Method of producing sodium salts of 5-nr1r2-tetrazolo[1,5-a]-1,3,5-triazin-7-ones

FIELD: chemistry.

SUBSTANCE: described is a method of producing novel compounds of general formula , where NR1R2=NH2; NHAlk, where Alk=C1-C6, or cycloalkyl-C3-C6; NAlk2, where Alk=C1-C6, or cycloalkyl-C3-C6; N(CH2)n, where n=2, 3, 4, 5, 6; N(CH2CH2)2O; NHAr, where Ar=C6H5, C6H4R3, where R3=Alk(C1-C6), NO2, halide, which can be used as biologically active substances and intermediate products in synthesis of biologically active substances (anomalous nucleosides, nucleotides etc). Sodium salts of 5-NR1R2-tetrazolo[1,5-a]-1,3,5-triazin-7-ones are obtained via successive substitution of chlorine atoms in 2-NR1R2-4,6-dichloro-1,3,5-triazines with a hydroxy and azido group. The corresponding 2-NR1R2-4,6-dichloro-1,3,5-triazine reacts with aqueous sodium hydroxide solution followed by acidation and the obtained 4-NR1R2-6-chloro-(3H)-1,3,5-triazin-2-one is treated with sodium azide in an organic solvent such as acetone, acetonitrile, dimethylformamide or mixtures thereof.

EFFECT: obtaining sodium salts of 5-NR1R2-tetrazolo[1,5-a]-1,3,5-triazin-7-ones directly from 2-amino-4,6-dichloro-1,3,5-triazines without obtaining and use of bis- and mono-trinitromethyl-1,3,5-triazines.

1 cl, 2 tbl, 3 ex

 

The invention relates to the field of chemistry of condensed heterocyclic systems, specifically a method for producing sodium salts of 5-NR1R2-tetrazolo[1,5-a]-1,3,5-triazine-7-ones, of General formula:

where NR1R2=NH2; NHAlk, where Alk=C1-C6including branched or cycloalkyl-C3-C6; NAlk2where Alk=C1-C6including branched or cycloalkyl-C3-C6; N(CH2)nwhere n=2, 3, 4, 5, 6; N(CH2CH2)2O; NHAr, where Ar=C6H5C6H4R3where R3=Alk(C1-C6), NO2, F, Cl, Br, I.

Tetrazolo[1,5-a]-1,3,5-triazine represent 2,8-disanalogy purine, 5-aminotetrazole[1,5-a]-1,3,5-triazine-7-ons are 2,8-disanalogy guanine.

Therefore, the sodium salt of 5-aminotetrazole[1,5-a]-1,3,5-triazine-7-ones can be used as biologically active substances and intermediates in the synthesis of biologically active substances (abnormal nucleosides, nucleotides, and so on).

There are three known method (method-similar) structure tetrazolo[1,5-a]-1,3,5-triazine. The first lies in the interaction of 2,4,6-triazido-1,3,5-triazine with triphenylphosphine [1] [1. Keβenich E., Klapotke T.M., J. Knizek, H. Noth, A. Schulz Characterization, crystal structureof 2,4-bis(triphenylphosphanimino)tetrazolo[5,1-a]-[1,3,5]triazine and improved crysnal structure of 2,4,6-triazido-1,3,5-triazine. // Eur. J. Inorg. Chem. - 1998. - P.2013-2016].

The second method consists in the interaction of 5-aminotetrazole N-elliminate benzoic and p-Truelove acids [2] [2. Berican O., Kuxuk M, Kahveci Century, Kolayli S. Convenient synthesis of fused heterocyclic 1,3,5-triazines from some N-acyl imidates and heterocyclic amines as anticancer and antioxidant agents. // Arch. Pharm. Chem. Life Sci. - 2005. - P.365-372]:

In the basis of the third method is the reaction Tetramethylammonium salt of 2-hydroxy-4,6-bis(trinitromethyl)-1,3,5-triazine with sodium azide, it is Tetramethylammonium salt 5-trinitroglycerol[1,5-a]-1,3,5-triazine-7-it [3] [3. Fedorov BS, Fadeev M.A., gidaspow A.A., Bakharev CENTURIES, Kosareva E.A. Condensed tetrazolo-1,3,5-triazine. 1. Synthesis of salts of 5-polyaromatic-tetrazolo[1,5-a]-1,3,5-triazine-7-it. // Chemistry of heterocycle. connections. - 2005. No. 2. - S-266]:

