Fungicidal derivatives of 2-pyridylmethylenecarboxamide

FIELD: medicine.

SUBSTANCE: invention refers to derivatives of 2-pyridylmethylenecarboxamide of formula (I), where: -A represents a substituted or unsubstituted 5-member heterocyclyl group bound with carbonyl through carbon atom; -Z1 and Z2 which can be equal or different, represent hydrogen atom; C1-C5-alkyl; C5-alkoxycarbonyl; -Z3 represents substituted or unsubstituted C3-C7cycloalkyl; -Y represents C1-C5-halogenalkyl, containing to 5 halogen atoms which can be equal or different; X which can be equal or different, represents halogen atom, - n=0, 1, 2 or 3; and to their salts. Besides the invention describes a method of plant pathogenic fungi control with the use of such compounds.

EFFECT: there are prepared and described new derivatives of 2-pyridylmethylenecarboxamide which can be effective as fungicidal active agents.

8 cl, 96 ex, 4 tbl

 

The present invention relates to derivatives of 2-pyridinecarboxamide, method of production thereof, their use as fungicide active agents, particularly in the form of fungicidal compositions, and to methods for controlling phytopathogenic fungi, especially in plants, using these compounds or compositions.

In international patent application WO-01/11966 some derivatives of 2-pyridinecarboxamide in General covered a broad description of the numerous compounds.

However, in this document definitely not disclosed and are not proposed for the selection of such compounds in which the nitrogen atom carboxamide residue may be substituted by cycloalkyl.

In international patent application WO-02/22583 revealed some nitrogen-containing derivatives.

However, the document is not opened and not made assumptions about what such compounds, the substituted 5-membered heterocyclyl groups, and in which the nitrogen atom may be substituted by cycloalkyl can provide biological activity. In addition, the compounds disclosed in this document are replaced by two a and b pyridinoline groups.

In agriculture the use of new pesticide compounds are always of great interest in order to avoid the development of strains that are resistant to the active ingredients, or podavljat the development. Of great interest is also the use of new compounds which are more active than the already known compounds, with the aim of decreasing the quantity of active connections while maintaining efficiency at least equivalent to the efficiency of already known compounds.

The inventors have now discovered a new family of compounds with the above properties or benefits.

In accordance with this present invention relates to derivatives of 2-pyridinecarboxamide formula (I):

where A represents A substituted or unsubstituted 5-membered heterocyclyl group associated with the carbonyl through a carbon atom;

Z1and Z2that may be the same or different, represent a hydrogen atom; C1-C5-alkyl, C2-C5alkenyl; C2-C5-quinil; cyano; nitro; a halogen atom; C1-C5-alkoxy, C2-C5-alkenylamine; C2-C5-alkyloxy; C3-C7-cycloalkyl; C1-C5-alkylsulfonyl; amino; C1-C5-alkylamino; di-C1-C5-alkylamino; C1-C5-alkoxycarbonyl; C1-C5-allylcarbamate; di-C1-C5-allylcarbamate; N-C1-C5-alkyl-C1-C5-alkoxycarbonyl; or

Z 1and Z2together with the carbon atom to which they are bound, may form a 3-, 4-, 5 - or 6-membered Carbo - or heterocyclic ring which may be substituted;

Z3represents a substituted or unsubstituted C3-C7-cycloalkyl;

Y represents C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

X, which may be the same or different, represents a halogen atom; nitro; cyano; hydroxyl; carboxyl group; C1-C8-alkyl, C1-C6-halogenated containing up to 5 halogen atoms which can be the same or different; C1-C8-alkylamino; di-C1-C8-alkylamino; C1-C8-alkoxy, C1-C6-halogenoalkane containing up to 5 halogen atoms which can be the same or different; C1-C8-alkylthio; C1-C6-allogenicity containing up to 5 halogen atoms which can be the same or different; C2-C8-alkenylamine; C2-C8-halogenations containing up to 5 halogen atoms which can be the same or different; C3-C8-alkyloxy; C3-C8-halogenaryloxy containing up to 5 halogen atoms which can be the same is mi or different; C3-C8-cycloalkyl; C1-C8-alkoxycarbonyl; C1-C8-alkylsulfanyl; C1-C8-alkylsulfonyl; C1-C8-halogenacetylenes containing up to 5 halogen atoms which can be the same or different; C1-C8-halogenallylacetic containing up to 5 halogen atoms which can be the same or different, or C1-C6-alkoxyimino-C1-C6-alkyl;

n=0, 1, 2 or 3;

and also their salts, N-oxides, metal complexes, metallogeny complexes and optically active isomers.

Any connection according to the invention may exist in one or more optical or chiral isomeric forms depending on the number of asymmetric centres in the connection. Therefore, the invention equally applies to all optical isomers and racemic or selamicesme mixtures (the term "kalamajska" means a mixture of enantiomers in different proportions), and mixtures of all possible stereoisomers in all proportions. Diastereoisomer and/or optical isomers can be separated according to methods known per se to the person skilled in the field.

Any connection according to the invention may also exist in one or more geometrically isomeric forms depending on the number of double connection is in the connection. Consequently, the invention applies equally to all geometric isomers and to all possible mixtures in all ratios. Geometric isomers can be separated according to General methods known per se to the person skilled in the field.

For compounds according to the invention the halogen means any atom of fluorine, bromine, chlorine or iodine, and the heteroatom can be nitrogen, oxygen or sulphur.

Preferred compounds of formula (I) according to the invention are compounds in which Z3is not substituted, in particular cyclopropyl.

Other preferred compounds of formula (I) according to the invention are compounds in which A is selected from the list consisting of:

- heterocycle of formula (A1)

where R1-R3that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

- heterocycle of formula (A2)

(A2)

where R4-R6that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated, containing the s up to 5 halogen atoms, which may be the same or different;

- heterocycle of formula (A3)

where R7represents a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R8represents a hydrogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or C1-C5-alkyl;

- heterocycle of formula (A4)

where R9-R11that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl; amino; C1-C5-alkoxy, C1-C5-alkylthio or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

- heterocycle of formula (A5)

(A5)

where R12and R13that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl, C1-C5-alkoxy; amino or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R14represents a hydrogen atom; a halogen atom; C1-C5alkyl; amino or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

- heterocycle of formula (A6)

where R15represents a hydrogen atom; halogen atom; cyano; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R16and R18that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkoxycarbonyl; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R17represents a hydrogen atom or a C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different or a phenyl substituted by a halogen atom or C1-C5-alkyl;

- heterocycle of formula (A7)

where R19represents a hydrogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or C1-C5-alkyl;

R20-R22that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or Csub> 1-C5-halogenated containing up to 5 halogen atoms which can be the same or different

- heterocycle of formula (A8)

where R23represents a hydrogen atom; a halogen atom; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R24represents a hydrogen atom or a C1-C5-alkyl;

- heterocycle of formula (A9)

where R25represents a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R26represents a hydrogen atom or a C1-C5-alkyl;

- heterocycle of formula (A10)

where R27represents a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R28represents a hydrogen atom; a halogen atom; amino; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different or a phenyl substituted by a halogen atom or C1-C5-what Kilom;

- heterocycle of formula (A11)

where R29represents a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R30represents a hydrogen atom; a halogen atom; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; amino; C1-C5-alkylamino; di-C1-C5-alkylamino;

- heterocycle of formula (A12)

where R31represents a hydrogen atom; a halogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or C1-C5-alkyl;

R32represents a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

R33represents a hydrogen atom; halogen atom; nitro or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

- heterocycle of formula (A13)

where R34represents a hydrogen atom; a halogen atom; C1-C5-alkyl, C3 -C5-cycloalkyl; C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; C1-C5-alkoxy, C2-C5-alkyloxy; C1-C5-halogenoalkane containing up to 5 halogen atoms which can be the same or different or a phenyl substituted by a halogen atom or C1-C5-alkyl;

R35represents a hydrogen atom; a halogen atom; C1-C5-alkyl; cyano; C1-C5-alkoxy, C1-C5-alkylthio; C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; C1-C5-halogenoalkane containing up to 5 halogen atoms which can be the same or different; amino; C1-C5-alkylamino or di(C1-C5-alkyl);

R36represents a hydrogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or C1-C5-alkyl;

- heterocycle of formula (A14)

where R37and R38that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; C1-C5 -alkoxy or C1-C5-alkylthio;

R39represents a hydrogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or C1-C5-alkyl;

- heterocycle of formula (A15)

where R40and R41that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

- heterocycle of formula (A16)

where R42and R43that may be the same or different, represent a hydrogen atom; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; amino or phenyl, substituted by halogen atom or C1-C5-alkyl;

- heterocycle of formula (A17)

where R44and R45that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

- heterocycle of formula (A18)

where R 46represents a hydrogen atom; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different, or C1-C5-alkylsulfanyl;

R47represents a hydrogen atom; halogen atom or C1-C5-alkyl;

- heterocycle of formula (A19)

where R48and R49that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;

- heterocycle of formula (A20)

where R50represents a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different.

