The invention relates to new heterocyclic o-dicarbonitrile formula (I), whereThe compounds obtained can be used to obtain hexatriene-fluorophores. Such hexatriene can be used as active media in liquid and solid lasers for display of hard radiation, for the transformation of short-wave radiation long-wave and other Technical result obtained new connections. table 2.The invention relates to the field of production of new heterocyclic o-dicarbonitriles. o-Dicarbonitrile can be used to obtain hexatriene-fluorophores, as a fragment of the donor to obtain hexatriene-bifluorophors besed and hexatriene-trifluoroprop. Such hexatriene promising for use as active media of liquid and solid lasers, scintillators, especially for indication of hard radiation, for the transformation of shortwave radiation in the long wavelength in the transmission of information through fiber-optic communication lines, to increase the power of solar panels for protection of securities made for the receipt of hexatriene. (Sealing C. A., Feofanov B. N., Lambs N.N. and other Polyhexamethylene based heterocyclic diamines. // Polymer sciense ser. Conn. B. 1988, T. 30, 4, S. 286-291).This hexatrien has the following spectral characteristics: band emission 540 nm when excited in the band 312 nm.The problem solved by the present invention is the obtaining of new heterocyclic o-dicarbonitriles.Come heterocyclic o-dicarbonitrile General formula:whereThe claimed compounds include 3-ferdinant[b,f][1,2,4]triazolo[4,3-d][1,4]oxazepine-6,7-dicarbonitrile (I):3 phenylbenzo[b] oil[2,3-f] [1,2,4] triazolo[4,3-d][1,4]oxazepine-6,7-dicarbonitrile (II):
The connection data is obtained by reaction of aromatic nucleophilic substitution of the bromine atom and the nitro group in 4-bromo-5-nitrophthalonitrile the corresponding bifunctional nucleophile generated in situ from triazolinones in the presence of potassium carbonate according to the scheme:
This reaction is carried out in DMF in the presence of potassium carbonate at a temperature of 130...140oWith over 2...3 o'clockThe invention is illustrated by the trace of the positive load 30 ml of DMF, 2.37 g (0.01 mol) of 2-(5-phenyl-4H-1,2,4-triazole-3-yl)phenol, 2.8 g (0.02 mol) of anhydrous potassium carbonate, 2,52 g (0.01 mol) 4-bromo-5-nitrophthalonitrile. The temperature of the reaction mixture is raised to 130...140oWith and maintain it in this state under vigorous stirring for 2 hours. Then, cooled to room temperature, the reaction mixture is poured into 100 ml water, the precipitate is filtered off, washed with 20 ml of water.Obtain 2.9 g (80.2% of theory) of 3-phenylpiperidines[b,f][1,2,4] triazolo[4,3-d] [1,4] oxazepine-6,7-dicarbonitrile. This beige crystalline powder, MP. >300oC.Found, % 73,18; N 3,01; N 19,29
Calculated,%: 73,12; N: 3,07; N: 19,3825H11H5O
1H NMR ([N] DMSO):, M. D.: 8.55 (s, 1H), 8.45 (s, 1H), 8.23 (m, 2H), 8.10 (d, 1H, J=8.6 Hz), 7.70 (m, 1H), 7.50 (m, 5H)
Example 2. The reaction is carried out analogously to example 1, except that the reagent (2-(5-phenyl-4H-1,2,4-triazole-3-yl)phenol) is 3-(5-phenyl-4H-1,2,4-triazole-3-yl)-2-naphthol. Conditions and results of the synthesis are presented in table. 1.Example 3. Condensation of I with rhodamine 123. In a flask equipped with stirrer, thermometer, reflux condenser and capillary to enter argon, download 3.6 g (0.01 mol) I, 3.8 g (0.01 mol) of rhodamine 123 and 10 g of phenol. the with stirring in a stream of argon prior to the termination of excretion of ammonia. After the reaction, the reaction mixture was poured into 20 ml of ethanol, and the precipitated precipitate is filtered off, washed with 3 ml of ethanol and dried at T= 60oC for 2 hours, then vacuum over P2O5. Get 6.42 per g (93% of theory) of hexatriene.Found, % 74,73; H 3,81; N 12,12
Calculated, % 74,76; N. Of 3.80; N 12,17: (C86H52N12O8)
The IR spectrum of hexatriene no band 2220 cm-1-CN, there is a band at 680 cm-1- C=N-.The structural formula of hexatriene derived from I and rhodamine 123:
Macroheterocycles derived from I and rhodamine 123 has the following spectral characteristics: the maximum of a spectrum of radiation - 387 nm at the maxima of the absorption spectrum of 283 and 320 nm.Example 4. The reaction is carried out analogously to example 3, except that instead of phthalonitrile I used an equimolar amount of phthalonitrile II.Conditions and results of the synthesis and spectral characteristics of the received macroheterocycles are given in table. 2.