Prototype method of obtaining sodium salts of 5-aminotetrazole[1,5-a]-1,3,5-triazine-7-ones lies in the sequential substitution trinitromethyl groups in 2-amino-4,6-bis(trinitromethyl)-1,3,5-triazine on hydroxy - and sidegroup. The resulting 6-amino-4-azido-1H-1,3,5-triazine-2-ones under the action of an aqueous solution of sodium hydroxide into sodium salt of 5-aminotetrazole[1,5-a]-1,3,5-triazine-7-ones [4] [4. Bakharev CENTURIES, gidaspow A.A., I.A. Litvinov, D. B. Krivolapov, Mironov E.V. Condensed face the Asolo-1,3,5-triazine. 4. Synthesis of salts of 5-amino-tetrazolo[1,5-a]-1,3,5-triazine-7-it. // Chemistry of heterocycle. connections. - 2006. No. 8. - S-1219]:

The original 2-amino-4,6-bis(trinitromethyl)-1,3,5-triazine synthesized by the reaction of 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride, the churches of Christ) with ammonium and amine salts of trinitromethane [5] [5. RF patent 2330026; gidaspow A.A.; Samara state technical University; bull. izopet., 2008, №21, 867]:

Thus, in the method prototype sodium salt of 5-aminotetrazole[1,5-a]-1,3,5-triazine-7-ones are synthesized from the churches of Christ in four stages through intermediate obtaining bis-trinitromethyl-1,3,5-triazines and the subsequent replacement of two trinitromethyl groups. Prototype method presupposes obtaining bis - and mono-trinitromethyl-1,3,5-triazines, which are explosives. At the same time in the target compounds trinitromethyl groups. So instead of trinitromethyl-1,3,5-triazines it is advisable to use derivatives of 1,3,5-triazine containing two easily replaceable under the action of nucleophiles group. Such derivatives can be 2-amino-4,6-dichloro-1,3,5-triazine, easily obtainable by known methods [6-8] [6. Smolin E.M., L. Rappoport S-Triazines and derivatives. In: "The Chemistry of Heterocyclic Compounds". Vol.13. (Ed. A. Weisberger) - New York, London:Wiley,1959. - P.1-668. 7. Thurston J.T., J.D. Dudley, Kaiser D.W., I. Hechenbleikner, Schaefer F.C., Holm-Hansen D. Cyanuric chloride derivatives. 1. Aminochloro-s-triazines. // J. A. Chem. Soc. - 1951. - V.73. No. 7. - P.2981-2983. 8. Poghosyan G.M., Pankratov B.A., Zaplishny B.H., Macaan YEAR Policiesin. - Yerevan: Publishing house of Academy of Sciences of Armenian SSR, 1987. - 615 S.]. In cyanuric chloride is introduced amino, mono - or disubstituted amino group under the action of ammonia, mono - or disubstituted amines:

The technical result of the invention is to provide a sodium salt of 5-NR1R2-tetrazolo[1,5-a]-1,3,5-triazine-7-ones from 2-NR1R2-4,6-dichloro-1,3,5-triazines in two stages, bypassing the intermediate receiving bis - and mono-trinitromethyl-1,3,5-triazines. Technical result is achieved by successive substitution of chlorine atoms in the 2-NR1R2-4,6-dichloro-1,3,5-triazino on hydroxy - and sidegroup:

In the first stage by the reaction of 2-NR1R2-4,6-dichloro-1,3,5-triazines with an aqueous solution of sodium hydroxide is the substitution of one chlorine atom and formed sodium salt of 2-hydroxy-4-NR1R2-6-chloro-1,3,5-triazines, which without isolation in the processing of dilute acid as a result of lactim-lactam tautomeric transformations give insoluble in water 4-NR1R2-6-chloro-(3H)-1,3,5-triazine-2-ones.