The heterocycle A13it is especially preferred as A Deputy for of the compounds according to the invention.

Some other preferred compounds according to the invention are compounds of formula (I), where A represents A 5-membered heterocycle, substituted in the ortho-position. Such compounds can also be defined As representing the α-substituted 5-membered heterocycle.

Other predpochtite the further compounds of the formula (I) according to the invention are compounds, in which X, which may be the same or different, represents a halogen atom; C1-C8-alkyl, C1-C6-halogenated containing up to 5 halogen atoms which can be the same or different; C1-C8-alkoxy, C1-C6-halogenoalkane containing up to 5 halogen atoms which can be the same or different.

Other preferred compounds of formula (I) according to the invention are compounds where Y is trifluoromethyl.

Other preferred compounds of formula (I) according to the invention are compounds where n is 1.

The above preferred substituents for the compounds according to the invention can be combined in various ways. These combinations of preferred features, therefore, are subclasses of compounds according to the invention. Examples of such preferred subclasses of compounds according to the invention can combine:

preferred characteristics of A with preferred features Z3;

preferred characteristics of A with preferred features of Y;

preferred characteristics of A with preferred features of X;

preferred characteristics of A with preferred features n;

preferred characteristics of A with preferred features Z3and Y;

Pres is respectful signs of A with preferred features Z 3and X;

preferred characteristics of A with preferred features Z3and n;

preferred characteristics of A with preferred features Z3, Y and X;

preferred characteristics of A with preferred features Z3, Y and n;

preferred characteristics of A with preferred features Z3, X and n;

preferred characteristics of A with preferred features Z3, Y, X and n;

preferred characteristics Z3preferred indication Y;

preferred characteristics Z3with preferred features of X;

preferred characteristics Z3with the preferred characteristics n;

preferred characteristics Z3preferred traits X and Y;

preferred characteristics Z3preferred indication Y and n;

preferred characteristics Z3with preferred features of X and n;

preferred characteristics Z3with preferred features of Y, X and n;

- preferred indication Y with preferred features of X;

- preferred indication Y with preferred features n;

- preferred indication Y with preferred features of X and n.

In these combinations of preferred features of the substituents for the compounds according to the invention these preferred characteristics can also be selected is among the more preferred features of each of the Z 3and A to obtain the most preferred subclasses of compounds according to the invention.

The present invention also relates to a method for producing compounds of formula (I).

Therefore, in accordance with the following aspect of the invention presents a method P1 to obtain the compounds of formula (I) and illustrated in accordance with the following reaction scheme:

Method P1

where A, Z1, Z2, Z3, X, n and Y are defined herein;

W represents a halogen atom or hydroxyl.

How P1 can be carried out in the presence of an acid binder and in the presence of a solvent.

Amine derivatives of the formula (II) are known or can be obtained by known methods, for example as described in WO-01/11966, pages 20, 21 and 23.

Carboxylic acids, anhydrides, bromohydrin or foramerica formula (III) are known or can be obtained by known methods (WO-93/11117, p.16-20; Nucleosides &Nucleotides, 1987, p.737-759; Bioorg. Med. Chem. Lett., 2002, p. 2105-2108).

Suitable acid binders for implementing the method P1 according to the invention can be inorganic and organic bases which are conventional for such reactions. Preference is given to using hydroxides of alkaline-earth metals or alkali metals, such as sodium hydroxide, guide the calcium oxide, the potassium hydroxide, or other derivatives of ammonium hydroxide; carbonates of alkali metals such as sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate; acetates of alkali metals or alkaline-earth metals such as sodium acetate, potassium acetate, calcium acetate; and also tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, pyridine, N-methylpiperidine, N,N-dimethylaminopyridine, diazabicyclo (DABCO), diazabicyclo (DBN) or databaseconnect (DBU).

You can also work without additional acid binder.

Suitable solvents for implementing the method P1 according to the invention may be conventional inert organic solvents. Preference is given to using optionally halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; NITRILES, such as acetonitrile, propionitrile, n - or image is tyranical or benzonitrile; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformamide, N is an organic or triamide hexamethylphosphoric acid; esters such as methyl acetate or ethyl acetate, sulfoxidov, such as dimethylsulfoxide, or sulfones, such as sulfolane.

In the process P1 according to the invention the reaction temperature can vary within a wide range. Typically, these methods are carried out at temperatures from 0°C to 160°C, preferably from 10°C to 120°C. the temperature Control for the methods according to the invention is carried out using microwave technology.

Method P1 according to the invention is usually carried out at atmospheric pressure. It is also possible to work at elevated or reduced pressure.

In the process P1 according to the invention, the amine derivative of formula (II) can be used in the form of cleaners containing hydrochloride salt.

In the process P1 according to the invention can be used is 1 mol or an excess of amine derivative of the formula (II), or from 1 to 3 mol of acid binder per mole of acid derivatives (III).

You can also use the components of the reaction at different ratios. The study conducted by known methods.

Typically, the reaction mixture was concentrated under reduced pressure. The residue that remains can be separated by known method is mi, such as chromatography or recrystallization, from any impurities that may be present.

The compounds of formula (I) according to the invention can be obtained in accordance with the ways described here. However, it will be clear that on the basis of public information and available publications specialist will be able to adapt these methods to the characteristics of each of these compounds, which are necessary to synthesize.

In another aspect, the present invention also relates to fungicidal compositions containing an effective and non fitotoksicheskie the number of active compound of the formula (I).

The expression "effective and non fitotoksicheskie amount" means an amount of composition according to the invention which is sufficient to control or destroy fungi present or likely to appear on the crops, and which does not entail any visible signs of phytotoxicity for the specified crops. This number can vary within wide limits depending on mushrooms, which have the effect of crop type, climatic conditions and compounds included in the fungicidal composition according to the invention.

This quantity can be defined by systematic testing in Polev the x terms which are in the competence of the specialist in this field.

Thus, in accordance with the invention, presents a fungicidal composition containing as active ingredient an effective amount of the compounds of formula (I)defined herein, and a basis acceptable for use in agriculture, carrier or filler.

In accordance with the invention, the term "Foundation" means the natural or synthetic, organic or inorganic compound, with which the active compound of the formula (I) combine or link for ease of application, in particular, parts of the plant. Therefore, this framework is basically inert and should be acceptable for use in agriculture. The core can be solid or liquid. Examples of suitable bases include clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, water, alcohols, in particular butanol, organic solvents, mineral and vegetable oils and their derivatives. It is also possible to use mixtures of such bases.

The composition according to the invention may also contain additional components. In particular, the composition may further contain a surfactant. Surfactant can be an emulsifier, disperging is their agent or wetting agent of ionic or nonionic type, or a mixture of such surfactants. For example, can be mentioned salts of polyacrylic acids, salts of lignosulphonic acids, salts phenolsulfonate or naphtalenesulfonic acid, polycondensate of ethylene oxide with fatty alcohols or fatty amines, substituted phenols (in particular ALKYLPHENOLS or kilfenora), salts of esters sulfonterol acid derivative taurine (in particular alliterate), phosphoric esters polyoxyethylene alcohols or phenols, esters of fatty acids and of polyols, and derivatives of the presented compounds containing sulphate, sulphonate and phosphate functional groups. The presence of at least one surfactant is typically required when the active compound and/or an inert base is not soluble in water and when the vector agent for the application is water. Preferably, the content included surfactants may range from 5% to 40% by weight of the composition.

Optionally also may include additional components, for example protective colloids, adhesives, thickeners, thixotropic substances, substances that promote infiltration, stabilizers, compounds that bind metal ion in the chelate complex. More generally, the active compounds can be combined with louboutinas or liquid additive with conventional methods of obtaining compositions.

Basically, the composition according to the invention may contain from 0.05 to 99% by weight of active compound, preferably 10-70% by mass.

The composition of the invention can be used in various forms, such as aerosol dispenser, capsule suspension, cold atomized concentrate, fine powder, emulsifiable concentrate, emulsion oil in water, emulsion water in oil, encapsulated granule, fine granule, flowable concentrate for seed treatment, gas (under pressure), a substance emitting gas, pellet, hot atomized concentrate, microgranule, microgranule, dispersible in oil powder, mixed with oil flowable concentrate, mix with oil fluid, pasta, vegetable rodlet, powder for dry seed treatment, seeds, covered with pesticides, soluble concentrate, soluble powder, solution for seed treatment, suspension concentrate (flowable concentrate), liquid ultra-low volume (ULV)suspension of ultra-low volume (ULV), dispersible in water granules or tablets, dispersible powder in water for processing liquid clay, water-soluble granules or tablets, water soluble powder for seed treatment and wettable powder.

