Method for preparation of derivatives of pyrrolo[1,2-a][1,4]diazepine

FIELD: chemistry.

SUBSTANCE: invention relates to synthesis of heterocyclic compounds, which contain pyrrolo[1,2-а][1,4]diazepine fragment, annelated to aromatic and heteroaromatic ring. Method for preparation of derivatives of pyrrolo[1,2-а][1,4]diazepine of general formula I, where А =

, is described. The said derivatives may be of use as substances with potential CNS activity, or with analgesic, antimicrobial and antifungal effect. Method implies recyclization of furan ring of 5-methyl-furfurylamides of general formula 2, , where А stands for above shown groups, by exposure to temperature of 60-70°С in the mixture of glacial acetic acid and strong hydrochloric acid in volumetric ratio 1:0.15 for 10-15 minutes.

EFFECT: provides for simultaneous formation of pyrrole and diazepine rings and improves yield of end products due to less number of process steps.

 

The invention relates to the field of organic chemistry - synthesis of heterocyclic compounds containing pyrrolo[1,2-a][1,4]diazepinone fragment, annelirovannymi with aromatic and heteroaromatic ring.

The invention relates to a developing method of obtaining derivatives pyrrolo[1,2-a][1,4]diazepine General formula 1

which can find use as agents with potential activity against CNS [Mai, A.; Di Santo, R.; Massa, S.; Artico, M.; Pantaleoni, G.C.; Giorgi, R.; Coppolino, M.F.; Barracchini, A. Eur. J. Med. Chem., 1995, 30, 593], showing the potential analgesic and antibacterial [Ivashchenko, A.V.; Vvedensky, V.Yu.; Ilyn, A.P.; Kysel, V.M.; Khvat, A.V.; Kuzovkova, Yu.A.; Kutepov, S.A.; Dmitrieva, I.G.; Zolotarev, D.A.; Tkachenko, S.Ye.; Okun, I.M.; Kravchenko, D.V.; Kobak, V.V.; Trifilenkov, A.S.; Mishunina, Yu.S.; Loseva, M.V.; Rizhova, E.A.; Parchinsky, V.Z.; Tsirulnikov, S. A.; Kyselev, A.S. Pat. WO 2005105805 (2005)] and antifungal [Meerpoel, L.; Van Gestel, J.; Van Gerven, F.; Woestenborghs, F.; Marichal, P.; Sipido, V.; Gilkerson, T.; Nash, R.; Corens, D.; Richards, R. D. Bioorg. Med. Chem. Lett, 2005, 75(14), 3453] action.

Currently, among the existing methods of education pyrrolo[1,2-a][1,4]diazepino frame is widely known approach, in which the circuit diazepinones cycle happens when ready pyrrole core. Derivatives irradiation synthesized on the basis of 1-(2-aminomethylphenol)-1H-pyrrol under the reaction conditions of Bisleri-napieralski Protocol [Massa, S.; Di Santo, R.; Costi, R.; Artico, M. J. Heterocyclic Chem., 1993, 30, 749;], intramolecular alkylation of the pyrrole nucleus N-alliminium ions [Othman, M; Pigeon, P.; Netchitailo, P.; Daich, A.; Decroix, B. Heterocycles, 2000, 52, 273;], as a result of interaction with carbonyl compounds [Rault, I.; Rault, S.; Robba, M. Heterocycles, 1994, 38, 811].

An example of the use of other derivatives of 1-arylpyrol to get pyrrolidinedione system is the synthesis of pyrrolo[1,2-a][1,4]diazepino fragment-based bifunctional 1-(2-carboxyethyl)errorcorrected in the Ugi reaction conditions [Ilyn, A.P.; Trifilenkov, A.S.; Kuzovkova, Ju. A.; Kutepov, S.A.; Nikitin, A.V.; Ivachtchenko, A.V. J. Org Chem. 2005, 70, 1478].

The main drawbacks include the use of remote agents, as well as a multi-stage process that reduces the total yield of the target product. In addition, most of the known methods suitable for obtaining derivatives pyrrolotriazine, annelated with a benzene ring, whereas the methods of synthesis of pyrrolotriazine condensed with heterocyclic systems, small.

