Fungicide hydroximoyl-tetrazole derivatives

FIELD: chemistry.

SUBSTANCE: invention relates to hydroximoyl-tetrazole derivatives of formula (I), , where T is a tetrazole substitute, A is a phenyl or heterocycle, L1 and L2 are different linker groups, and Q is a carbocycle, use thereof as fungicide active agents, particularly in form of fungicide compositions, and methods of controlling phytopathogenic fungi, especially plants, using said compounds or compositions.

EFFECT: more effective use of the compounds.

13 cl, 2 tbl, 2 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.

Compounds described in the above two documents do not confirm that they provide a comparable benefit for the compounds according to this invention.

Agriculture has always been great interest in the use of 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, is it 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;

L2is a direct link Il is 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]halogen is of cloacina, 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)NR6R7N(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/sub> -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 NNR12R13;

Q is chosen from the group consisting of Q1-Q12

where X1-X11independently 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)R14, -C(=O)OR14, -C(=O)NR14R15, -C(=O)SR14, -C(=S)R , -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)2OR14, -S(=O)2NR14R15, nitro, nitroso, azido, cyano, -SF5and-SiR14R15R16;

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]Alcock and, [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, if A is chosen from the group consisting of A2, A5, A11, A16, A17, A18, A23, A24, A29, A30, A34and A36L1is CH2and L2represents a direct bond, and Q cannot represent Q1.

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 of monorail ways, 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 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 of the present invention relates to hydroxymelatonin derivative of the formula (Ia), (Ib), (Ic) and (Id)

where A, Q, L1and L2matter, similarly defined for the substituents of the compounds of formula (I) according to this invention;

E1you who eraut 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)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 and the finding are compounds where L1represents a direct bond or a divalent group selected from the group consisting 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 L 2represents 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.

Friend the mi the preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds 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)NR6R7, -N=CR5R6, -N=C-NR5 R6, -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 more preferred compounds of formula (I) and (Ia)to(Id) according to this invention are from the organisations, 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 K1and K2independently 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-Q7.

Other more preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where Q is equal to Q1.

Still other preferred compounds of formula (I) and (Ia)to(Id) according to this invention are compounds where X1-X11independently 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, 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-X11independently 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, Hairdryer who stated, 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=N-NR19R20, -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 predpochtitel the different compounds of the 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 can be combined in various 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 PR is doctitle values of one or more L 1L2, 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, in order to form most preferred 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, and X, 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 herein, 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, comprising the additional modification of this group, especially the acylation reaction, alkoxycarbonylmethyl, alkylaminocarbonyl or alkylaminocarbonyl, according to known methods. In this case, the proposed method P2 according to this invention and this too is 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 carrying out of the way 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. Preferably optionally halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as IER the silt 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, potassium bicarbonate, 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-dimethylamines the Dean, 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 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.

The treatment is carried out in the usual ways. Typically, 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 cleaned 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, on the basis of General knowledge and of available publications will be clear that the experts in this is blasty will be able to adapt these methods for each of the compounds according to this invention, which 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. BeIg. 1987, 96, 675).

In the following aspect, 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 "effective and non-toxic amount" means an amount of composition according to this invention that is sufficient to fight or destroy 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. This number can sonatica 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, which are in the competence of specialists 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 or 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 is a 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.

Also can optionally contain additional components such as semitically, 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-dispersible powder, a dispersible powder, flowable concentrate, mix with butter, mix with the oil liquid, paste, stick for plants, powder for dry seed treatment, seed coated with a pesticide, soluble concentrate, soluble powder, solution for seed treatment, suspension concentrate (flowable concentrate), liquid with extremely small the 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 are 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, Metalac the DRS-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, findingaid, 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, Gludio is Soylu, 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, 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, polio is Sinama, 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-(methoxyimino)-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-imidazole-1-carboxylate, 1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-3-(trifluoromethyl)-1H-pyrazole-4-ka is boxlid, 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 salts, 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, verison, flamethrower, fluopicolide, perimed, fluotitanic, fosetyl-aluminum, 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-imidazol-5-to rboxylic, 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]phenyl}imageformat, 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, the feast is anitrim, 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, it is proposed a method of therapeutic or prophylactic combating phytopathogenic fungi of 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 the but 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 treatment may 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, earthlings is th walnut), 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 modifitsirovannoe 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, Uromyces 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;

picsnatalie, 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; Colletotrichum 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, caused for example, Pyrenophora teres; Ramularia diseases caused, for example, Ramularia collo-cygni; 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 Zabol the tion, 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 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 p is chonnam rotting 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 elm disease, 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 are able in order to 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 doses presented 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 the production of 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 for improved agronomic qualities 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-II is illustrated a non-limiting manner 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 with about atoi 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