Heterocyclic o-dicarbonitrile General formula
< / BR>where W and X are both carbon, T is nitrogen, U represents CR1where R1represents hydrogen, or alkyl containing 1-8 carbon atoms, R represents-N(CH2R5)-SO2Z, Q represents -(C=O)-NHOH, with
< / BR>is a benzene ring, or is a heteroaryl ring of 5 to 6 atoms in the cycle, which may contain 0-2 heteroatoms selected from nitrogen, oxygen and sulfur, in addition to the heteroatom of nitrogen, denoted as W, where benzene or heteroaryl ring may optionally contain one or two substituent R1where permissible; Z is phenyl, which is optionally substituted by phenyl, alkyl with 1-8 carbon atoms, or a group OR2; R1represents halogen, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl from 1 to 4 carbon atoms, phenyl, optionally substituted by 1-2 groups OR2group-NO2group -(CH2)nZ, where Z is a phenyl which allows an alkyl with 1-8 carbon atoms, phenyl, optionally substituted with halogen, or heteroaryl radical containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; R5represents hydrogen, alkyl with 1-8 carbon atoms, phenyl, or heteroaryl containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; or their pharmaceutically acceptable salts
< / BR>where
-A= B-C= D - represents-CH=CH-CH=CH-group, in which 1 or 2 CH may be replaced by nitrogen;
Ar denotes phenyl or naphthyl, unsubstituted or one-, two - or three-fold substituted with H, Gal, Q, alkenyl with the number of C-atoms up to 6, Ph, OPh, NO2, NR4R5, NHCOR4, CF3, OCF3CN, OR4, COOR4, (CH2)nCOOR4, (CH2)nNR4R5, -N=C=O or NHCONR4R5phenyl or naphthyl;
R1, R2, R3each independently from each other, are absent or represent H, Gal, Q, CF3, NO2, NR4R5, CN, COOR4or CHCOR4;
R4, R5each independently of one another denote H or Q, or together also denote-CH2-(CH2)N-CH2-;
Q denotes alkyl with 1-6 C-atoms;
Ph denotes phenyl;
X denotes O or S;
Gal denotes F, Cl, Br or I;
"n" represents 1, 2 or 3;
and their salts, except 4-methyl-N-(2,1,3-benzothiadiazole - 5-yl)benzosulfimide, 4-nitro-N-(2,1,3-benzothiadiazole-5-yl)- benzosulfimide and 4-amino-N-(2,1,3-benzothiadiazole-5-yl)- benzolsulfonat
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) ,
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
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to oxazolo- and thiazolo-[4,5-c]-quinoline-4-amines of the general formula (I)
wherein R1 is taken among group consisting of oxygen and sulfur atoms; R2 is taken among hydrogen atom, alkyl, alkyl-OH (hydroxyalkyl), alkyl-X-alkyl, alkyl-O-C(O)-N(R5)2, morpholinyl, pyrrolidinyl, alkyl-X-aryl radical, alkenyl-X-aryl radical; each substitute R3 and R4 represents hydrogen atom or substitutes R3 and R4 taken in common form the condensed aromatic or [1,5]-naphthiridine system; X represents -O- or a single bond; R5 represents hydrogen atom. Also, invention describes intermediate compounds, pharmaceutical composition and a method for stimulating biosynthesis of cytokinins (cytokines) based on these compounds. Invention provides preparing new compounds eliciting valuable biological properties.
EFFECT: valuable properties of compounds.
21 cl, 2 tbl, 64 ex
FIELD: organic chemistry, madicine.
SUBSTANCE: tricyclic benzodiazepines of formula I as well as their pharmaceutical acceptable salts, pharmaceutical composition containing the same and methods for hypertension treatment are disclosed. In formula A is -C(O)-; Y is CH2 or CH as olefinic site; X is CH2 or CH as olefinic site S, O or NR3 (R3 is C1-C8-alkyl) with the proviso that when Y is CH, X also is CH; Z is N or CH; R1 is hydrogen, C1-C8-alkyl, C1-C8-alkoxy or halogen; R2 is NR4COAr (R4 is hydrogen; Ar is phenyl optionally substituted with 1-3 substitutes independently selected from C1-C8-alkyl, halogen, hydroxyl, fluorinated C1-C8-alkylthio and another phenyl optionally substituted with substitute selected from C1-C4-alkyl, halogen, and hydroxyl); R5 is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, fluorine, chlorine, hydroxyl or di-(C1-C4)-alkylamino.
EFFECT: improved pharmaceutical composition for hypertension treatment.
