Method of producing 1,3-dicarbonyl compounds containing dibenzosuberenyl fragment
SUBSTANCE: invention relates to a method of producing 1,3-dicarbonyl compounds containing a dibenzosuberenyl fragment, which are of interest as a starting compounds for synthesis of biologically active substances, as well as ligands capable of coordinating metals. The method includes reacting dibenzosuberenol and 1,3-dicarbonyl compounds at 40°C for 30-180 min in a medium of 1,2-dichloroethane or nitromethane with catalysis of 5 mol % scandium triflate.
EFFECT: method enables to obtain the desired compounds with output of 63-86%.
SUBSTANCE: invention relates to a method of obtaining chiral heterocyclic ligands based on 1,2-diaminocyclohexane, which contain heterocyclic fragments: thienyl-2-, thienyl-3-, furyl-2-, 5-methylfuryl-2-, (2,2'-bithiophen)-5-yl-, 5-(4'-methylcyclohex-1'-en-1'-yl)thiophene-2-, which can be included into a structure of complexes for carrying out enantioselective reactions and asymmetric catalysis, as well as possess luminescence properties. The method is realised due to the application of available reagents, application of an acceptable molar ratio of reagents, considerable reduction of the total time of the reaction, the reduction of production costs is achieved due to the simplification of the reactor scheme and the time of the reaction carrying out.
EFFECT: simplification of the technological process.
SUBSTANCE: invention relates to a method of producing substituted 4-nitro-5-(2-oxoethyl)phthalonitriles of formula , where R=4-Me-C6H4, 4-MeO-C6H4, 2-thienyl, which can be used as precursors for producing biologically active substances and synthesis of phthalocyanines. The method involves use of 4-bromo-5-nitrophthalonitrile and sodium salts of 2,4-dioxobutanoic acid derivatives as initial reagents for synthesis of substituted 4-nitro-5-(2-oxoethyl)phthalonitriles. Reaction of said reagents takes place at temperature 18…35°C and molar ratio 1:2, respectively, for 18-24 hours in dimethylformamide solution. The reaction mass is then diluted with ten-fold excess 5% hydrochloric acid solution. The crystalline precipitate is filtered off and recrystallised from alcohol.
EFFECT: method enables to obtain substituted compounds with good output.
1 tbl, 3 ex
SUBSTANCE: invention refers to new thiophene derivatives of formula (I) where A is represented by *-CO-CH2CH2-, *-CO-CH=CH, where the asterisks indicate the link through which the formula (I) thiophene group is bound; R1 is represented by C2-5alkyl; R2 is represented by hydrogen, methyl or ethyl; R3 is represented by hydrogen; R4 is represented by C1-4alkyl; R5 is represented by a hydroxy group, 2,3-di-hydroxypropoxygroup or -OCH2-CH(OH)-CH2-NHCOR52; R52 is represented by hydroxymethyl, and R6 is represented by C1-4alkyl; and to its salt. The invention also refers to the pharmaceutical composition that is agonistic in relation to S1P1/EDG1 receptor on the basis of the mentioned compounds.
EFFECT: new compounds and a composition based on them that may find their application in medicine as immunomodulating agents.
17 cl, 2 tbl, 44 ex
SUBSTANCE: invention relates to thiophene derivatives of formula (I) where A denotes *-CO-CN=CH-, *-CO-CH2CH2-, or where the sign * indicates the thiophene bonding site in formula (I), R1 denotes hydrogen or methyl, R2 denotes n-propyl or isobutyl, R3 denotes hydrogen, methyl, ethyl, n-propyl, isopropyl or isobutyl, R4 denotes hydrogen or methoxy, R5 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy or hydrogen, R6 denotes -(CH2)k-(CHR65)p-CHR66-CONR61R62 hydroxy, hydroxy(C2-C4)alkoxy, di(hydroxy(C1-C4)alkyl)(C1-C4)alkoxy, 2,3-dihydroxypropoxy, -OCH2-(CH2)m-NHCOR64, -OCH2-CH(OH)-CH2-NR61R62, -OCH2- CH(OH)-CH2-NHCOR64 or -OCH2-CH(OH)-CH2-NHSO2R63, R61 denotes hydrogen, 2-hydroxyethyl, 2-hydroxy-1-hydroxymethylethyl, carboxymethyl or C1-C4alkylcarboxymethyl, R62 denotes hydrogen, R63 denotes methyl or ethyl, R64 denotes hydroxymethyl, methyl aminomethyl or 2-methyl aminoethyl, R65 denotes hydrogen, R66 denotes hydrogen, m equals 1 or 2, k equals 0, p equals 1, R67 denotes hydrogen, C1-C4alkyl or halogen, and to a salt thereof. The invention also relates to a pharmaceutical composition for preventing or treating diseases or disorders associated with an activated immune system based on said compounds.
EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine as immunodepressants.