These compositions include not only the songs that are ready for application to a plant or seeds subjected to processing is by means of a suitable device, such as spray or spray device, and concentrated commercial compositions, which are subject to dilution before application per crop.

Compounds according to the invention can also be mixed with one or more insecticidal, fungicidal, bactericidal substances, attractant, acaricide or feromonami active substance or other compounds with biological activity. Thus obtained mixture have an expanded spectrum of activity.

Mix with other fungicidal compounds are particularly preferred. Examples of suitable pairs of mixed fungicides can be selected from the following lists:

B1) a compound capable to inhibit the synthesis of nucleic acids, like benalaxyl, benalaxyl-M, bupirimate, kiralakele, closelly, dimethirimol, ethirimol, paralexia, hymexazole, metalaxyl-M, furusa, oxadixyl, oksolinovoj acids;

B2) a compound capable to inhibit the mitosis and cell division like benomyl, carbendazim, tietopankki, fuberidazole, pencycuron, thiabendazole-methyl, zoxamide;

B3) a compound capable to inhibit the respiration for example,

as CI-inhibitor breathing like diplomatarium;

as CII-inhibitor breathing like boscalid, Carbo is sin, fanforum, flutolanil, parameter, mepronil, oxycarboxin, pantoporate, Leflunomide;

as CIII-inhibitor breathing like AZOXYSTROBIN, cyazofamid, dimoxystrobin, electroline, famoxadone, fenamidone, fluoxastrobin, kresoxim-methyl, mecamylamine, orysastrobin, pyraclostrobin, picoxystrobin, Trifloxystrobin;

B4) a compound capable of acting as a release agent, such as dinocap, fluazinam;

B5) a compound capable to inhibit ATP production, such as fentiazac, findingaid, silthiofam;

B6) a compound capable to inhibit AA and protein biosynthesis like anteprima, blasticidin-S, cyprodinil, hydrate chloride kasugamycin, mepanipyrim, Pyrimethanil;

B7) a compound capable to inhibit the signal transmission, like fenpiclonil, fludioxonil, jenoxifen;

B8) a compound capable to inhibit the synthesis of lipids and membranes, like chlozolinate, iprodione, procymidone, vinclozolin, pyrazophos, edifenphos, iprobenfos (IBP), isoprothiolane, tolclofos-methyl, biphenyl, yogacara, propamocarb, propamocarb-hydrochloride;

B9) a compound capable to inhibit the biosynthesis of ergosterol, such as fenhexamid, azaconazole, bitertanol, bromuconazole, tsyprokonazolu, diclobutrazol, difenoconazole, diniconazole, diniconazole-M, epoxiconazole, e is econazole, fenbuconazole, Fluconazol, flusilazol, flutriafol, vorconizole, vorconizole-CIS, hexaconazole, kabekona, ipconazole, metconazole, myclobutanil, paclobutrazol, penconazole, propiconazole, prothioconazole, simionato, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, uniconazole, voriconazole, imazalil, maslishat, Expocentr, fenarimol, flurried, nuarimol, pirivenas, triforine, peyratout, prochloraz, triflumizole, viceconsul, Aldemar, dodemont, dudemanpeace, fenpropimorph, tridemorph, fenpropidin, spiroxamine, naftifine, perimutter, terbinafine;

B10) a compound capable to inhibit cell wall synthesis like benthiavalicarb, bialaphos, dimethomorph, plumeria, iprovalicarb, polyoxins, polycoria, validamycin A;

B11) a compound capable to inhibit the biosynthesis of melanin, like cropropamide, dechlorinate, Theoxenia, phthalide, piroximone, tricyclazole;

B12) a compound capable of inducing protection of the host body, such as acibenzolar-S-methyl, provenzal, tudinal;

B13) a compound which has a multiple action, such as captafol, Captan, CHLOROTHALONIL, preparations of copper such as copper hydroxide, copper naphthenate, copper oxychloride, copper sulphate, copper oxide, a mixture of oxin-copper and Bordeaux liquid, dichlofluanid, dithianon, dodine, its the same basis Dodin, ferbam, fluorophore, folpet, guazatine, guazatine acetate, iminoctadine, iminoctadine aveilut, iminoctadine triacetate, marcopper (mancopper), MANCOZEB, MANEB, metiram, metiram zinc, propineb, sulfur and sulfur drugs, including calcium polysulfide, thiram, tolylfluanid, zineb, Zir;

B14) a compound selected from the following list: Librada, bentazon, beloxepin, capsaicin, carvon, chinomethionat, chlorpicrin, kurane, cyflufenamid, having cymoxanil, dazomet, dibakar, declomycin, dichlorophen, dicloran, difenzoquat, dibenzosuberone, diphenylamine, ethaboxam, verison, flamethower, glucolipid, fosetyl-aluminum, fosetyl-calcium, fosetyl-sodium, fluopicolide, perimed, hexachlorobenzene, 8-hydroxyquinoline solution sulfate, arunamarin, metasurfaces, metrafenone, methylisothiocyanate, millionizer, natamycin, Nickel dimethyldithiocarbamate, nitrates-isopropyl, Actelion, oxamate, oxidation, pentachlorophenol and salts, 2-phenylphenol and salt, phosphoric acid and its salts, Oberlin, propanoic-sodium, probenecid, pyrrolnitrin, hintzen, telital, tecnazene, triazoxide, trihemic, Suriname and 2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methyl-benzosulfimide, 2-amino-4-methyl-N-phenyl-5-thiazolecarboxamide, 2-chloro-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-3-pyridinecarboxamide, 3-[5-(4-chlorophenyl)-2,3-demetrisom solidin-3-yl]pyridine, CIS-1-(4-chlorophenyl)-2-(1H-1,2,4-triazole-1-yl)-cycloheptanol, methyl 1-(2,3-dihydro-2,2-dimethyl-1H-inden-1-yl)-1H-imidazole-5-carboxylate, 3,4,5-trichloro-2,6-pyridinedicarboxylic, methyl 2-[[[cyclopropyl[(4-methoxyphenyl)imino]methyl]thio]methyl]-alpha-(methoxymethyl)benzoylacetate, 4-chloro-alpha-propenyloxy-N-[2-[3-methoxy-4-(2-propenyloxy)phenyl]ethyl]benzoylacetone, (2S)-N-[2-[4-[[3-(4-chlorophenyl)-2-PROPYNYL]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulphonyl)amino]butanamide, 5-chloro-7-(4-methylpiperidin-1-yl)-6-(2,4,6-tryptophanyl)[1,2,4]triazole[1,5-a]pyrimidine, 5-chloro-6-(2,4,6-tryptophanyl)-N-[(1R)-1,2,2-trimethylpropyl][1,2,4]triazole[1,5-a]pyrimidine-7-amine, 5-chloro-N-[(1R)-1,2-dimethylpropyl]-6-(2,4,6-tryptophanyl)[1,2,4]triazole[1,5-a]pyrimidine-7-amine, N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2,4-dichloronicotinic, N-(5-bromo-3-chloropyridin-2-yl)methyl-2,4-dichloronicotinic, 2-butoxy-6-iodine-3-propylbenzene-4-one, N-{(Z)-[(cyclopropylmethoxy)imino][6-(deformedarse)-2,3-differenl]methyl}-2-phenylacetamide, N-(3-ethyl-3,5,5-trimethylcyclohexyl)-3-formylamino-2-hydroxybenzamide, 2-[[[[1-[3(1-fluoro-2-phenylethyl)oxy]phenyl]ethylidene]amino]oxy]methyl]-alpha-(methoxyimino)-N-methyl-Alfie-benzoylacetone, N-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-2-(trifluoromethyl)benzamide, N-(3',4'-dichloro-5-forbiden-2-yl)-3-(deformity)-1-methyl-1H-pyrazole-4-carboxamide, 2-(2-{[6-(3-chloro-2-methylphenoxy)-5-ftorpirimidinu-4-yl]oxy}phenyl)-2-(methoxyimino)-N-methylacetamide, 1-[4-methoxyphenoxy)methyl]-2,2-dimethylpropyl-1H-imidazole-1-carboxylic acid, O-[1-[(4-methoxyphenoxy)methyl]-2,2-dimethylpropyl]-1H-imidazol-1-carbothioate.

Particularly preferred may also be a composition according to the invention containing a mixture of compounds of formula (I) with a bactericidal compound. Examples of suitable pairs of bactericidal compounds for the mixture can be selected from the following list: bronopol, dichlorophen, nitrapyrin, Nickel dimethyldithiocarbamate, kasugamycin, Actelion, francebuy acid, oxytetracycline, provenzal, streptomycin, telital, copper sulphate and other drugs of copper.