Closest to the claimed among the known methods of synthesis is a method in which for forming pyrrolidinedione structure uses a derivative of furan [Hara, T.; Kayama, Y.; Mori, T.; Itoh, K.; Fujimori, H.; Sunami, T.; Hashimoto, Y.; Ishimoto, S. J. Med. Chem., 1978, 27(3), 263].

Cruciamentum of this strategy are: a) formation of pyrrole nucleus as a result of recyclization derivative of furan in the interaction of intermediate products of opening the furan ring tetrahydrofuran (THF) or 1,4-diketone In the - amino group of an aromatic ketone and (b) forming diazepinones rings during intramolecular cyclization product of hydrogenolysis received phthalimide C.

Significant disadvantages of this method are its multi-stage, since the method includes the successive stages of obtaining substituted pyrrole and their cyclization to pyrrolidinedione structure and, as a consequence, low total yields of final products (25-38%).

The technical result is to ensure the simultaneous formation of pyrrole and diazepinones rings and increase the yield of the final product by reducing the number of stages of the process.

The technical result is achieved in that in the method of obtaining derivatives pyrrolo[1,2-a][1,4]diazepine General formula 1

5-methylpyrrolidone General formula 2, where a has the above values, is maintained at a temperature of 60-70°in a mixture of glacial acetic and concentrated hydrochloric acid at a volume ratio of 1:0.15 in 10-15 minutes

Use of derivatives of furan for Sint who for various heterocycles known [Butin, A.V.; Stroganova, T.A.; Abaev, V.T; Gutnov, A.V. Targets in Heterocyclic systems: Chemistry and Properties, 2001, 5, 131], but any information about the intramolecular recyclizations of furan compounds, leading to the formation of pyrrolidinedione systems in the literature are missing.

The difference of the proposed method of obtaining derivatives pyrrolo[1,2-a][1,4]diazepine (1) is used as starting compound derivatives of 5-methylpentylamino 2-benzoic or 3-aminothieno[2,3-b]pyridine-2-carboxylic acid, furan cycle which acts as a hidden 1,4-dicarbonyl compounds involved in the formation of two heterocyclic rings diazepinones and pyrrole.

The choice of solvent of acetic acid due to good solubility in her initial substances, to achieve complete conversion of the original furfurylamine in derivatives pyrrolo[1,2-a][1,4]diazepine in a short time and thereby reducing the duration of the reaction to avoid strong resinification of the reaction mass and to increase the total yield of the target products.

On the basis of the obtained experimental data it was established that the optimum is to conduct the reaction at 60-70°because in this case, the outputs derived pyrrolo[1,2-a][1,4]-diazepine reach 47-65%and deletelines the ü process is 10-15 minutes

Thus, the set of essential features set forth in the claims, allows to achieve the desired technical result.

The identity and structure of the synthesized compounds 1 are confirmed by the data of 1H NMR spectroscopy and elemental analysis.

Below are examples of the proposed method of obtaining derivatives pyrrolo[1,2-a][1,4]diazepine (1).

Source furfurylamine benzoic acid obtained by the sequential acylation of 5-methylpentylamine anhydrides 2-nitrobenzoic acid and recovering the products of the acylation of hydrazine hydrate in the presence of Raney Nickel according to the methods similar to that shown in [Titze L., Eicher, T. preparative organic chemistry: Reactions and synthesis in the laboratory of organic chemistry and research laboratory: TRANS. with it. - M.: Mir, 2004. - 704]. 5-Methylformamide 3-aminothieno[2,3-b]pyridine-2-carboxylic acid synthesized outputs 80-87% by the reaction of pyridines with 5-methylpentylamino Chloroacetic acid under the reaction conditions Thorpe-Ziegler method, analogous to those presented in [Kaygorodova E.A., Konushkin L.D., Mikhailichenko, S.N., Vaselin VK, kulenovic VG, Chemistry of heterocycle. connect., 1996, 10, 1432].

Physico-chemical characteristics of furfurylamine benzoic acid and 3-aminothieno[2,3-b]pyridine-2-carboxylic acid Ave is presented in table 1.

