Fungicide hydroximoyl-tetrazole derivatives

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I) and salts thereof (I), where T is a tetrazolyl group which is not substituted or substituted with [C1-C8]alkyl; L1 denotes (CR1R2)n-, where n equals 1, 2, 3 or 4; R1 and R2 denote hydrogen; L2 denotes a direct bond; A is selected from a group comprising A2, A8 and A20 , where Z1, Z2, Z3 and Z4 are independently selected from a group comprising hydrogen, -NR5R6, -N(R5)C(=O)R6, -N(R5)C(=O)OR6, -N(R5)C(=O)NR6R7, -N(R5)C(=S)NR6R7; Q is selected from a group comprising , where X1, X2 and X3 are independently selected from a group comprising hydrogen, halogen, [C1-C8]alkyl, phenyl or phenyl which is substituted by 1-5 halogen atoms; R5-R7 are independently selected from a group comprising hydrogen, [C1-C8]alkyl, [C1-C8]halogenalkyl, [C2-C8]alkenyl, [C3-C6]cycloalkyl, phenyl and phenyl [C1-C8]alkyl.

EFFECT: invention also relates to a fungicide composition containing an active ingredient in form of an effective amount of the disclosed compound, use of the disclosed compound or fungicide composition thereof for treatment or prophylactic control of phytopathogenic fungi of plants or agricultural crops and a method for treatment or prophylactic control of phytopathogenic fungi of plants or agricultural crops.

14 cl, 3 tbl, 12 ex

 

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

In European patent application No. 1426371 described certain tetrazocine derivatives of the following chemical structure:

where A represents tetrazolyl group, Het represents or specific pyridinyl group, or specific thiazolino group.

In Japanese patent application No. 2004-131392 described certain tetrazocine derivatives of the following chemical structure:

where Q may be selected from group 15 different heterocyclic groups.

In Japanese patent application No. 2004-131416 described certain tetrazocine derivatives of the following chemical structure:

where Q may be selected from pyridinoline group or thiazolidine group.

Compounds described in the documents do not confirm that they provide comparable usefulness with the compounds according to this invention.

Agriculture has always been great interest in the use of the Finance for new pesticide compounds, in order to avoid or to deal with sustainable development to the active ingredients strains. Also of great interest is the use of new compounds that are more active than the already known compounds, to reduce the number of active connections that you want to use, while maintaining efficiency at least equivalent to the known compounds. Currently, the authors discovered a new family of compounds which have the above effects or advantages.

Accordingly, the present invention relates to hydroxymelatonin derivative of the formula (I)

where T represents a substituted or unsubstituted tetrazolyl group;

L1represents a direct bond or a divalent group selected from the group consisting of

-(CR1R2)n-, -(CR1R2)m-C(=O)-(CR1R2)p-,

-(CR1R2)m-(CR1=CR2)-(CR1R2)p-, -(CR1R2)m-C(=O)-O-(CR1R2)p,

-(CR1R2)m-C≡C-(CR1R2)p-, -(CR1R2)m-O-C(=O)-(CR1R2)p-,

-(CR1R2)m-O-(CR1R2)p-, -(CR1R2)m-C(=O)-NH-(CR1R2)p -,

-(CR1R2)m-NH-(CR1R2)p-, -(CR1R2)m-NH-C(=O)-(CR1R2)p-,

where n is 1, 2, 3 or 4;

m and p independently are 0, 1, 2 or 3;

L2represents a direct bond or a divalent group selected from the group consisting of

-(CR3R4)q, -(CR3R4)a-C(=O)-(CR3R4)b-,

-(CR3R4)a-(CR3=CR4)-(CR3R4)b-, -(CR3R4)a-C(=O)-O-(CR3R4)b,

-(CR3R4)a-C≡C-(CR3R4)b-, -(CR3R4)a-O-C(=O)-(CR3R4)b-,

-(CR3R4)a-O-(CR3R4)b-, -(CR3R4)a-C(=O)-NH-(CR3R4)b-,

-(CR3R4)a-NH-(CR3R4)b-, -(CR3R4)a-NH-C(=O)-(CR3R4)b-,

where q is 1, 2, 3 or 4;

a and b are independently 0, 1, 2 or 3;

A is chosen from the group consisting of A1-A116

where Z1, Z2, Z3, Z4, Z5, Z6, Z7, Z8and Z9independently selected from the group consisting of hydrogen, halogen, [C1 -C8]alkyl,

[C1-C8]halogenoalkane, [C2-C8]alkenyl, [C2-C8]halogenoalkane,

[C2-C8]quinil, [C2-C8]halogenoalkane, [C3-C6]cycloalkyl,

[C3-C6]halogennitroalkane, aryl, aryl[C1-C8]alkyl,

hydroxy [(C1-C8]alkyl, [(C1-C8]alkoxy, [(C1-C8]alkyl, -C(=O)R5,

-C(=O)OR5, -C(=O)NR5R6, -C(=O)SR5, -C(=S)R5, -C(=S)OR5,

-C(=S)NR5R6, -C(=S)SR5, -CR5=NR6, -CR5=NOR6, -CR5=N-NR6R7, -OR5,

-OSiR5R6R7, -OC(=O)R5, -OC(=O)OR5, -OC(=O)NR5R6, -OC(=S)NR5R6,

-NR5R6, -N(R5)C(=O)R6, -N(R5)C(=O)OR6, -N(R5)C(=O)NR6R7,

-N(R5)C(=S)R6, -N(R5)C(=S)NR6R7, -N=CR5R6, -N=C-NR5R6,

-N(R5)C(=NR6)NR7R8, -N(R5OR6, -N(R5)NR6R7, -N=NR5, -N(R5)S(=O)R6,

-N(R5)S(=O)2R6, -N(R5)S(=O)2OR6, -N(R5)S(=O)OR6, -N(R5)S(=O)NR6R7,

N(R5)S(=O)2NR6R7, -SR5, -S(=O)R5, -S(=O)2R5, -S(=O)OR5, -S(=O)NR5R6,

-S(=O)2OR5, -S(=O)2NR5R6 , nitro, nitroso, azido, cyano, -SF5and

-SiR5R6R7;

K1and K2independently selected from the group consisting of hydrogen, [C1-C8]alkyl, [(C1-C8]halogenoalkane, [C2-C8]alkenyl,

[C2-C8]halogenoalkane, [C2-C8]quinil, [C2-C8]halogenoalkane,

[C3-C6]cycloalkyl, [C3-C6]halogennitroalkane, aryl,

aryl[C1-C8]alkyl, hydroxy [(C1-C8]alkyl,

[C1-C8]alkoxy, [(C1-C8]alkyl, -C(=O)R9, -C(=O)OR9, -C(=O)NR9R10,

-C(=O)SR9, -C(=S)R9, -C(=S)OR9, -C(=S)NR9R10, -C(=S)SR9, -CR9=NR10,

-CR9=NOR10, -CR9=N-NR10R11, -S(=O)R9, -S(=O)2R9, -S(=O)OR9,

-S(=O)NR9R10, -S(=O)2OR9, -S(=O)2NR9R10and-SiR9R10R11;

G1and G2independently selected from the group consisting of oxygen, sulfur, NR12, NOR12and N-NR12R13;

Q is chosen from the group consisting of Q1-Q72

where X1X2X3X4and X5independently selected from the group consisting of hydrogen, halogen, [C1-C 8]alkyl,

[C1-C8]halogenoalkane, [C2-C8]alkenyl, [C2-C8]halogenoalkane,

[C2-C8]quinil, [C2-C8]halogenoalkane, [C3-C6]cycloalkyl,

[C3-C6]halogennitroalkane, aryl, aryl[C1-C8]alkyl,

hydroxy [(C1-C8]alkyl, [(C1-C8]alkoxy, [(C1-C8]alkyl, -C(=O)R14,

-C(=O)OR14, -C(=O)NR14R15, -C(=O)SR14, -C(=S)R14, -C(=S)OR14,

-C(=S)NR14R15, -C(=S)SR14, -CR14=NR15, -CR14=NOR15, -CR14=N-NR15R16,

-OR14, -OSiR14R15R16, -OC(=O)R14, -OC(=O)OR14, -OC(=O)NR14R15,

-OC(=S)NR14R15, -NR14R15, -N(R14)C(=O)R15, -N(R14)C(=O)OR15,

-N(R14)C(=O)NR15R16, -N(R14)C(=S)R15, -N(R14)C(=S)NR15R16, -N=CR14R15,

-N=C-NR14R15, -N(R14)C(=NR15)NR16R17, -N(R14OR15, -N(R14)NR15R16,

-N=NR14, -N(R14)S(=O)R15, -N(R14)S(=O)2R15, -N(R14)S(=O)2OR15,

-N(R14)S(=O)OR15, -N(R14)S(=O)NR15R16N(R14)S(=O)2NR15R16, -SR14,

-S(=O)R14, -S(=O)2R14, -S(=O)OR14, -S(=O)NR14R15, -S(=O)2 OR14,

-S(=O)2NR14R15, nitro, nitroso, azido, cyano, -SF5and-SiR14R15R16;

W1selected from the group consisting of hydrogen, [C1-C8]alkyl,

[C1-C8]halogenoalkane, [C2-C8]alkenyl, [C2-C8]halogenoalkane,

[C2-C8]quinil, [C2-C8]halogenoalkane, [C3-C6]cycloalkyl,

[C3-C6]halogennitroalkane, aryl, aryl[C1-C8]alkyl,

hydroxy [(C1-C8]alkyl, [(C1-C8]alkoxy, [(C1-C8]alkyl, -C(=O)R9,

-C(=O)OR9, -C(=O)NR9R10, -C(=O)SR9, -C(=S)R9, -C(=S)OR9,

-C(=S)NR9R10, -C(=S)SR9, -CR9=NR10, -CR9=NOR10, -CR9=N-NR10R11,

-S(=O)R9, -S(=O)2R9, -S(=O)OR9, -S(=O)NR9R10, -S(=O)2OR9,

-S(=O)2NR9R10and-SiR9R10R11;

R1, R2, R3and R4independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl, [(C1-C4]halogenoalkane,

[C2-C4]alkenyl, [C2-C4]halogenoalkane, [C2-C4]quinil,

[C2-C4]halogenoalkane, [C3-C5]cycloalkyl,

[C3-C5]halogennitroalkane, [C1-C4 ]alkoxy,

[C1-C4]alkoxy, [(C1-C4]alkyl, [(C1-C4]alkoxy, [(C1-C4]alkoxy,

[C1-C4]halogenoalkane, [C1-C4]halogenoalkane[C1-C4]alkyl and cyano;

R5-R17independently selected from the group consisting of hydrogen, [C1-C8]alkyl, [C1-C8]halogenoalkane, [C2-C8]alkenyl, [C2-C8]halogenoalkane, [C2-C8]quinil, [C2-C8]halogenoalkane, [C3-C6]cycloalkyl, [C3-C6]halogennitroalkane, aryl and aryl[C1-C8]alkyl;

and their salts, N-oxides, metallic complexes and metalloenzyme complexes.

Any of these compounds according to this invention can exist as one or more stereoisomers, depending on the number of stereogenic units (as defined by the IUPAC rules) in the connection. Thus, this invention applies equally to all stereoisomers and mixtures of all possible stereoisomers in any ratio. Stereoisomers can be separated by methods known for being specialists in this field.

According to this invention the following terms are commonly used with the following values:

halogen means fluorine, chlorine, bromine or iodine;

the heteroatom can is to be nitrogen, oxygen or sulfur;

halogenated groups, especially halogenation, halogenoalkane and cycloalkyl group can contain up to nine same or different halogen atoms;

the term "aryl" means phenyl or naphthyl, optionally substituted by 1-5 groups selected from the group consisting of halogen, [C1-C6]alkyl, [C1-C6]halogenoalkane, [C2-C6]alkenyl, [C2-C6]halogenoalkane, [C2-C6]quinil, [C2-C6]halogenoalkane, [C1-C6]alkoxy, [C1-C4]alkoxy[C1-C4]alkyl, [C1-C4]alkoxy[C1-C4]alkoxy, [C1-C6]halogenoalkane and [C1-C4]halogenoalkane[C1-C4]alkyl.