The compound of formula (I) and fungicidal composition according to the invention can be used for the treatment or prevention of control of phytopathogenic fungi of plants or crops. Thus, in accordance with an additional aspect of the invention presents a method of treatment or preventive control of phytopathogenic fungi of plants or crops, characterized in that the compound of formula (I) or fungicidal composition according to the invention is applied on the seed, the plant or the fruit of plants or to the soil in which it grows, the plant or in which it has to grow.

The method of treatment according to the invention can also be used for the treatment of seed, such as tubers or rhizomes, and seeds, seedlings or transplants RA the gardens and plants or transplanted plants. This treatment can also be used for processing roots. The method of treatment according to the invention can also be used for processing ground parts of the plant, such as stems, stalks or stalks, leaves, flowers and fruits of the considered plants.

Among the plants that can be protected by the method according to the invention, mention can be made of cotton; flax; vine; fruit or vegetable crops such asRosaceae sp. (for example, one-seeded fruit, such as apples and pears, but also stone fruits such as apricots, almonds and peaches),Ribesioidae sp.,Juglandaceae sp.,A sp.,Anacardiaceae sp.,Fagaceae sp.,Moraceae sp.,Oleaceae sp.,Actinidaceae sp.,Lauraceae sp.,Musaceae sp. (for example, banana trees and bananas vegetable),Rubiaceae sp.,Theaceaesp.,Sterculiceae sp.,Rutaceae sp. (for example, lemons, oranges and grapefruit);Solanaceae sp.(for example, tomatoes),Liliaceae sp.,Asteraceae sp. (e.g., lettuce),Umbelliferae sp.,Cruciferaesp.,Chenopodiaceae sp.,Cucurbitaceae sp.,Papilionaceae sp. (for example, peas),Rosaceae sp. (for example, strawberries); major crops such asGraminae sp. (for example, corn, grass or cereals, such as wheat, rice, barley and triticale),Asteraceae sp. (for example sunflower),Cruciferae sp. (for example, rape),Fabacae sp. (e.g., peanuts),Papilionaceae sp. (EmOC is emer, soya),Solanaceae sp. (for example, potatoes),Chenopodiaceae sp. (for example, beetroots); horticultural and forest crops; as well as genetically modified homologues of these crops.

Among the diseases of plants or crops that can be controlled using the method according to the invention can be specified:

diseases powdery mildew, such as:

powdery mildew, caused by, for example,Blumeria graminis;

powdery mildew of Apple caused by, for example,Podosphaeraleucotricha;

diseases powdery mildew by sperately caused by, for example,Sphaerotheca fuliginea;

disease marsupial fungus Uncinula caused by, for example,Uncinula necator;

disease rust, such as:

disease gymnosporangium caused by, for example,Gymnosporangium sabinae;

disease hemileia caused by, for example,Hemileiavastatrix;

disease phakopsora caused by, for example,PhakopsorapachyrhiziorPhakopsorameibomiae;

disease Puccinia caused by, for example,Pucciniarecondita;

diseases of mushrooms uromyces caused by, for example,Uromycesappendiculatus;

diseases of the oomycetes, such as:

disease bremia caused by, for example,Bremialactucae;

disease peronosporales caused by, for example,Peronospora. pisiorP.brassicae;

the disease late blight, caused by, n the example, Phytophthorainfestans;

disease plasmopara caused by, for example,Plasmoparaviticola;

disease pseudoperonospora caused by, for example,Pseudoperonospora humuliorPseudoperonospora cubensis;

disease Pythium caused by, for example,Pythium ultimum;

diseases leaf spot, such as:

disease early blight, caused by, for example,Alternariasolani;

disease Cercospora caused by, for example,Cercosporabeticola;

disease Cladosporium caused by, for example,Cladiosporium cucumerinum;

disease cochliobolus caused by, for example,Cochliobolus sativus;

diseases of mushrooms by Colletotrichum caused by, for example,Colletotrichum lindemuthanium;

diseases of mushrooms Cycloconium caused by, for example,Cycloconium oleaginum;

diseases of mushrooms diaporthe caused by, for example,Diaporthe citri;

disease fungi of the genus elsinoe caused by, for example,Elsinoe fawcettii;

disease fungi of the genus of gleosporium caused by, for example,Gloeosporium laeticolor;

disease fungi of the genus of Glomerella caused by, for example,Glomerella cingulata;

diseases of mushrooms Guignardia caused by, for example,Guignardia bidwelli;

diseases of mushrooms leptosphaeria caused by, for example,Leptosphaeria maculans;Leptosphaeria nodorum;

diseases of mushrooms, magnaporthe caused by, for example,Magnaporthe grisea;

dis is evania fungi of the genus of Mycosphaerella, caused by, for example,Mycosphaerella graminicola;Mycosphaerella arachidicola;Mycosphaerella fijiensis;

diseases of mushrooms Phaeosphaeria caused by, for example,Phaeosphaeria nodorum;

disease fungi of the genus of Pyrenophora caused by, for example,Pyrenophora teres;

disease regularizes blotch, caused by, for example,Ramularia collo-cygni;

disease ringopening blotch, caused by, for example,Rhynchosporium secalis;

diseases of mushrooms Septoria caused by, for example,SeptoriaapiiorSeptorialycopercisi;

disease fungi of the genus Tipula caused by, for example,Typhula incarnata;

disease fungi of the genus Venturia caused by, for example,Venturia inaequalis;

diseases of roots and stems, such as:

disease fungi of the genus Corticium caused by, for example,Corticium frost;

disease Fusarium caused by, for example,Fusariumoxysporum;

disease ophiobolus caused by, for example,Gaeumannomyces graminis;

disease Rhizoctonia caused by, for example,Rhizoctoniasolani;

disease fungi of the genus Tapesia caused by, for example,Tapesia acuformis;

disease fungi of the genus Thielaviopsis caused by, for example,Thielaviopsis basicola;

diseases of the ears and spikelets, such as:

disease early blight, caused by, for example,Alternariaspp.;

disease aspergillosis vyzyvae is s, for example,Aspergillusflavus;

diseases scab, caused by, for example,Cladosporium spp.;

disease LPV caused by, for example,Clavicepspurpurea;

disease Fusarium caused by, for example,Fusariumculmorum;

disease fungi of the genus of Gibberella caused by, for example,Gibberella zeae;

disease fungi of the genus Monographella caused by, for example,Monographella nivalis;

the disease is common, such as:

disease fungi of the genus Sphacelotheca caused by, for example,Sphacelotheca reiliana;

disease fungi of the genus Tilletia, caused by, for example,Tilletia caries;

disease fungi of the genus Urocystis caused by, for example,Urocystis occulta;

disease fungi of the genus, Ustilago caused by, for example,Ustilago nuda;

diseases of fruit rot and mould, such as:

disease aspergillosis, caused by, for example,Aspergillusflavus;

disease fungi of the genus Botrytis cinerea caused by, for example,Botrytis cinerea;

diseases produced by fungi of the genus Penicill caused by, for example,Penicillium expansum;

disease Sclerotinia caused by, for example,Sclerotinia sclerotiorum;

disease fungi of the genus Verticillium caused by, for example,Verticilium alboatrum;

diseases seed and soil rot, mould, wilt, rot and disease black leg:

diseases of fusaria the Ohm, caused by, for example,Fusariumculmorum;

the disease late blight, caused by, for example,Phytophthoracactorum;

disease Pythium caused by, for example,Pythium ultimum;

disease Rhizoctonia caused by, for example,Rhizoctoniasolani;

disease sclerotium caused by, for example,Sclerotiumrolfsii;

disease fungi of the genus Microdochium caused by, for example,Microdochium nivale;

disease necrosis of fruit trees, "witch's broom" and death, such as:

disease nectria caused by, for example,Agentgalligena;

diseases of plants characterized by zalaganjem, rotting or cessation of growth, such as:

disease fungi of the genus Monilinia caused by, for example,Monilinia laxa;

disease puzyrchatogo leaves and crinkle leaves, such as:

disease fungi of the genus Taphrina caused by, for example,Taphrina deformans;

withering forest plants, for example:

Eska caused by, for example,Phaemoniella clamydospora;

diseases of flowers and seeds such as:

disease partrition caused by, for example,Botrytiscinerea;

diseases of the shafts, such as:

disease Rhizoctonia caused by, for example,Rhizoctoniasolani.

The fungicidal composition according to the invention can also be used against fungal diseases, the spread is nausica on logs or inside of it. The term "timber" means all types of wood and all types of processing of this wood used for construction, such as solid wood, high density, laminated wood, and plywood. The method of processing wood according to the invention mainly consists in contacting one or more compounds according to the invention or the composition according to the invention that includes, for example, direct application, spraying, soaking, introduction, or any other suitable method.

The dose commonly used in the method of treatment according to the invention, typically and preferably ranges from 10 to 800 g/ha, preferably from 50 to 300 g/ha when applied to the leaves are processed. The dose used active substances, typically and preferably ranges from 2 to 200 g per 100 kg of seed, preferably from 3 to 150 g per 100 kg of seed in the case of seed treatment.