Table 1
Physico-chemical characteristics of furfurylamine 2A-d

No.AndMP.,

°
Calculated/Found %1H NMR(300 MHz), δ (ppm), coupling constants (J, Hz)
NN
2A64-65of 2.28 (s, 3H, CH3), of 4.54 (d, 2H, J=5,3, CH2), 5,54 (USS, 2H, NH2),5,91 (d, 1H, J=3.0 a, HFur), 6,16 (d, 1H, J=3.0 a, HFur), 6,29 (ush. s, 1H, NH), 6,61-6,69 (m, 2H, HAr); 7,18-7,33 (m, 2H, HAr).
2B125-126to 2.29 (s, 3H, CH3), 3,82 (s, 3H, och3), 3,86 (s, 3H, och3), a 4.53 (d, 2H, J=5,3, CH2), 5,42 (ush. s, 2H, NH2), of 5.92 (d, 1H, J=3.0 a, HFur), to 6.22 (d, 1H, J=3.0 a, HFur), to 6.19 (USS, 2H, NH+3-HAr), 6,82 (c, 1H, 6-HAr).
2B 125-1262,24 (s, 3H, CH3-Fur), of 2.51 (s, 3H, CH3-PY), by 2.73 (s, 3H, CH3-PY), 4,34 (s, 2H, CH2), 5,97 (d, 1H, J=3.0 a, HFur), 6,10 (d, 1H, J=3.0 a, HFur), 6,78 (USS, 2H, NH2), 7,02 (c, 1H, HRu), 8,04(USS, 1H, NH)
2G154-1552,24 (s, 3H, CH3-Fur), 2,69 (s, 3H, CH3-PY), is 2.88 (s, 3H, CH3-PY), 4,34 (s, 2H, CH2), 5,97 (d, 1H, J=3.0 a, HFur), 6,10 (d, 1H, J=3.0 a, HFur), 6,86 (USS, 2H, NH2), 8,19 (USS, 1H, NH)

Continuation of table 1
No.AndMP.,

°
Calculated/Found %1H NMR (300 MHz), δ (ppm), coupling constants (J, Hz)
NN
2D77-78 2,24 (s, 3H, CH3-Fur), to 2.57 (s, 3H, CH3-Ru), to 3.38 (s, 3H, och3), 4,34 (d, 2H, J=5,2, CH2-Fur), a 4.83 (s, 2H, CH2-Och3), 5,98 (d, 1H, J=3.0 a,HFur), 6,10 (d, 1H, J=3.0 a, HFur), 6,91 (USS, 2H, NH2), from 7.24 (s, 1H, CHPy), 8,13 (t, 1H, J=5,2, NH)

Example 1.

8,9-Dimethoxy-1-methyl-5,6-dihydro-4H-benzo[f]pyrrolo[1,2-a][1,4]-diazepin-6-he (1B)

A mixture of N-(5-methylfentanyl)amide of 2-amino-4,5-dimethoxybenzoic acid (2 mmol), glacial acetic acid (10 ml) and conc. hydrochloric acid (1.5 ml) maintained at a temperature of 40-50°40 min until complete consumption of the source material (TLC control). After the reaction, the reaction mixture was poured into ice water (100 ml), neutralized NaHCO3to pH˜7. Precipitated crystalline precipitate was separated by filtration, air-dried. A hot solution of the obtained product in a mixture of ethyl acetate/petroleum ether (volume ratio 4:1) is passed through a layer of silica gel and left for crystallization, receiving compound 1B as a transparent colorless crystals with a yield of 42%. MP. 195-196°C.1H NMR (300 MHz, CDCl3): δ=of 2.34 (s, 3H, CH3), 3,93 (s, 3H, och3), of 3.96 (s, 3H, och3), 4,18 is 4.13 (m, 2H, CH2), of 5.99 (d, 1H, J=3.2, And NPyr), to 6.22 (d, 1H, J=3.2, And NPyr), 6,77 (s, 1H, 3-HAr), 7,01 (USS, 1H, NH), 7,44 (s, 1H, 6-HAr).

Calculated for C15Hi6N2O3: 66,16, N OF 5.92, N 10,29.

Found Is: 66,10, N OF 5.99, N 10,23.

Example 2.