As an additional aspect, the present invention relates to hydroxymelatonin derivative of the formula (Ia), (Ib), (Ic) and (Id)

where

A, Q, L1and L2are as defined for the corresponding substituents of compounds of formula (I) according to this invention;

E1selected from the group consisting of hydrogen, [C1-C8]alkyl,

[C1-C8]halogenoalkane, [C2-C8]alkenyl, [C2-C8]halogenoalkane,

[C2-C8]quinil, [C2-C8]halogenoalkane, C 3-C6]cycloalkyl,

[C3-C6]halogennitroalkane, aryl, aryl[C1-C8]alkyl,

hydroxy [(C1-C8]alkyl, [(C1-C8]alkoxy, [(C1-C8]alkyl, -C(=O)R18,

-C(=O)OR18, -C(=O)NR18R19, -C(=O)SR18, -C(=S)R18, -C(=S)OR18,

-C(=S)NR18R19, -C(=S)SR18, -CR18=NR19, -CR18=NOR19, -CR18=N-NR19R20,

-S(=O)R18, -S(=O)2R18, -S(=O)OR18, -S(=O)NR18R19, -S(=O)2OR18,

-S(=O)2NR18R19, cyano, and-SiR18R19R20;

E2selected from the group consisting of hydrogen, halogen,

[C1-C8]alkyl, [(C1-C8]halogenoalkane, [C2-C8]alkenyl,

[C2-C8]halogenoalkane, [C2-C8]quinil, [C2-C8]halogenoalkane,

[C3-C6]cycloalkyl, [C3-C6]halogennitroalkane, aryl,

aryl[C1-C8]alkyl, hydroxy [(C1-C8]alkyl,

[C1-C8]alkoxy, [(C1-C8]alkyl, -C(=O)R18, -C(=O)OR18, -C(=O)NR18R19,

-C(=O)SR18, -C(=S)R18, -C(=S)OR18, -C(=S)NR18R19, -C(=S)SR18,

-CR18=NR19, -CR18=NOR19, -CR18=N-NR19R20, -OR18, -OSiR18R19R20,

-OC(=O)R18, -OC(=O)OR18 , -OC(=O)NR18R19, -OC(=S)NR18R19, -NR18R19,

-N(R18)C(=O)R19, -N(R18)C(=O)OR19, -N(R18)C(=O)NR19R20,

-N(R18)C(=S)R19, -N(R18)C(=S)NR19R20, -N=CR18R19, -N=C-NR18R19,

-N(R18)C(=NR19)NR20R21, -N(R18OR19, -N(R18)NR19R20, -N=NR18,

-N(R18)S(=O)R19, -N(R18)S(=O)2R19, -N(R18)S(=O)2OR19,

-N(R18)S(=O)OR19, -N(R18)S(=O)NR19R20N(R18)S(=O)2NR19R20, -SR18,

-S(=O)R18, -S(=O)2R18, -S(=O)OR18, -S(=O)NR18R19, -S(=O)2OR18,

-S(=O)2NR18R19, cyano, -SF5and-SiR18R19R20;

R18-R20independently selected from the group consisting of, hydrogen, [C1-C8]alkyl, [(C1-C8]halogenoalkane, [C2-C8]alkenyl, [C2-C8]halogenoalkane, [C2-C8]quinil, [C2-C8]halogenoalkane, [C3-C6]cycloalkyl, [C3-C6]halogennitroalkane, aryl and aryl[C1-C8]alkyl.

Preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where L1represents a direct bond or a divalent group selected from the group status is the present of

-(CR1R2)n-, -C(=O)-(CR1R2)p-,

-(CR1R2)m-O-, -(CR1R2)m-C(=O)-O-,

-(CR1R2)m-NH-, -(CR1R2)m-C(=O)-NH-,

-(CR1R2)m-C(=O)-, -(CR1R2)m-NH-C(=O)

where n is 1 or 2;

m and p are independently 0 or 1;

R1and R2independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl, [(C1-C4]halogenoalkane, [C2-C4]alkenyl, [C2-C4]quinil, [C3-C5]cycloalkyl, [C1-C4]alkoxy, [(C1-C4]halogenoalkane and cyano.

More preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where L1represents a direct bond or a divalent group selected from the group consisting of -(CR1R2)-, -C(=O)-(CR1R2)- and-C(=O)-; where R1and R2independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, isopropyl, trifloromethyl, diformate, allyl, ethinyl, propargyl, cyclopropyl, methoxy, triptoreline and cyano.

Other preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where L2represents a direct bond or a divalent group selected from the group consisting of

-(CR3R4)q, -(CR3R4)a-C(=O)-,

-(CR3=CR4)-, -(CR3R4)a-C(=O)-O-,

-C≡C-, -(CR3R4)a-O-C(=O)-,

-(CR3R4)and-O-, -(CR3R4)a-C(=O)-NH-,

-(CR3R4)a-NH-, -(CR3R4)a-NH-C(=O)-,

where q and a independently is 1 or 2;

R3and R4independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl, [(C1-C4]halogenoalkane, [C2-C4]alkenyl, [C2-C4]quinil, [C3-C5]cycloalkyl, [C1-C4]alkoxy, [(C1-C4]halogenoalkane and cyano.

Other more preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where L2represents a direct bond or -(CR3R4)-, where R3and R4independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, isopropyl, trifloromethyl, diformate, allyl, ethinyl, propargyl, cyclopropyl, methoxy, triptoreline and cyano.

Still other preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where A is chosen from the group consisting of A1-A32.

Other more preferred compounds of formula (I) and (Ia)to(Id) according to this invention is the fast connection, where A is selected from the group consisting of A2, A6, A8, A15, A16, A17and A18.

Other more preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where Z1selected from the group consisting of hydrogen, -C(=O)R5,

-C(=O)OR5, -C(=O)NR5R6, -C(=S)NR5R6, -CR5=NR6, -CR5=NOR6,

-CR5=N-NR6R7, -OR5, -OC(=O)R5, -OC(=O)OR5, -OC(=O)NR5R6,

-OC(=S)NR5R6, -NR5R6, -N(R5)C(=O)R6, -N(R5)C(=O)OR6,

-N(R5)C(=O)NR6R7, -N(R5)C(=S)R6, -N(R5)C(=S)NR6R7, -N=CR5R6,

-N=C-NR5R6, -N(R5)C(=NR6)NR7R8, -N(R5OR6, -N(R5)NR6R7, -N=NR5,

-N(R5)S(=O)2R6, -N(R5)S(=O)2OR6, -N(R5)S(=O)2NR6R7, -SR5, -S(=O)2R5,

-S(=O)2OR5, -S(=O)2NR5R6and cyano.

Other even more preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where Z1selected from the group consisting of hydrogen,

-NR5R6, -N(R5)C(=O)R6, -N(R5)C(=O)OR6, -N(R5)C(=O)NR6R7,

-N(R5)C(=S)NR6, R 7, -N=CR5R6, -N=C-NR5R6, -N(R5)C(=NR6)NR7R8,

-N(R5)S(=O)2R6, -N(R5)S(=O)2OR6, -N(R5)S(=O)2NR6R7and cyano.

Still other preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where Z2, Z3, Z4, Z5, Z6, Z7, Z8and Z9independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl,

[C1-C4]halogenoalkane, [C2-C4]alkenyl, [C2-C4]halogenoalkane,

[C2-C4]quinil, [C2-C4]halogenoalkane, [C3-C5]cycloalkyl,

-C(=O)R5, -C(=O)OR5, -C(=O)NR5R6, -OR5, -OSiR5R6R7, -OC(=O)R5,

-NR5R6, -N(R5)C(=O)R6, -SR5, -S(=O)2R5, -S(=O)2OR5, -S(=O)2NR5R6,

cyano, and-SiR5R6R7;

where R5, R6and R7independently selected from the group consisting of hydrogen, [C1-C4]alkyl, [(C1-C4]halogenoalkane, [C2-C4]alkenyl, [C2-C4]halogenoalkane, [C2-C4]quinil, [C2-C4]halogenoalkane and [C3-C5]cycloalkyl.

Other preferred link the mi formula (I) and (Ia)to(Id) according to this invention are compounds where Z2, Z3, Z4, Z5, Z6, Z7, Z8and Z9independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl, methyl, ethyl, isopropyl, isobutyl, tert-butyl, [C1-C4]halogenoalkane, trifloromethyl, diformate, allyl, ethinyl, propargyl, cyclopropyl, methoxy, triptoreline, acetyl, TRIFLUOROACETYL and cyano.

Still other preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where K1, K2and W1independently selected from the group consisting of hydrogen, [C1-C4]alkyl, methyl, ethyl, isopropyl, isobutyl, tert-butyl, allyl, propargyl, cyclopropyl, acetyl, TRIFLUOROACETYL and mesila.

Still other preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where Q is chosen from the group consisting of Q1-Q26.

Other more preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where Q is chosen from the group consisting of Q3, Q4, Q6, Q7, Q9, Q12and Q15.

Still other preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where X1-X5independently selected from the group consisting of the C hydrogen

halogen, [C1-C4]alkyl, [(C1-C4]halogenoalkane, [C2-C4]alkenyl, [C2-C4]halogenoalkane, [C2-C4]quinil, [C2-C4]halogenoalkane,

[C3-C5]cycloalkyl, [C3-C5]halogennitroalkane, aryl,

aryl[C1-C2]alkyl, -C(=O)R14, -C(=O)OR14, -C(=O)NR14R15, -CR14=NOR15,

-CR14=N-NR15R16, -OR14, -OSiR14R15R16, -OC(=O)R14, -OC(=O)OR14,

-OC(=O)NR14R15, -NR14R15, -N(R14)C(=O)R15, -SR14, -S(=O)2R14,

-S(=O)2OR14, -S(=O)2NR14R15, cyano, and-SiR14R15R16;

where R14, R15and R16independently selected from the group consisting of hydrogen, [C1-C4]alkyl, [(C1-C4]halogenoalkane, [C2-C4]alkenyl, [C2-C4]halogenoalkane, [C2-C4]quinil, [C2-C4]halogenoalkane, [C3-C5]cycloalkyl, aryl and aryl[C1-C2]alkyl.

Other more preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where X1-X5independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl, methyl, isopropyl, isobutyl, tert-butyl, [C1 -C4]halogenoalkane, trifloromethyl, diformate, allyl, ethinyl, propargyl, cyclopropyl, benzyl, Venetia, methoxy, triptoreline, acetyl, TRIFLUOROACETYL and cyano.

Preferred compounds of formula (Ia)to(Id) according to this invention are compounds where E1selected from the group consisting of [C1-C4]alkyl, [(C1-C4]halogenoalkane,

[C2-C4]alkenyl, [C2-C4]halogenoalkane, [C2-C4]quinil,

[C2-C4]halogenoalkane, [C3-C5]cycloalkyl,

[C3-C5]halogennitroalkane, -C(=O)R18, -C(=O)OR18, -C(=O)NR18R19,

-CR18=NR19, -CR18=NOR19, -CR18=N-NR19R20, -S(=O)2R18, -S(=O)2OR18,

-S(=O)2NR18R19, cyano, and-SiR18R19R20;

where R18, R19and R20independently selected from the group consisting of hydrogen, [C1-C4]alkyl, [(C1-C4]halogenoalkane and cyclopropyl.