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

5-Methyl-1-(cyclohexylcarbonyl)tetrazol

To a solution of cyclohexanecarboxaldehyde (35,6 g, 280 mmol) in DMF (300 ml) was added in portions N-chlorosuccinimide (39,2 g, 294 mmol), maintaining the reaction temperature below 45°C. For the Le you are finished adding the mixture was stirred over night at room temperature before adding saturated aqueous solution of NH 4Cl (900 ml). The mixture was extracted with ethyl acetate. The organic layer was washed successively with water (500 ml) and saturated salt solution (500 ml), dried (MgSO4), filtered and concentrated. The residue and 5-methyltetrazol (24,7 g, 294 mmol) was dissolved in dichloromethane (400 ml) was added dropwise at room temperature, triethylamine (50,8 ml, 364 mmol). After stirring overnight the mixture was concentrated and the residue was dissolved in ethyl acetate. The solution was washed successively with a saturated aqueous solution of NH4Cl, water, and saturated salt solution, then dried (MgSO4), filtered and concentrated. Chromatography on silica gel of the residue gave 16.6 g of 5-methyl-1-(cyclohexylcarbonyl)tetrazolo [exit 28,3%;1H-NMR (CDCl3) δ ppm: 1,1-1,5 (m, 4H), 1,62-to 1.98 (m, 6H), to 2.55 (s, 3H), 2,8 (m, 1H), 9,3 (broadened, 1H); HPLC/MS: m/z=210 (M+H)].

O-(2-Phthalimidopropyl-6-yl)methyl(5-methyltetrazol-1-yl)cyclohexylmethoxy (compound 22)

To a cooled solution (0-5°C) 5-methyl-1-(cyclohexylcarbonyl)tetrazole (0.5 g, 2,39 mmol) in acetonitrile (14 ml) was added DBN (0,31 ml, 2,63 mmol). After complete addition, the mixture was stirred for five minutes and added portions 6-methyl bromide-2-phthalimidopropyl (0,83 g, 2,63 mmol). After complete addition, the mixture was stirred five minutes before cooling in an ice bath After stirring overnight, the mixture was concentrated. Chromatography on silica gel of the residue gave of 0.62 g of compound 22 [output 58,1%; HPLC/MS: m/z=445 (M+H); LogP=of 3.46].

O-(2-Aminopyridine-6-yl)methyl(5-methyltetrazol-1-yl)cyclohexylmethoxy (compound 23)

To a solution of compound 22 (0.8 g, 1.8 mmol) in THF (23 ml) was added hydrazinehydrate (0,38 ml, 9 mmol). After stirring over night the reaction mixture was filtered. The solid residue washed with THF. The combined filtrates were concentrated. The residue was dissolved in chloroform (150 ml). The mixture was filtered. Concentration of the filtrate gave of 0.54 g of compound 23 [exit 95,1%; HPLC/MS: m/z=315 (M+H); LogP=1,43].

O-(2-n-intercorporeality-6-yl)methyl(5-methyltetrazol-1-yl)cyclohexylmethoxy (compound 27)

To a solution of compound 23 (0.15 g, 0.48 mmol) in dry dichloromethane (5 ml) was added triethylamine (of 0.07 ml, 0.52 mmol)was then added dropwise n-hexanoate (0.05 ml, 0.52 mmol). After completion of the reaction, determined by TLC, the reaction mixture was concentrated. Chromatography on silica gel of the residue gave 0.18 g of compound 27 [exit 81,2%; HPLC/MS: m/z=413 (M+H); LogP=4,39].

O-(5-Amino-1,2,4-thiadiazole-3-yl)methyl(3-chlorophenyl)-(5-methyltetrazol-1-yl)metrorock (compound 65)

To a solution of 5-methyl-1-(2-chlorophenylacetic email)tetrazole (2.9 g, 12.2 mmol) in dry dichloromethane (50 ml) was added to the resin PL-TBD-MP 1.8 mmol/g (13,6 g) and 5-amino-3-chloromethyl-1,2,4-thiadiazole (2 g, a 13.4 mmol). After stirring over night the reaction mixture was filtered and concentrated. Chromatography on silica gel of the residue gave of 0.43 g of compound 65 [output of 9.6%; HPLC/MS: m/z=351 (M+H); LogP=2,17].