12 cl, 5 tbl, 52 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
FIELD: organic chemistry, biochemistry, medicine, pharmacology.
SUBSTANCE: invention relates to gyrase inhibitors that reduce amount of microorganisms in biological sample by contacting the indicated sample with compound of the formula (I): , to a method for treatment of bacterial infection by using compounds of the formula (I), compounds of the formula (I) and a pharmaceutical composition comprising compounds of the formula (I). Invention provides the enhanced effectiveness of treatment.
EFFECT: valuable medicinal properties of gyrase.
54 cl, 5 tbl, 13 ex
FIELD: organic chemistry, medicine, hematology.
SUBSTANCE: invention elates to new compounds that inhibit activated blood coagulating factor X (Fxa factor) eliciting the strong anti-coagulating effect. Invention proposes compound of the formula (1): Q1-Q2-C(=C)-N-(R1)-Q3-N(R2)-T1-Q4(1) wherein R1, R2, Q1, Q2, Q4 and T1 have corresponding values, and Q2 represents the group of the formula: wherein R9, R10 and Q5 have corresponding values also, or its salt, solvate or N-oxide. Invention provides the development of a novel compound possessing strong Fxa-inhibiting effect and showing the rapid, significant and stable anti-thrombosis effectin oral administration.
EFFECT: valuable medicinal properties of compounds.
13 cl, 1 tbl, 195 ex
FIELD: biochemistry, medicine, in particular new bioactive compounds having peptide hormone vasopressin agonistic activity.
SUBSTANCE: disclosed are compounds of general formula 1 or 2 or tautomers, or pharmaceutically acceptable salts thereof, wherein W represents N or C-R4; R1-R4 are independently H, F, Cl, Br, alkyl, O-alkyl, NH2, NH-alkyl, N(alkyl)2, NO2 or R2 and R3 together may form -CH=CH-CH=CH-; G1 represents bicyclic or tricyclic condensed azepine derivatives selected from general formulae 3-8 wherein A1, A4, A7, and A10 are independently CH3, O, and NR5; A2, A3, A9, A11, A12, A14, and A15 are independently CH and N; or A5 represents covalent bond and A6 represents S; or A5 represents N=CN and A6 represents covalent bond; A8 and A12 are independently NH, N-CH3 and S; A16 and A17 both represent CH2 or one of A16 and A17 represents CH2 and the other represents CH(OH), CF2, O, SOa, and NR5; R5 represents H, alkyl, CO-alkyl, and (CH2)bR6; R6 represents phenyl, pyridyl, OH, CO2H; a = 0-2; b = 1-4; Y represents CH or N; Z represents CH=CH or S; and G2 represents group selected from groups of formulae 9-11 wherein Ar represents phenyl, pyridyl, naphthyl, and mono- or polysubstituted phenyl, pyridyl, wherein substituents are selected from F, Cl, Br, alkyl, NO2; D represents covalent bond or NH; E1 and E2 both are H, OMe, F, or one of E1 and E2 represents OH, O-alkyl, OBn, OPh, OAc, F, Cl, Br, N2, NH2, NHBn or NHAc and the other represents H; or E1 and E2 together form =O, -O(CH2)gO- or -S(CN2)gS-; F1 and F2 both represent H or together form =O or =R; L represents OH, O-alkyl, NH2, NH-alkyl, and NR9R10; R7 represents COR8; R8 represents OH, O-alkyl, NH2, NH-alkyl, N(alkyl)2, pyrolidinyl, and piperidinyl; R9 and R10 both are alkyl or together form -(CH2)h-; V represents O, N-CN or S; c = 0 or 1; d = 0 or 1, e = 0 or 1; f = 0-4; g = 2 or 3; h = 3-5, with the proviso, that both d and e are not 0. Also disclosed are pharmaceutical composition having agonistic activity in relate to V2 receptor, method for treatment one or more diseases (e.g., enuresis, nycturia, diabetes insipidus, hemorrhage disorders, urinary incontinence.
EFFECT: new compounds with value biological characteristics.
