Method for preparing bis-benzazolyl compounds

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (1): wherein Y means -O-, -S- or -N(R2)- wherein R2 means hydrogen atom, (C1-C10)-alkyl or aralkyl; Z means 2,5-furanyl, 2,5-thiophenyl, 4,4'-stilbenyl or 1,2-ethyleneyl residue; R1 means hydrogen or halogen atom, (C1-C10)-alkyl, (C1-C10)-alkoxy-group, cyano-group, -COOM or -SO3M wherein M means hydrogen atom or alkaline or alkaline-earth metal atom. Method for synthesis involves carrying out the reaction of compound of the formula (2): with dicarboxylic acid of the formula: HOOC-Z-COOH (3) or with it ester wherein Y, Z and R1 have values given above in N-methylpyrrolidone or N,N-dimethylacetamide medium in the presence of an acid catalyst and optionally in the presence of an accessory solvent able to remove water from the reaction mixture.

EFFECT: improved method of synthesis.

11 cl, 7 ex

 

The present invention relates to a method for besensitive compounds that can be used as optical brighteners for natural and synthetic materials.

Known various methods for obtaining such compounds.

For example, in US 4508903 describes the obtaining of 4,4'-bisbenzimidazole-, -benzothiazol - and-benzimidazole-2-installboot dimerization of the corresponding p-chloromethylbenzene. However, such methods suffer from the drawback consisting in the fact that the production of intermediate products includes several reaction stages, which subsequently leads to the low total value of output.

Of particular practical interest are the ways in which carry out the reaction of dicarboxylic acids or derivatives thereof, with a bifunctional aromatic compounds with getting heterocyclic rings in one reaction stage.

For example, in the publication EP 31296 describes a method for benzoxazolinone and benzimidazolium compounds by the reaction of condensation of organic carboxylic acids with o-aminophenols and o-phenylendiamine in a solvent mixture comprising diphenyl ether and diphenyl in the presence of acid catalysts. Moreover, in the United Kingdom patent 1201287 described getting 2.5-bisbenzimidazole-2-istifanus reaction of condensation of thiophene-2,5-dicarbon the Oh of the acid with o-aminophenol, for example in boiling 1,2,4-trichlorobenzene in the presence of boric acid. Such methods inherently flawed because they require extremely high reaction temperature, leading to the formation of impurities, the removal of the end products is associated with problems of a technological nature, resulting in a reduction of output of the product. In addition, the removal of such high-boiling solvents of the products of interaction also involves problems of a technological nature and may, in addition, may lead to the formation of deposits inside the reaction vessel, thereby making it difficult processing of the final products. In addition, the application currently chlorinated aromatic solvents is undesirable for environmental reasons.

Currently developed a new, economical way to receive besensitive connections, which allows high outputs to obtain these compounds excellent purity in the reaction conditions, which are well suited for industrial processes.

Thus, the present invention proposes a method of obtaining compounds of formula

in which

Y represents-O-, -S-or-N(R2)-,

and

R2denotes a hydrogen atom, a C1 -C10alkyl or aralkyl;

Z denotes a 2,5-furrily, 2,5-tofinally, 4,4'-stillbelieve or 1,2-etilenovyi residue, and R1denotes a hydrogen atom or halogen, C1-C10alkyl, C1-C10alkoxy, cyano, SOOMA or SO3M,

and

M denotes a hydrogen atom or an atom of alkali or alkaline earth metal, characterized by conducting the reaction of compounds of formula

with a dicarboxylic acid of the formula

or its ester, and Y, Z and R1have the meanings specified above, in N-organic or N,N-dimethylacetamide in the presence of an acid catalyst and optionally in the presence of an auxiliary solvent capable of removing water from the reaction mixture.

The molar ratio between the compound of the formula (2) and the compound of the formula (3) can be varied within wide ranges. However, it is advisable to carry out the reaction of at least two moles of a compound of the formula (2) with at least one mol of dicarboxylic acid of the formula (3). Alternatively, you can use mono - or fluids, preferably fluids, compounds of formula (3). The corresponding esters are those esters which derivationally from C1-C10-preferably from1-C4sleep is the one the most preferred diethyl ethers.

Proposed according to the invention is particularly suitable for obtaining the compounds of formula (1), in which

Y represents-O-, -S - or-N(R2)-,

R2denotes a hydrogen atom or a C1-C4alkyl;

Z has the values listed above,

R1denotes a hydrogen atom or a C1-C4alkyl, and more preferably for producing compounds of formula (1), in which

Z denotes a 2,5-furrily or 2.5-teofilovic the rest,

and to obtain those compounds which do

Z represents the 4,4'-stillbelieve or 1,2-etilenovyi the rest.