More preferred compounds of formula (Ia)to(Id) according to this invention are compounds where E1selected from the group consisting of methyl, ethyl, isopropyl, allyl, propargyl, cyclopropyl, -C(=O)R18, -C(=O)OR18, -C(=O)NR18R19, -CR18=NR19, -CR18=NOR19, -CR18=NNR 19R20, -S(=O)2R18, -S(=O)2OR18, -S(=O)2NR18R19and-SiR18R19R20; where R18, R19and R20independently selected from the group consisting of methyl and trifloromethyl.

Other preferred compounds of formula (Ia)to(Id) according to this invention are compounds where E2selected from the group consisting of halogen, [C1-C4]alkyl,

[C1-C4]halogenoalkane, [C2-C4]alkenyl, [C2-C4]halogenoalkane,

[C2-C4]quinil, [C2-C4]halogenoalkane, [C3-C5]cycloalkyl,

[C3-C5]halogennitroalkane, -C(=O)R18, -C(=O)OR18, -C(=O)NR18R19,

-CR18=NOR19, -CR18=N-NR19R20, -OR18, -OSiR18R19R20, -OC(=O)R18,

-OC(=O)OR18, -OC(=O)NR18R19, -NR18R19, -N(R18)C(=O)R19,

-N(R18)C(=O)OR19, -N(R18)C(=O)NR19R20, -N(R18)C(=S)R19,

-N(R18)C(=S)NR19R20, -N=CR18R19, -N=C-NR18R19, -N(R18)S(=O)2R19,

-N(R18)S(=O)2OR19, -N(R18)S(=O)2NR19R20, -SR18, -S(=O)2R18,

-S(=O)2OR18, -S(=O)2NR18R19, cyano, and-SiR18R19R20;

where R18 , R19and R20independently selected from the group consisting of hydrogen, [C1-C4]alkyl and [C1-C4]halogenoalkane.

Other more preferred compounds of formula (Ia)to(Id) according to this invention are compounds where E2selected from the group consisting of methyl, ethyl, isopropyl, trifloromethyl, diformate, allyl, ethinyl, propargyl,

cyclopropyl, cyano, -C(=O)R18, -C(=O)OR18, -C(=O)NR18R19,

-CR18=NOR19, -CR18=N-NR19R20, -OR18, -OSiR18R19R20, -OC(=O)R18,

-OC(=O)OR18, -OC(=O)NR18R19, -NR18R19, -N(R18)C(=O)R19,

-N(R18)C(=O)OR19, -N(R18)C(=O)NR19R20, -N(R18)C(=S)R19,

-N(R18)C(=S)NR19R20, -N=CR18R19, -N=C-NR18R19, -N(R18)S(=O)2R19,

-N(R18)S(=O)2OR19, -N(R18)S(=O)2NR19R20, -SR18, -S(=O)2R18,

-S(=O)2OR18, -S(=O)2NR18R19and-SiR18R19R20;

where R18, R19and R20independently selected from the group consisting of hydrogen, methyl and trifloromethyl.

The above preferred values of the substituents of the compounds of formula (I) and (Ia)to(Id) according to this invention it is possible to combine different is the ways. Thus, these combinations of preferred values provide subclasses of compounds according to this invention. Examples of such preferred subclasses of compounds according to this invention can be combined:

preferred values of A with preferred values of one or more L1L2, Q, E1and E2;

preferred values of L1preferred values of one or more A, L2, Q, E1and E2;

preferred values of L2preferred values of one or more A, L1, Q, E1and E2;

preferred values of Q with preferred values of one or more A, L1L2E1and E2;

preferred values of E1preferred values of one or more A, L1L2, Q and E2;

preferred values of E2preferred values of one or more A, L1L2, Q and E1.

In these combinations of preferred meanings of the substituents of the compounds according to this invention, the above preferred values can be selected from the preferred values of each A, Q, L1L2E1and E2; thus, to make the most of predpochtitel the major subclasses of compounds according to this invention.

Preferred values of other substituents of the compounds according to this invention can also be part of such preferred subclasses of compounds according to this invention, especially the group of substituents R, Z, K, G, X and W, and integers a, b, m, n, p and q.

The present invention also relates to a method for producing compounds of formula (I), (Ia), (Ib), (Ic) and (Id). Thus, according to an additional aspect of the present invention, it is proposed a method P1 obtain compounds of formula (I), (Ia), (Ib), (Ic) and (Id), as defined in this description as illustrated by the following reaction scheme.

Method P1

where A, L1L2, Q, E1and E2are as defined in the description, and LG represents a leaving group. Suitable leaving groups can be selected from the group consisting of a halogen atom, or other typical groups nucleofuge, such as triflate, mesilate or toilet.

For compounds of formula (I) according to this invention, when Z1, Z2, Z3, Z4, Z5, Z6, Z7, Z8or Z9represents the amino group, the method P1 according to this invention can be completed in an additional stage, including before anicello modification of this group, especially the reaction of acylation, alkoxycarbonylmethyl, alkylaminocarbonyl or alkylaminocarbonyl, according to known methods. In this case, the proposed method P2 according to this invention, and this method P2 can be illustrated by the following reaction scheme:

The way P2

where A, L1L2, T, Q, and R5are as defined in this specification.

If Z1, Z2, Z3, Z4Z5, Z6, Z7, Z8or Z9represents a protected amino group, the process P2 will be pre-claim stage of removal of the protective group to obtain the amino group. The protective group for the amine and used for their removal methods are known and can be found in T.W. Greene and P. G. M. Wuts, Protective Groups in organic Chemistry, 3rd ed., John Wiley & Sons.

According to this invention the methods P1 and P2 can be carried out, if appropriate, in the presence of a solvent and if appropriate in the presence of a base.

Suitable solvents for the implementation of the methods P1 and P2 according to the invention are customary inert organic solvents. It is preferable to use of optional halogenerator the e 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, tert-butyl methyl ether, tert-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; NITRILES, such as acetonitrile, propionitrile, n - or isobutyronitrile or benzonitrile; amides such as N,N-dimethylformamide N,N-dimethylacetamide, N-methylformamide, N is an organic or triamide of hexamethylphosphoric; esters such as methyl acetate or ethyl acetate, sulfoxidov, such as dimethylsulfoxide, or sulfones, such as sulfolane.

Suitable bases for the implementation of the methods P1 and P2 according to the invention are inorganic and organic bases, which are usually used for such reactions. It is preferable to use hydroxides of alkali and alkaline earth metals or alkoxides of alkali metals such as sodium hydroxide, sodium hydride, calcium hydroxide, potassium hydroxide, tert-piperonyl potassium or other ammonium hydroxide, carbonates of alkali metals such as sodium carbonate, potassium carbonate, bicarbonate Kali is, sodium bicarbonate, cesium carbonate, acetates, alkali and alkaline earth metals, such as sodium acetate, potassium acetate, calcium acetate, and also tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, pyridine, N-methylpiperidine, N,N-dimethylaminopyridine, 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

When implementing methods P1 and P2 according to the invention the reaction temperature can be independently changed in a relatively wide range. Usually the way P1 according to the invention is carried out at a temperature of 0°C-160°C.

Methods P1 and P2 according to this invention is generally independently carried out at atmospheric pressure. However, it is also possible implementation at elevated or reduced pressure.

In the process P1 according to the invention, generally 1 mol or an excess of the derived formula A-L1-LG and 1-3 mol of base are used per mole of hydroxyvalerate formula (IVa), (IVb), (Va) or (Vb). It is also possible to use the components of the reaction in other respects.

Treatment is carried out in the usual ways. Usually the reaction mixture is treated with water and separate the organic phase, after drying, concentrated under reduced pressure. If appropriate, the remaining residue can be purified by conventional methods, such as chromatography or recrystallization, from any impurities that are present.

Compounds according to this invention can be obtained by the above described methods. However, it will be clear on the basis of General knowledge and of available publications that specialists in this field will be able to adapt these methods for each connection according to this invention, it is desirable to synthesize.

The compounds of formula (IVa) and (IVb), suitable as starting material, can be obtained, for example, the interaction of hydroxylamine with the corresponding ketones, which can be obtained, for example, by the methods described by R. Raap (Can. J. Chem. 1971, 49, 2139) by adding particles tetrazolate to esters of the formula Q-L2-CO2Me, or Q-L2-CO2Et, or any suitable synthetic equivalents, for example: Q-L2-C(=O)-N(OMe)Me, Q-L2-CN, Q-L2-C(=O)Cl.

Compounds of General formula (Va) and (Vb), are suitable as starting material can be obtained, for example, from Asimov formula Q-L2-CH=N-OH and 5-substituted tetrazole according to the method described by J. Plenkiewicz et al. (Bull. Soc. Chim. Belg. 1987, 96, 675).

The following aspect of the present invention also relates to fungicidal compositions containing an effective and nontoxic amount of the active compounds of formula (I) or (Ia)to(Id).

The expression "the effect of the main and non-toxic amount" means an amount of composition according to the invention, which is sufficient for fighting or killing the fungus that is present or likely to occur on crops, and which does not cause any visible symptoms of phytotoxicity for the above crops. Such an amount can vary in a wide range depending on the fungus, which must be fought, by crop type, climatic conditions and compounds contained in the fungicidal compositions according to this invention. This quantity can be defined by systematic tests that are included in the competence of the experts in this field.

Thus, according to this invention offers a fungicidal composition containing as active ingredient an effective amount of the compounds of formula (I) or (Ia)to(Id), as defined in this description and usable in agriculture substrate, carrier or filler.

According to this invention, the term "substrate" means a natural or synthetic, organic or inorganic compound, which combine and bind the active compound of the formula (I)to facilitate the application, especially on parts of plants. Thus, this substrate is generally inert and should be used in agriculture. The substrate C is solid or liquid. Examples of suitable substrates include clays, natural and synthetic silicates, silica, resins, waxes, solid fertilizers, water, alcohols, in particular butanol, organic solvents, mineral and vegetable oils and their derivatives. You can use a mixture of these substrates.

The composition according to this invention may also contain additional components. In particular, the composition may further contain a surfactant. Surfactant can be an emulsifier, dispersing agent or wetting agent of ionic or non-ionic type or a mixture of such surfactants. It should be noted, for example, salts of polyacrylic acids, salts of lignosulphonic acids, salts phenolsulfonate or naphthalenesulfonate acids, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols (in values, with ALKYLPHENOLS or allfemale), salts of esters sulfonterol acid derivative taurine (values, alliterate), esters of phosphorus polyoxyethylene alcohols or phenols, fatty acid esters of polyols, and derivatives of the above compounds containing sulphate, sulphonate and phosphate functional groups. The presence of at least one surface-sports the substance is usually essential, when the active compound and/or an inert substrate are insoluble in water, and when the agent for applying for the application is water. Preferably the content of the surfactant may comprise 5-40% by weight of the composition.

Also can optionally contain additional components, for example protective colloids, adhesives, thickeners, thixotropic agents, agents promoting penetration, stabilizers, complexing agents. Typically, the active compounds can be combined with any solid or liquid additive, which is compatible with conventional methods of obtaining compositions.

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

Compositions according to this invention can be used in various forms, such as aerosol dispersion, capsule suspension concentrate for cold spray irrigation, the powder can form dust, emulsifiable concentrate, emulsion oil in water, emulsion water in oil, encapsulated granule, fine granule, flowable concentrate for seed treatment, gas (under pressure), the product of the generating gas, pellets, concentrate for hot aerosol spray, microgranule, microgranules, oil Vara is sny powder, disperse powder, flowable concentrate, mix with butter, mix with the oil liquid, paste, stick to plants, powder for dry seed treatment, seed coated with a pesticide, soluble concentrate, soluble powder, solution for seed treatment, suspension concentrate (flowable concentrate), a liquid with an extremely low volume (ULV)suspension with an extremely low volume (ULV), dispersible in water granules or tablets, water dispersible powder for processing suspensions, water-soluble granules or tablets, water soluble powder for seed treatment and wettable powder. Such compositions include not only compositions which are ready for use on plants or seeds that need to be processed using a suitable device, such as a sprayer and spray gun, concentrated, commercially available compositions which must be diluted before application to crop.