In the second stage by the reaction of 4-NR1R2-6-chloro-(3H)-1,3,5-triazine-2-ones with sodium azide in acetone (acetonitrile, smesa the acetone-dimethylformamide or acetonitrile-dimethylformamide) by replacing the last chlorine atom on sidegroup, azido-tetrazole tautomeric transformations target formed sodium salt of 5-NR 1R2-tetrazolo[1,5-a]-1,3,5-triazine-7-ones.

For a better understanding of the proposed method let us consider a few examples of the synthesis of the sodium salt of 5 - NR1R2-tetrazolo[1,5-a]-1,3,5-triazine-7-ones.

Example 1

To a solution of 3.2 g (0.08 mol) of sodium hydroxide in 28 ml of water at 20-25°C and stirring covered 2.64 g (0,016 mol) 2-amino-4,6-dichloro-1,3,5-triazine. The reaction mass stood before using up the original 2-amino-4,6-dichloro-1,3,5-triazine (20 hours, monitoring by TLC). The mass was acidified with diluted hydrochloric acid to pH=3-4, when it fell sediment. After soaking for 1 hour the precipitate was filtered and washed 3 times with 20 ml water, dried in the air. Received 1.85 g (78,7%) 4-amino-6-chloro-(3H)-1,3,5-triazine-2-it.

To a solution of 1.85 g (0,0126 mol) 4-amino-6-chloro-(3H)-1,3,5-triazine-2-it in 20 ml of a mixture of acetone-dimethylformamide (1:1) at 20-25°C and stirring covered 1.64 g (0,0252 mol) of sodium azide. The reaction mass was sustained until the complete disappearance of the original 4-amino-6-chloro-(3H)-1,3,5-triazine-2-it (24 hours, monitoring by TLC). Then the reaction mass was evaporated to dryness in a fume hood and the residue was treated with 5 ml of a mixture of water-methanol (1:1). The insoluble residue was filtered, dried in the air. Received 1.19 g (54%) of sodium salt of 5-aminotetrazole[1,5-a]-1,3,5-triazine-7-it.

Example 2

To a solution of 7.0 g (0,175 mol) of sodium hydroxide is 63 ml of water at 20-25°C and stirring covered 4,22 g (0,0175 mol) 2-phenylamino-4,6-dichloro-1,3,5-triazine. The reaction mass stood before using up the original 2-phenylamino-4,6-dichloro-1,3,5-triazine (16 hours, monitoring by TLC). The mass was acidified with diluted hydrochloric acid to pH=3-4, when it fell sediment. After soaking for 1 hour the precipitate was filtered and washed 3 times with 20 ml water, dried in the air. Got the 3.65 g (93,7%) 4 phenylamino-6-chloro-(3H)-1,3,5-triazine-2-it.

To a solution of 3.65 g (0,0164 mol) of 4-phenylamino-6-chloro-(3H)-1,3,5-triazine-2-it in 20 ml of a mixture acetonitrile-dimethylformamide (1:1) at 20-25°C and stirring sprinkle of 2.13 g (0,0328 mol) of sodium azide. The reaction mass was sustained until the complete disappearance of the original 4-phenylamino-6-chloro-(3H)-1,3,5-triazine-2-it (32 hours; control by TLC). Then the reaction mass was evaporated to dryness in a fume hood and the residue was treated with 8 ml of a mixture of water-methanol (1:1). The insoluble residue was filtered, dried in the air. Got to 2.57 g (62,5%) of sodium salt of 5-phenyliminomethyl[1,5-a]-1,3,5-triazine-7-it.

Similarly, received 5-propylamino-, 5-ISO-propylamino-, 5-cyclohexylamino-, 5-(4'-were)aminotetrazole[1,5-a]-1,3,5-triazine-7-ons.

Example 3

To a solution of 9.3 g (0,2325 mol) of sodium hydroxide in 84 ml of water at 20-25°C and stirring covered 3,40 g (0,0155 mol) 2-pyrrolidinyl-4,6-dichloro-1,3,5-triazine. The reaction mass stood before using up the original 2-pyrrolidinyl-4,6-dichloro-1,3,5-triazine (18 hours, monitoring by TLC). Masses who was acidified with diluted hydrochloric acid to pH=3-4, thus fell the sediment. After soaking for 1 hour the precipitate was filtered and washed 3 times with 20 ml water, dried in the air. Got to 1.76 g (56,5%) 4-pyrrolidinyl-6-chloro- (3H)-1,3,5-triazine-2-it.