As reaction medium for implementing the method according to the invention, the most preferred are N-organic, N,N-dimethylacetamide and mixtures thereof. You can also use N-methylpyrrolidone or N,N-dimethylacetamide or mixtures thereof, together with the additional high-boiling inert solvent, for example toluene or xylene. Particularly preferably, the application of N-methylpyrrolidone.

The acid catalyst used in the method according to the invention may be selected from the group comprising boric acid, phosphoric acid, titans1-C4areavery or tin derivative, preferably boric acid or titans1-C4orthoepy, about what bennoti tetrapropylene or TetraSociology ether. The amount of catalyst can vary within wide intervals, it depends on the chemical structural element. For example, it can be used in amounts varying from 0.01 to 50 mol % in terms of number of connections (2), preferably from 0.1 to 30 mol %.

The reaction of compounds of the formulas (2) and (3) can be performed in a wide temperature range, but preferably in the range from 100 to 250°With, in particular in the temperature range from 150 to 200°C.

The presence of an auxiliary solvent has a special significance, when a compound of the formula (3) is in the form of monoether or features of the free dicarboxylic acid. In these cases, the water formed during the reaction, the reaction mixture is continuously removed. Examples of acceptable solvents, although their selection is not limited to, selected from the group comprising toluene, xylenes and mixtures of their isomers, and also pyridine, and particularly effective toluene and xylene.

According to the invention the reaction is generally carried out under atmospheric pressure. However, in some circumstances it may be advisable to conduct this reaction under elevated or reduced pressure.

When the definition of the compounds of formulas (1) and (2) R1denotes a halogen atom, it may be a fluorine atom, bromine, iodine or PR is a property of chlorine.

C1-C10the alkyl groups of R1and/or R2can be branched or unbranched, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 2-ethylbutyl, n-pentyl, isopentyl, 1-methylpentyl, 1,3-dimethylbutyl, n-hexyl, 1-etylhexyl, n-heptyl, isoheptyl, 1,1,3,3-TETRAMETHYLBUTYL, 1-methylheptan, 3-methylheptan, n-octyl, 2-ethylhexyl, 1,1,3-trimethylpentyl, 1,1,3,3-TETRAMETHYLBUTYL, n-nonyl and n-decyl. Accordingly substituted C1-C10alkalemia esters of compounds of formula (3).

C1-C10alkoxygroup R1can be branched or unbranched, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, 2-ethylbutane, n-pentox, isopentane, 1 methylphenoxy, 1,3-Dimethylbutane, n-hexose, 1 methylhexane, n-heptose, isoheptane, 1,1,3,3-TETRAMETHYLBUTYL, 1 methylheptane, 3 methylheptane, n-actoxy, 2-ethylhexoxy, 1,1,3-trimethylhexane, 1,1,3,3-tetramethylpentane, n-nonoxy or n-detoxi.

Uralkalij groups R2may be benzyl and phenethyl, which may be substituted by a halogen atom, a C1-C10alkyl or C1-C10alkoxygroup or, preferably, are unsubstituted.

Atom of alkali or alkaline earth metal M may be selected from the group vkluchaysya To, Na, Ca and Mg, but preferably K and Na.

Further, the essence of the invention is illustrated in the following examples, which are for limiting its scope is not intended.

Example 1

In the reaction vessel load of 250 g of N-methylpyrrolidone and with stirring, 82 g 98%stilbene-4,4'-dicarboxylic acid, after which 75 g of 99%2-aminophenol, 10 g of boric acid and 30 g of xylene. In the apparatus equipped with water trap Dean-stark create a vacuum and the vacuum is replaced by nitrogen. Light yellow suspension is heated to 195°and at this temperature, stirred for 18 h, and during this time through a water trap distilled 23-25 ml of water and approximately 25 g of xylene. The reaction mixture is cooled to 20°and at this temperature, stirring is continued for 1 h Yellow suspension was filtered and washed with 100 g of N-methylpyrrolidone to obtain 350 g of a brown solution, which can be used as a solvent for the next boot, and then three 80-gram portions of water. The resulting filter pressnow cake is dried under vacuum at 50 mbar at 100°obtaining in the form of a yellow solid 120 g of compound of formula (101), characterized by the maximum UV absorption λmaxat 368 nm with a repayment rate ε 71000.

Example 2

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Analogously to example 1, but replacing 2-aminophenol 82 g 98%2-thiophenol and boric acid 3 g of Tetra-isopropyl ester of Titanic acid in the form of a yellow solid obtain 115 g of compound of the formula (102), characterized by the maximum UV absorption λmaxat 375 nm with a repayment rate ε 62000 and the following data1H-NMR in D6-DMSO: 8,12, 4H, m; 8,00, 6N, m; a 7.85, 4H, m, and of 7.48, 4H, m.