8,9-Dimethoxy-1-methyl-5,6-dihydro-4H-benzo[f]pyrrolo[1,2-a][1,4]-diazepin-6-he (1B) are obtained similarly, by conducting the reaction at a temperature of 60-70°C. the Duration of the reaction in this case is 15 min (TLC control), the reaction product yield 53%.

Example 3.

8,9-Dimethoxy-1-methyl-5,6-dihydro-4H-benzo[f]pyrrolo[1,2-a][1,4]-diazepin-6-he (1B) are obtained similarly, by conducting the reaction at a temperature of 80-90°C. the Duration of the reaction is 10 min (TLC control), the reaction product yield 48%.

Example 4.

8,9-Dimethoxy-1-methyl-5,6-dihydro-4H-benzo[a]pyrrolo[1,2-a][1,4]-diazepin-6-he (1B) are obtained similarly, by conducting the reaction at the boiling reaction mixture. The duration of the reaction is 5 min (TLC control), the reaction product yield 40%.

As follows from the above examples, lowering the reaction temperature causes an increase in the duration of the process that leads to greater resinification of the reaction mixture and, consequently, to decrease the yield of the target product. Strong resinification and the reduction of yield pyrrolotriazine was also observed when attempting to recyclization 5-methylpentylamino 2-aminopentanoic acid at 80-90° (Example 3) and boiling of the reaction mixture (Example 4). Thus, the best option is to conduct the reaction at 60-70°because in this case, the output of 8,9-dimethoxy-1-methyl,6-dihydro-4H-benzo[f]pyrrolo[1,2-a][1,4]-diazepin-6-she (1B) reaches 53%, and the processing time is 15 minutes

The claimed method obtained a number of derivatives pyrrolo[1,2-a][1,4]diazepine (1a, C-e), for which table 2 shows the duration of the reaction, the yields, melting points and spectral characteristics.

The method of obtaining derivatives pyrrolo[1,2-a][1,4]diazepine General formula 1

A=

namely, that 5-methylpyrrolidone General formula 2

where a has the above values, is maintained at a temperature of 60-70°in a mixture of glacial acetic and concentrated hydrochloric acid at a volume ratio of 1:0.15 in 10-15 minutes



 

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10 cl, 4 tbl, 26 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compound of the general formula (I): wherein R0 represents hydrogen atom; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 can be similar or different and each represents independently hydrogen atom, halogen atom, perhalogenalkyl, substituted or unsubstituted groups, such as linear or branched (C1-C12)-alkyl, (C3-C7)-cyclaoalkyl, (C1-C12)-alkoxy, cyclo-(C3-C7)-alkoxy group, hydroxyalkyl; R13 and R14 can be similar or different and each represents independently hydrogen atom, substituted or unsubstituted groups, such as linear or branched (C1-C4)-alkyl, (C3-C7)-cycloalkyl, optionally, R13 and R14 in common with nitrogen atom can form 5-6-membered heterocyclic ring wherein heterocycle can be substituted also, and it can comprise one, two or three double bonds or "additional heteroatoms" chosen from nitrogen atom (N); "n" means a whole number in the range 1-6, and pharmaceutical compositions based on its. Indicated compounds are ligands of 5-HT (serotonin) and can be used in treatment in cases if modulation of activity of 5-HT and melatonin is desirable.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

21 cl, 31 ex

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to novel hydrogenated pyrrolo[4,3-b]indoles of the general formula (1): , their racemates, optical isomers, geometric isomers, pharmaceutically acceptable salts and/or hydrates that can be used, for example, in treatment and prophylaxis of different neurodegenerative diseases, such as Alzheimer's syndrome. In the general formula (1): a dotted line with accompanying unbroken line represents ordinary or double bond; R1 and R2 represent independently of one another substitutes of amino group chosen from hydrogen atom, possibly substituted (C1-C6)-alkyl substituted possibly with aryl, possibly substituted phenyl, possibly substituted carbonylamino or thiocarbonylamino group, substituted acyl, possibly substituted aryl sulfonate wherein substituted in indicated R1 and R2 are chosen from (C1-C6)-alkyl, halogen atoms, nitro, carboxy, alkoxy group, aryl; R1n represents one or some similar or different substituted of cyclic system chosen from hydrogen atom, alkyl, aryl, cyano group, halogen atom, 5-6-membered nitrogen-containing heteroaryl. Also, invention relates to methods for synthesis of these compounds, pharmaceutical compositions and their using, and to using compounds in libraries with their using.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions, improved methods of synthesis.