To a solution of 1.76 g (0,0088 mol) of 4-phenylamino-6-chloro-(3H)-1,3,5-triazine-2-it in 20 ml of acetone at 20-25°C and stirring sprinkle of 1.15 g (0,0176 mol) of sodium azide. The reaction mass was sustained until the complete disappearance of the original 4-pyrrolidinyl-6-chloro-(3H)-1,3,5-triazine-2-it (12 hours, monitoring by TLC). Then the reaction mass was evaporated to dryness in a fume hood and the residue was treated with 4 ml of a mixture of water-methanol (1:1). The insoluble residue was filtered, dried in the air. Received 1.86 g (92,3%) of sodium salt of 5-pyrrolidineethanol [1,5-a]-1,3,5-triazine-7-it.

Similarly, received 5-dimethylamino-, 5-piperidino-, 5-morpholinomethyl[1,5-a]-1,3,5-triazine-7-ons.

In table 1-2 shows the melting point, elemental analysis data and IR spectroscopy of the synthesized 4-amino-6-chloro-(3H)-1,3,5-triazine-2-ones and sodium salts of 5-aminotetrazole[1,5-a]-1,3,5-triazine-7-ones, confirming the structure of the obtained compounds. Elemental analysis performed on a CHN-analyzer Eurovector EA 3000. IR spectra are taken on the device Avatar 360ESP tablets CVG.

Thus, the proposed method allows to obtain the sodium salt of 5-aminotetrazole[1,5-a]-1,3,5-triazine-7-ones in two stages of 2-amino-4,6-dichloro-1,3,5-triaz the new, excluding the receipt and use of bis - and mono-trinitromethyl-1,3,5-triazines.

The method of obtaining sodium salts of 5-NR1R2-tetrazolo[1,5-a]-1,3,5-triazine-7-ones of General formula

where NR1R2mean NH2; NHAlk, where Alk - C1-C6including branched or cycloalkyl-C3-C6; NAlk2where Alk - C1-C6including branched or cycloalkyl-C3-C6; N(CH2)nwhere n=2, 3, 4, 5, 6; N(CH2CH2)2About; NHAr, where Ar - C6H5C6H4R3where R3- Alk(C1-C6), NO2, F, Cl, Br, I, characterized in that 2-NR1R2-4,6-dichloro-1,3,5-triazine, where NR1R2mean NH2; NHAlk, where Alk - C1-C6including branched or cycloalkyl-C3-C6; NAlk2where Alk - C1-C6including branched or cycloalkyl-C3-C6; N(CH2)nwhere n=2, 3, 4, 5, 6; N(CH2CH2)2O; NHAr, where Ar - C6H5C6H4R3where R3- Alk(C1-C6), NO2, F, Cl, Br, I, is injected into the interaction with the aqueous sodium hydroxide solution with the consequences is the missing acidification and the formation of 4-NR 1R2-6-chloro-(3H)-1,3,5-triazine-2-ones, where NR1R2mean NH2; NHAlk, where Alk - C1-C6including branched or cycloalkyl-C3-C6; NAlk2where Alk - C1-C6including branched or cycloalkyl-C3-C6; N(CH2)nwhere n=2, 3, 4, 5, 6; N(CH2CH2)2O; NHAr, where Ar - C6H5C6H4R3where R3- Alk(C1-C6), NO2, F, Cl, Br, I, which enter into interaction with sodium azide in an organic solvent, such as acetone, acetonitrile, dimethylformamide or mixtures thereof.



