10,65.

Example 43

Hydrochloride 5-[2-(dimethylamino)ethyl]-10,11,12,13-tetrahydro-4H-benzo[b] pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained from the compound of Example 4 as described in Example 5.

FAB mass spectrometry m/z: 362 ([M+H]+).

1H-NMR (DMSO-d6): (M. D.): 1,79 is 2.01 (m, 4H), 2,89 (s, 6H), 2,90 (Shir. t, J=6.0 Hz, 2H), 3,24 (Shir. t, J=6.0 Hz, 2H), 3.46 in (lat. t, J=5.6 Hz, 2H), 4,39 (Shir. t, J=6.0 Hz, 2H), 7,38 (d, J=8,8 Hz, 1H), 7,65 (t, J=8.0 Hz, 1H), of 8.06 (d, J= 8.0 Hz, 1H), 8,13 (d, J=8,8 Hz, 1H), to 8.41 (DD, J=0,8; 8.0 Hz, 1H), 9,74 (Shir. s, 1H)

Elemental analysis: C22H23N3O2HCl0,75H2O

calculated: C 64,23; H 6,25; N OF 10.21;

found: C 64,35; H 6,20; N 10,15.

Example 44

Hydrochloride 12,13-dihydro-to 11.11-dimethyl-5-[2-(dimethylamino)ethyl] -4H-benzo [C]pyrimido[5,6,1-jk]carbazole-4,6,10 (5H,11H)-trione:

< / BR>
The named compound was obtained as described in Example 2.

1H-NMR (DMSO-d6): (M. D.): 1,20 (s, 6H), 2,13 (t, J=6,1 Hz, 2H), 2,88 (s, 6H), 3.43 points (Shir. s, 2H), 3,52 (t, J=6,1 Hz, 2H), to 4.38 (t, J=5.7 Hz, 2H), 7,71 (t, J=7,4 Hz, 1H), 8,11 (d, J=7,4 Hz, 1H), to 8.20 (d, J=8,8 Hz, 1H), 8,35 (d, J=8,8 Hz, 1H), 8,54 (d, J=7,4 Hz, 1H), 10,08 (Shir. s, 1H)

Elemental analysis: C24H25N3O3HClH2O
Mino)ethyl] -2-methoxy-4H-benzo[pyrimido [5,6,1-jk]carbazole-4,6 (5H)-dione:

< / BR>
The named compound was obtained using tetralone hydrochloride and 2-hydrazino-5-methoxybenzoic acid and repeating the procedures of Examples of the preparation of 1,2 and 3 and Example 2.

1H-NMR (DMSO-d6): (M. D.): 2,89 (Shir. s, 6H), 3,40-to 3.52 (m, 2H), a 4.03 (s, 3H), and 4.40 (t, J=6.0 Hz, 2H), 7,60 (d, J=2.4 Hz, 1H), 7,63-of 7.70 (m, 1H), 7,76-a 7.85 (m, 1H), 8,17 (DD, J=0,4; and 8.4 Hz, 1H), 8,21 (d, J=8,8 Hz, 1H), 8,49 (d, J= 2.4 Hz, 1H), to 8.57 (d, J=8,8 Hz, 1H), 8,84 (DD, J=0,4; and 8.4 Hz, 1H), to 9.57 (Shir. s, 1H)

Elemental analysis: C23H21N3O3HClH2O

calculated: C 62,51; H vs. 5.47; N 9,51;

found: C 62,44; H 5,22; N 9,48.

Example 46

Hydrochloride 5-[2-(dimethylamino)ethyl] -11-hydroxy-4H-benzo[C] pyrimido[5,6,1-jk]carbazole-4,6 (5H)-dione:

< / BR>
The compound of Example 22 was heated under reflux in 47% Hydrobromic acid. Then the reaction mixture is catalytically restored at room temperature using palladium on coal as a catalyst. The obtained product was converted into hydrochloride accepted way of obtaining the connection specified by name.