Of course, these doses are given as illustrative examples of the method according to the invention. The person skilled in the art will know how to modify the applied dose, in particular, in accordance with the nature of the cultivated plants or agricultural crops.

The fungicidal composition according to the invention can be used for handling genetically modified organisms connection what changes according to the invention or agrochemicals according to the invention. Genetically modified plants are plants, the genome of which is stably integrated heterologous gene that encodes a protein of interest. The expression "heterologous gene that encodes a protein of interest" essentially means the genes that give a transformed plant with new agronomic properties or genes to improve the agronomic quality of the modified plant.

The composition of the invention can also be used to obtain a composition suitable for treatment or prevention of fungal diseases in humans or animals, such as, for example, fungal infections, dermatitis, trichophytosis and candidiasis, or diseases caused byAspergillus spp., for example,Aspergillus fumigatus.

Various aspects of this invention are illustrated by reference to the following connection table and examples. The following tables illustrate, without limiting, examples of compounds according to the invention.

In the following examples, M+1 (or M-1) mean peak molecular ions, plus or minus 1 Amu (atomic mass unit) respectively, as measured by mass spectroscopy and M (ApcI+) means the peak of the molecular ion found by positive chemical ionization at atmospheric pressure mass spectroscopy.

In the following examples, the logP values were determined in accordance with EEC Directive 79/31 Annex V.A8 by HPLC (high performance liquid chromatography) on a column with reversed phase (C 18), using the way described below.

Temperature: 40°C; mobile phase: 0.1% aqueous formic acid and acetonitrile; linear gradient from 10% acetonitrile to 90% acetonitrile.

The calibration is carried out using unbranched Alkan-2-ones (containing from 3 to 16 carbon atoms) with known logP values (determination of the logP values by the retention times using linear interpolation between the two alkenone, following one after the other).

The values of lambda max was determined at the point of maximum of the chromatographic signals using UV spectra from 190 nm to 400 nm.

The following examples illustrate, without limitation, the receipt and effectiveness of the compounds of formula (I) according to the invention.

Example: N-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (compound 45)

A solution of 2.7 g (10,7 mmol) N-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}cyclopropylamine, 1.9 grams (to 10.7 mmol) 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonylchloride and 3.0 ml (21.5 mmol) of t is ethylamine in THF (60 ml) was stirred at room temperature for 1 hour.

The solvent is removed under reduced pressure. The residue is partitioned between aqueous hydrochloric acid and ethyl acetate. The organic phase is separated, washed with aqueous potassium carbonate, dried over magnesium sulfate and the solvent is evaporated. The resulting viscous oil was dissolved in heptane, and after 2 minutes you roll a solid white color, which is filtered and dried to obtain of 3.45 g of the desired N-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide in the form of a solid white color.

Mass spectrum: [M+1]=391

An example of the effectiveness of A: testin vivoonLeptosphaeria(leaf blotch of wheat)

Solvent: 49 parts by weight of N,N-dimethylformamide

Emulsifier: 1 part by weight alkylsilanes ether polyglycol

To obtain a suitable preparation of active compound, 1 part by weight of active compound is mixed with specified amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

Young plants are sprayed with a preparation of active compound at a certain speed application. After drying, the plants are sprayed with a spore suspensionLeptosphaeria nodorum. Plants left for 48 hours in an incubation chamber at 20°C and a relative atmospheric humidity of 100%. The Rast is s placed in a greenhouse at a temperature of approximately 22°C and a relative atmospheric humidity of approximately 100%.

The results of the tests evaluate 12-14 days after infection. In these circumstances, there has been good (at least 70% of disease control) and complete protection (100% of disease control) at a dose of 500 ppm (h/million) with the following compounds: 45 and 50 in accordance with the invention, whereas poor protection (less than 30% of disease control) and the lack of protection was observed at a dose of 500 hours/million with the compounds of examples 2, 8 and 50, disclosed in patent application WO-01/11966. Examples 2, 8 and 50, described in patent application WO-01/11966, correspond to the following compounds:

N-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}thiophene-2-carboxamide

N-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide

2-bromo-N-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide, respectively

These results show that the compounds according to the invention have a much greater biological activity than the structurally closest compounds described in WO-01/11966.

An example of the effectiveness of B: testin vivoonErysiphegramini(powdery mildew of barley)

Solvent: 49 parts by weight of N,N-dimethylformamide

Emulsifier: 1 part by weight alkylsilanes ether polyglycol

To obtain a suitable preparation of active compound, 1 part by weight of actinopodidae mixed with specified amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

To test for protective activity, young plants are sprayed with a preparation of active compound at a certain speed application. After drying the plants they pollinate sporesErysiphe graminis f.sp. hordei. Plants are placed in a greenhouse at a temperature of approximately 18°C and a relative atmospheric humidity of approximately 70% to facilitate the development of spore masses mildew.

The test results are assessed in 7 days after infection. In these circumstances, there has been good (at least 70% of disease control) and complete protection (100% of disease control) at a dose of 500 hours/million with the following compounds: 45 and 50 according to the invention, whereas poor protection (less than 30% of disease control) and the lack of protection was observed at a dose of 500 hours/million with the compounds of examples 2, 8 and 50, disclosed in patent application WO-01/11966.

This again confirms that the compounds according to the invention have a much better biological activity than the structurally closest compounds disclosed in WO-01/11966.

An example of the effectiveness of C: testin vivoon Pyrenophorateres(net blotch of barley)

Solvent:10% by volume of acetone
5% by volume of dimethyl sulfoxide
85% by volume of water
EmulsifierTween 80: 0,5 µl per mg of the active ingredient

Test the active ingredient is mixed with an appropriate amount of solvent and emulsifier to obtain the desired concentration of the active substance.

Barley plants (varieties Express or Plaisant) in starter cups, sown on a 50/50 peat soil-substrate volcanic tuff and grown at 12°C, treated in stage 1 sheet (10 cm) by spraying the above-described liquid suspension. Plants used as control, treated with an aqueous solution not containing the active substance.

After 24 hours infect plants by spraying them water suspension of sporesPyrenophora teres(12000 spores per ml). Spores collected from a 12-day culture. The infected barley plants are incubated for 24 hours at about 20°C and 100% relative humidity, and then for 12 days at a relative humidity of 80%.

Sorting spend 12 days after infection, compared with the control plants. In these circumstances, there has been good (at least 70%) and full protection at a dose of 500 hours/million with the following compounds: 5, 6,7, 12, 15, 16, 27, 30, 35, 37, 42, 45, 46, 47, 50 and 55.

An example of the effectiveness of D: testin vivoonPucciniarecondita f. Sp. tritici(brown rust of wheat)

Solvent:10% by volume of acetone
5% by volume of dimethyl sulfoxide
85% by volume of water
EmulsifierTween 80: 0,5 µl per mg of the active ingredient

Test the active ingredient is mixed with an appropriate amount of solvent and emulsifier to obtain the desired concentration of the active substance.

Wheat plants (variety Scipion) in starter cups, sown on a 50/50 peat soil-substrate volcanic tuff and grown at 12°C, treated in stage 1 sheet (10 cm) by spraying the above-described liquid suspension. Plants used as control, treated with an aqueous solution not containing the active substance.

After 24 hours the plants infect, splashing on them aqueous suspension of sporesPuccinia recondita f. sp. tritici(of 100,000 spores per ml). Spores are harvested from 10-day culture at the plant. Infected wheat plants incubated for 48 hours about n and 20°C and 100% relative humidity, and then within 10 days at a relative humidity of 80%.

Sorting spend 10 days after infection, compared with the control plants. In these circumstances, there has been good (at least 60%) and full protection at a dose of 500 hours/million with the following compounds: 5, 26, 45 and 50.

An example of the effectiveness of E : testin vivoonAlternariabrassicae(leaf spot of crucifers)

Solvent:10% by volume of acetone
5% by volume of dimethyl sulfoxide
85% by volume of water
EmulsifierTween 80: 0,5 µl per mg of the active ingredient

Test the active ingredient is mixed with an appropriate amount of solvent and emulsifier to obtain the desired concentration of the active substance.

Plant radish (sort Pernot) in starter cups, sown on a 50/50 peat soil-substrate volcanic tuff and grown at 18-20°C, treated at the stage of cotyledon spraying with an aqueous suspension described above.

Plants used as control, treated with an aqueous solution not containing active substances is STV.

After 24 hours infect plants by spraying them water suspension of sporesAlternaria brassicae(40000 dispute on cm3). Spores collected from (12-13)-day culture. Infected plants of radish incubated for 6-7 days at about 18°C, at atmospheric humidity.

Sorting was performed on the 6-7th day after infection, compared with the control plants. In these circumstances, there has been good (at least 70%) and full protection at a dose of 500 hours/million with the following compounds: 6, 7, 12, 16, 23, 27, 30, 35, 42, 46, 50 and 56.