 

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7 cl, 2 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to novel pyrasolbenzodiazepines of formula I 1 (in formula R1 is hydrogen, -NO2, -CN, halogen, -OR5, -COOR7, -CONR8R9, -NR10R11, NHCOR12, NHSO2R13; each R2 and R4 independently of one another are hydrogen, halogen, -NO2, -CF3; R3 is hydpegen, C3-C8-cycloalkyl, aryl, in particular C6-C10-aromatic group having 1 or 2 rings, 5-10-membered heteroaryl, having 1 or 2 rings and1-3 heteroatoms, selected from N, O, and S, -COOR7, CN, C2-C6-alkenyl, -CONR8R9 or C1-C6-alkyl optionally substituted with OR9-group, F or aryl as mentioned above; R5 is C1-C6-alkyl; R7 is hydrogen or C1-C6-alkyl; each independently of one another are hydrogen or C1-C6-alkyl optionally substituted with hydroxyl or NH2, or alternatively R8 and R9 together form morpholino group; each R10,R11 and R12 independently of one another are hydrogen or C1-C6-alkyl; R13 is C1-C6-alkyl optionally substituted with halogen or -NR14R15; each R14 and R15 independently of one another are hydrogen or C1-C6-alkyl optionally substituted with halogen; or alternatively -NR14R15 is morpholino group) or pharmaceutically acceptable salts thereof, as well as to certain pyrasolbenzodiazepine derivatives, thiolactam intermediates for production of compound (I) and pharmaceutical compositions containing the same. Compound and pharmaceutical composition of present invention are cycline-dependent kinase (CDK2) inhibitors and antiproliferation agents used in treatment or controlling disorders associated with cell proliferation, in particular breast, colon, lung and/or prostate tumors.

EFFECT: new antiproliferation agents.

20 cl, 12 tbl, 8 ex

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: compounds satisfying the formula I 1 are disclosed, wherein each R1 and R2 independently to one another are H, OH, OA or Hal; or R1 and R2 together are -O-CH2-O- or -O-CH2-CH2-O-; R3 and R4 are A-group; X - group monosubstituted with R8, R5 or R7; R5 is linear or branched C1-C10-alkylene, wherein one or two CH2-groups may be substituted with oxygen atom; R7 is phenyl or phenylmethyl; R8 is COOH, COOA, CONH2, CONHA, CON(A)2 or CN; F is C1-C6-alkyl; and Hal is F, Cl, Br, or I, as well as physiologically acceptable salts or solvates thereof. Methods for production of claimed compounds (I) and pharmaceutical composition containing the same also are disclosed. Said compounds and pharmaceutical composition have activity as phosphodiesterase V inhibitors and are useful in treatment of cardiovascular diseases and potency disorders.

EFFECT: pharmaceutically applicable compounds and compositions.

7 cl, 16 ex

FIELD: organic chemistry, medicine, gastroenterology, pharmacy.

SUBSTANCE: invention relates to a pyrrolopyridazine derivative of the following formula: wherein R1 represents (C3-C7)-cycloalkyl-(C1-C6)-alkyl group that can be substituted optionally with (C1-C6)-alkyl group; R2 represents (C1-C6)-alkyl group; R3 represents hydroxymethyl group, (C2-C6)-aliphatic acyloxymethyl group, (C6-C10)-arylcarbonyloxymethyl group, (C1-C6)-alkoxycarbonyloxymethyl group, formyl group, carboxyl group, (C1-C6)-alkoxycarbonyl group or (C6-C10)-aryloxycarbonyl group; R4 represents (C6-C10)-aryl group that can be substituted optionally with substitutes taken among the group consisting of (C1-C6)-alkyl groups, halogen-(C1-C6)-alkyl groups, (C1-C6)-alkoxy-groups, halogen-(C1-C6)-alkoxy-groups and halogen atoms; A represents imino-group, oxygen or sulfur atom, or its pharmaceutically acceptable salt. Pyrrolopyridazine derivatives elicit inhibitory activity with respect to gastric juice secretion and protective activity with respect to stomach mucosa and can be useful as a curative agent for prophylaxis or treatment of ulcer disease. Except for, invention relates to a pharmaceutical composition based on compounds of the invention and to a method for prophylaxis and treatment of ulcer disease.

EFFECT: valuable medicinal properties of compound.