Compounds according to this invention can also be mixed with one or more insecticides, fungicides, bactericides, attractants, acaricides or substances, activating pheromone or other compounds with biological activity. Thus, the resulting mixtures possess an expanded spectrum of activity. Mix with other fungicidal compounds is particularly preferred.

Examples of suitable fungicide partners for mixing can be selected from the following groups:

B1) a compound capable to inhibit the nucleic acid synthesis like benalaxyl, benalaxyl-M, bupirimate, kasiakou, dimethirimol, ethirimol, furlanello, hymexazol, mefenoxam, metalaxyl, metalaxyl-M, operas, oxadixyl, oksolinovoj acid;

B2) compounds, sposobnye to inhibit the mitosis and cell division like benomyl, carbendazim, dietotherapy, ethaboxam, fuberidazole, pencycuron, thiabendazole, thiophanate-stands, zoxamide;

B3) a compound capable to inhibit the respiration for example: CI-inhibitor breath, like diplomatiya; in the form of CII-inhibitor breath, like boscalid, carboxin, fanforum, flutolanil, parameter, pharmacyclics, mepronil, oxycarboxin, pantoporate, thioglutamic; III inhibitor breath, like amisulbrom, AZOXYSTROBIN, cyazofamid, dimoxystrobin, Anastasio, famoxadone, fenamidone, fluoxastrobin, kresoxim-stands mecamylamine, orysastrobin, picoxystrobin, pyraclostrobin, Trifloxystrobin;

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

B5) a compound capable to inhibit ATP production like fantinato, fenti the chloride, fistinginaction, silthiofam;

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

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

B8) a compound capable to inhibit the synthesis of lipids and membranes, like biphenyl, chlozolinate, edifenphos, etridiazole, itcanbe, iprobenfos, iprodione, isoprothiolane, procymidone, propamocarb, hydrochloride propamocarb, pyrazophos, ethylcellulose-m, vinclozolin;

B9) a compound capable to inhibit ergosterol biosynthesis, like altimore, azaconazole, bitertanol, bromuconazole, cyproconazole, diclobutrazol, difenoconazole, diniconazole, diniconazole-M, dodemont, documentatino, epoxiconazole, metaconsole, fenarimol, fenbuconazole, fenhexamide, fenpropidin, fenpropimorph, fluconazole, flurriedly, flusilazole, flutriafol, vorconizole, vorconizole-CIS, hexaconazole, imazalil, kazalishte, imilinganiselo, ipconazole, metconazole, myclobutanil, naftifine, nuarimol, Expocentr, paclobutrazole, paparatto, penconazole, prochloraz, propiconazole, prothioconazole, polybutylene, purifiers, simionato, spiroxamine,tebuconazole, the terbinafine, terconazole, triadimefon, triadimenol, tridemorph, triflumizole, triforine, triticonazole, uniconazole, wineconsole, voriconazole;

B10) a compound capable to inhibit cell wall synthesis like benthiavalicarb, dimethomorph, fluoro, iprovalicarb, mandipropamid, policyname, polycaronate, validamycin A;

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

B12) a compound capable to induce protective mechanisms of the host, like acibenzolar-S-stands, rabenasolo, tadinya;

B13) a compound capable to have multiple action like Bordeaux mixture, captafol, Captan, CHLOROTHALONIL, copper naphthenate, copper oxide, copper oxychloride, copper compounds such as copper hydroxide, copper sulfate, dichlofluanide, dithianon, Dodin, the free base Dodin, ferbam, formalpara, polperro, guazatine, guazatine, iminoctadine, iminoctadine, iminoctadine, marcopper, MANCOZEB, MANEB, metiram, mediacinco, oxine copper, propineb, sulfur and sulfur compounds, including calcium polysulfide, thiram, tolylfluanid, zineb, Zir;

B14) compounds selected from the following group: (2E)-2-(2-{[6-(3-chloro-2-methylphenoxy)-5-ftorpirimidinu-4-yl]oxy}phenyl)-2-(methoxime is about)-N-methylacetamide, (2E)-2-{2-[({[(1E)-1-(3-{[(E)-1-fluoro-2-phenylphenyl]oxy}phenyl)ethylidene]amino}oxy)methyl]phenyl}-2-(methoxyimino)-N-methylacetamide, 1-(4-chlorophenyl)-2-(1H-1,2,4-triazole-1-yl)cycloheptanol, 1-[(4-methoxyphenoxy)methyl]-2,2-dimethylpropyl-1H-imidazol-1-carboxylate, 1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide, 2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine, 2-butoxy-6-iodine-3-propyl-4H-chromen-4-one, 2-chloro-N-(1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)nicotinamide, 2-phenylphenol and salt, 3(deformity)-1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-1H-pyrazole-4-carboxamide, 3-(deformity)-N-[(9R)-9-isopropyl-1,2,3,4-tetrahydro-1,4-methanation-5-yl]-1-methyl-1H-pyrazole-4-carboxamide, 3-(deformity)-N-[(9S)-9-isopropyl-1,2,3,4-tetrahydro-1,4-methanation-5-yl]-1-methyl-1H-pyrazole-4-carboxamide, 3-(deformity)-N-[4'-(3,3-dimethylbutan-1-yl)-biphenyl-2-yl]-1-methyl-1H-pyrazole-4-carboxamide, 3,4,5-trichloropyridine-2,6-dicarbonitrile, 3-[5-(4-chlorophenyl)-2,3-dimethylisoxazole-3-yl]pyridine, 3-chloro-5-(4-chlorophenyl)-4-(2,6-differenl)-6-methylpyridazine, 4-(4-chlorophenyl)-5-(2,6-differenl)-3,6-dimethylpyridine, 5-chloro-7-(4-methylpiperidin-1-yl)-6-(2,4,6-tryptophanyl)[1,2,4]triazolo[1,5-a]pyrimidine, 8-hydroxyanisole, bentazon, beloxepin, capsaicin, carvon, chinomethionat, kurane, cyflufenamid, having cymoxanil, dazomet, dibakar, dichlorophen, declomycin, dicloran, difenzoquat, difenoconazole, diphenylamine, Ecomat, f is reason, flamethrower, fluopicolide, perimed, fluotitanic, foretelling, poetically, facitility, hexachlorobenzene, arunamarin, isotianil, metasurfaces, methyl (2E)-2-{2-[({cyclopropyl[(4-methoxyphenyl)imino]methyl}thio)methyl]phenyl}-3-ethoxyacrylate, methyl 1-(2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)-1H-imidazole-5-carboxylate, methylisothiocyanate, metrafenone, millionizer, N-(3',4'-dichloro-5-forbiden-2-yl)-3-(deformity)-1-methyl-1H-pyrazole-4-carboxamide, N-(3-ethyl-3,5,5-trimethylcyclohexyl)-3-(formylamino)-2-hydroxybenzamide, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide, N-(4-Chlorobenzyl)-3-[3-methoxy-4-(prop-2-in-1 yloxy)phenyl]propanamide, N-[(4-chlorophenyl)(cyano)methyl]-3-[3-methoxy-4-(prop-2-in-1 yloxy)phenyl]propanamide, N-[(5-bromo-3-chloropyridin-2-yl)methyl]-2,4-dichloronicotinic, N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2,4-dichloronicotinic, N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2-fluoro-4-idnicating, N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide, N-{(Z)-[(cyclopropylmethoxy)imino][6-(deformedarse)-2,3-differenl]methyl}-2-phenylacetamide, N-{2-[1,1'-bi(cyclopropyl)-2-yl]phenyl}-3-(deformity)-1-methyl-1H-pyrazole-4-carboxamide, N-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-2-(trifluoromethyl)benzamid, natamycin, N-ethyl-N-methyl-N'-{2-methyl-5-(trifluoromethyl)-4-[3-(trimethylsilyl)propoxy]phenyl}imageformat, N-ethyl-N-methyl-N'-{2-methyl-5-(deformity)-4-[3-(trimethylsilyl)propoxy]f the Nile}imageformat, the Nickel dimethyldithiocarbamate, nitratenitrogen, O-{1-[(4-methoxyphenoxy)methyl]-2,2-dimethylpropyl}1H-imidazol-1-carbothioate, Actelion, oxamate, oxidation, pentachlorophenol and salts, phosphoric acid and its salts, piperalin, propanecarboxylate, propanoic-sodium, probenecid, purbanchal, pyrrolnitrin, quintozene, S-allyl-5-amino-2-isopropyl-4-(2-were)-3-oxo-2,3-dihydro-1H-pyrazole-1-carbothioate, telital, tecnazene, triazoxide, trickled, valerenal, Suriname.

The composition according to this invention containing a mixture of compounds of formula (I) or (Ia)-(Id) with a bactericidal compound, may also be of particular advantage. Examples of suitable antibacterial partners for mixing can be selected from the following group: bronopol, dichlorophen, nitrapyrin, Nickel dimethyldithiocarbamate, kasugamycin, Actelion, francebuy acid, oxytetracycline, provenzal, streptomycin, telital, copper sulphate and other copper compounds.

The compounds of formula (I) or (Ia)to(Id) and the fungicidal compositions according to this invention can be used for therapeutic or preventive combating phytopathogenic fungi of plants or crops.

Thus, according to further aspect of the present invention proposes a method for the treatment or prevention of combating phytopathogenic fungi and plants or crops, characterized in that the compound of formula (I) or (Ia)-(Id) or fungicidal composition according to this invention applied to seeds, plants or fruits of the plants or the soil where a plant grows or where it is desirable to grow. The processing method according to this invention may also be useful for material processing for reproduction, such as tubers or rhizomes, and seeds, seedlings or transplant seedlings and plants or transplanted plants. This method of processing can also be useful for processing roots. The processing method according to this invention may also be useful for treatment of aerial parts of the plant, such as stems, stalks, leaves, flowers and fruits of the considered plants.

Among the plants that can be protected by the method according to this invention, it is possible to produce cotton; flax; vine; fruit or vegetable crops such as Rosaceae sp. (for example, one-seeded, such as Apple and pear tree, but also stone fruits such as apricot tree, almond tree and a peach tree), 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 sycamores), Rubiaceae sp., Theaceae sp., Sterculiceae sp., Rutaceae sp. (for example, lemons or oranges and grapefruit); Solanaceae sp. (for example tomatoes), Liliaceae sp. Asteraceae sp. (for example lettuce), Umbelliferae sp., Cruciferae sp., Chenopodiaceae sp., Cucurbitaceae sp., Papilionaceae sp. (for example, pears), Rosaceae sp. (for example, strawberries); major crops such as Graminae sp. (for example maize, lawn or cereals such as wheat, rice, barley and triticale), Asteraceae sp. (for example sunflower), Cruciferae sp. (for example, canola), Fabacae sp. (for example, groundnut), Papilionaceae sp. (for example soya beans), Solanaceae sp. (for example potatoes), Chenopodiaceae sp. (for example, red beetroots); horticultural and forest crops; as well as genetically modified homologues of these crops.