20 cl, 2 tbl, 12 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to 1,4,5,6-tetrahydro-6-oxo-5-(2-piperazinoethyl)-4-phenyl-3-(4-chlorophenyl)pyrrolo[3.4]pyrazole dihydrochloride of the formula (I): . This compound is synthesized by interaction of 1-(2-piperazinoethyl)-5-phenyl-4-(4-chlorobenzoyl)-3-hydroxy-3-pyrrolin-2-one dihydrochloride with hydrazine hydrate. Synthesized compound can be used in medicine as agent decreasing arterial blood pressure and blood coagulation. Invention provides synthesis of a novel compound not described early that possesses hypotensive and anti-coagulant effect simultaneously.

EFFECT: valuable medicinal properties of compound.

3 tbl, 1 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention describes novel derivatives of 1,2,4-triazole of the general formula (I): wherein A and b can be taken separately or in common being when they are taken separately then A means (C1-C6)-alkyl or phenyl, and B means (C1-C6)-alkyl; A and B taken in common mean (C2-C5)-alkanediyl, and they form with C-atoms 3-6-membered cycle optionally substituted with (C1-C4)-alkylene, oxo, ethylenedioxy group, (C1-C4)-alkyl, 1-2 halogen atoms, (C1-C3)-alkoxy-(C1-C3)-alkoxy or hydroxy group; each R1 means independently hydrogen atom, -OH, halogen atom, (C3-C6)-cycloalkyl, (C1-C6)-alkyl optionally substituted with 1-3 halogen atoms; or two R1 groups near adjacent carbon atoms form 6-membered aryl cycle; R2 and R3 can be taken in common or separately, and when they are taken in common then they represent (C3-C8)-alkanediyl that forms condensed 5-10-membered nonaromatic cycle; when R2 and R3 are taken separately then R2 means (C1-C6)-alkyl possibly substituted with 1-3 halogen atoms or cyclopropyl, and R3 means cyclopropyl possibly substituted with (C1-C4)-alkyl, naphthyl, phenyl possibly substituted with halogen atom, -OH, (C1-C6)-alkyl wherein indicated (C1-C6)-alkyl is optionally substituted with 1-3 halogen atoms, -O-(C1-C6)-alkyl wherein indicated -O-(C1-C6)-alkyl is optionally substituted with 1-3 halogen atoms, phenyl or benzyloxy group, dihydrobenzofuranyl, benzothiadiazolyl or benzoimidazolyl possibly substituted with (C1-C6)-alkyl, their pharmaceutically acceptable salts or solvates, and pharmaceutical composition based on thereof. Proposed compounds are inhibitor of 11β-hydroxysteroid dehydrogenase I, and can be used in medicine in treatment of diabetes mellitus, obesity and dyslipidemia.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