1H-NMR (DMSO-d6): (M. D.): 2,92 (d, J=5.5 Hz, 6H), 3,48 (K, J=5.5 Hz, 2H), to 4.41 (t, J=5.5 Hz, 2H), was 7.36-7,42 (m, 2H), 7,73 (t, J=8,1 Hz, 1H), 8,00 (d, J=9.4 Hz, 1H), 8,11 (d, J=8,1 Hz, 1H), 8,49 (d, J=8,1 Hz, 1H), 8,71 (d, J=9.4 Hz, 1H), to 8.94 (d, J=pyrimido [5,6,1-jk]carbazole-4,6 (5H)-dione:

< / BR>
The compound of Example 37 was first made in the presence of a catalyst of palladium on coal at ordinary temperature under atmospheric pressure to get the connection specified by name.

1H-NMR (DMSO-d6): (M. D.): 2,89 (d, J=4,1 Hz, 6H), 3,44-3,51, (m, 2H), and 4.40 (t, J=5.8 Hz, 2H), to 7.67 (t, J=8,2 Hz, 1H), to 7.77 (s, 1H), to 7.84 (t, J=8,2 Hz, 1H), 8,19 (d, J=8,2 Hz, 1H), they were 8.22 (d, J=9,3 Hz, 1H), to 8.57 (d, J=9,3 Hz, 1H), 8,61 (d, J=8,2 Hz, 1H), 8,63 (s, 1H), 9,94 (Shir. s, 1H)

Example 48

Hydrochloride 5-[2-(dimethylamino)ethyl]-11-(4-methylbenzenesulfonamide)-4H - benzo[C]pyrimido[5,6,1-jk]carbazole-4,6 (5H)-dione:

< / BR>
The compound of Example obtaining 24 were processed as described in Example receiving 3 receiving N-[2-(dimethylamino)ethyl]-3- (4-methylbenzenesulfonamide)-7H-benzo[C]carbazole-8 - carboxamide. Then this product is reacted with sodium hydride and etelcharge.com in dimethylformamide while cooling with ice with the formation of 5-[2-(dimethylamino)ethyl]-11-(N-etoxycarbonyl-4-methylbenzenesulfonamide)-4H-benzo[C] pyrimido[5,6,1-jk] carbazole-4,6(5H)-dione. Then this product was treated with 1 N. aqueous solution of sodium hydroxide in a mixture of methanol-tetrahydrofuran (1:1) and then converted into the hydrochloride conventional manner, followed by recrystallization from ethanol to obtain compounds specified is, 2H), 7,33 (d, J=9,2 Hz, 2H), 7,60 (d, J=8,8 Hz, 1H), 7,70 for 7.78 (m, 3H), of 7.82 (s, 1H), of 8.09 (d, J=9,2 Hz, 1H), 8,12 (d, J=8.0 Hz, 1H), 8,54 (d, J=8,4 Hz, 1H), 8,76 (d, J =8,4 Hz, 1 H), to 8.94 (d, J=8,4 Hz, 1H), 9,56 (Shir. s, 1H), is 10.68 (s, 1H)

Example 49

The dihydrochloride 11-amino-5-[2-(dimethylamino) ethyl] -4H-benzo[C] pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
341 mg (0,648 mmol) of free base of the compound of Example 48 and 419 mg (of 4.45 mmol) of phenol was heated under reflux in 47% Hydrobromic acid (15 ml) for 9 hours and 30 minutes and then allowed to cool to room temperature. Then the reaction mixture was podslushivaet adding thereto a saturated aqueous solution of sodium bicarbonate. Then the mixture was extracted by addition of ethyl acetate and tetrahydrofuran. The organic layer was washed successively with water and saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The organic layer was concentrated and the obtained residue was recrystallized from ethanol to obtain 141 mg of the free base compound of the title. Then this free base was converted into the hydrochloride an accepted way of obtaining the connection specified by name.

(Free base)1H-NMR (DMSO-d6): (M. D.): 2,22 (s, 6H), 2,8,0 Hz, 1H), scored 8.38 (d, J=8,8 Hz, 1H), charged 8.52 (d, J=9,2 Hz, 1H), 8,84 (d, J=7,6 Hz, 1H)

Example 50

Hydrochloride 11-acetamido-5-[2-(dimethylamino) ethyl] -4H-benzo[C]pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
4 ml of triethylamine and 2 ml of acetic anhydride was sequentially added to a suspension of 141 mg (0,379 mmol) of free base of the compound of Example 49 in dichloromethane (20 ml) with stirring at room temperature and stirring continued for 16 hours. After concentration the residue was added 30 ml of methanol. Then the mixture was podslushivaet adding thereto an aqueous solution of sodium bicarbonate. The precipitate was removed by filtration and washed with water. The thus obtained solid matter suspended in ethanol and was added concentrated hydrochloric acid with stirring at room temperature. After further addition of methanol and dichloromethane stirring continued. After concentration was added ethanol and the resulting mixture was heated under reflux and then allowed it to cool to room temperature. The precipitate was recovered by filtration to obtain 148 mg of the compound indicated in the title of the example.