O-(5-n-intelcorporation-1,2,4-thiadiazole-3-yl)methyl(3-chlorophenyl)-(5-methyltetrazol-1-yl)metrorock (compound 67)

To a solution of compound 65 (0,19 g, 0.55 mmol) in dry dichloromethane (5 ml) was added to the resin PL-DIPAM 1.7 mmol/g (0.65 g) and PS-DMAP 1.38 mmol/g (16 mg), then n-hexanoate (and 0.09 ml, 0.66 mmol). After stirring over night the reaction mixture was filtered and concentrated. Chromatography on silica gel of the residue gave 0.14 g of compound 67 [exit 51,9%; HPLC/MS: m/z=449 (M+H); LogP=3,85].

The following examples illustrate non-limiting way, 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 water rest the rum, not containing active compounds. 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: 23, 24, 27, 29, 31, 32, 65 and 67.

Example B: 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 the existing connections: 6, 8, 9, 17, 24, 27, 29, 32, 66 and 67.

1. The compound of formula (I)

where T represents tetrazolyl group of formula T1or T2

where E1and E2independently selected from the group consisting of hydrogen, [C1-C8]alkyl, [C1-C8]halogenoalkane, [C2-C8]alkenyl, [C2-C8]halogenoalkane, [C2-C8]quinil, [C1-C5]halogenoalkane;
L1and L2represents a direct bond or -(CR1R2)n-where n is 1, 2, 3 or 4;
R1and R2independently selected from the group consisting of hydrogen, [C1-C4]alkyl;
And are selected from the group consisting of


where Z1-Z7and K1independently selected from the group consisting of water the ode, -NR5R6, -N(R5)C(=O)R6, -N(R5)C(=O)OR6, -N(R5)C(=O)NR6R7, -N-CR5R6, -N-CNR5R6, -N=(R5)C(=NR6)NR7R8, -N(R5)C(=S)R6, -N(R5)C(=S)R6R7, [C1-C8]alkyl;
Q is chosen from the group consisting of

where X1-X11independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl, [C1-C4]halogenoalkane;
R5-R8independently selected from the group consisting of hydrogen, [C1-C8]alkyl, [C3-C8]cycloalkyl, phenyl and phenyl [C1-C8]alkyl;
and its salts, provided that, if And are selected from the group consisting of And2and A16L1is CH2and L2represents a direct bond, and Q cannot represent Q1.

2. The compound according to claim 1, where L1is -(CR1R2)n-where R1and R2represent hydrogen and n is 1 or 2.

3. The connection of claim 1, where L2represents a direct bond or -(CR1R2)n-where R1and R2imagine the waters of the genus and n is 1 or 2.

4. The compound of formula (I) according to claim 1, where a is chosen from the group consisting of And2And16And31and32.

5. The compound of formula (I) according to claim 1, where Z1selected from the group consisting of hydrogen, -NR5R6, -N(R5)C(=O)R6, -N(R5)C(=O)OR6.

6. The compound of formula (I) according to claim 1, where Z2, Z3, Z4, Z5, Z6and Z7represent hydrogen.

7. The compound of formula (I) according to claim 1, where Q is Q1or Q4.

8. The compound of formula (I) according to claim 1, where X1-X11independently selected from the group consisting of hydrogen, halogen, [C1-C4]alkyl.

9. The compound of the formula according to claim 1, where E1and E2represent [S1-C4]alkyl.

10. The compound of formula (I) p, where E1and E2represent methyl.

11. Fungicidal composition containing as active ingredient an effective amount of the compounds of formula (I) according to claims 1-10 and fit in agriculture substrate, carrier or filler.

12. The use of the compounds of formula (I) according to claims 1 to 10 or fungicidal composition according to claim 11 for the treatment or prevention of combating phytopathogenic fungi of plants or crops.

13. The method of therapeutic or prophylactic combating phytopathogenic fungi of plants or crops, otlichalis the same time, the compound of formula (I) according to claims 1 to 10 or fungicidal composition according to claim 11 applied to seeds, plants or the fruit of plants or to the soil in which the plant is growing or in which it is desirable to grow.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel diarylamine-containing compounds of formula (I) or formula (4b), pharmaceutically acceptable salts thereof, which have c-kit inhibiting properties. In formulae (I) and (4b), each R1 independently denotes H, -C(O)OH and -L1-C1-6alkyl, where L1 denotes -O- or -C(O)O-, or any two neighbouring R1 groups can together form a 5-6-member heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, a 6-member heterocyclic ring with one or two nitrogen atom s as heteroatoms, optionally substituted with a C1-4alkyl, and R5 denotes hydrogen or C1-C6alkyl; values of radicals Ar and Q are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds, and a method of treating diseases whose development is promoted by c-kit receptor activity.

EFFECT: more effective use of the compounds.