25 cl, 1 tbl, 11 ex

FIELD: organic chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention describes bicyclical nitrogen-containing heterocycles of the general formula (I): , wherein R1 means hydrogen atom, (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl, pyridyl, naphthyl, furyl-(C1-C4)-alkyl, phenyl optionally substituted with di-(C1-C7)-alkylamino-(C1-C7)-group, halogen atom, (C1-C7)-alkoxy-group or hydroxy-(C1-C7)-alkyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxy-group, amino-(C1-C7)-alkyl, amino-group or di-(C1-C7)-alkylamino-(C1-C7)-alkoxy-group; R2 means (C1-C7)-alkyl, (C3-C7)-cycloalkyl, furyl-(C1-C4)-alkyl, pyridyl or its N-oxide; phenyl optionally substituted with halogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, hydroxy-group or trifluoromethyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxy-group; R3 means hydrogen atom, (C1-C7)-alkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl, (C3-C7)-cycloalkenyl, pyridyl-(C1-C4)-alkyl, naphthyl, phenyl optionally substituted with phthalimido-(C1-C4)-alkyl, amino-(C1-C7)-alkyl, hydroxy-(C1-C7)-alkyl, (C1-C7)-alkylamino-(C1-C7)-alkyl, di-(C1-C7)-alkylamino-(C1-C7)-alkyl, morpholino-(C1-C4)-alkyl or piperazinyl-(C1-C4)-alkyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxycarbonyl or carboxy-group. Also, invention relates to pharmaceutically acceptable salts of compounds of the formula (I) as a base with acids or pharmaceutically acceptable salts of compounds of the formula (I) as acid with bases, and pharmaceutical composition based on thereof. Compounds described above show inhibitory activity with respect to tyrosine kinase and can be used in treatment or prophylaxis of inflammatory, immunological, oncological, bronchopulmonary, dermatological and cardiovascular diseases, for treatment of asthma, disorders in the central nervous system or complications associated with diabetes mellitus, or for prophylaxis against transplant rejection after surgery transplantation.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 1 tbl, 92 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new azaheterocycles comprising fragment of piperidin-2-yl- of the general formula (1):

as separate enantiomers or mixture of enantiomers, or their pharmaceutically acceptable salts, oxides or hydrates. In compounds of the formula (1) R1 represents hydrogen atom, inert substitute or NH-protecting substitute; W represents optionally substituted azaheterocycle, such as: pyridin-3-yl, pyrazolo[1,5-a]pyridin-6-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-7-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-9-yl, imidazo[1,2-a]pyrimidin-6-yl, imidazo[1,2-a]pyrimidin-8-yl or [1,8]naphthyridin-3-yl. Compounds elicit activity with respect to nicotine receptors and can be used in pharmaceutical industry. Also, invention relates to the focused library for search of physiologically active compound-leaders, and to pharmaceutical compositions based on new compounds of the formula (1).

EFFECT: valuable medicinal and pharmacological properties of compounds.

9 cl, 1 tbl, 15 sch, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the general formula (1)

wherein A represents bicyclic or tricyclic azepine derivative; V1 and V2 both represent hydrogen atom (H) or one among V1 and V2 represents hydrogen atom (H), OMe, OBn, OPh, O-acyl, Br, Cl, F, N3, NH2, NHBn and another represents hydrogen atom (H); or V1 and V2 represent in common =O or -O(CH2)pO-; W1 represents oxygen (O) or sulfur (S) atom; X1 and X2 both represent hydrogen atom (H) or in common represent =O or =S; Y represents OR5 or NR6R7; R1 means hydrogen atom (H), lower alkyl, F, Cl and Br; R2 means lower alkoxy-group or values given for R1; R3 and R5 are taken independently among hydrogen atom (H) and lower alkyl; R4 means hydrogen atom (H); R6 and R7 are taken independently among hydrogen atom (H) and lower alkyl, or they in common mean -(CH2)n-; n = 3, 4, 5 or 6; p = 2 or 3. These compounds are agonists of vasopressin V2 receptors and useful as antidiuretic and procoagulants, and also to pharmaceutical compositions comprising these vasopressin agonists. These compositions are useful especially in treatment of diabetes insipidus of the central origin and night enuresis.

EFFECT: valuable medicinal properties of compounds, improved method for treatment.

26 cl, 1 tbl, 119 ex

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