Among the diseases of plants or crops that can be treated by the method according to this invention, one can cite: diseases powdery mildew, such as:

Blumeria diseases caused, for example, Blumeha graminis; Podosphaera diseases caused, for example, Podosphaera leucotricha; Sphaerotheca diseases caused, for example, Sphaerotheca fuliginea; Uncinula diseases caused, for example, Uncinula necator;

diseases that cause rust, such as Gymnosporangium diseases caused, for example, Gymnosporangium sabinae; Hemileia diseases caused, for example, Hemileia vastatrix;

Phakopsor diseases caused, for example, Phakopsora pachyrhizi or Phakopsora meibomiae; Puccinia diseases, caused for example, Puccinia recondita; Uromyces diseases caused for example Uromycs appendiculatus;

oomycete diseases, such as Bremia diseases caused, for example, Bremia lactucae; Peronospora. diseases caused, for example, Peronospora. pisior P. brassicae; Phytophthora diseases caused for example Phytophthora infestans; Plasmopara diseases, caused for example, Plasmopara viticola; Pseudoperonospora diseases, caused for example, Pseudoperonospora humuli or Pseudoperonospora cubensis;

pitanie diseases caused, for example, Pythium ultimum;

diseases with different types of leaf spots, such as Alternaria diseases caused, for example, Alternaria solani; Cercospora diseases caused, for example, Cercospora beticola; Cladiosporum diseases caused, for example, Cladiospohum cucumerinum; Cochliobolus diseases, caused for example, Cochliobolus sativus; Colletotrihum diseases caused, for example, Colletotrichum lindemuthanium; Cycloconium diseases, caused for example, Cycloconium oleaginum; Diaporthe diseases caused, for example, Diaporthe citri; Elsinoe diseases, caused for example, Elsinoe fawcettii; Gloeosporium diseases, caused for example, Gloeosporium laeticolor; Glomerella diseases caused, for example, Glomerella cingulata; Guignardia diseases, caused for example, Guignardia bidwelli; Leptosphaeria diseases, caused for example, Leptosphaeria maculans; Leptosphaeria nodorum; Magnaporthe diseases, caused for example, Magnaporthe grisea; Mycosphaerella diseases caused, for example, Mycosphaerella graminicola; Mycosphaerella arachidicola; Mycosphaerella fijiensis; Phaeosphaeria diseases caused, for example, Phaeosphaeria nodorum; Pyrenophora diseases, which are called, for example, Pyrenophora teres; Ramularia diseases caused, for example, Ramularia collocygni; Rhynchosporium diseases caused, for example, Rhynchosporium secalis; Septoria diseases caused, for example, Septoria apii or Septoria lycopercisi; Typhula diseases, caused for example, Typhula incarnata; Venturia diseases, caused for example, Venturia inaequalis;

diseases of roots and stems, such as Corticium diseases caused, for example, Corticium graminarum; Fusarium diseases caused, for example, Fusarium oxysporum; Gaeumannomyces diseases caused, for example, Gaeumannomyces graminis; Rhizoctonia diseases, caused for example, Rhizoctonia solani; Tapesia diseases caused, for example, Tapesia acuformis; Thielaviopsis diseases caused, for example, Thielaviopsis basicola;

diseases of the ears and spikelets, such as Alternaria diseases caused, for example, Alternaria spp.; Aspergillus diseases, caused for example, Aspergillus flavus; Cladosporium diseases, caused for example, Cladosporium spp.; Claviceps diseases caused, for example, Claviceps purpurea; Fusarium diseases caused, for example, Fusarium culmorum; Gibberella diseases, caused for example, Gibberella zeae; Monographella diseases, caused for example, Monographella nivalis;

smut diseases, such as: Sphacelotheca diseases caused, for example, Sphacelotheca reiliana; Tilletia diseases caused, for example, Tilletia caries; Urocystis diseases caused, for example, Urocystis occulta; Ustilago diseases caused, for example, Ustilago nuda;

diseases of fruit is rot and mould diseases, such as: Aspergillus diseases, caused for example, Aspergillus flavus; Botrytis diseases, caused for example, Botrytis cinerea; Penicillium diseases, caused for example, Penicillium expansum; Sclerotinia diseases, caused for example, Sclerotinia sclerotiorum; Verticilium diseases, caused for example, Verticilium alboatrum;

diseases associated with rotting of seeds and soil rot, rotting, fading, debate and black leg, such as: Fusarium diseases, caused for example, Fusarium culmorum; Phytophthora diseases caused, for example, Phytophthora cactorum; Pythium diseases caused, for example, Pythium ultimum; Rhizoctonia diseases, caused for example, Rhizoctonia solani; Sclerotium diseases, caused for example, Sclerotium rolfsii; Microdochium diseases caused, for example, Microdochium nivale;

diseases associated with chronic inflammation of dead shells, broom and apical drying, such as: Agent of the disease, caused, for example, Agent galligena;

diseases accompanied by aging, rotting and termination of growth, such as Monilinia diseases caused, for example, Monilinia laxa;

diseases with puzyrchatogo and crinkle leaves, such as: Taphrina diseases caused, for example, Taphrina deformans; disease characterized by the decay of woody plants, such as Esca diseases, caused for example, Phaemoniella clamydospora; Eutypa die-caused, for example, Eutypa lata; Dutch disease in the call, caused, for example, Ceratocystsc ulmi; diseases of flowers and seeds such as Botrytis diseases, caused for example, Botrytis cinerea;

diseases of tubers such as Rhizoctonia diseases, caused for example, Rhizoctonia solani.

Fungicidal compositions according to this invention can also be used against fungal diseases that can develop on or inside the wood. The term "timber" means all types of wood, all types of processing this tree, intended for construction, such as solid wood, wood with high density, laminated wood, and plywood. The method of processing wood according to the invention mainly consists of a contact of one or more compounds according to the invention, or compositions according to this invention; the method includes, for example, direct application, spraying, etching, injection or any other suitable methods.

The dose of the active compounds usually applied in the method of processing according to this invention is usually and preferably 10-800 g/ha, preferably 50-300 g/ha for applying for deciduous processing. The applied dose of the active substance is typically and preferably 2-200 g per 100 kg of seed, preferably 3-150 g per 100 kg of seed in the case of seed treatment.

It will be obvious that the dose of t is undertaken in this description, are provided as illustrative examples of the method according to this invention. Professionals in this field know how to find the used doses, especially according to the nature of the plants or crops that need to be processed.

Fungicidal compositions according to this invention can also be used for handling genetically modified organisms compounds according to the invention or an agrochemical compositions according to this invention. Genetically modified plants are plants, the genome of which is stably integrated heterologous gene that encodes an important protein. The expression "heterologous gene that encodes an important protein" essentially means the genes that gives the transformed plant new agronomic properties or genes to improve the agronomic quality of the modified plant.

The compounds or mixtures according to the invention can also be used to obtain compositions suitable for therapeutic or prophylactic treatment of fungal diseases of humans and animals, such as, for example, fungal infections, dermatitis, diseases caused Shearer versicolor and candidiasis or diseases caused by Aspergillus spp., for example Aspergillus fumigatus.

In the following tables I-III presents neogranichinymi the way examples of compounds according to this invention.

In the following examples compounds M+H represents the ratio of mass-to-charge values (m/z) monoprotonated molecular ion, as observed in mass spectroscopy in positive chemical ionization at atmospheric pressure (APCI+) or positive ionization when elektrorazpredelenie (ES+).

In the following examples, the logP values were determined according to EEC Directive 79/831 Annex V.A8 HPLC (high performance liquid chromatography) on a column of reverse phase (C18), using the method described below: temperature: 40°C; mobile phase: 0.1% aqueous formic acid and acetonitrile; linear gradient of 10% acetonitrile to 90% acetonitrile.

The calibration is carried out using unbranched Alkan-2-ones (containing 3-16 carbon atoms) with known logP values (determination of the logP values by using the retention times using linear interpolation between two successive alkanes).

Value lambda max was determined in the maxima of the chromatographic signals using UV spectra of 190 nm-400 nm.

Table I

Table II

Table III

The following examples illustrate non-limiting method of obtaining compounds of formula (I) according to this invention.

5-Methyl-1-(3-thiophencarboxylic)tetrazole and 5-methyl-2-(3-thiophencarboxylic)tetrazol

To a solution of 3-thiophenecarboxaldehyde (8 g, with 62.9 mmol) in DMF (80 ml) was added in portions N-chlorosuccinimide (8.8 g, 66 mmol), maintaining the reaction temperature below 45°C. After complete addition, the mixture was stirred one hour at room temperature before pouring it into a saturated aqueous solution of NH4Cl. The mixture was extracted with ethyl acetate. The organic layer was washed successively with water and a saturated solution, dried (MgSO4), filtered and concentrated. The residue and 5-methyltetrazol (5.3g, with 62.9 mmol) was dissolved in dichloromethane (80 ml) and added dropwise at room temperature, triethylamine (11,4 ml, to 82.1 mmol). After PE is emiliania during the night) was added a saturated aqueous solution of NH 4Cl. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed successively with water and a saturated solution, dried (MgSO4), filtered and concentrated. Chromatography on silica gel of the residue gave 5.5 g of 5-methyl-1-(3-thiophencarboxylic)tetrazolo [exit 37,6%;1H-NMR (DMSO-d6) δ ppm: 2,48 (s, 3H), 7,42 (d, 1H), 7,51 (d, 1H), 7,74 (DD, 1H), 12.7mm (s, 1H)] and 2 g of 5-methyl-2-(3-thiophencarboxylic)tetrazolo [output of 13.7%;1H-NMR (DMSO-d6) δ ppm: 2,62 (s, 3H), 7,40 (m, 2H), 7,73 (DD, 1H), and 12.6 (s, 1H)].

O-(2-Amino-1,3-thiazol-4-yl)methyl(Tien-3-yl)-(5-methyltetrazol-1-yl)metrorock (compound 20)

To a cooled solution (0-5°C) 5-methyl-1-(3-thiophencarboxylic)tetrazole (18.7 g, 89,4 mmol) in acetonitrile (100 ml) was added DBN (22,4 ml, 187,7 mmol). After complete addition, the mixture was stirred for five minutes and added portions of the hydrochloride of 4-chloromethyl-2-amino-1,3-thiazole (18.2 g, 98,3 mmol). After complete addition, the mixture was stirred for five minutes before removing the cooling bath. After stirring overnight the solvent was evaporated. Chromatography on silica gel of the residue gave an 18.4 g of compound 20 [out of 60.8%; HPLC/MS: m/z=325 (M+H); LogP=1,32].

O-(2-tributylammonium-1,3-thiazol-4-yl)methyl(Tien-3-yl)-(5-methyltetrazol-1-yl)metrorock (compound 18)

To Heidenau solution (0-5°C) compound 20 (8 g, 24,9 mmol) in dry dichloromethane (250 ml) was added triethylamine (3.6 ml, and 26.1 mmol) and catalytic amount of DMAP, then was added dropwise pivaloate (3.2 ml, and 26.1 mmol). After complete addition, the mixture was stirred for ten minutes before removing the cooling bath. After stirring overnight was added water. After separation the organic layer was dried (MgSO4), filtered and concentrated to obtain not quite white solid. Rubbing with methanol, filtering, washing with methanol and drying gave 3.2 g of compound 18 [yield of 60.5%; HPLC/MS: m/z=406 (M+H); LogP=2.94].

(2-Phenyl-1,3-thiazol-4-yl)-(1-methyltetrazol-5-yl)methanon

To a solution of 1-methyltetrazole (2 g, to 23.8 mmol) and TMEDA (10 ml, 66,2 mmol) in THF (100 ml) cooled to -78°C was added dropwise 2.5m n-BuLi in hexane (9,5 ml of 23.8 mmol) with vigorous stirring and maintaining the reaction temperature below -65°C. After complete addition, the mixture was stirred for 20 minutes before adding dropwise the solution of N-methyl-N-methoxy-(2-phenyl-1,3-thiazol-4-yl)carboxamide (5.9 g, 23,8 mmol) in THF. After complete addition, the mixture was stirred for 6 hours at -78°C before the slow addition of a solution of 1 N. HCl in water (100 ml). When the reaction mixture was warmed to room temperature, added water (500 ml) and the reaction mixture was neutralized nassen the m aqueous solution of NaHCO 3and were extracted with ethyl acetate (500 ml). After separation the organic layer was dried (MgSO4), filtered and concentrated. Chromatography on silica gel of the residue gave 4.7 g (2-phenyl-1,3-thiazol-4-yl)-(1-methyltetrazol-5-yl)methanone [exit 72,8%;1H-NMR (CDCl3) δ ppm: 4,48 (s, 3H), 7.5 (m, 3H), 8,08 (m, 2H), 9,44 (s, 1H)].