17 cl, 3 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R denotes a thiazolyl group of formula R2 and R3 are selected from: hydrogen, C1-C3linear alkyl; R4 is selected from: C1-C3linear or C3cyclic alkyl, phenyl and thiophenyl; Z denotes a group of formula: -(L)n-R1; R1 is selected from: i) C1-C3linear or branched alkyl, optionally substituted with C1-C4alkoxycarbonyl, halogen; ii) substituted phenyl or substituted with one or two substitutes selected from halogen, methoxy- or hydroxy group, C1-C4alkoxycarbonyl; iii) dioxopiperazinyl and 2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl, substituted with C1-C3alkyl; or iv) heteroaryl rings containing 5-10 atoms selected from thiazole, triazole, 1H-imidazole, thiadiazole, oxazole, isoxazole, oxadiazole, benzodioxole, benzo(1,4)dioxepanyl, pyridine, pyrimidine, 1H-indole, 2,3-dihydrobenzo[b][1,4]dioxynil, which can be substituted with oine or two substitutes selected from: a) hydroxy; b) C1-C3alkyl (which can be substituted with one more two substitutes selected from: ) phenyl; ii) C1-C4alkoxycarbonyl; iii) naphthalenyl; iv) 2-methylthiazolyl) ; c) NHC(O)C1-C3alkyl; d) C1-C4alkoxycarbonyl; e) 1 -(tert-butoxycarbonyl)-2-phenylethyl; f) methoxybenzyl; g) phenyl which can be substuted with C1-C4alkoxy, halogen, methoxycarbonyl or >NHC(O)CH3; h) (methoxy-2-oxoethyl)carbamoyl; L denotes a group selected from: i) C(O)NH[C(R5aR5b)]w-; ii) -C(O)[C(R6aR6b)]x-; iii) -C(O)[C(R7aR7b)]yC(O)-; iv) -SO2[C(R8aR8b)]z-; R5a, R5b, R6a, R6b, R7a, R7b, R8a and R8b, each independently denotes: i) hydrogen; ii) C1-C3 linear alkyl which can be substituted with 1 or 2 halogen atoms; iii) phenyl which can be substituted with 1-2 substitutes selected from halogen and lower alkoxy; iv) heteroaryl rings selected from imidazolyl, imidazolyl substituted with methyl, benzo(1,4)oxazinyl, oxadiazolyl substituted with methyl; index n equals 0 or 1; indices w, x, y and z are each independently equal to a number from 1 to 3. The invention also relates to pharmaceutically acceptable salts of compounds of formula (I) and use of compounds of formula (I) to prepare a medicinal agent for treating protein tyrosine phosphatase beta-mediated conditions.

EFFECT: obtaining compounds of formula (I) as human protein tyrosine phosphatase beta (HPTP-β) inhibitors.

15 cl, 17 dwg, 13 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an isoxazoline-substituted benzamide derivative of formula or salt thereof, where A1 denotes a carbon or nitrogen atom, A2 and A3 independently denote a carbon atom, G denotes a benzene ring, W denotes an oxygen or sulphur atom, X denotes a halogen atom or C1-C6alkyl, arbitrarily substituted with a radical R4, Y denotes a halogen atom, cyano, nitro, C1-C6alkyl, C1-C6alkyl arbitrarily substituted with radical R4, -OR5, -N(R7)R6, phenyl, D-41, when n equals 2, each Y can be identical or different from each other, R1 denotes -C(R1b)=NOR1a, M-5, -C(O)OR1c, -C(O)SR1c, -C(S)OR1c, -C(S)SR1c, -C(O)N(R1e)R1d, -C(S)N(R1e)R1d, -C(R1d)=NN(R1e)R1lf, phenyl, phehnyl substituted with (Z)p1, or D-3, D-8, D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59, R2 denotes C1-C6alkyl, -CH2R14a, E-5, C3-C6alkynyl, -C(O)R15, -C(O)OR15, -C(O)C(O)OR15 or -SR15, where, when R1 denotes -C(R1b)=NOR1a, M-5, or -C(R1b)=NN(R1e)R1f, R2 can denote a hydrogen atom, when R1 denotes -C(O)OR1c, -C(O)SR1c, -C(S)OR1c or -C(S)SR1c, R2 can denote hydrogen, when R denotes -C(O)N(R1e)R1d or -C(S)N(R1c)R1d, R2 can denote a hydrogen atom, when R1 denotes phenyl, phenyl substituted with (Z)p1, or D-3, D-8, -D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59 R2 can denote C1-C6halogenalkyl, C1-C6alkyl arbitrarily substituted with a radical R14a, C3-C6alkenyl, -C(O)NH2, -C(O)N(R16)R15, or R2 together with R1 can form =C(R2b)R2a, R3 denotes C1-C6alkyl arbitrarily substituted with radical R4, D-1, D-3, D-8, D-13-D-15, D-21, D-35, D-41, D-52-D-55, D-57-D-59 denote aromatic heterocyclic rings, m equals an integer from 2 to 3, n equals an integer from 0 to 2.