FAB mass spectrometry m/z: 415([M+H]+).

1H-NMR (DMSO-d6
Elemental analysis: C24H22N4O3HCl0,6H2O

calculated: C 62,43; H 5,28; N 12,13;

found: C 62,54; H to 5.03; N 11,82.

Example 51

The dihydrochloride of 5-[2-[N-[2-(dimethylamino)ethyl]-N-methylamino]ethyl]-4H-benzo [C]pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained as described in Example 2.

(Free base)1H-NMR (CDCl3): (M. D.): 2,20 (s, 6H), 2,42 (t, J=7.2 Hz, 2H), of 2.45 (s, 3H), 2.63 in (t, J=7.2 Hz, 2H), of 2.81 (t, J=7.2 Hz, 2H), 4,35 (t, J=7.2 Hz, 2H), to 7.59 (t, J=7.8 Hz, 1H), to 7.64 (t, J=7.8 Hz, 1H), 7,74 (t, J=7.8 Hz, 1H), 8,01 (d, J=9,2 Hz, 1H), 8,03 (d, J=7.8 Hz, 1H), 8,14 (d, J=7.8 Hz, 1H), 8,56-8,61 (m, 2H), 8,66 (d, J=9,2 Hz, 1H),

Elemental analysis: C25H26N4O22HCl0,8H2O

calculated: C 59,83; H 5,78; N 11,17;

found: C 59,83; H of 6.02; N 11,16.

Example 52

Hydrochloride 5-[2-[N-(2-hydroxyethyl)-N-methylamino] ethyl] -4H-benzo[C] pyrimido[5,6,1-jk]carbazole-4,6(5H)-dione:

< / BR>
The named compound was obtained as described in Example 2.

1H-NMR (DMSO-d6): (M. D.) : at 2.93 (s, 3H), 3,14-of 3.80 (m, 2H), 3,71-of 3.80 (m, 2H), 4,40-of 4.49 (m, 2H), 5,33 of 5.39 (m, 1H), of 7.64-of 7.70 (m, 1H), 7,73-7,86 (m, 2H), 8,10 compared to 8.26 (m, 3H), 8,59-8,65 (m, 1H), 8,83-8,89 (m, 1H), 9,00-9,04 (m, 1H), 9,60(Shir. s, 1H)

Elemental analysis: C23H21N3O
< / BR>
The named compound was obtained by treating compound of Example 45, as described in Example 46.

1H-NMR (DMSO-d6): (M. D. ): 2,89 (Shir. s, 6H), 3,39-of 3.54 (m, 2H), 4,32-to 4.46 (m, 2H), 7,53-7,56 (m, 1H), 7,65-7,71 (m, 1H), 7,81-7,87(m, 1H), 8,19 (d, J=8.0 Hz, 1H), 8,23 (d, J=8,8 Hz, 1H), 8,35-8,39 (m, 1H), at 8.60 (d, J=8,8 Hz, 1H), 8,73 (d, J=8.0 Hz, 1H), 9,29-9,39(Shir. 1H), of 10.25 (s, 1H)

Elemental analysis: C22H19N3O3HClH2O

calculated: C 61,76; H 5,18; N 9,82;

found: C 6,92; H 4,90; N 9,84.

Example 54

Hydrochloride of 2-[2-(dimethylamino)ethyl] -9-methoxy-1H-benzo[a] pyrimido[5,6,1-jk]carbazole-1,3(2H)-dione:

< / BR>
The named compound was obtained using methoxy-1 - tetralone hydrochloride and 2-hydrazinobenzene acid and by repeating the procedure of Example 18.