1-Methyl-5-[(2-phenyl-1,3-thiazol-4-yl)carbohydraterich]tetrazol

A solution of 1-methyl-5-[(2-phenyl-1,3-thiazol-4-yl)carbohydraterich]tetrazole (5,1 g of 18.8 mmol) and hydroxylamine hydrochloride (3.3 g, 47 mmol) in pyridine (60 ml) was stirred for three hours at 50°C and overnight at room temperature. The solvent was evaporated and added to the crude mixture of the water. The resulting suspension was filtered. The solid residue was washed with water and dried to obtain 5 g of 1-methyl-5-[(2-phenyl-1,3-thiazol-4-yl)carbohydraterich]tetrazolo [yield of 92.9%;1H-NMR (DMSO-d6) δ ppm: 4,08 (s, 3H), 7.5 (m, 3H), 7,9 (m, 2H), 8,02 (s, 1H), and 12.9 (s, 1H)].

O-(2-Phthalimidopropyl-6-yl)methyl(2-phenyl-1,3-thiazol-4-yl)-(1-methyltetrazol-5-yl)metrorock (compound 173)

To a cooled solution (0-5°C) 1-methyl-5-[(2-phenyl-1,3-thiazol-4-yl)carbohydraterich]tetrazole (2.5 g, 8,7 mmol) in acetonitrile (10 ml) was added DBN (2.2 ml, and 18.3 mmol). After complete addition, the mixture was stirred for five minutes and added portions 6-br is methyl-2-phthalimidopropyl (3,05 g, 9.6 mmol). After complete addition, the mixture was stirred for five minutes before removing the cooling bath. After stirring overnight was added water and the reaction mixture was extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated. Chromatography on silica gel of the residue gave 2.1 g of compound 173 [exit 41,4%; HPLC/MS: m/z=523 (M+H); LogP=of 3.46].

O-(2-Aminopyridine-6-yl)methyl(2-phenyl-1,3-thiazol-4-yl)-(1-methyltetrazol-5-yl)metrorock (compound 174)

To a solution of compound 173 (1.8 g, 3.1 mmol) in THF (45 ml) was added hydrazinehydrate (0.75 ml, of 15.5 mmol). After stirring over night the reaction mixture was filtered and concentrated. Chromatography on silica gel of the residue gave 1 g of compound 174 [exit with 82.2%; HPLC/MS: m/z=393 (M+H); LogP=1,57].

O-(2-intercorporeality-6-yl)methyl(2-phenyl-1,3-thiazol-4-yl)-(1-methyltetrazol-5-yl)metrorock (compound 178)

To a solution of compound 174 (0.15 g, 0.38 mmol) in dry dichloromethane (5 ml) was added to the resin PS-BEMP 2.2 mmol/g (0.34 g) and hexanoate (77 mg, or 0.57 mmol). After stirring over night the reaction mixture was filtered and concentrated. Chromatography on silica gel of the residue gave 0.16 g of compound 178 [exit 61,8%; HPLC/MS: m/z=491 (M+H); LogP=4,06].

The following examples illustrate non-limiting what procedure the biological activity of the compounds of formula (I) according to this invention.

Example a: Test in vivo on Peronospora. parasitica (cruciferous disease)

Seedlings of cabbage (view - cardinal) in cups, sown on a mixture of 50/50 peat soil-pozzolanic substrate and grown at 18-20°C, was treated at the stage of cotyledon spraying with an aqueous suspension described above. The seedlings used as a control, was treated with an aqueous solution containing no active compound. After 24 hours, the seedlings were infected by spraying them with an aqueous suspension of spores Peronospora. parasitica (50000 spores per ml). Spores were collected from infected plants. Infected seedlings of cabbage was kept for five days at 20°C in a humid atmosphere. The evaluation was performed five days after infection, compared with control seedlings.

Under these conditions, good protection (at least 70%) was observed at doses of 500 hours/million with the following compounds: 1, 2, 3, 5, 13, 16, 17, 18, 19, 20, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 34, 36, 37, 38, 39, 42, 43, 44, 46, 48, 49, 50, 51, 62, 63, 64, 65, 66, 67, 68, 69, 72, 73, 74, 75, 88, 90, 92, 93, 95, 96, 97, 98, 101, 106, 107, 110, 111, 112, 114, 115, 116, 118, 119, 120, 123, 124, 125, 126, 127, 128, 129, 130, 151, 152, 153 and 154.

Example B: Test in vivo on Phytophthora infestans (tomato blight)

Seedlings of tomato (view - Marmande), seeded into a Cup with a mixture of 50/50 peat soil-pozzolanic substrate and grown at 20-25°C, was treated at the stage Z16 spraying with an aqueous suspension described above. The seedlings used in ishemia as a control, was treated with an aqueous solution containing no active compound. After 24 hours, the seedlings were infected by spraying them with an aqueous suspension of spores of Phytophthora infestans (20000 spores per ml). Spores were collected from infected plants. Infected seedlings of tomato were kept for 5 days at 20°C in a humid atmosphere. The evaluation was performed five days after infection, compared with control seedlings.

Under these conditions, good protection (at least 70%) was observed at doses of 500 hours/million with the following compounds: 3, 18, 19, 22, 24, 36, 38, 95, 101, 124, 126, 127 and 152.

Example C: Test in vivo on Plasmopara parasitica (grape peronospora)

Grape seedlings (view - Cabernet), grown on a mixture of 50/50 peat soil-pozzolanic substrate was treated at the stage Z15 spraying with an aqueous suspension described above. The seedlings used as a control, was treated with an aqueous solution containing no active compound. After 24 hours, the seedlings were infected by spraying the underside of leaves with an aqueous suspension of spores Plasmopara viticola (100000 spores per ml). Spores were collected from infected plants. Infected grape seedlings kept for 7-8 days at 20°C in a humid atmosphere. The evaluation was performed after 7-8 days after infection, compared with control seedlings.

Under these conditions, good protection (at least 70%) watched the ri doses of 500 hours/million the following compounds: 16, 18, 19, 22, 24, 28, 42, 43, 67, 88, 90, 92, 95, 96, 97, 101, 106, 110, 116, 119, 124, 125, 126, 127, 128 and 152.

Example D: Cell test Pythium ultimum (blackleg)

Growing Pythium ultimum were performed in the environment PDB at 20°C for 7 days. Wednesday PDB was prepared by mixing 24 grams PDB (Difco) in 1 liter of demineralized water. The medium was sterilized in the autoclave for 15 minutes at 121°C. After 7 days of growth, the mycelium Pythium ultimum were crushed and used as inoculum. Compounds were dissolved in DMSO and added to sterile liquid medium glucose/mikepatton (14.6 g/l D-glucose, 7,1 g/l mycological peptone (Oxoid) and 1.4 g/l yeast extract (Merck)) with a concentration of 2 hours/million Wednesday with crushed micelles were sown during the initial OD at 620 nm of 0.025. The effectiveness of the compounds was evaluated by measuring the OD at 620 nm after five days at 20°C compared to control.

Under these conditions, good protection (at least 70%) was observed at doses 6 hours/million with the following compounds: 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 44, 45, 46, 47, 48, 59, 60, 63, 64, 65, 67, 68, 74, 75, 86, 87, 88, 90, 91, 92, 93, 94, 95, 96, 97, 98, 100, 101, 102, 103, 104, 106, 107, 108, 110, 111, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 129, 134, 138, 151, 152, 153, 154, 160, 166, 170, 175, 177 and 178.

1. The compound of formula (I)

where T represents tetrazolyl group, unsubstituted or substituted C 1-C8]alkyl;
L1is -(CR1R2)n-where n is 1, 2, 3 or 4;
R1and R2represent hydrogen;
L2is a direct link;
And are selected from the group consisting of And2And8and20

where Z1, Z2, Z3and Z4independently selected from the group consisting of hydrogen, -NR5R6, -N(R5)C(=O)R6, -N(R5)C(=O)OR6, -N(R5)C(=O)NR6R7, -N(R5)C(=S)NR6R7;
Q is chosen from the group consisting of

where X1X2and X3independently selected from the group consisting of hydrogen, halogen, [C1-C8]alkyl, phenyl or phenyl substituted from one to five halogen atoms;
R5-R7independently selected from the group consisting of hydrogen, [C1-C8]alkyl, [C1-C8]halogenoalkane, [C2-C8]alkenyl, [C3-C6]cycloalkyl, phenyl and phenyl [C1-C8]alkyl;
and its salts.

2. The compound of formula (I) according to claim 1, where T represents a substituted or unsubstituted tetrazolyl group of the formula One b, TC or Td:

where E1and E2selected from hydrogen or [(C1-C8]alkyl.

3. The compound of formula (I) according to claim 1, where T is the replacement of the military or unsubstituted tetrazolyl group of the formula TA or TC:

where E1and E2selected from hydrogen or [(C1-C8]alkyl.

4. The compound of formula (I) according to claim 1, where n is 1 or 2.

5. The compound of formula (I) according to claim 1, where a represents A2.

6. The compound of formula (I) according to claim 1, where Z2, Z3and Z4represent hydrogen.

7. The compound of formula (I) according to claim 1, where X1-X3independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl, methyl, isopropyl, isobutyl, tert-butyl, phenyl.

8. The compound of formula (I) according to claim 2, where E1is [C1-C4]alkyl.

9. The compound of formula (I) of claim 8, where E1selected from the group consisting of methyl and ethyl.

10. The compound of formula (I) according to claim 2, where E2is [C1-C4]alkyl.

11. The compound of formula (I) according to claim 10, where E2selected from the group consisting of methyl and ethyl.

12. Fungicidal composition containing as active ingredient an effective amount of the compounds of formula (I) according to claims 1-11, and suitable for agriculture substrate, carrier or filler.

13. The use of the compounds of formula (I) according to claims 1 to 11 or fungicidal composition according to item 12 for therapeutic or prophylactic combating phytopathogenic fungi of plants or crops.

14. The method of therapeutic or prophylactic is Orby with phytopathogenic fungi of plants or crops, characterized in that the compound of formula (I) according to claims 1 to 11 or fungicidal composition according to item 12 is applied to seeds, plants or fruits of the plants or the soil where a plant grows or where it is desirable to grow.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel carbostyril compounds of general formula (1) or salts thereof with common pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds, having activity on promotion of TFF2 production, a pharmaceutical composition based on said compounds, an agent based on disclosed compounds used in case of a disorder where up-regulation of TFF has a prophylactic and/or therapeutic effect, use of disclosed compounds to prepare said agent and a method of producing disclosed compounds. The invention also relates to novel specific carbostyril compounds or salts thereof with common pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds. In structural formula (1), A is a direct bond, a lower alkylene group or lower alkylidene group, X is an oxygen or sulphur atom, the bond between positions 3 and 4 of the carbostyril backbone is a single bond or a double bond, R4 and R5 each denotes a hydrogen atom provided that, when the bond between positions 3 and 4 of the carbostyril backbone is a double bond, R4 and R5 can instead be bonded to each other in form of a -CH=CH-CH=CH- group, and R1, R2 and R3 assume values given in the claims.

EFFECT: high efficiency of compositions based on said compounds.