EFFECT: isoxazoline-substituted benzamide derivative and salt thereof are used in pest control, against harmful arthropods in agriculture and horticulture or in livestock farming and in the field of hygiene.

12 cl, 18 tbl, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 1,7-bis[4(5)-methyl-1,3-thiazol-2-yl]-3,5-dithia-1,7-diazaheptanes of general formula (1), which can be used in organic synthesis to produce macro-heterocyclic rings, as well as sorbents and extraction agents for precious and rare-earth metals. The method is realised by reacting hydrogen sulphide-saturated aqueous formaldehyde solution (37%) with 2-amino-4(5)-methylthiazole with molar ratio of initial reagents 2-amino-4(5)-methylthiazole: formaldehyde: hydrogen sulphide equal to 20:30:20, at temperature -5-5°C and atmospheric pressure for 8-12 hours.

EFFECT: improved method.

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 a use of N-(2-thiazolyl)amide derivatives of formula

,

where R1 and R2 are independently selected from H, -NO2, halogen, C1-C6 alkyl with a straight chain, where at least one of R1 and R2 is different from H; m equals 0, 1, 2 or 3; X is selected from a group consisting of: indole of formula (A) bound in position 2, indole of formula (B) bound in position 3 and indazole of formula (C) bound in position 3:

, , ,

where R3 is selected from H and C1-C6 alkyl with a straight chain; R4, R5, R6 and R7 are independently selected from H and C1-C6 alkoxy group; R8 is selected from H and C1-C6 alkyl, or any of its pharmaceutically acceptable salts to obtain a medicinal agent for treating or preventing diseases or conditions mediated by GSK-3, especially neurodegenerative diseases such as Alzheimer's disease or insulin-independent sugar diabetes. The invention also relates to a compound of formula (I), a pharmaceutical composition based on said compound and synthesis method thereof.

EFFECT: high efficiency of using said derivatives.

30 cl, 3 tbl, 7 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 general formula (11) given below and pharmaceutically acceptable salts thereof: chemical formula 1

in which: each of G1, G2, G3 and G8 independently denotes -N=, -CR1= or -C(-G9-X)=; one of G1, G2, G3 and G8 is-C(-G9-X)=; X is C1-6 alkyl (where C1-6 can be optionally substituted with a group selected from a halogen atom, hydroxy, cyano and -NR56R57), aryl, heterocycle (where the heterocycle denotes a 5-9-member saturated or unsaturated cyclic group containing one or more heteroatoms selected from nitrogen, oxygen and sulphur atoms, and can be a monocycle or condensed ring, and can be optionally substituted with a halogen atom, C1-6 alkyl; C1-6 alkoxy, R33R34NCS-, R3R4NCO-); G9 denotes a single bond, an oxygen atom, a sulphur atom, ring G6 denotes a divalent aryl group or divalent pyridyl group (where the divalent pyridyl group can be optionally substituted with a halogen atom); A is a group of formula (2) given below, or a group of formula (3) given below. Chemical formula 2

, chemical formula 3 , G4 is an oxygen atom or sulphur atom; G5 is an oxygen atom or sulphur atom; G7 is an oxygen atom, -CR42R43-, -CONR44-, -NR44CO, -NR45-, CR42R43NR45-, -S-, -NR44S(=O)2-; R1 is a hydrogen atom, a halogen atom, cyano, C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a halogen atom), carbamoyl or C2-7 alkynyl (where C2-7 alkynyl can be optionally substituted with C1-4 acyl); when G2 or G3 denotes -CR1=, then G8 is -C(-G9-X)=, and X is R3R4NCO-, R33R34NCS-; when G8 is -CR1=, then G3 denotes -C(-G9-X)=, and X is R3R4NCO, or R33R34NCS-; when G1 or G8 denotes -CR4 then G2 is -C(-G9-X)=, and X denotes R3R4NCO-, or R33R34NCS-; or when G2 is -CR1=, then G1 denotes -C(-G9-X)=, and X denotes R3R4NCO-, or R33R34NCS-; R1 can form a single bond or -CH2- with R4 or R34; R2 denotes hydroxy or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from a halogen atom, hydroxy, C1-6 alkoxy, formyl and -CO2R50); R3, R4, R9 and R10 each independently denotes a hydrogen atom, C3-8 cycloalkyl or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from cyano, a halogen atom, hydroxy, C1-6 alkoxy, -NR13R14, and CONR28R29); R6 and R7 each independently denotes a hydrogen atom, C1-6 alkoxy, C3-8 cycloalkyl or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from cyano, halogen atom, hydroxy, C1-6 alkoxy, -NR13R14, and CONR28R29); R33 and R34 each independently denotes a hydrogen atom, C1-6 alkyl, the combination of R3 and R4 together with a nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom or C1-6 alkyl; the combination of R6 and R7 together with the nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom, C1-6 alkyl or an oxo group; R45 is a hydrogen atom, R13 and R14 each independently denotes a hydrogen atom, C1-6 alkyl or COR32; R56 and R57 each independently denotes a hydrogen atom or C1-6 alkyl, and R5, R8, R28, R29, R32, R42, R43, R44, and R50 each independently denotes a hydrogen atom or C1-6 alkyl. The invention also relates to a pharmaceutical composition, as well as to a medicinal agent for treating cell proliferative disorder.