Example 3

Analogously to example 1, but replacing 2-aminophenol 72 g 99%1,2-phenylenediamine, in the form of a yellow solid obtain 110 g of compound of formula (103), characterized by high UV-absorption λmaxat 370 nm with a repayment rate ε 63000 and the following data1H-NMR in D6-DMSO:

13,0, 2H, s; by 8.22, 4H, d, J=7 Hz; 7,80, 4H, d, J=7 Hz); 7.68 per, 2H, d, J=7 Hz; 7,54, 2H, d, J=7 Hz; of 7.48, 2H, s, and 7,22, 4H, t, J=7 Hz.

Example 4

In the reaction vessel load of 200 g of N-methylpyrrolidone and with stirring, 52 g 98%thiophene-2,5-dicarboxylic acid, and then 72 g of 99%2-aminophenol, 10 g of boric acid and 30 g of toluene. In the apparatus equipped with water trap Dean-stark create a vacuum and the vacuum is replaced by nitrogen. Light yellow suspension is heated to 185°C and stirred at this temperature for 1 h, moreover, during this time, through the water trap distilled 23-25 ml of water and approximately 25 g of toluene. The reaction mixture is cooled to 20°and at this temperature, stirring is continued for 1 h Yellow suspension was filtered, washed with 100 g of N-methylpyrrolidone obtaining 300 g of a brown solution, which can be used as a solvent for the next boot, and then three 80-gram portions of water. The resulting filter pressnow cake is dried under vacuum at 50 mbar at 100°obtaining in the form of a yellow solid (75 g of the compound of the formula (104), characterized by high UV-absorption λmaxat 372 nm with a repayment rate ε 52000 and the following data1H-NMR in D6-DMSO: 8,10, 2H, s; 7,82, 4H, m and 7.50, 4H, m.

Example 5

Analogously to example 4, but replacing 2-aminophenol 110 g of 2-amino-4-tert-butylphenol, boric acid 2.2 g isopropyl-ortho-titanate and toluene and 30 g of xylene, in the form of a yellow solid obtain 125 g of compound of formula (105), characterized by the maximum UV absorption λmaxat 375 nm with a repayment rate ε 51000 and a singlet at 1,30 frequent./million1H-NMR spectral analysis in the D6-DMSO.

Example 6

In the reaction vessel load of 200 g of N,N-dimethylurea the IDA and with stirring, add 35 g 98%fumaric acid, then 82 g of 2-amino-4-METHYLPHENOL, 10 g of boric acid and 30 g of xylene. In the apparatus equipped with water trap Dean-stark create a vacuum and the vacuum is replaced by nitrogen. Light yellow suspension is heated to 160°C and stirred at this temperature for 10 h, and during this time through a water trap distilled 23-25 ml of water and approximately 25 g of xylene. The reaction mixture is cooled to 20°and at this temperature, stirring is continued for 1 h Yellow suspension was filtered, washed with 100 g of N,N-dimethylacetamide, and then three 80-gram portions of water. The resulting filter pressnow cake is dried under vacuum at 50 mbar at 100°obtaining in the form of a yellow solid in 85 g of compound of formula (106), characterized by the maximum UV absorption λmaxat 365 nm with a repayment rate ε 42000.

Example 7

In the reaction vessel load of 200 g of N-methylpyrrolidone and 65 g of furan-2,5-dicarboxylic acid, and then stirring 72 g 99%1,2-phenylenediamine and 10 g of boric acid. In the apparatus equipped with water trap Dean-stark create a vacuum and the vacuum is replaced by nitrogen. Light yellow suspension is heated to 175°and at this temperature, stirred for 12 h, and during this time, under a weak vacuum distilled 28 g of ethanol. obrazovavshijsya the solution is cooled to 20° C and at this temperature, stirring is continued for 1 h Yellow suspension was filtered and washed with 100 g of N-methylpyrrolidone obtaining 300 g of a brown solution, which can be used as a solvent for the next boot, and then three 80-gram portions of water. The resulting filter pressnow cake is dried under vacuum at 50 mbar at 100°obtaining in the form of a yellow solid 95 g of compound of formula (107), characterized by high UV-absorption λmaxat 375 nm with a repayment rate ε 42000.