32 cl, 23 dwg, 184 tbl, 1535 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

, where R is a group selected from: i) hydrogen; ii) phenyl and iii) thiophenyl; Z is a substituted or unsubstituted [1,3,4]thiadiazol-2-yl group, R1 is selected from: i) hydrogen; ii) straight C1-C6alkyl; iii) C6 or C10 aryl; iv) C(O)OR5; and v) 2-methylthiazol-4-yl; R5 denotes a straight or branched C1-C6alkyl; and index x equals 0 or 1. The invention also relates to use of compounds of formula (I) to prepare a medicinal agent having human protein tyrosine phosphatase beta (HPTP-β) inhibiting action and use in treatment.

EFFECT: compounds can be used as human protein tyrosine phosphatase beta inhibitors.

11 cl, 1 dwg, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I or pharmaceutically acceptable salts thereof, which have receptor tyrosine kinase type I inhibiting properties and can be used in treating hyperproliferative disorders in mammals. In general formula

,

A is O or S; G is N; B is a 6-member aryl or 5-6-member heteroaryl ring containing a sulphur atom as a heteroatom; E is

, , , , , X is N or CH; D1, D2 and D3 independently denote N or CR19; D4 and D5 independently denote N or CR19 and D6 is O, S or NR20, where at least one of D4 and D5 is CR19; D7, D8, D9 and D10 independently denote N or CR19, where at least one of D7, D8, D9 and D10 is N; R1 is H or C1-C6 alkyl; each R2 independently denotes halogen, cyano, nitro etc, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, -SR18, -OR15, -C(O)R15, -C(O)OR15, -NR14C(O)OR18, -OC(O)R15, -NR14SO2R18, -SO2NR15R14, -NR14C(O)R15, -C(O)NR15R14, -NR15C(O)NR15R14, -NR13C(NCN)NR15R14, -NR15R14, C1-C12alkyl, C2-C12 alkenyl, alkynyl, saturated or partially unsaturated C3-C10cycloalkyl, C3-C10cycloalkyl-C1-C12alkyl, -S(O)p(C1-C6alkyl), -S(O)p(CR13R14)q-phenyl, phenyl, phenyl-C1-3-alkyl, 5-6-member heteroaryl, 5-6-member heteroaryl-C1-C3-alkyl, saturated or partially unsaturated 3-8-member heterocyclyl, 5-6-member heterocyclyl-C1-C3-alkyl, -O(CR13R14)q-phenyl, NR15(CR13R14)q-phenyl, O(CR13R14)q-(5-6-member heteroaryl), NR13(CR13R14)q-(5-6-member heteroaryl, -O(CR13R14)q-(3-8-member heterocyclyl) or -NR15(CR13R14)q-3-8-member heterocyclyl), each R3 denotes Z, where Z is selected from and , W is O or S; W2 is O or S;V is CR8R9, R8b is H or C1-C6alkyl; each of R6, R8, R8a and R9 independently denotes hydrogen, trifluoromethyl, C1-C12alkyl etc.

EFFECT: improved properties and high efficiency of using the compounds.

25 cl, 13 dwg, 1 tbl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In formula (I) Y is C-R4 and Z is CH; or Y is C-R4 and Z is N; or Y is N and Z is CH; R1 is a 5- or 6-member ring of formula (II) or (III): R2 is H, C1-C7-alkyl; R3 is phenyl, pyrazolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, which can possibly be substituted with one, two or three substitutes selected from a group consisting of: CN, CI, F, Br, CF3, CHF2, C1-C7-alkyl, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CH2F, -O-CHF2, -O-CF3, -S(O)2-Rd; R4 is H, C1-C7-alkyl; R5 is H, CI, F, Br, CN, CF3, CHF2, C1-C7-alkyl, -C3-C6-cycloalkyl, -(CH2)m-Re or -(CO)-NRiRj; R6 is C1-C7-alkyl; R7 is H, CI, F, CN or C1-C7-alkyl; Rc is -OH; Rd is C1-C7-alkyl; Re is -CH2F, -CHF2, -CF3, CN, C1-C7-alkoxy; Ri, Rj independently denote H or C1-C7-alkyl; m equals 1-4. The invention also relates to a medicinal agent having mGluR5a receptor antagonist properties, containing one or more of the disclosed compounds as an active component.

EFFECT: high efficiency of the medicinal agent.

24 cl, 208 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds have activity and selectivity towards the GABA A receptor subunit α5. In formula I , R1 denotes hydrogen, halogen, phenyl, a 6-member heterocycyl with 2 heteroatoms selected from N, O, a 5-member heteroaryl with 1-2 heteroatoms selected from S, N, cyano, lower alkyl, -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl or -(CH2)n-OH; equals 0, 1 or 2; R denotes hydrogen or lower alkyl; R2 denotes C3-C7-cycloalkyl, phenyl, 5-6-member heteroaryl with 1 heteroatom selected from N, S or a 9-10-member bicyclic heteroaryl with 1-3 heteroatoms selected from N, which are possibly substituted with one or more substitutes selected from a group comprising halogen, cyano, nitro, oxo group, lower alkyl, lower alkyl substituted with a halogen, lower alkoxy, lower alkoxy substituted with a halogen, -C(O)O-lower alkyl, lower alkylsulphonyl, -NRaRb, -C(O)-NRaRb, -C(O)-(6-member heterocyclyl with 2 heteroatoms selected from N, O), benzyloxy, 6-member heterocyclyl with 1-2 heteroatoms selected from N, S, O, possibly substituted with hydroxy, 1-2 oxo-groups, halogen or lower alkyl, or selected from a 5-6-member heteroaryl with 1-3 heteroatoms selected from N, possibly substituted with lower alkyl; Ra and Rb independently denote hydrogen, lower alkylsulphonyl, -C(O)H, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl, -(CH2)n-S-lower alkyl, -(CH2)n-S(O)2-lower alkyl, (5-member heteroaryl with 1 heteroatom selected from S)-sulphonyl, lower alkyl, -(CH2)n-(5-6-member heterocyclyl with 1 heteroatom selected from O, N), possibly substituted with lower alkyl, oxo group, or denotes -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-(5-6-member heteroaryl with 1-2 heteroatoms selected from N), possibly substituted with an oxo group, -(CH2)n-OH, -(CO)-R', where R' denotes C3-C7-cycloalkyl, a 5-member heteroaryl with 1 heteroatom selected from S, or lower alkyl; R' denotes a phenyl or a 6-member heteroaryl with 1 heteroatom selected from N which are possibly substituted with a halogen or lower alkyl, optionally substituted with a halogen. The invention also relates to a medicinal agent containing one or more compounds of formula I and use of the disclosed compounds to prepare a medicinal agent.

EFFECT: high effectiveness of derivatives.

16 cl, 145 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R3 has any

of the formulae , where R1 is selected from

,

where each R2 independently denotes hydrogen, halogen, C1-C8alkyl, C1-C8alkoxy- C1-C8alkyl, C1-C8alkoxy; R4 denotes a five- or six-member monocyclic ring system, having two heteroatoms selected from O, N and S, such as pyrazinyl, isoxazole or thiazolyl, each of which can be optionally substituted with one or more of the following substitutes: C1-C8alkyl or C1-C8alkoxy; R5 and R6 independently denote hydrogen or C1-C8alkyl; R7 and R8 together form a cyclopentyl ring; R9 independently denotes C1-C8alkyl; R9a independently denotes C1-C8alkylcarbonyl or phenylcarbonyl; R10 denotes hydrogen; R11 independently denotes C1-C8alkyl or C1-C8alkoxy; R12 denotes hydrogen or -COOR17; R13 independently denotes hydrogen, phenyl and a 6-member heteroaryl containing one heteroatom selected from N; R17 denotes hydrogen; R23 denotes (a) C1-C8alkyl, phenyl, a 5-member heteroaryl containing 1-2 heteroatoms selected from S and N, where any phenyl or heteroaryl residue is optionally substituted with a halogen, C1-C8alkyl or C1-C8alkoxy; R24 denotes C1-C8alkyl; R27 denotes H, C1-C8alkyl, C1-C8alkoxy, O-phenyl, S-phenyl; R29 denotes -(CH2)w-COOR17; where w=0; R31 denotes hydrogen; and pharmaceutically acceptable salts thereof. The invention also relates to a method of producing the disclosed compounds, a pharmaceutical composition, having dual acting ATI and ETA receptor antagonist properties, containing the disclosed compound as an active component, use of the compound in preparing a medicinal agent and methods of treating arterial hypertension.

EFFECT: high effectiveness of the compounds.

8 cl, 1 dwg, 39 ex

FIELD: chemistry.

SUBSTANCE: compound of formula (I) has antiviral activity toward the human cytomegalovirus (HCMV) or some other representative of the Herpes virida group. In formula (I)

, R1 is a group of formula , where * denotes the point of bonding to a carbonyl group, R3 denotes a pyridyl which can be substituted with a substitute independently selected from a group comprising C1-C6alkyl or a cyano group, R5 and R6 independently denote hydrogen, R2 denotes a phenyl which can be substituted with a substitute selected from a group comprising a trifluoromethoxy group, a difluoromethoxy group and a monofluoromethoxy group, A is a group of formula

or , where * denotes the point of bonding to the carbonyl group, # denotes the point of bonding to the nitrogen atom of urea, R7 denotes C1-C6alkyl which can be substituted with a substitute selected from a group comprising C3-C6cycloalkyl, R8 and R9 independently denote hydrogen, halogen or C1-C6alkyl. The invention also relates to a method of producing a compound of formula (I) from a compound of formula , a method of producing a compound of formula (V), a medicinal agent containing the disclosed compound, use of the compound in preparing a medicinal agent and a method of fighting viral infections, among them human cytomegalovirus (HCMV) or some other representative of the Herpes viridae group.

EFFECT: high antiviral activity.

9 cl, 1 tbl, 39 ex

FIELD: chemistry.

SUBSTANCE: formula (I) compound has antibacterial activity and can be used as a medicinal agent. In formula ,

R1 is hydrogen, halogen, C1-4alkyl; R2 is selected from hydrogen, halogen, C1-4alkyl; R3 is selected from hydrogen, halogen, cyano, C1-4alkyl; W is -N(R6)-; X is a single bond; ring A is an unsaturated or partially saturated ring containing 5-6 atoms, one or two of which are independently selected from nitrogen and sulphur; or an unsaturated or partially saturated bicyclic ring containing 9-10 atoms, one, two or three of which are selected from nitrogen and sulphur; R4 and R5 are substitutes on a carbon atom and are independently selected from a halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, formyl, hydroxy iminomethyl, C1-4alkoxyminomethyl, C1-4alkyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkoxy)carbamoyl, N-(C1-4alkyl)-N-(C1-4alkoxy)carbamoyl, C1-4alkylS(O)a, where a equals 0-2, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, C1-4alkylsulphonylamino, (saturated or unsaturated carbocycle containing 3-7 atoms)-R10- or (saturated, partially saturated or unsaturated ring containing 5-6 atoms, one or two of which are selected from nitrogen, oxygen and sulphur)-R11-; where R4 and R5 can independently and optionally substituted at the carbon atom with one or more R12; R6 is hydrogen; n equals 1-4; where values of R4 can be identical or different; m equals 0-4; where values of R5 can be identical or different; R12 is selected from azido, halogen, cyano, hydroxy, amino, carboxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, C1-4alkylS(O)a, where a equals 0-2, (saturated or unsaturated cabocycle containing 3-7 atoms)-R14- or (saturated, partially saturated or unsaturated ring containing 5 or 6 atoms, one or two of which are selected from nitrogen, oxygen and sulphur)-R15-; where R12 can independently and optionally be substituted at the carbon atom with one or more R9; R10, R11, R14 and R15 are independently selected from a single bond, -C(O)-, -N(R19)C(O)- or -C(O)N(R20)-; where R19 and R20 are independently selected from hydrogen or C1-4alkyl; R16 is selected from halogen, cyano, hydroxy, carboxy, methyl and methoxy. The invention also relates to a pharmaceutical composition, having antibacterial activity, containing the disclosed compound as an active ingredient, use of the disclosed compound to prepare a medicinal agent and a method of producing the compound of formula (I).