EFFECT: obtaining novel biologically active compounds having inhibitory effect on cell proliferation.

15 cl, 2 tbl

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: invention relates to novel imidazole derivatives of general formula I and pharmaceutically acceptable salts thereof, where R1 is selected from a group comprising aryl and alkyl, optionally substituted hydroxy; R2 is selected from a group comprising hydrogen and alkyl; R3 is selected from a group comprising hydrogen and -X-A, where X is selected from a group comprising -C(O)- and -S(O)2-; and A is selected from a group comprising hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle and optionally substituted cycloalkyl, where the optionally substituted groups are substituted with 1-2 substitutes selected from a group comprising alkyl, substituted alkyl, alkoxy, substituted amine which is a -NRR group, substituted aryloxy, heteroaryl, heterocycle, halogen, hydroxy and -S(O)2-R9, where R9 is an alkyl; or R1 and R3 together with a carbon atom bonded to R1 and a nitrogen atom bonded to R3 form a heterocyclic or substituted heterocyclic group; R4 is selected from a group comprising hydrogen, linear alkyl, -alkylene-aminoacyl-, -alkylene-hydroxy-, -[alkylene]p-nitrogen-containing heterocycle, -[alkylene]p-nitrogen-containing substituted heterocycle, -[alkylene]p-nitrogen-containing heteroaryl, -[alkylene]p-nitrogen-containing substituted heteroaryl and -[alkylene]p-NR10R11, where p equals 0 or 1, the alkylene contains 1-5 carbon atoms and can have 1 or 2 substitutes selected from a group comprising amine, hydroxy and halogen, aminoacyl relates to a group -C(O)NRR, where each R is independently selected from a group comprising hydrogen and alkyl, R10 and R11 are independently selected from a group comprising hydrogen, alkyl, substituted alkyl, -S(O)2-alkyl, substituted aryl, substituted heteroaryl, cycloalkyl, or when R10 is hydrogen, R11 is hydroxy, alkoxy or substituted alkoxy; or when R1 and R3 together with carbon and nitrogen atoms respectively bonded to them do not form a heterocyclic or a substituted heterocyclic group, R3 and R4 together with a nitrogen atom to which they are bonded form a spiro-condensed heterocyclic group; R5 is selected from a group comprising L-A1, where L is selected from a group comprising C1-C5alkylene, where the alkylene is defined above; and A1 is selected from a group comprising aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle; and one of R6 or R7 is selected from a group comprising aryl and heteroaryl, each of which can optionally be substituted with -(R8)m, where m equals a whole number from 1 to 2, and the other of R6 or R7 is selected from a group comprising hydrogen, halogen and alkyl; or R6 as well as R7 denotes hydrogen; R8 is selected from a group comprising cyano, alkyl, -CF3, alkoxy, halogen, where alkyl, aryl, aryloxy, cycloalkyl, heterocycle, heteraryl and substituted alkyl, aryl, aryloxy, cycloalkyl, heterocycle and heteroaryl are described in claim 1. The invention also relates to specific compounds, a pharmaceutical composition based on the compound of formula I, a method of inhibiting KSP and use of the composition to prepare a medicinal agent.

EFFECT: novel imidazole derivatives are useful as kinesin spindle protein inhibitors for treating cancer.

25 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel diarylamine-containing compounds of formula (I) or formula (4b), pharmaceutically acceptable salts thereof, which have c-kit inhibiting properties. In formulae (I) and (4b), each R1 independently denotes H, -C(O)OH and -L1-C1-6alkyl, where L1 denotes -O- or -C(O)O-, or any two neighbouring R1 groups can together form a 5-6-member heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, a 6-member heterocyclic ring with one or two nitrogen atom s as heteroatoms, optionally substituted with a C1-4alkyl, and R5 denotes hydrogen or C1-C6alkyl; values of radicals Ar and Q are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds, and a method of treating diseases whose development is promoted by c-kit receptor activity.