1. The method of obtaining the compounds of formula

in which Y represents-O-, -S - or-N(R2)-, and

R2denotes a hydrogen atom, a C1-C10alkyl or aralkyl;

Z denotes a 2,5-furrily, 2,5-tofinally, 4,4'-stillbelieve or 1,2-etilenovyi balance, and

R1denotes a hydrogen atom or halogen, C1-C10alkyl, C1-C10alkoxy, cyano, SOOMA or SO3M, and

M denotes a hydrogen atom or an atom of alkali or alkaline earth metal, characterized by conducting the reaction of compounds of formula

with a dicarboxylic acid of the formula

or its ester, p is item Y, Z and R1have the meanings specified above, in N-organic or N,N-dimethylacetamide in the presence of an acid catalyst and optionally in the presence of an auxiliary solvent capable of removing water from the reaction mixture.

2. The method according to claim 1, in which at least 2 mol of the compounds of formula (2) interact with at least 1 mol of dicarboxylic acid of the formula (3) or its ester.

3. The method according to claim 1 or 2 for obtaining compounds of formula (1), in which

Y represents-O-, -S - or-N(R2)-;

R2denotes a hydrogen atom or a C1-C4alkyl;

Z has the meanings indicated in claim 1, and

R1denotes a hydrogen atom or a C1-C4alkyl.

4. The method according to claim 3, where

Z denotes a 2,5-furrily or 2.5-teofilovic the rest.

5. The method according to claim 3, where Z denotes 4,4'-stillbelieve or 1,2-etilenovyi the rest.

6. The method according to any one of claims 1 to 5, in which the reaction of the compounds of formulas (2) and (3) is carried out in N-organic.

7. The method according to any one of claims 1 to 6, in which the acid catalyst is chosen from the group comprising boric acid, phosphoric acid, titans1-C4orthoepy and tin-containing derivatives.

8. The method according to claim 7, in which the acid catalyst is a boric acid or titans1-C4orthoepy.

9. The method according to any and what claims 1 to 8, in which the reaction of the compounds of formulas (2) and (3) is carried out in the temperature interval from 100 to 250°C.

10. The method according to claim 6, in which the reaction of the compounds of formulas (2) and (3) is conducted in the temperature range from 150 to 200°C.

11. The method according to any one of claims 1 to 10, in which the auxiliary solvent capable of removing water from the reaction mixture, chosen from the group comprising toluene, xylene, mixtures of their isomers and pyridine.



 

Same patents:

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SUBSTANCE: invention relates to heterocyclic o-dicarbonitriles. Invention describes heterocyclic o-dicarbonitriles of the general formula: wherein R means the following compounds: . Heterocyclic o-dicarbonitriles can be used for preparing hexazocyclanes-fluorophores as a donor-fragment used for preparing hexazocyclanes-bifluorophores and hexazocyclanes-trifluorophores. Invention provides preparing new compounds possessing valuable properties.

EFFECT: valuable properties of compounds.

2 tbl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of dihydrobenzo[b][1,4]diazepine-2-one. Invention describes derivatives of dihydrobenzo[b][1,4]diazepine-2-one of the general formula (I): wherein X means a simple bond or ethynediyl group wherein if X means a simple bond then R1 means cyano-group, halogen atom, lower alkyl, (C1-C3)-cycloalkyl, (lower)-alkoxyl, fluoro-(lower)-alkyl or it means pyrrole-1-yl that may be free or substituted with 1-3 substitutes taken among the group consisting of fluorine, chlorine atom, cyano-group, -(CH2)1-4-hydroxyl group, fluoro-(lower)-alkyl, lower alkyl, -(CH2)n-(lower)-alkoxyl, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'', hydroxy-(lower)-alkoxyl and -(CH2)n-COR'R'', or it means free phenyl or phenyl substituted with one or two substitutes taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, fluoro-(lower)-alkoxyl and cyano-group; if X means ethynediyl group then R1 means free phenyl or phenyl substituted with 1-3 substituted taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (C3-C6)-cycloalkyl, (lower)-alkoxyl and fluoro-(lower)-alkoxyl; R2 means -NR'R'', fluoro-(lower)-alkoxyl or 3-oxopiperazin-1-yl, pyrrolidin-1-yl, or piperidin-1-yl wherein their rings are substituted optionally with R''; R' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl or 2-(lower)-alkoxy-(lower)-alkyl; R'' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl, 2-(lower)-alkoxy-(lower)-alkyl, -(CH2)2-4-di-(lower)-alkylamino-group, -(CH2)2-4-morpholinyl, -(CH2)2-4-pyrrolidinyl, -(CH2)2-4-piperidinyl or 3-hydroxy-(lower)-alkyl; Y means -CH= or =N-; R3 means halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, cyano-group, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'' or it means optionally substituted 5-membered aromatic heterocycle that can be substituted with halogen atom, fluoro-(lower)-alkyl, fluoro-(lower)-alkoxyl, cyano-group, -(CH2)n-NR'R'', -(CH2)n-C(O)OR'', -(CH2)n-C(O)NR'R'', -(CH2)n-SO2NR'R'', -(CH2)n-C(NH2)=NR'', hydroxyl, (lower)-alkoxyl, (lower)-alkylthio-group or lower alkyl that is optionally substituted with fluorine atom, hydroxyl, (lower)-alkoxyl, cyano-group or carbamoyloxy-group; n means 0, 1, 2, 3 or 4, and their pharmaceutically acceptable additive salts. Also, invention describes a medicinal agent as antagonist of mGlu receptors of group II based on compounds of the formula (I). Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 496 ex