19 cl, 17 tbl, 4 ex

FIELD: organic chemistry, medicine, oncology, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): or their pharmaceutically acceptable salts possessing the inhibitory effect on activity of tyrosine kinase. Proposed compounds can be used in treatment of proliferative disease, such as tumor. In the formula (I) each R1 and R2 means independently of one another hydrogen atom, methyl, ethyl, isopropyl, hydroxyethyl, piperidine-1-ylmethylcarbonyl, pyrrolidine-1-ylmethylcarbonyl, morpholine-4-ylmethylcarbonyl, 4-methylpiperazine-1-ylmethylcarbonyl, N,N-dimethylaminomethylcarbonyl, 4-ethylpiperazine-1-ylmethylcarbonyl, piperidine-1-ylethylcarbonyl, N,N-diethylaminoethylcarbonyl, N,N-dimethylaminopropylcarbonyl, 2-pyridylcarbonyl, tetrahydropyrane-4-yl, morpholine-4-ylethyl, N,N-diethylaminoethyl, tert.-butyl; or R1 and R2 in common with nitrogen atom to which they are bound form 4-ethylpiperazine-1-yl, pyrrolidine-1-yl, 4-methylpiperazine-1-yl, piperidine-1-yl, morpholine-4-yl, 3,5-dimethylpiperazine-1-yl; R3 is chosen from 3-chloro-4-fluorophenyl, phenyl, 4-benzyloxyphenyl, 3-hydroxy-4-methylphenyl, 3-hydroxy-4-methoxyphenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 2,5-dichlorophenyl, 3-methoxyphenyl, benzo[1,3]dioxol-5-yl, 6-methoxypyridine-3-yl, 2-methoxypyridine-4-yl, pyridine-2(1H)-one-5-yl, pyridine-2(1H)-one-4-yl, 3-methoxyphenyl, 3-methylphenyl, pyridine-2(1H)_one-4-yl; G means -CH2-; Q means -NH-; X absents or means -CH(CH3)-, -CH2- under condition that if X absents then R3 is bound by ring carbon atom. Also, invention relates to variants of methods for synthesis of compounds of the formula (I), preparing a pharmaceutical composition and using compounds proposed.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition, improved method for synthesis and preparing.

13 cl, 147 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): that are antagonists of CRF receptors and wherein Ar means optionally substituted phenyl or monocyclic 6-membered heteroaryl comprising one heteroatom chosen from nitrogen, oxygen or sulfur atoms; R1-R4 have values given in the invention claim, or to their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of indicated compounds and to pharmaceutical compositions containing these compounds that are useful for administration to a patient suffering from diseases that are relived in therapy using antagonists of CRF receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

26 cl, 10 tbl, 17 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivative of 1-[(indole-3-yl)carbonyl]piperazine of the formula (I): wherein R means substitute chosen from hydrogen atom (H), (C1-C4)-alkyl, (C1-C4)-alkyloxy-group (optionally substituted with halogen atom), halogen atom, -OH, -NH2, -CN and -NO2; R1 means (C5-C8)-cycloalkyl or (C5-C8)-cycloalkenyl; R2 means H, methyl or ethyl; radicals R3, R'3, R4, R'4, R5, R'5 and R'6 means independently hydrogen atom or (C1-C4)-alkyl optionally substituted with halogen atom or -OH; R6 means hydrogen atom or (C1-C4)-alkyl optionally substituted with (C1-C4)-alkoxy-group or halogen atom; or R6 in common with R7 forms 5-6-membered saturated heterocyclic ring; R7 means H, (C1-C4)-alkyl optionally substituted with -OH, halogen atom or (C1-C4)-alkoxy- group, or (C3-C5)-cycloalkyl, or its pharmaceutically acceptable salt. Compounds of the formula (I) possess agonistic activity with respect to CB1 receptors. Also, invention describes pharmaceutical composition possessing agonistic activity with respect to CB1 receptors and using compound of the formula (I) for preparing a drug used in pain treatment.

EFFECT: valuable medicinal and pharmacological properties of compounds and pharmaceutical composition.

9 cl, 1 tbl, 21 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel azaheterocycles of the general formula (I): possessing inhibitory effect on activity of tyrosine kinase and can be used in treatment of different diseases mediated by these receptors. In compound of the general formula (1) W represents azaheterocycle comprising 6-13 atoms that can be optionally annelated with at least one (C5-C7)-carbocycle and/or possibly annelated with heterocycle comprising 4-10 atoms in ring and comprising at least one heteroatom chosen from oxygen (O), sulfur (S) or nitrogen (N) atom; Ra1 represents a substitute of amino group but not hydrogen atom, such as substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-10-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; Rb represents carbamoyl group -C(O)NHRa wherein Ra represents a substitute of amino group but not hydrogen atom, such as possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyc comprising at least one heteroatom chosen from O, S or N; Rc represents a substitute of cyclic system, such as possibly substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-6-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; or Rb and Rc form in common aminocyanomethylene group [(=C(NH2)CN], or their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of these compounds (variants), a pharmaceutical composition, combinatory and focused libraries.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods for synthesis and preparing.

35 cl, 16 sch, 13 tbl, 43 ex

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

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