41 cl, 19 tbl, 193 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new amide derivatives of carboxylic acid that are antagonists of NMDA receptors of the formula (I): , wherein one radical among R1, R2, R3 and R4 represents -OH or NH2-group and others are hydrogen atoms; or two adjacent groups R1, R2, R3 and R4 in this case in common with one or more similar or different additional heteroatoms and -CH= and/or -CH2-groups form 5-6-membvered homo- or heterocyclic ring but preferably pyrrole, pyrazole, imidazole, oxazole, oxooxazolidine or 3-oxo-1,4-oxazine ring; two other groups among R1, R2, R3 and R4 radicals represent hydrogen atoms; R5 and R6 in common with nitrogen atom between them form saturated or unsaturated 4-6-membered heterocyclic ring that is substituted with phenoxy-, phenyl-[(C1-C4)-alkoxy]-, phenoxy-[(C1-C4)-alkyl]-, benzoyl-group optionally substituted in aromatic ring with one or more halogen atoms, (C1-C4)-alkyl or (C1-C4)-alkoxy-group; X and Y mean independently oxygen, nitrogen atom or group -CH=, and to their salts formed with acids and bases. Also, invention relates to a method for preparing compounds of the formula (I) and pharmaceutical compositions showing activity as selective antagonists of NR2B receptor based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of the following diseases: chronic neurodegenerative diseases, chronic painful states, bacterial and viral infections.
EFFECT: improved preparing method, valuable medicinal properties of compounds and compositions.
11 cl, 2 tbl, 27 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to derivatives of benzoxazepine and describes derivative of benzoxazepine of the general formula (I): wherein X represents -CO or -SO2; R1, R2, R3 and R4 are chosen independently from hydrogen atom (H), (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkyloxy-(C1-C4)-alkyl, -CF3, halogen atom, nitro-group, cyano-group, -NR8R9, -NR8COR10 and -CONR8R9; R5, R6 and R7 represent independently hydrogen atom (H) or (C1-C4)-alkyl; R8 and R9 represent independently hydrogen atom (H) or (C1-C4)-alkyl; or R8 and R9 in common with nitrogen atom to which they are bound form 5- or 6-membered saturated heterocyclic ring comprising optionally the additional heteroatom chosen from oxygen atom (O), sulfur atom (S) or the group -NR11; R10 represents (C1-C4)-alkyl; R11 represents (C1-C4)-alkyl; A represents residue of 4-7-membered saturated heterocyclic ring comprising optionally oxygen atom wherein ring is substituted optionally with 1-3 substitutes chosen from (C1-C4)-alkyl, (C1-C4)-alkoxy-, hydroxy-group, halogen atom and oxo-group, or to its pharmaceutically acceptable salt under condition that compounds of the formula (I) are excluded wherein X represents -CO, and each among R1-R7 represents hydrogen atom (H), and A represents -(CH2)3 or -(CH2)4; compounds of the formula (I) wherein X represents -CO; R1 represents hydrogen atom (H); R2 represents methyl (CH3); each among R3-R7 represents hydrogen atom (H), and A represents -(CH2)3; compounds of the formula (I) wherein X represents -CO; R1 and R2 represent hydrogen atom (H); R3 represents methyl; each among R4-R7 represents hydrogen atom (H), and A represents -(CH2)3; compounds of the formula (I) wherein X represents -CO; each among R1-R3 represents hydrogen atom (H); R4 represents methyl; each among R5-R7 represents hydrogen atom (H), and A represents -(CH2)3, and compounds of the formula (I) wherein X represents -CO; each among R1-R4 represents hydrogen atom (H); R5 represents methyl; R6 and R7 represent hydrogen atom (H), and A represents -(CH2)3. Also, invention describes pharmaceutical compositions comprising indicated derivatives and using these benzoxazepine derivatives in treatment of neurological diseases and psychotic disorders sensitive to enhancing responses mediated by AMPA receptors in the central nervous system. Invention provides preparing new compounds possessing the useful biological properties.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
8 cl, 1 tbl, 31 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel anellated carbamoylazaheterocycles of the general formula (1) that possess inhibitory property of kinase activity and eliciting, for example, an anticancer activity. Also, compounds can be used as agonists, antagonists, receptor modulating agents, antiparasitic and antibacterial agents. Also, invention relates to a method for synthesis of compounds of the formula (1), a pharmaceutical composition based on thereof and a focused library for assay of leader-compounds. In compounds of the general formula (1) W represents 6-oxopiperazine, [1,4]-thiazepane, [1,4]-oxazepane or [1,4]-diazepane cycle anellated with at least one optionally substituted and optionally condensed heterocycle or carbocycle Q; Q represents optionally substituted thiophene, optionally substituted pyrrole, optionally substituted imidazole, optionally substituted thiazole, optionally substituted pyrrolidine, optionally substituted indole, optionally substituted benzofuran, optionally substituted pyridine, optionally substituted quinoline, optionally substituted benzene or optionally substituted naphthalene cycle; R1, R2 and R represent independently of each another hydrogen atom, inert substitute, optionally substituted (C1-C6)-alkyl, optionally substituted (C3-C8)-cycloalkyl, optionally substituted phenyl, optionally substituted aryl, optionally substituted heterocyclyl.
EFFECT: improved preparing method, valuable biological and medicinal properties of compounds and pharmaceutical composition.
15 cl, 5 tbl, 6 ex