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FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of sulfonamide of the general formula (I): wherein A means a substitute chosen from 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms chosen from oxygen (O), nitrogen (N) or sulfur (S) optionally substituted with 1 or 2 halogen atoms, (C1-C4)-alkyl or phenyl radical, or 5- or 6-membered heteroaryl radical comprising 1 or 2 atoms of O, N or S; bicyclic heteroaromatic ring comprising from 1 to 3 heteroatoms chosen from O, N or S and optionally substituted with 1 or 2 halogen atoms or (C1-C4)-alkyl; R1 means hydrogen atom (H), (C1-C4)-alkyl, benzyl; n means 0, 1, 2, 3 or 4; R2 means -NRR5 or the group of the formula: wherein a dotted line means optional chemical bond; R, R4 and R5 mean independently H or (C1-C4)-alkyl; or one of its physiologically acceptable salts. Compounds of the formula (1) possess antagonistic activity with respect to serotonin HT6-receptors that allows their using in pharmaceutical composition and for preparing a medicament.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

10 cl, 2 tbl, 7 ex

FIELD: organic chemistry, anti-microbial preparations.

SUBSTANCE: invention relates to compounds useful as anti-microbial agents. Claimed compounds are effective against to certain human and animal pathogens, including Gram-positive aerobic bacteria such as multi-resistant staphylococcus, streptococcus and enterococcus, as well as anaerobic organisms such as species Bacterioides spp. and Clostridia spp., and acid resistant organisms such as Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium spp.

EFFECT: new anti-microbial agents.

2 ex, 5 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel class of 5-membered heterocyclic compounds of the general formula (I): or cosmetically acceptable salts. Invention describes a compound represented by the formula (I) and its pharmaceutically or cosmetically acceptable salt wherein R1 is chosen from linear or branched (C1-C12)-alkyl, (C3-C7)-cycloalkyl, phenyl, naphthyl, C3-, C4-, C5- or C8-heteroaryl wherein one or some heteroatoms when they present are chosen independently from oxygen (O), nitrogen (N) or sulfur (S) atom and substituted optionally wherein substitutes are chosen from the first group comprising halogen atom, hydroxy0, nitro-, cyano-, amino- oxo-group and oxime, or from the second group comprising linear or branched (C1-C8)-alkyl wherein a substitute from indicated second group is optionally substituted with R10, or wherein heteroaryl is substituted with -CH2-C(O)-2-thienyl; Y is absent or chosen from the group consisting of (C1-C12)-alkyl-Z or (C2-C8)-alkyl wherein Z is chosen from sulfur, oxygen or nitrogen atom; A and B are chosen independently from nitrogen atom (N), -NH, -NR6, sulfur, oxygen atom to form heteroaromatic ring system; R2, R3 and R4 are chosen independently from the first group comprising hydrogen, halogen atom, or R3 and R4 form phenyl ring in adjacent positions; R5 is absent or chosen from the group comprising -CH2-phenyl, -CH2(CO)R7, -CH2(CO)NHR8 and -CH2(CO)NR8R9 that are substituted optionally with R10; R6, R7, R8 and R are chosen independently from the group comprising linear or branched (C1-C8)-alkyl, (C3-C7)-cycloalkyl, C5-heterocycloalkyl, benzylpiperidinyl, phenyl, naphthyl, heteroaryl, alkylheteroaryl, adamantyl, or R8 and R9 form piperidine ring, and R means 3,4-ethylenedioxyphenyl wherein substitutes in indicated group are substituted optionally with R10, and heteroaryl means C3-, C4-, C5- or C8-heteroaryl wherein one or some heteroatom when they present are chosen independently from O, N or S; R10 is chosen from halogen atom, hydroxy-, nitro-, cyano-, amino-, oxo-group, perhalogenalkyl-(C1-C6) or oxime; X means halide ion under condition that when groups/substitutes present at the same or at adjacent carbon or nitrogen atoms then can form optionally 5-, 6- or 7-membered ring optionally containing one o some double bonds and containing optionally one or some heteroatoms chosen from O, N or S. Also, invention describes a method for synthesis of these compounds, their therapeutic and cosmetic using, in particular, in regulation of age and diabetic vascular complications. Proposed compounds show effect based on the triple effect as agent destroying AGE (terminal products of enhanced glycosylation), inhibitors of AGE and scavengers of free radicals that do their suitable in different therapeutic and cosmetic using. Also, invention relates to pharmaceutical and cosmetic compositions comprising these compounds and to methods for treatment of diseases caused by accumulation of AGE and/or free radicals in body cells. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds.