31 cl, 2 tbl, 114 ex
SUBSTANCE: invention relates to novel compounds - arylamidrazone derivatives of formula ,
where R1 is a C2-C8 alkyl group or a C2-C8 alkoxy group, which can be substituted with a halogen or a C1-C8 alkoxy group; a 5-7-member aromatic heterocycle containing 1 or 2 oxygen, nitrogen or sulphur atoms, or phenyl, which can be substituted with a halogen, a C1-C8 alkyl group, a haloC1-C8alkyl group or a C1-C8alkoxy group; or NR4R5; R2 and R3 are identical or different, and each is a hydrogen atom, a halogen atom, a halogenC1-C8alkyl group, a C1-C8alkyl group, a C2-C6alkynyl group, a C1-C8alkoxy group, a cyano group, a C2-C6alkanoyl group or a C1-C8alkylsulphonyl group; A is a benzene, pyridine, quinoline or isoquinoline ring; D is a single bond or methylene; m assumes values from 1 to 3 and n assumes values from 1 to 5, having antagonistic effect on S1P3 receptors, as well as to medicinal agents and pharmaceutical compositions containing such compounds as an active ingredient.
EFFECT: improved properties.
13 cl, 161 ex, 19 tbl
SUBSTANCE: present invention describes novel compounds of formula (I), where substitutes R1, R2, R3, Ar and A are described in the formula of invention, having histone deacetylase inhibiting activity, use thereof and methods for synthesis of said compounds.
EFFECT: improved composition properties.
15 cl, 72 ex, 9 tbl, 6 dwg
SUBSTANCE: present invention is related to thiophen amidines of general formula I or their solvate, hydrate or pharmaceutically acceptable salt, where Z stands for -S(O2)-; R1 - halogen, amino, C1-6alkylthio; Ar - phenyl, piridyl, thiazolyl, phuranyl, benzothiazolyl, benzimidazolyl, every of which is not necessarily substituted; R2, R3, R4 and R7- hydrogen Compounds may be used for inhibition of ferment Cls, protease of classical pathway of complement system. Pharmaceutical compositions are also described on the basis of formula I compounds.
EFFECT: compounds may find application for treatment of certain acute and chronic immunological diseases, some neurogenerative diseases.
24 cl, 1 tbl, 337 ex
< / BR>where Ar is phenyl, which is optionally substituted by at least one group selected from halo (including, but not limited to, fluorine), lower alkoxy (including methoxy), lower aryloxy (including phenoxy), cyano, or R3;
m = 1;
W is independently - AN(OM)C(O)N(R3R4, -AN(R3)C(O)N(OM)R4, -AN(OM)C(O)R4AC(O)N(OM)R4, -C(O)N(OM)R4or-C(O)NHA;
A - lower alkyl, lower alkenyl or lower quinil, in which one or more carbons optionally may be replaced by O, N or S;
M is hydrogen, a pharmaceutically acceptable cation;
X IS O,S;
Y is O, S, hydrogen, lower alkyl, lower alkenyl, lower quinil, alkaryl;
R1and R2independently is hydrogen, lower alkyl, halo, or-COOH;
R3and R4independently is hydrogen, alkyl, alkenyl, quinil,1-6alkoxy-C1-C10alkyl or C1-6alkylthio-C1-10alkyl,
which possess anti-inflammatory activity through inhibition of 5-lipoxygenase as PAF receptor antagonists and are dual activity, t
SUBSTANCE: invention relates to an improved method for synthesis of 2-(benzylthio)pyrimidine-4,6 (1H, 5H) dione of formula . Said compound can be used as an intermediate product in preparation of medicinal agents. The method involves reaction of a sodium salt obtained from condensation reaction of thiourea with malonic ester in the presence of sodium methylate, which is then dissolved in aqueous dioxane, preferably 50%, and then reacted with benzyl chloride in molar ratio 1:1.1 at room temperature, preferably 25°C, for 2 hours.
EFFECT: method simplifies the process and enables to obtain the desired product with high output.
the hydrogenolysis of compounds of formula II
in which R2denotes a chlorine atom or CH3About-using agent hydrogenolysis in an inert solvent in the presence of meteorologi reagent, followed by interaction with an alkali metal methylate in methanol
A method of obtaining thiobarbiturate acid from malonic acid and thiourea by heating a mixture in vacuum at a residual pressure of 9 mm RT
SUBSTANCE: invention relates to a method of purifying barbituric acid. The method involves dissolving barbituric acid in distilled water at temperature of 70-90°C to concentration of 1-10 wt %, subsequently adding 9-30 wt % aluminium oxide while stirring, holding at that temperature for 10-30 minutes, followed by filtration and cooling the filtrate to temperature of 5-10°C. Crystals of barbituric acid formed at that temperature are filtered off and dried.
EFFECT: obtaining barbituric acid with high degree of purity and high output.
1 tbl, 24 ex
FIELD: organic chemistry, biochemistry, pharmacy.
SUBSTANCE: invention relates to new compounds of the formula (I):
eliciting inhibitory activity with respect to metalloproteinases and wherein R1 means phenoxy-group wherein phenyl residue can be substituted with one or some halogen atoms, hydroxy-, (C1-C6)-alkoxy-group, (C1-C6)-alkyl, cyano- or nitro-group; R2 means pyrimidine, pyrazine or its N-oxide or phenyl substituted with -SO2NR3R4 wherein R3 and R4 can be similar or different and mean hydrogen atom, direct-chain or branch-chain (C1-C6)-alkyl that can be substituted once or some times with the group OH, N(CH3)2, or it can be broken by oxygen atom, or it represents COR5 wherein R5 means (C1-C)-alkyl group that can be substituted with NH2. Also, invention relates to a pharmaceutical composition comprising above said compounds.
EFFECT: valuable biochemical properties of compounds and composition.
5 cl, 1 sch, 1 tbl, 10 ex