1. The compound of formula (I) or its salt

where a represents a substituted or unsubstituted 5-membered heterocyclyl group associated with the carbonyl through a carbon atom;
Z1and Z2that may be the same or different, represent a hydrogen atom; C1-C5-alkyl; C5-alkoxycarbonyl;
Z3is substituted or unsubstituted With3-C7-cycloalkyl;
Y represents C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
X, which may be the same or different, represents a halogen atom
n=0, 1, 2 or 3;
and also their salts.

2. The compound according to claim 1, in which Z3is unsubstituted.

3. The compound according to claim 2, in which Z3is cyclopropyl

4. The compound according to claims 1 to 3, in which a is selected from the list consisting of:
heterocycle of formula (A1)

where R1-R3that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A2)

where R4-R6that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A3)

where R7represents a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms,
which may be the same or different;
R8represents a hydrogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or With1-C5-alkyl;
heterocycle of formula (A4)

where R9-R11that may be the same or different, represent a hydrogen atom; a halogen atom is; With1-C5-alkyl; amino; C1-C5-alkoxy; C1-C5-alkylthio or1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A5)

where R12and R13that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl; C1-C5-alkoxy; amino or1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
R14represents a hydrogen atom; a halogen atom; C1-C5-alkyl; amino or1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A6)

where R15represents a hydrogen atom; halogen atom; cyano; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
R16and R18that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkoxycarbonyl; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which, which may be the same or different;
R17represents a hydrogen atom or a C1-C5-alkyl; C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different or a phenyl substituted by a halogen atom or C1-C5-alkyl;
heterocycle of formula (A7)

where R19represents a hydrogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or With1-C5-alkyl;
R20-R22that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A8)

where R23represents a hydrogen atom; a halogen atom; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
R24represents a hydrogen atom or a C1-C5-alkyl;
heterocycle of formula (A9)

where R25represents a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
R26represents a hydrogen atom or a C1-C5-alkyl;
heterocycle of formula (A10)

where R27represents a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
R28represents a hydrogen atom; a halogen atom; amino; C1-C5-alkyl; C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different or a phenyl substituted by a halogen atom or With1-C5-alkyl;
heterocycle of formula (A11)

where R29represents a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
R30represents a hydrogen atom; a halogen atom; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; amino; C1-C5-alkylamino; di-C1-C5-alkylamino;
heterocycle of formula (A12)

where R31represents a hydrogen atom; a halogen atom; C1-C5-alkyl or phenyl, Samedan is th a halogen atom or With 1-C5-alkyl;
R32represents a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
R33represents a hydrogen atom; halogen atom; nitro or1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A13)

where R34represents a hydrogen atom; a halogen atom; C1-C5-alkyl; C3-C5-cycloalkyl; C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; C1-C5-alkoxy; C2-C5-alkyloxy; C1-C5-halogenoalkane containing up to 5 halogen atoms which can be the same or different or a phenyl substituted by a halogen atom or With1-C5-alkyl;
R35represents a hydrogen atom; a halogen atom; C1-C5-alkyl; cyano; C1-C5-alkoxy, C1-C5-alkylthio; C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; C1-C5-halogenoalkane containing up to 5 halogen atoms which can be the same or different; amino; C1-C5-alkylamino or di(C1-C5-alkyl);
R36represents a hydrogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or C1-C5-alkyl;
heterocycle of formula (A14)

where R37and R38that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl, C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different; C1-C5-alkoxy or C1-C5-alkylthio;
R39represents a hydrogen atom; C1-C5-alkyl or phenyl, substituted by halogen atom or With1-C5-alkyl;
heterocycle of formula (A15)

where R40and R41that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A16)

where R42and R43that may be the same or different, represent a hydrogen atom; C1-C5-alkyl; C1-C5-halogenated containing up to 5 atoms Gal is gene which may be the same or different; amino or phenyl substituted by a halogen atom or With1-C5-alkyl;
heterocycle of formula (A17)

where R44and R45that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A18)

where R46represents a hydrogen atom; C1-C5-alkyl; C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different, or With1-C5-alkylsulfanyl;
R47represents a hydrogen atom; halogen atom or C1-C5-alkyl;
heterocycle of formula (A19)

where R48and R49that may be the same or different, represent a hydrogen atom; a halogen atom; C1-C5-alkyl or C1-C5-halogenated containing up to 5 halogen atoms which can be the same or different;
heterocycle of formula (A20)

where R50represents a halogen atom; C1-C5-alkyl or C1-C5 -halogenated containing up to 5 halogen atoms which can be the same or different.

5. The compound according to claim 4, where a represents a heterocycle of formula (A13), as defined here, or where a represents a 5-membered heterocycle, which is substituted in anthopology.

6. The compound according to claim 1, where n=1.

7. The compound according to claim 1, where Y represents trifluoromethyl.

8. A method of combating phytopathogenic fungi in the infected area or site, prone to infection, which comprises applying to the specified location of the connection according to claims 1-6.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: disclosed compounds can be used as a medicinal agent having CXCR2 inhibiting properties. In formula I , X denotes -CR3=CR4-, -CR5=N-, -N=CR6-, -NR7- or -S-; R3, R4, R5 and R6 independently denote hydrogen, F, CI, Br, I; R7 denotes hydrogen; Y1, Y2, Y3 and Y4 independently denote -CR8- or nitrogen, provided that at least two of Y1, Y2, Y3 and Y4 denote -CR8-; where R8 denotes hydrogen, F, CI, Br, I; A denotes a cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; a bicyclic partially saturated 9-member cycloalkyl; a bicyclic partially saturated 9-10-member heterocycle in which two atoms in the ring are oxygen atoms; phenyl; naphthyl; a 5-6-member heteroaryl in which 1-3 atoms in the ring are oxygen, sulphur and nitrogen atoms; a 9-10-member bicyclic heteroaryl in which 1-3 atoms in the ring are nitrogen, oxygen and sulphur atoms; a 6-member heterocycle in which one atom in the ring is a nitrogen atom and which can be unsubstituted or substituted with alkyl having 1, 2, 3 or 4 carbon atoms, -C(O)CH3, -C(O)CH2CH3, -C(O)cyclopropyl, -C(O)CF3 and -C(O)OC(CH3)3; where phenyl, heterocyclic or heteroaryl radical is substituted with 1, 2 or 3 radicals selected from a group consisting of F, O, Br, I, OH, CN, NO2, SCF3, SF3, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; cycloalkyl having 3, 4, 5 or 6 carbon atoms; alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -NR9R10, C(O)R44, S(O)SR47, -(CH2)k-phenyl, 5-6-member heteroaryl, in which 1-3 atoms in the ring are nitrogen and sulphur atoms; where the phenyl radical may be substituted with F, CI, Br, I; R9 is an alkyl having 1, 2, 3 or 4 carbon atoms; R10 is an alkyl having 1, 2, 3 or 4 carbon atoms; R44 is an alkyl having 1, 2, 3 or 4 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; alkoxy having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms; R47 is an alkyl having 1, 2, 3 or 4 carbon atoms; k equals 0, 1, 2 or 3; s equals 1 or 2; B is -O-C(R11R12), -C≡C-, -CR52=CR53-, -C(R13R14)C(R15R16), -NR17-C(R18R19); R11, R12, R13, R14, R15, R16, R17, R18, R19, R52, R53 independently denote hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; D is C(O)OH, C(O)NHR21 or C(=NR58)NHR22; R21 and R22 independently denote hydrogen, -SO2-alkyl having 1, 2, 3 or 4 carbon atoms, -SO2-phenyl; R58 is OH; R1 and R2 independently denote an alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where the alkyl radicals are unsubstituted or substituted with 1 radical selected from a group consisting of F, Cl, Br, I, phenyl substituted with OH; or R1 and R2, taken together with a carbon atom with which they are bonded form a 3-, 4-, 5- or 6-member carbocycle. The invention also relates to use of formula I compounds in preparing a medicinal agent which has CXCR2 inhibiting properties, to a medicinal agent which containing an effective amount of the disclosed compound and having CXCR2 inhibiting properties, as well as to use of formula II compounds (formula and values of radicals are given in the formula of invention) in preparing a medicinal agent having CXCR2 inhibiting properties.

EFFECT: high effectiveness of application.

10 cl, 384 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel compounds of formula (I), where R1 represents hydroxymethyl; R2 is selected from -C(O)NR4R5; HET-1 represents 5- or 6-member heteroaryl ring, bound by atom C; R3 represents halogeno; R4 and R5 together with nitrogen atom, to which they are bound, can form heterocyclyl ring system, as it is defined for HET-3; HET-3 represents possibly substituted azetidinyl; m equals 1; n equals 0, 1 or 2; or their pharmaceutically acceptable salt, which can be applied as glucokinase (GLK) activators or active ingredient of pharmaceutical compositions, also described are methods of obtaining them.