73 cl, 4 tbl, 63 ex

FIELD: organic chemistry, medicine, pharmacy.

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

and their salts wherein ring A comprises optionally heteroatom oxygen (O); dotted lines represent the optional unsaturation; R1 represents (C1-C4)-alkoxy-group; R2 and R3 represent independently hydrogen atom (H), optionally halogenated (C1-C4)-alkyl, optionally substituted aromatic group, or R2 and R3 in common can form substituted or unsubstituted 5-7-membered ring condensed with ring E; k = 0-4; L1 represents a covalent bond or (C1-C6)-alkyl optionally comprising nitrogen atom (N); X represents unsubstituted or substituted carbon © atom or N, or represents O or sulfur (S) atom; Ar represents phenylene; each n = 0-2 independently; each R represents independently H or (C1-C6)-alkyl; Y represents optionally substituted aromatic or heteroaromatic group or 5-11-membered heterocyclic group comprising 1-4 heteroatoms cgosen from N, O and S that are bound with chemokine receptors comprising CXCR4 and CCR5, and elicit the protective affect against damage of host-cells by human immunodeficiency virus (HIV).

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes novel derivatives of N-triazolylmethylpiperazine of the general formula (I): , wherein R1 means hydrogen atom or (lower)-alkyl; R2 means (lower)-alkyl, di-(lower)-alkylamino-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, cycloalkyl with 5-6 carbon atoms in cycle, pyridinyl-(lower)-alkyl, possibly bi-substituted phenyl-(lower)-alkyl, phenyloxy-(lower)-alkyl substituted with halogen atom in phenyl ring; R3 means (lower)-alkyl, (lower)-alkyloxycarbonyl-(lower)-alkyl or (C5-C6)-cycloalkyl, or both R2 and R3 in common with nitrogen atom to which they are bound form substituted pyrrolidine ring or cyclic group of the formula (a): , wherein A means nitrogen, oxygen atom, methylene or methylidene group wherein its double bond is formed in common with adjacent carbon atom at position 3 of the group (a), and if A means nitrogen atom then this nitrogen atom has substitute R4', and in this case n means 2 or 3, and R4' means (lower)-alkyl, possibly substituted phenyl-(lower)-alkyl, possibly substituted pyridyl, pyridyl-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, pyrimidyl-(C5-C6)-cycloalkyl, (C5-C6)-cycloalkyl-(lower)-alkyl or morpholinyl-(lower)-alkyl; R4 and R5 mean hydrogen atom and in all cases n means a whole number from 1 to 2; R4 means hydrogen atom, (lower)-alkyl, (lower)-alkoxy-(lower)-alkyl, (lower)-alkoxycarbonyl, (lower)-alkoxycarbonyl-(lower)-alkyl, di-(lower)-alkylamino-(lower)-alkyl, phenyl, pyrrolidinyl, pyrrolidinyl-(lower)-alkyl, pyridyl or piperidinyl, cyclohexyl, cyclohexyl-(lower)-alkyl, phenyl-(lower)-alkyl, pyridyl monosubstituted with (lower)-alkyl, phenyl-(lower)-alkyl monosubstituted with (lower)-alkyl, pyrimidyl, pyridyl-(lower)-alkyl, morpholinyl-(lower)-alkyl; R5 means hydrogen atom, (lower)-alkyl or (lower)-alkoxy-(lower)-alkyl, or R4 and R5 taken in common mean spiroethylenedioxy-group bound with carbon atom of the group (a), (C3-C4)-alkylene bound with two adjacent atoms of the group (a) or phenyl anellated by two adjacent carbon atoms of the group (a), and their physiologically acceptable acid-additive salts also. Also, invention relates to methods for synthesis of these compounds, a medicinal agent based on thereof and intermediate compound in synthesis of novel compounds. Novel compounds are antagonists of neurokinin receptors and display effect in peripheral region preferably and can be used in treatment of functional and inflammatory disorders of digestive tract.