1H-NMR (DMSO-d6): (M. D.): 2,92 (s, 6H), 3.46 in-3,55 (m, 2H), was 4.02 (s, 3H), 4,42-to 4.46 (m, 2H), 7,16 (d, J=7,1 Hz, 1H), 7,60 (t, J=7,1 Hz, 1H), 7,73 (t, J=7,1 Hz, 1H), 8,12 (d, J=7,1 Hz, 1H), 8.34 per-8,44 (m, 2H), 8,63 (d, J=7,1 Hz, 1H), 9.28 are (d, J=9,2 Hz, 1H), 9,78 (Shir. s, 1H)

Example 55

The dihydrochloride 9-[2-(1-pyrrolidinyl)ethyl] -8H-pyrido[2,3-C] pyrimido[5,6,1-jk]carbazole-8,10 (9H)-dione:

< / BR>
The named compound was obtained as described in Example 36.

1H-NMR (DMSO-d6+D2O): (M. D.): 1,84-of 1.94 (m, 2H), 2,01 and 2.13 (m, 2H), 3,13-of 3.25 (m, 2H), 3,57-to 3.64 (m, 2H), 3,65-3,74 (m, 2H), 4,43 figure-4.49 (m, 2H), 7,85 (40-9,45 (m, 1H)

Example 56

The dihydrochloride 9-[2-(dimethylamino)ethyl]-13-fluoro-8H-pyrido[2,3-C]pyrimido [5,6,1-jk]carbazole-8,10(9H)-dione:

< / BR>
The named compound was obtained as described in Example 36.

1H-NMR (DMSO-d6): (M. D.): 2,92 (s, 3H), of 2.93 (s, 3H), 3,47-3,55 (m, 2H), to 4.41-4,47 (m, 2H), 7,69 (DD, J=8,4; 12.0 Hz, 1H), to 7.93 (DD, J=4,4; and 8.4 Hz, 1H), 8,29 (DD, J=4,4; and 8.4 Hz, 1H), 8,45 (d, J=9,2 Hz, 1H), 8,97 (d, J= 9,2 Hz, 1H), 9,10-to 9.15 (m, 1H), 9,25 - 9,31 (m, 1H)

Example 57

The dihydrochloride 9-[2-(dimethylamino)ethyl]-3-methyl-8H-pyrido[2,3-C]pyrimido [5,6,1-jk]carbazole-8,10(9H)-dione:

< / BR>
The named compound was obtained as described in Example 36.

1H-NMR (DMSO-d6): (M. D.): at 2.93 (s, 3H), 2.95 and (s, 6H), 3,51 is 3.57 (m, 2H), of 4.44-4,50 (m, 2H), 7,86 (t, J=8.0 Hz, 1H), 7,98 (d, J=8,8 Hz, 1H), 8,25 (d, J=8.0 Hz, 1H), 8,39 (d, J=9,2 Hz, 1H), 8,98 (d, J=9,2 Hz, 1H), a 9.09 (d, J=8.0 Hz, 1H), of 9.55 (d, J=8,8 Hz, 1H)

Example 58

7-[2-(Dimethylamino)ethyl] -6H-benzo[c, i] pyrimido[1,6,5-lm] - -carbolin-6,8(7H)-dione:

< / BR>
1.06 g (3.1 mmol) of the compound of Example receive 25 was dissolved in a mixture of methanol (20 ml) with tetrahydrofuran (20 ml). After adding to the solution 1 N. aqueous sodium hydroxide solution (10 ml) the mixture was heated under reflux for 1 hour and then gave her to cool down. Then thereto was added 1 N. aqueous solution of hydrochloric acid (10 ml) and the solvent athenacentral) carbodiimide, 540 mg (4 mmol) of 1-hydroxybenzotriazole and 0.4 ml (3.7 mmol) of N,N-dimethylethylenediamine and the resulting mixture was stirred at room temperature overnight. Then thereto was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated. Thus obtained residue was washed with ethanol and recovered by filtration to obtain 660 mg of the intermediate product (yield 55%).

100 mg (0.26 mmol) of this intermediate product was dissolved in N,N-dimethylformamide (20 ml) was added to a solution of 22 mg (0.55 mmol) of sodium hydride (60% in oil) under a current of hydrogen gas. After stirring the mixture for 1 hour, thereto was added 0,046 ml (0.6 mmol) of methylchloroform at room temperature. The mixture is then immediately acidified 1 N. hydrochloric acid and then slightly podslushivaet saturated aqueous sodium bicarbonate, followed by extraction with ethyl acetate. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated to dryness. The residue was purified speakers chromatog the spectrometry m/z: 409 ([M+H]+).