EFFECT: high activity of the compounds.

22 cl, 52 tbl, 721 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention describes compounds of formula I: formula I or its pharmaceutically acceptable salt, where the radical values R3, R4, R2, X1, X2, R1 are such as presented in claim 1. Also, the invention describes a pharmaceutical composition exhibiting a Tec-family kinase inhibitor activity and based on the compounds of formula I, a method of Tec-family kinase activity inhibition, and a method of producing the compound of formula I.

EFFECT: produced and described new compounds which are effective as Tec-family (eg, Tec, Btk, Itk/Emt/Tsk, Bmx, Txk/Rlk) protein kinase inhibitors, and acceptable compositions are applicable for treatment or prevention of some diseases, disorders or conditions including but not limited, autoimmune, inflammatory, proliferative or hyperproliferative, or immunologically mediated diseases.

50 cl, 18 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: in formula (I) , the ring A represents 6-members aryl or 5-6-members heteroaryl containing 1-2 heteroatoms selected from nitrogen and sulphur; Q means C3-8 cycloalkyl, 5-6-members heterocycle containing 1 heteroatom selected from oxygen, nitrogen or sulphur, C1-6 alkyl or C2-6 alkenyl; the ring T represents 5, 6, 9 or 10-members heteroaryl or 9-members heterocycle optionally additionally substituted by 1-3 heteroatoms independently selected from nitrogen or sulphur. The values of other substitutes are specified in the patent claim. Also, the invention refers to methods for preparing oxime derivatives of general formula (I), to pharmaceutical compositions containing the compound of the invention as an active ingredient and to applications of the compounds of the invention in preparing a drug.

EFFECT: compounds of the invention exhibit properties of a glucokinase activator.

33 cl, 1499 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel carbamoyl benzotriazole derivatives of general formula , (values of radicals are given in the description), tautomers thereof and pharmaceutically acceptable salts and use thereof as endothelial lipase inhibitors.

EFFECT: improved properties of the derivatives.

11 cl, 148 ex

FIELD: chemistry.

SUBSTANCE: compound of formula (I) has antiviral activity toward the human cytomegalovirus (HCMV) or some other representative of the Herpes virida group. In formula (I)

, R1 is a group of formula , where * denotes the point of bonding to a carbonyl group, R3 denotes a pyridyl which can be substituted with a substitute independently selected from a group comprising C1-C6alkyl or a cyano group, R5 and R6 independently denote hydrogen, R2 denotes a phenyl which can be substituted with a substitute selected from a group comprising a trifluoromethoxy group, a difluoromethoxy group and a monofluoromethoxy group, A is a group of formula

or , where * denotes the point of bonding to the carbonyl group, # denotes the point of bonding to the nitrogen atom of urea, R7 denotes C1-C6alkyl which can be substituted with a substitute selected from a group comprising C3-C6cycloalkyl, R8 and R9 independently denote hydrogen, halogen or C1-C6alkyl. The invention also relates to a method of producing a compound of formula (I) from a compound of formula , a method of producing a compound of formula (V), a medicinal agent containing the disclosed compound, use of the compound in preparing a medicinal agent and a method of fighting viral infections, among them human cytomegalovirus (HCMV) or some other representative of the Herpes viridae group.

EFFECT: high antiviral activity.

9 cl, 1 tbl, 39 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

where R1 is a phenyl group (said phenyl group is substituted with one or more C1-6alkyl groups, one C1-3alkyl group (said C1-3alkyl group is substituted with one or more halogen atoms), one C1-3alkoxy group (said C1-3alkoxy group is substituted with one or more halogen atoms) or one or more halogen atoms), R2 is a C1-3alkyl group, R3 is a phenyl group (said phenyl group is substituted with one or more substitutes selected from a group comprising halogen atoms or a (C=O)R5' group (where R5' is NR6'R7', (where R6' is a hydrogen atom, and R7' is a C1-6alkyl group substituted with a hydroxyl group))), a thienyl group (said thienyl group is substituted with one or more substitutes selected from a group comprising hydrogen atoms and a (C=O)R5 group (where R5 is NR6R7 (where R6 is a hydrogen atom or a C1-3alkyl group, and R7 is a C1-6alkyl group (said C1-6alkyl group can be substituted with one or more hydroxyl groups, one C1-3alkoxy group or a 5-6-member aromatic heterocyclic group containing 1-2 heteroatoms selected from oxygen or nitrogen (where the 5-6-member aromatic heterocyclic group can be substituted with one or more C1-3alkyl groups, one or more C1-3alkoxy groups, and in case of a 5-6-member aromatic heterocyclic group containing one nitrogen atom, can be in be in form of N-oxides)), a pyridyl group, or overall NR6R7 is a nitrogen-containing heterocyclic group which is a 5-6-member hetero-monocyclic group which contains one or two nitrogen atoms and can additionally contain on oxygen atom (said nitrogen-containing heterocyclic group can be substituted with one or more hydrogen atoms, one or more C1-6alkyl group, one or more hydroxyl groups)) or C1-6alkyl group (said C1-6alkyl group can be substituted with one or more halogen atoms and is substituted with one cyano group))), and R4 is a hydrogen atom or to a pharmaceutically acceptable salt of said compound. The invention also relates to a medicinal agent for preventing or treating diseases, in which activation of the thrombopoietin receptor is effective, based on said compounds.

EFFECT: obtaining novel compounds and agents based thereon, which can be used in medicine to increase the number of thrombocytes.

33 cl, 7 tbl, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention describes compounds of formula I: formula I or its pharmaceutically acceptable salt, where the radical values R3, R4, R2, X1, X2, R1 are such as presented in claim 1. Also, the invention describes a pharmaceutical composition exhibiting a Tec-family kinase inhibitor activity and based on the compounds of formula I, a method of Tec-family kinase activity inhibition, and a method of producing the compound of formula I.

EFFECT: produced and described new compounds which are effective as Tec-family (eg, Tec, Btk, Itk/Emt/Tsk, Bmx, Txk/Rlk) protein kinase inhibitors, and acceptable compositions are applicable for treatment or prevention of some diseases, disorders or conditions including but not limited, autoimmune, inflammatory, proliferative or hyperproliferative, or immunologically mediated diseases.

50 cl, 18 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound having structure

, radicals are as described in the formula of invention, as well as pharmaceutically-acceptable salt, prodrug, tautomer and stereoisomer thereof. The invention also relates to a composition, a set for modulating PPAR based on said compound, a method of treating a patient suffering from a disease or condition or at risk of a disease or condition, for which PPAR modulation is therapeutically useful.

EFFECT: novel compounds which are active towards PPAR are obtained and described.

41 cl, 622 ex, 8 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

where there are R3/R3', R4/R4' and R5/R5' where at least one of either R4/R4' or R5/R5' always represents a fluorine atom, and the other radical values are disclosed in the description.

EFFECT: making the compounds which are γ-secretase inhibitors, and can be effective in treating Alzheimer's disease or advanced cancers, including but not limited to carcinoma of uterine cervix and breast carcinoma and malignant tumours of hematopoietic system.

15 cl, 3 tbl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of formula I in which cycle A represents unsaturated carbocycle with double bonds, which is selected from phenyl or naphtyl; 1 can take value from 1 to 3; m can take value 0, 2 or 3; n can take value 0 or 2; R1 represents a hydrogen atom, (C1-3)alkyl group; R2 represents(C1-6)alkyl group, which is possibly substituted with substituent, selected from C6-cycloalkyl, monocyclic heteroaryl, selected from thiophene, aryl group, selected from phenyl, in form of base or salt of bonding with an acid. Invention also relates to pharmaceutical composition, based on formula I compound, to application of formula I compound for obtaining medication, to method of obtaining formula I compound and to application of formula compound for obtaining formula 1 compound.

EFFECT: obtained are novel isoquinoline and benzo[h]isoquinoline derivatives, possessing properties of antagonists of histamine type H3 receptor.

9 cl, 1 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula 2: and to its pharmaceutically acceptable salts and their mixtures, where values of R, M, Q, Z, W, D radicals are described in i.1 of the invention formula. Invention also relates to pharmaceutical compositions, which possess inhibiting activity with respect to Btk, based on formula 2 compounds.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions which can be applied in medicine for treatment of patients with diseases associated with inhibiting Btk activity and/or B-cell activity.

55 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A is a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-member cyclic system containing at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N; optionally substituted with one or more substitutes independently selected from a group comprising halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, C1-4alkoxy and a hydroxyl group; B is a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from S and N; optionally substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, aryl and C1-8alkylthio; either a) R1 is a group of formula: -L-(CR'R")n-G, where L is a binding group selected from a group consisting of a direct bond, -(CO)-, -(CO)NR'- and -SO2-; R' and R" is independently selected from hydrogen atoms; n assumes values from 0 to 1; and G is selected from a group consisting of a hydrogen atom and C1-4alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic groups, where heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one or two carbon atoms are substituted with a N heteroatom; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted with one or more substitutes selected from halogen atoms; and R2 is a group selected from hydrogen atoms, halogen atoms and C1-4alkyl, C2-5alkynyl, C1-4alkoxy, -NH2 and cyano groups, where alkyl and alkynyl groups may be unsubstituted or substituted with one aryl group; or b) R2, R1 and -NH- group to which R1 is bonded form a group selected from groups of formulae and , where: Ra is selected from a hydrogen atom or groups selected from C1-4alkyl, C3-8cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O and N; saturated heterocyclic rings, where the heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one carbon atom is substituted with a heteroatom selected from O and N; and C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted with one or more groups selected from halogen atoms, cyano group, trifluoromethoxy and carbamoyl; Rb denotes hydrogen; and pharmaceutically acceptable salts thereof and N-oxides; provided that the compound is not selected from N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, and N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]formamide. The invention also relates to a pharmaceutical composition, use of compounds in any of claims 1-20, a method of treating a subject, as well as a composite product.

EFFECT: obtaining novel biologically active compounds having adenosine A2B receptor antagonist activity.

27 cl, 160 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel pyrimidine derivatives or their pharmaceutically acceptable salts, possessing inhibiting activity with respect to glycogensintase kinase-3 (GSK3). In compound of formula I: R1 is selected from hydrogen, cyano, C1-3alogenoalkinyl, SO2NRbRc, C0-2alkyl(O)NRbRc, C1-4alkylNBbRc, SO2Ri, C(O)ORa, CH(OH)Rj and C(O)Rj; R2 and R4 are independently selected from hydrogen, halogeno, cyano, NO2, C1-4alkyl, C1-3ahalogenoalkyl, ORa, C(O)NRbRc, SO2Ri, and C(O)ORa; or R1 and R2 together with atoms, to which they are bound, are bound with formation of 5- or 6-member heterocyclic ring, which contains one S, any of the hydrogen atoms of group CH2 in said heterocyclic ring can be substituted by oxo, hydroxy, and sulphur atom in said heterocyclic ring is probably oxydised to -SO2-; R3 and R5 represent hydrogen; R6 represents tetrahydropyran; R7 is selected from hydrogen, C1-3alkyl, cyano and C1-3halogenoalkyl; R8 represents hydrogen; Ra is selected from C1-3alkyl and C1-3halogenoakryl. Other radicals are given in formula of invention.

EFFECT: compounds can be applied in manufacturing medication for prevention and/or treatment of predemential states, moderate cognitive failure and type II diabetes, Alzheimer's disease and Parkinson disease, as well as bone-associated malfunctions.

40 cl, 3 dwg, 1 tbl, 122 ex

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