EFFECT: improved preparing method, valuable medicinal properties of derivatives.

10 cl, 4 tbl, 4 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new benzofuran derivatives of formula 1 , wherein X represents group of formula -N= or -CH=; Y represents optionally substituted amino group, optionally substituted cycloalkyl group, or optionally substituted saturated heterocycle; A represents direct bond, carbon chain optionally containing double bond in molecular or in the end(s) thereof, or oxygen atom; R1 represents hydrogen, halogen, lower alkoxy, cyano, or amino optionally substituted with lower alkyl B represents optionally substituted benzene ring of formula ; and R2 represents hydrogen or lower alkyl; or pharmaceutically acceptable salt thereof. Invention also relates to pharmaceutical composition containing abovementioned compounds, uses thereof and method for thrombosis treatment.

EFFECT: new compounds for thrombosis treatment.

27 cl, 2 tbl, 429 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I)

or their pharmaceutically acceptable salts or esters hydrolyzing in vivo and possessing activity inhibiting the cellular cycle and selective with respect to CDK-2, CDK-4 and CDK-6. Compounds can be used in cancer treatment. In the formula (I) R1 represents halogen atom, amino-group, (C1-C)-alkyl, (C1-C6)-alkoxy-group; p = 0-4 wherein values R1 can be similar or different; R2 represents sulfamoyl or group Ra-Rb-; q = 0-2 wherein values R2 can be similar or different and wherein p + q = 0-5; R3 represents halogen atom or cyano-group; n = 0-2 wherein values R3 can be similar or different; R4 represents hydrogen atom, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl or heterocyclic group bound with carbon atom wherein R4 can be optionally substituted at carbon atom with one or some groups Rd; R5 and R6 are chosen independently from hydrogen, halogen atom, (C1-C)-alkyl, (C2-C6)-alkenyl or (C3-C8)-cycloalkyl wherein R5 and R6 can be substituted at carbon atom independently of one another with one or some groups Re; Ra is chosen from (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C6)-alkyl, phenyl, heterocyclic group, phenyl-(C1-C)-alkyl or (heterocyclic group)-(C1-C6)-alkyl wherein Ra can be substituted optionally at carbon atom with one or some groups Rg and wherein if indicated heterocyclic group comprises residue -NH- then its nitrogen atom can be optionally substituted with group chosen from the group Rh; Rb represents -N(Rm)C(O)-, -C(O)N(Rm)-, -S(O)r-, -OC(O)N(Rm)SO2-, -SO2N(Rm)- or -N(Rm)SO2- wherein Rm represents hydrogen atom or (C1-C6)-alkyl, and r = 1-2. Also, invention relates to methods for synthesis of these compounds, a pharmaceutical composition, method for inhibition and using these compounds.

EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical compositions.

24 cl, 3 sch, 166 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of amide of the general formula (I)

wherein X means -CH; Y means -CH or nitrogen atom (N); m = 1 or 2; R1 means (C1-C6)-alkyl, (C1-C)-alkoxy-group, N,N-di-[(C1-C6)-alkyl]-amino-group, heterocyclyl-(C1-C6)-alkyl wherein heterocyclyl represents piperazinyl or homopiperazinyl; n = 3; R2 means halogen atom, (C1-C6)-alkyl; R3 means hydrogen atom; Q means phenyl optionally substituted with cyano-group, or pyridyl optionally substituted with morpholino-group, or their pharmaceutically acceptable salts, to methods for synthesis of indicated compounds, pharmaceutical compositions containing thereof and their using in treatment of diseases or states mediated by cytokines.

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

10 cl, 2 tbl, 7 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to anthranylamide derivative selected from compound of formula I or N-oxides thereof, wherein R1 represents methyl, F, Cl, Br; R2 represents F, Cl, Br, I, CF3; R3 represents CF3, Cl, Br, OCH2CF3; R4a represents C1-C4-alkyl; R4b represents H, CH3; and R5 represents Cl, Br, and agriculturally acceptable salt thereof. Also disclosed are composition for pest controlling containing biologically effective amount of formula I and at least one additional component selected from group comprising surfactants, solid and liquid diluents; composition for invertebrate insect controlling containing biologically effective amount of formula I and at least one additional biologically active compound or agent. Also disclosed are method for insect controlling as well as intermediates such as benzoxazinone and parasolocarboxylic acid derivatives.

EFFECT: compounds with insecticide activity, useful in insect controlling.

20 cl, 16 tbl, 33 ex

FIELD: organic chemical, pharmaceuticals.