EFFECT: more effective use of the compounds.

17 cl, 3 tbl, 9 ex

7FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a combination of a co-drug (an auxiliary) and a compound o formula (IV) in which radicals and symbols have the values defined in cl. 1 of the patent claim, or salts, or tautomers, or N-oxides, or solvates of this compound; where the specified auxiliary is specified from a monoclonal antibody, an alkylating agent, a malignant growth agent, other cycline-dependent kinase (CDK) inhibitor and a hormone, a hormone agonist, a hormone antagonist or a hormone-modulating agent specified in cl. 1 of the patent claim. The offered combination is used for tumour cell growth inhibition.

EFFECT: invention also refers to a pharmaceutical composition based on the offered combination, application of the combination and its separate ingredients and methods of treating, preventing and relieving the cancer symptoms in a patient.

77 cl, 2 dwg, 8 tbl, 257 ex

FIELD: chemistry.

SUBSTANCE: described are novel derivatives of azabicyclo{3,1,0}hexane of general formula (I) or pharmaceutically acceptable salts thereof (values of radicals are given in the claim), synthesis method thereof, intermediate compounds, a pharmaceutical composition and use of the novel compounds in therapy as dopamine receptor D3 modulators, for example, for treating drug dependence or as antipsychotic agents.

EFFECT: improved properties of the derivatives.

34 cl, 122 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel amide derivatives of formula (I), isomers and pharmaceutically acceptable salt thereof, which have cancer cell selective inhibiting properties, caused by an epidermal growth factor receptor (EGFR), selected from EGFR or caused by EGFR mutation. In formula (I): (I) (a) or (b), A denotes a group (a) or (b), R4, R5, R6 and R7, each independently denote hydrogen, halogen, N-C1-6alkyl or N-hydroxyamido or inverse C-C1-6alkylamido (-NHCOC1-6alkyl), hydroxycarbonyl(-COOH), C1-6 alkyloxycarbonyl(-COOC1-6), C1-6alkyl or C1-6alkyl, substituted with a hydroxy group, C1-6dialkylamino or a saturated 5-6-member heterocyclic group with 1-2 heteroatoms and selected from nitrogen and oxygen atoms; R1 denotes a phenyl or a 6-member heteroaryl group with a nitrogen atom as a heteroatom, each of which is substituted with 1-3 X, or C1-6alkyl, substituted with a phenyl, which can be substituted with halogen atoms; R2 denotes hydrogen, hydroxy, C1-6alkoxy or C1-6alkoxy, substituted C1-6alkoxy or 5-6-member saturated heterocyclic group; R3 denotes hydrogen, -COOH, C1-6alkyloxycarbonyl or amido, N-unsubstituted or N-substituted Y; na and nb each is a whole number ranging from 1 to 3; where: X denotes hydrogen, halogen, hydroxy, cyano, nitro, (mono-, di- or trihalogen)methyl, mercapto, C1-6alkylthio, acrylamido, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, phenyloxy, C1-6dialkylamino or C1-6alkyl or C1-6alkoxy, substituted with Z, provided that when the number of substitutes X equals two or more, groups X can be condensed with each other to form a 5-member cyclic structure, possibly containing 2 nitrogen atoms in the ring as heteroatoms; Y denotes hydroxy, C1-6alkyl or C1-6alkyl substituted with Z, C1-6alkyl has 1-4 fragments selected from a group consisting of N, O, S, SO and SO2; and Z denotes C1-6alkyl, phenyl or a 6-member heterocyclic group containing one or more heteroatoms selected from N or O. Said phenyl or heterocyclic group is unsubstituted or substituted with a halogen.

EFFECT: improved properties of the derivatives.

4 cl, 7 tbl, 144 ex

FIELD: oil and gas production.

SUBSTANCE: invention refers to improved procedure for production of antioxidant additive to lubricating oils consisting in interaction of mono-ethers of di-carbonic acids with poly-ethylene-poly-amine at presence of catalyst. As poly-ethylene-poly-amine in the procedure there is used tetra-ethylene-pentamine. Interaction is performed together with mono-ether of di-carbonic acid on base of poly-ethylene-glycol and mono-ether of the same acid on base of fatty alcohol at temperature 120-125°C. As a catalyst there is used mixture of cation-exchanging resin KU-2 with caustic potassium at ratio of 1:1 taken at amount of 1.5-2.0 wt % from total amount of mono-ethers. Produced additive is used for mineral lubricating oils, oil lubricating-cooling substances and other oil products with tendency to oxidation.

EFFECT: simplified procedure for production of antioxidant additives, improvement of their operational properties.