EFFECT: creation of novel compounds applied as glucokinase (GLK) activators in treatment of diabetes.

13 cl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which possess properties inhibiting HIV replication, of general formula (I) , in form of E-isomer, in which -a1=a2-a3=a4- represents bivalent radical of formula -CH=CH-CH=CH- (a-1); -b1=b2-b3=b4. Represents bivalent radical of formula -CH=CH-CH=CH- (b-1); n equals 0; m equals 2; each of R1 radicals independently on each other stands for hydrogen atom; C1-6alkyl; R2a stands for cyanogroup; X1 stands for -NR1-; R3 represents C2-6alkenyl, substituted with cyanogroup; R4 stands for C1-6alkyl; R5 represents radical of formula -Y-Alk-L, -Alk'-Y-L or -Alk'-Y-Alk-L; each of radicals Alk or Alk' independently represents bivalent C1-6alkyl or C2-6 alkenyl group; L stands for aryl or Het; Y stands for NR1; -CH=N-O-; Het stands for 5- or 6-member fully saturated ring system, in which one, two or three ring elements represent heteroatoms, each of which is independently selected from group, including nitrogen, oxygen and sulphur, and in which other ring elements represent carbon atoms; and, if possible, any nitrogen ring element can be optionally substituted with C1-6alkyl; and ring system can be optionally bound with benzene ring; and in which any carbon atom of ring, including any carbon atom of optionally bound benzene ring, each independently can be substituted with substituent selected from such groups as halogen atom, C1-6alkyl, hydroxyC1-4alkyl, carboxyC1-4alkyl, C1-4 alkylcarbonyloxyC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, aryloxy, morpholinyl, aryl, Het1; Het1 stands for thienyl, isoxazolyl, thiadiazolyl, each of which can be optionally substituted with one or two C1-4alkyl radicals; Q stands for hydrogen atom; each aryl represents phenyl or phenyl, substituted with one, two substituents, each of which is independently selected from such groups as halogen atom, C1-6alkyl, C2-6alkinyl, cyano, polyhalogen C1-6alkyl or Het1, as well as to its pharmaceutically acceptable additive salts Invention also relates to pharmaceutical composition.

EFFECT: creation of novel compounds, which possess properties inhibiting HIV replication

5 cl, 7 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline, represented by formula , where R1 represents (1-6C)alkyl; R2 represents halogen, (1-4C)alcoxy; R3 represents OH, NO2, CN, fluoridated with (1-4C)alkoxy, (1-4C)alkoxy(2-4C)alkoxy. hydroxy(2-4C)alkoxy, (1-4C)alkoxycarbonyl, R7, R8-amino, R9, R10-amino, R9, R10-aminocarbonyl, R9, R10-aminosulfonyl or phenyl(1-4C)alkoxy, where phenyl ring in composition phenyl(1-4C)alkoxy is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R4 represents R11-phenyl or R11-(4-5C)heteroaryl, which represents heteroaromatic group, containing 4-5 carbon atoms and at least one heteroatom, selected from N and S, where phenyl or heteroaryl group is optionally additionally substituted with one or several substituents, selected from nitro, (1-4C)alkyl, (1-4C)alkoxy; R7 represents H, (1-4C)alkyl; R8 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl, (1-4C)alkoxy(1-4C)alkylcarbonyl, furylcarbonyl; phenyl(1-4C)alkylcarbonyl, where phenyl ring is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R9 and R10 are not necessarily selected from H, (1-6C)alkyl and (1-4C)alkoxy(2-4C)alkyl; or R9 and R10 can be bound together with formation of morpholinyl ring; R11 represents H, R12, R13-amino, R14, R15-aminocarbonyl or R14, R15-aminosulfonyl; R12 represents H; R13 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyperazinyl(1-4C)alkylcarbonyl; R14 and R15 are independently selected from H, (1-6C)alkyl, (1-4C)alkoxy(2-4C)alkyl and imidazolyl(1-4C)alkyl; X represents O or R16-N; Y represents CH2 or C(O);Z represents CN; R16 represents H, (1-4C)alkyl, (1-4C)alkylcarbonyl; or their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition, as well as to application of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline derivatives by any of i.i. 1-10.

EFFECT: obtaining novel biologically active compounds, which possess agonistic activity with respect to FSH receptor.

13 cl, 43 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-(2-thiazolyl)amide of 2-(2-oxo-3-indolinylidene)hydrazine-4-oxo-4-phenyl-2-butenoic acid of formula: .

EFFECT: obtaining a compound having antibacterial and analgesic activity.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I): , optical isomers of said compounds, as well as salts thereof having peroxisome proliferator-activated receptor subtype y (PPARy) modulating property. Values of R1, R2, X, Ar1 and Ar2 are given in the formula of invention.

EFFECT: preparation of compositions based on said compounds, as well as use of said compounds in cosmetic and pharmaceutical industry.

11 cl, 30 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I): wherein dashed lines present single or double bonds, and the values of radicals R1, R2, R3, R4 are described in cl. 1 of the patent claim. Besides the invention refers to application and a based pharmaceutical composition for prevention and treatment of neurodegenerative diseases and other diseases wherein cell dystrophy and/or cell loss (apoptosis) caused by free radicals act the main part.

EFFECT: production of new compounds and the based pharmaceutical composition which can find application in medicine for prevention and treatment of neurodegenerative diseases.

6 cl, 3 ex

FIELD: chemistry.

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

, pharmaceutical compositions based on the said compounds, as well as methods of using said compounds in preparing medicinal agents.

EFFECT: obtaining compounds and a composition which can inhibit phosphatase cdc25, particularly phosphatase cdc25-C and can be particularly used for treating cancer.

12 cl, 56 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula I and their pharmaceutically acceptable salts and esters. The disclosed compounds have inhibitory effect on cyclin-dependant kinase. In formula I R1 denotes , R3 is selected from a group consisting of H, CO2R6, C(O)R6, SO2R6 and SO2NR5R6, R5 and R6 are each independently selected from a group which includes H and (lower)alkyl, R2 is phenyl which contains one, two or three substitutes independently selected from a group which includes halogen or -O-(lower)alkyl.

EFFECT: preparation of a pharmaceutical composition which contains an effective amount of a formula I compound as an active ingredient.

6 cl, 1 tbl, 22 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds exhibiting antiproliferative activity of formula (1) where W means N or C-R2; X means -NH-; Y means CH; Z means halogen, -NO2, C2-C3alkynyl-, halogen-C1-C3alkyl- and -C(=O)-C1-C3alkyl, A means a group of formula (i), (ii) or (iii) Q1 means phenyl; B1, B2, B3 and B4 independently mean C-RgRh, N-Ri or O; R1 means hydrogen; R2 means a residue specified from the group including hydrogen, halogen and -OR4; Ra, Rb, Rc, Rd, Re and Rf independently mean hydrogen; Rg and Rh independently mean a residue specified from the group including hydrogen, =O, -OR4 and -NR4C(=O)R5; or mean optionally a residue monosubstituted or twice-substituted with equal or different substitutes and specified from the group including C1-C6alkyl and phenyl, the substitute/substitutes is/are specified from the group including R8/, -OR4, -C(=O)R4, -C(=O)OR4 and -C(=O)NR4R5 where R8/ and other values of radicals are specified in the patent claim, optionally in the form of their pharmacologically noncontaminating acid addition salts. The invention also concerns a pharmaceutical composition.

EFFECT: new compounds have effective biological properties.

8 cl, 6 dwg, 1086 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel compounds of formula (I), where R1 represents hydroxymethyl; R2 is selected from -C(O)NR4R5; HET-1 represents 5- or 6-member heteroaryl ring, bound by atom C; R3 represents halogeno; R4 and R5 together with nitrogen atom, to which they are bound, can form heterocyclyl ring system, as it is defined for HET-3; HET-3 represents possibly substituted azetidinyl; m equals 1; n equals 0, 1 or 2; or their pharmaceutically acceptable salt, which can be applied as glucokinase (GLK) activators or active ingredient of pharmaceutical compositions, also described are methods of obtaining them.

EFFECT: creation of novel compounds applied as glucokinase (GLK) activators in treatment of diabetes.

13 cl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel acylsulfonamide peri-substituted condensed bicyclic compounds of general formula (I), values of radicals are given in invention formula. Also described is pharmaceutical composition based on formula (I) compound.

EFFECT: compounds can be used for inhibition of prostaglandin E2 binding with receptor EP3.

30 cl, 371 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: in embodiments of the invention, specific compounds are used to prepare a medicinal agent for treating, relieving and preventing conditions associated with dysfunction of monoamine transmission. The compounds have general formula (1) , where: R1 and R2 are identical or different and denote hydrogen, alkyl, alkenyl, alkynyl, aryl, thio or alkylthio, or R1 and R2 may have extra substitutes which are selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkyloxy, morpholin-4-ylalkoxy, piperidin-1-ylalkyloxy, alkylamino, dialkylamino, arylamino.