1H-NMR (CDCl3): (M. D.): 2,39 (s, 6H), 2,80 (t, J=6,7 Hz, 2H), 4,51 (t, J=6,7 Hz, 2H), 7,66 for 7.78 (m, 2H), a 7.85-to 7.93 (m, 2H), 8,01-8,07 (m, 2H), 8,51 (d, J= 8.6 Hz, 1H), 8,57-8,63 (m, 1H), 8,73-8,79 (m, 1H), 9,74 (DD, J=0,7; 8.6 Hz, 1H).

1. Derivatives of condensed polycyclic heterocyclic compounds of General formula I

< / BR>
where the ring And indicates benzene, optionally substituted by oxo, or disilicate condensed ring in which at least one of the rings is an aromatic ring and selected from the group including: 1) naphthalene, optionally hydrogenated in a single ring and/or optionally substituted with halogen, hydroxy, lower alkyl, optionally containing a hydroxy-group, lower alkoxy, nitro, amino, lower acyl, oxo, cyano, benzosulfimide, substituted lower alkyl, and lower acylamino; 2) inden, optionally hydrogenated in a single ring and/or optionally substituted by oxo; 3) benzofuran, optionally hydrogenated in a single ring and/or optionally substituted by hydroxy or oxo in the heterocyclic ring; 4) isobenzofuran, optionally hydrogenated and/or optionally substituted by oxo; 5) benzothiophen, optionally substituted by oxo; b) benzopyran, optionally hydrogenated and/or tsiklicheskom ring and/or optionally substituted by oxo or lower alkyl;

the ring represents pyrrole, 4H-1,4-oxazin, 4H-1,4-thiazin or 4(1H)-pyridone;

ring denotes a monocyclic or disilicate aromatic ring selected from: 1) phenyl, optionally substituted with halogen, hydroxy, lower alkoxy, lower alkyl, nitro or amino; 2) naphthyl, and (3) chinoline;

Y denotes a group represented by the formula-e-f where e denotes the lowest alkylen and f denotes a lower alkylamino, di-lower alkylamino, pyrrolidinyl, N-(dimethylamino)ethyl-N-methylamino and N-(hydroxyethyl)-N-methylamino;

or their pharmacologically acceptable salts.

2. Connection on p. 1, where the ring a represents a naphthalene, which is optionally substituted as specified in paragraph 1, and optional gidrirovanny in a single ring, or its pharmacologically acceptable salt.

3. Connection on p. 1, where ring a is a quinoline, isoquinoline, 4H-1-benzopyran, 1H-2-benzopyran, 1,3-benzodioxol, benzofuran, isobenzofuran, benzothiophene are not substituted as indicated century. 1, optional gidrirovanny in one ring and the condensed ring In the benzene ring, or its pharmacologically acceptable salt.

4. Connection on p. 1, where the ring And represents tetralin Il Connection on p. 1, where ring a is oxazolidinyl tetralin or indan, and condensed with the benzene ring In the ring, or its pharmacologically acceptable salt.

6. Connection on p. 1, where the ring a represents an optionally substituted as specified in paragraph (1 chroman or isochroman, tetrahydrofuran or tetrahydrothiopyran, and condensed with the benzene ring In the ring, or its pharmacologically acceptable salt.

7. Connection on p. 1, where the ring is a pyrrole, or a pharmacologically acceptable salt.

8. Connection on p. 1, where the ring represents optionally substituted with halogen, lower alkyl, lower alkoxy, amino, nitro, hydroxy-group phenyl, or its pharmacologically acceptable salt.

9. The method of obtaining compounds on p. 1 or its pharmacologically acceptable salts, characterized in that interact compounds of General formula II

< / BR>
where rings AA and Sa have the meanings specified in paragraph 1 for rings a and C, respectively, in which respective substituents are optionally protected;

ring VA denotes 4H-1,4-oxazin, 4H-1,4-thiazin, 4(1H)-pyridone;

f matter f specified in paragraph 1;

e has a value which represents the group that you want,

with the removal of the protective group or groups, if any, of the thus obtained product.

 

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< / BR>
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