1 tbl, 4 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: invention relates to novel compounds of formula (I), which have protein kinase inhibiting properties and can be used in treating diseases which are dependent on any one or more protein kinases from FGFR1, FGFR2, FRF3 and/or FGFR4, KDR, HER1, HER2, Bcr-Abl, Tie2 and/or Ret Such diseases can be proliferative diseases, for example bladder cancer, breast cancer and multiple myeloma. In formula

the left-side ring , right-side ring , there are the following fragments, denoted "left-side ring" and "right-side ring", respectively: where X denotes C-R5, and Y and Z both denote N. The left-side ring corresponds to fragment (A):

n equals 0, 1, 2, 3, 4 or 5, X1 denotes hydrogen, where R1 denotes a group of formula Rz-NRa-, where Ra denotes hydrogen and Rz is selected from (1) a straight or branched C1-C4alkyl or (2) a group of formula , where ring A denotes phenyl, cyclohexenyl, cyclohexyl or pyridyl, m equals 0, 1 or 2, one or each of Rb is independently selected from a group -L2-NRcRd; -L2-RING, where RING denotes a 5- or 6-member saturated heterocyclic ring containing 1 or 2 heteroatoms selected from nitrogen and oxygen, optionally substituted, as indicated below, halogen; hydroxy; amino; cyano, and a straight or branched C1-C4alkyl optionally substituted with one or more halogens and/or one or two hydroxy groups, wherein the hydroxy and amino groups are in turn optionally substituted on at least one heteroatom with one or, if necessary, more C1-C7aliphatic groups, where L2 denotes a direct bond, a link selected from a group comprising -O-, -S-, -C(O)-, -OC(O)-, -NRaC(O)-, -C(O)-NRa -OC(O)-NRa, -NRa-; or denotes a straight C1-C4alkyl which is optionally interrupted and/or ends in one terminal fragment or in two terminal fragments with the said link, and where Rc and Rd are each independently selected from a group comprising hydrogen and straight or branched C1-C4alkyl, or Rc and Rd together with a neighbouring nitrogen atom form a 5- or 6-member heterocyclic ring which optionally contains an additional heteroatom selected from nitrogen and oxygen, and optionally substituted as indicated below, said optionally substituted rings are independently substituted with 0, 1, 2, 3, 4 or 5 C1-C7aliphatic substitutes which are optionally substituted with one or more halogen atoms; R2 denotes hydrogen or C1-C4alkyl; R3 denotes hydrogen or straight or branched C1-C4alkyl or straight C1-C4alkyl substituted with a 5- or 6-member saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatoms in the ring, selected from nitrogen, oxygen and sulphur; R4 is selected from hydroxy, protected hydroxy group, alkoxy, alkyl, trifluoromethyl and halogen, where the alkyl or alkyl part of the alkoxy is straight or branched and contains 1, 2, 3 or 4 carbon atoms; or R5 denotes hydrogen or C1-C4alkyl; or pharmaceutically acceptable salts, hydrates, solvates, ethers, N-oxides thereof, optionally in form of trans-isomers thereof.

EFFECT: improved properties of the compound.

38 cl, 1 tbl, 231 ex

FIELD: chemistry.

SUBSTANCE: invention discloses a compound of formula I

, in which radicals and groups are described in the claims. Said compounds are 5-hydroxytryptamine-6 (5-HT6) ligands and can be used to treat central nervous system disorders associated with or influenced by the 5-HT6 receptor. The invention also relates to a pharmaceutical composition and a method of treating said disorders.

EFFECT: high efficiency of using said derivatives.

19 cl, 13 tbl, 204 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: invention relates to a novel salt - monohydrate of monohydrochloride of 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)benzamide, having protein kinase inhibiting properties. The invention also relates to a method of obtaining said compound. The method involves the following steps: (a) merging 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)benzamide in form of a free base and hydrochloric acid in methanol in a nitrogen atmosphere; (b) heating the reaction mixture to temperature in the range of approximately 42-50°C; (c) stirring the reaction mixture; (d) filtering the reaction mixture while maintaining temperature higher than 40°C to obtain a transparent solution; (e) cooling the transparent solution to approximately 30°C while stirring in a nitrogen atmosphere; (f) adding an inoculant to the solution; (g) cooling the solution containing the inoculant to approximately 23°C; (h) stirring the solution to obtain a suspension; (i) cooling the obtained suspension to approximately -10°C; (j) stirring the obtained suspension; (k) filtering solid substances, washing the solid substance with cold methanol; and (l) drying the solid substance at approximately 50-55°C and 10-20 torr to obtain the end product.

EFFECT: monohydrate of monohydrochloride of said compound has high solubility compared to a base and hydrochloride salt and has high bioavailability in vivo compared to said compounds.

4 cl, 17 tbl, 11 ex

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