EFFECT: more efficient use of compounds in preparing medicinal agents.

8 cl, 3 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel 5-6-member nitrogen-containing heterocyclic compounds, selected form derivatives of pyridine, pyrimidine, imidasoline, oxadiasoline, such as, for instance , which possess inhibiting activity with respect to aspartylprotease, such as "ВАСЕ-1".

EFFECT: obtaining pharmaceutical composition, method of aspartylprotease inhibition aimed at application of compounds for preparation of medication intended for treatment of state, mediated by aspartylprotease, such as "ВАСЕ-1".

4 cl, 1 tbl, 1832 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives having FAK inhibitory activity of formula (I), where R0 is hydrogen; R1 is a 5- or 6-member heterocycle containing 1 or 2 nitrogen atoms substituted with (C1-C7)alkyl, hydroxyl group, dialkylamino group or a 6-member heterocycle containing one nitrogen atom; R2 is hydrogen; R3 is carbamoyl substituted once or twice with (C1-C7)alkyl; a 5-member heterocycle containing 4 nitrogen atoms; SO2N(R12)R13, where R12 is hydrogen or (lower)alkyl, and R13 is hydrogen, (C1-C7)alkyl, (C1-C7)alkoxy(C1-C7)alkyl, di(C1-C7)alkylamino(C1-C7)alkyl, hydroxy(C1-C7)alkyl, or R12 and R13 together a nitrogen atom with which they are bonded form a 6-member heterocycle containing two nitrogen atoms, where the said heterocycle is not substituted or substituted with (C1-C7)alkyl; R4 is hydrogen; R5 is a halide; R6 is hydrogen; R7 is hydrogen; (C1-C7)alkoxy; carbamoyl which is not substituted or substituted with (lower)alkyl; a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with di(C1-C7)alkylamino, (C1-C7)alkyl, hydroxy, 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms, unsubstituted or substituted with (C1-C7)alkyl; 6-member heterocycle-oxy containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms which is not substituted or substituted with (C1-C7)alkyl; R8 is hydrogen; halide; (C1-C7)alkoxy, carbamoyl unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5-member heterocycle containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with one or two substitutes independently selected from hydroxy, (C1-C7)alkyl, aminocarbonyl and (C1-C7)alkylamino; 6-member heterocycle-oxy, containing 1 nitrogen ring atom, unsubstituted or substituted 1-5 times with (C1-C7)alkyl or di(C1-C7)alkylamino; or R7 and R8 together with atoms with which they are bonded form a 6-member heterocycle containing two nitrogen or oxygen atoms, unsubstituted or substituted once or twice with (C1-C7)alkyl or oxo group; R9 is hydrogen; R10 is (C1-C7)alkoxy, as well as to their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition and synthesis method.

EFFECT: novel compounds have useful biological activity.

4 cl, 167 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry, and specifically to compounds of general formula I , where A is an oxygen atom, an alkylene, alkenyl or hetero alkylene group, in which the CH2 group is substituted with a NH group, where the said groups can be optionally substituted with OH, =O or CH2OH groups, X1, X2, X3, X4 and X5 independently represent nitrogen atoms or groups of formula CH or CR4, Cy is cycloalkylene or heterocycloalkylene group containing at least one nitrogen atom, R1 is a hydrogen atom, an alkyl or alkyloxy group, R2 is a halogen atom, a hydroxy group, an alkyl or heteroalkyl residue, where the said groups can be optionally substituted with OH, NH2 groups and/or a =O group, R3 is a group of formula -B-Y, in which B denotes an alkylene, alkenyl or heteroalkylene group, where the said groups can be optionally substituted with OH, NH2, COOH groups or a =O group, and Y is an optionally substituted phenyl, optionally substituted heteroaryl group containing 5 or 6 ring atoms, or an optionally substituted bicyclic heterocycle in which one ring is phenyl or pyridyl, and the other is a 5-, 6- or 7-member heteroaryl or heterocycloalkyl group which contains up to 3 heteroatoms selected from nitrogen, oxygen and sulphur atoms, R4 is a halogen atom, n equals 0, 1 or 2 and m equals 0 or 1, or their pharmaceutically acceptable salts, solvates and hydrates. The invention also relates to a pharmaceutical composition based on the formula I compound and use of the compound or the pharmaceutical composition to treat bacterial infections.

EFFECT: obtaining novel compounds possessing useful biological properties.

12 cl, 7 ex

Amide derivatives // 2396259

FIELD: chemistry.

SUBSTANCE: claimed invention relates to compound of formula I where m equals 0 or 1; R1 represents halogeno, (C1-6)alkyl, (C1-6)alkoxy, amino-(C2-6)alkoxy, (C2-6)alkylamino-(C2-6)alkoxy, di-[(C1-6)alkyl]amino-(C2-6)alkoxy, (C1-6)alkoxy-(C2-6)alkoxy, carbamoyl-(C1-6)alkoxy, N-(C1-6)alkylcarbamoyl-(C1-6)alkoxy, amino-(C1-6)alkyl, (C1-6)alkylamino-(C1-6)alkyl, di(C1-6)alkyl]amino-(C1-6)alkyl, carbamoyl-(C1-6)alkyl, N-(C1-6)alkylcarbamoyl-(C1-6)alkyl, (C1-6)alkoxy-(C2-6)alkylamino, heteroaryloxy, heterocyclyl-(C1-6)alkyl, heterocyclyloxy or heterocyclyl-(C1-6)alkoxy, and where any heteroaryl or heterocyclyl group in substituent R1 probably can have 1 or 2 substituents, selected from hydroxy, halogeno, (C1-6)alkyl, (C1-6)alkoxy, (C2-6)alkanoyl, hydroxy-(C1-6)alkyl, (C1-6)alkoxy-(C1-6)alkyl, and where any of determined above R1 substituents, which contains CH2 group bound with 2 carbon atoms, or group CH3, bound with an atom of carbon or nitrogen, probably can have on each said CH2 or CH3 group one or more substituents, selected from halogeno, hydroxy, amino, oxo, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkinyl,. (C3-6)cycloalkyl, (C3-6)cycloalkoxy, (C1-6)alkoxy, (C1-6)alkoxy-(C1-6)alkyl, (C1-6)alkylsulphamoyl, heteroaryl, heteroaryl-(C1-6)alkyl and heterocyclyl, and where any heterocyclyl group in substituent R1 probably can have 1 or 2 oxo or tioxo substituents; R2 represents (C1-6)alkyl; R3 represents hydrogen; R4 represents (C3-6)cycloalkyl, (C1-6)alkyl or heteroaryl, and R4 probably can be substituted with one or more substituents, selected from halogeno, (C1-6)alkyl, (C1-6)alkoxy; and R5 represents hydrogen, halogeno or (C1-6)alkyl; or its pharmaceutically acceptable salt, to method of obtaining said compounds, to pharmaceutical composition for application in treatment of diseases mediated by based on them cytokines. Invention also relates to methods of inhibiting p38α-kinase enzymes, TNFα production and production of cytokines.

EFFECT: obtained and described are novel compounds, which can be applied in treatment of medical conditions mediated by cytokines.

14 cl, 31 ex, 9 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of general formula (I) and its pharmaceutically acceptable salts. In general formula (I) , Y represents group -CONH(Q)- or -NHCONH(Q)-; Q represents 6-member aromatic ring or 5-10-member heteroaromatic ring, containing one or two N heteroatoms or two O heteroatoms; R represents hydrogen, halogen, linear or branched (C1-C6)alkyl; (C1-C6)alkoxy; di-(C1-C6)alkylamino, 5-member heteroaromatic ring, containing one O or S heteroatom; 6- or 9-member heteroaromatic ring, containing one or two N heteroatoms; phenyl, mono- or disubstituted with halogen, (C1-C6)alkyl, halogeno(C1-C6)alkyl, (C1-C6)alkoxy, acyl; hydroxy; piano; di-(C1-C6)alkylamino, acylamino' carbamoyl; X represents group : where Z represents CH2, N or O; m represents integer number from 1 to 3; p is equal 0, 1; R" is selected from group, consisting of di-( C1-C6)alkylaminocarbonyl, (C1-C6)alkyl, acyl. Invention also relates to pharmaceutical composition, containing as active ingredient, invention compound, to application of invention compound for manufacturing pharmaceutical composition, to method of inhibition of nicotinic acetylcholine receptor α7.

EFFECT: obtaining compound, which possesses agonistic activity with respect to nicotinic acetylcholine receptor (nAChR) α7.

7 cl, 2 tbl, 4 dwg, 270 ex

Up!