SUBSTANCE: invention relates to new compounds having JAK3 kinase inhibitor activity, methods for production thereof, intermediates, and pharmaceutical composition containing the same. In particular disclosed are aromatic 6,7-disubstituted 3-quinolinecarboxamide derivatives of formula I and pharmaceutically acceptable salts thereof useful in production of drugs for treatment of diseases mediated with JAK3. In formula n = 0 or 1; X represents NR3 or O; Ar is selected from phenyl, tetrahydronaphthenyl, indolyl, pyrasolyl, dihydroindenyl, 1-oxo-2,3-dihydroindenyl or indasolyl, wherein each residue may be substituted with one or more groups selected from halogen, hydroxy, cyano, C1-C8-alkoxy, CO2R8, CONR9R10 C1-C8-alkyl-O-C1-C8-alkyl, etc., wherein R-groups are independently hydrogen atom or C1-C8-alkyl; meanings of other substitutes are as define in description.

EFFECT: new compounds having value biological properties.

17 cl, 222 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (1): wherein R1 means (C1-C6)-alkyl that can be substituted with phenyl; R2, R3, R4 and R5 represent independently each of other hydrogen halogen atom, nitro-group, (C1-C4)-alkyl, (C6-C10)-aryl-(C1-C4)-alkyloxy-, (C6-C10)-aryloxy-group, (C6-C10)-aryl that can be mono-, di- or tri-substituted with halogen atom; 2-oxopyrrolidine-1-yl, 2,5-dimethylpyrrole-1-yl or -NR6-A-R7 under condition that R2, R3, R4 and R5 can't mean simultaneously hydrogen atom and at least one residue among R2, R3, R4 and R5 represents 2-oxopyrrolidine-1-yl, 2,5-dimethylpyrrole-1-yl or -NR6-A-R7 at value R6 - hydrogen atom, (C1-C4)-alkyl or (C6-C10)-aryl-(C1-C4)-alkyl wherein aryl can be substituted with halogen atom; A means a simple bond, -COn, -SOn or -CONH; n = 1 or 2; R7 means hydrogen atom; (C1-C18)-alkyl or (C2-C18)-alkenyl that can be substituted from one to three times with (C1-C4)-alkyl, (C1-C4)-alkyloxy-group, -N-((C1-C4)-alkyl)2-group, -COOH, (C1-C4)-alkyloxycarbonyl, (C6-C12)-aryl, (C6-C12)-aryloxy-group, (C6-C12)-arylcarbonyl, (C6-C10)-aryl-(C1-C4)-alkoxy-group, halogen atom, -CF3 or oxo-group wherein aryl, in turn, can be substituted with halogen atom, (C1-C)-alkyl, aminosulfonyl- or methylmercapto-group; (C6-C10)-aryl-(C1-C4)-alkyl, (C5-C8)-cycloalkyl-(C1-C4)-alkyl, (C5-C8)-cycloalkyl, (C6-C10)-aryl-(C2-C6)-alkenyl, (C6-C10)-aryl, diphenyl, diphenyl-(C1-C4)-alkyl, indanyl that can be mono- or di-substituted with (C1-C18)-alkyl, (C1-C18)-alkyloxy-group, (C3-C8)-cycloalkyl, hydroxy-group, (C1-C4)-alkylcarbonyl, (C6-C10)-aryl-(C1-C4)-alkyl, (C6-C10)-aryl-(C1-C4)-alkyloxy-group, (C6-C10)-aryloxy-group, nitro-, cyano-group, (C6-C10)-aryl, fluorosulfonyl, (C1-C6)-alkyloxycarbonyl, (C6-C10)-arylsulfonyloxy-group, pyridyl, -NHSO2-(C6-C10)-aryl, halogen atom, -CF3 or -OCF3 wherein alkyl can be substituted once again with halogen atom, -CF3 or (C1-C4)-alkyloxy-group; or group Het-(CH2)r wherein r = 0, 1, 2 or 3 wherein Het means saturated or unsaturated 5-7-membered heterocycle comprising atoms nitrogen (N), oxygen (O) or sulfur (S) and can be condensed with benzene and substituted with (C1-C4)-alkyl, (C6-C10)-aryl, halogen atom, (C1-C4)-alkyloxy-group, (C6-C10)-aryl-(C1-C4)-alkyl, (C6-C10)-aryl-(C1-C)-alkylmercapto- or nitro-group and wherein aryl condensed with benzene can be, in turn, substituted with halogen atom, (C1-C4)-alkyloxy-group; and to their pharmacologically acceptable salts and additive salts of acids, and to a method for their preparing. Proposed compounds show inhibitory effect on activity of hormone-sensitive lipase.

EFFECT: improved preparing method, valuable biochemical and medicinal properties of compounds.

14 cl, 199 ex

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