Compounds and methods for kinase modulation and indications for use of said compounds and methods

FIELD: chemistry.

SUBSTANCE: disclosed is a compound having chemical formula or a salt thereof, where: Ar is an optionally substituted heteroaryl; R1 in each case is independently selected from a group which includes halogen, lower alkyl, optionally substituted with one or more substitutes selected from fluorine, lower alkoxy, fluorine-substituted lower alkoxy, monoalkylamino, dialkylamino, -O-R5, -N(R5)-R6 and -N(R5)-C(X)-R7; m equals 0 or 1; n equals 0, 1 or 2; R2 is hydrogen or a halogen; L2 is -S(O)2-; R3 is a lower alkyl, optionally substituted with fluorine, C3-6 cycloalkyl, optionally substituted with a lower alkyl, a 5- or 6-member nitrogen-containing heterocycloalkyl, optionally substituted with one or more substitutes selected from fluorine, lower alkyl, fluorine-substituted lower alkyl, lower alkoxy, fluorine-substituted lower alkoxy, lower alkylthio or fluorine-substituted lower alkylthio, aryl, optionally substituted with a halogen, lower alkyl, optionally substituted with a halogen or lower alkoxy, optionally substituted with a halogen, or a heteroaryl, optionally substituted with a halogen or a lower alkyl; L1 is selected from a group which includes -O-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)-, -(R11)-C(R12R13)-, -C(X)-N(R11)-, -N(R11)-C(X)-; X is O; R11 is hydrogen; R4 is hydrogen or a lower alkyl; R5 and R6 in each case are independently selected from a group which includes hydrogen, lower alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, where each is optionally substituted with one or more substitutes selected from fluorine, lower alkoxy, fluorine-substituted lower alkoxy, lower alkylthio, fluorine-substituted lower alkylthio, monoalkylamino, dialkylamino; R7 in each case is independently selected from a group which includes lower alkyl; where the terms "lower alkyl", "lower alkoxy", "lower alkylthio", "monoalkylamino", "dialkylamino", "cycloalkyl", "heterocycloalkyl", "aryl", "heteroaryl", are as described in the claim. The invention also discloses a pharmaceutical composition for treating Raf kinase mediated diseases which is based on a compound of formula I; use of the compound of formula I to produce a medicinal agent is also disclosed.

EFFECT: novel compound which can be useful in treating diseases and conditions associated with aberrant activity of protein kinases is obtained and described.

9 cl, 13 ex, 2 tbl

 

The technical FIELD

[0001] the Present invention relates to kinase and compounds modulating kinase, as well as the application of these compounds. According to specific variants of implementation, the present invention includes indications of diseases treatable by modulation of kinase activity using the compounds according to the present invention.

BRIEF description of the INVENTION

[0002] the present invention proposed compounds with activity against protein kinases in General, including, but not limited to, Abl, Akt1, Akt2, Akt3, ALK, Alk5, A-Raf, B-Raf, Brk, Btk, Cdk2, CDK4, CDK5, CDK6, CHK1, c-Raf-1, Csk, EGFR, EphA1, EphA2, EphB2, EphB4, Erk2, Fak, FGFR1, FGFR2, FGFR3, FGFR4, Flt1, Flt3, Flt4, Fms, Frk, Fyn, Gsk3α, Gsk3β, HCK, Her2/Erbb2, Her4/Erbb4, IGF1R, IKK beta, Irak4, Itk, Jak1, Jak2, Jak3, Jnk1, Jnk2, Jnk3, Kdr, Kit, Lck, Lyn, MAP2K1, MAP2K2, MAP4K4, MAPKAPK2, Met, Mnk1, MLK1, p38, PDGFRA, PDGFRB, PDPK1, Pim1, Pim2, Pim3, PKC alpha, PKC beta, PKC theta, Plk1, Pyk2, Ret, ROCK1, ROCK2, Ron, Src, Stk6, Syk, TEC, Tie2, TrkA, TrkB, Yes, and/or Zap70, including any mutations of these kinases. According to some aspects, these compounds exhibit activity against protein kinases Raf, including A-Raf, B-Raf and/or c-Raf-1 and any mutations of these kinases. According to some aspects, the compounds are compounds of formula I, below.

[0003] the present invention also suggested ways to use the above-mentioned compounds for the treatment of Zab the diseases and conditions associated with the regulation of the activity of the above kinases. In particular, the proposed use of the compounds in methods of treatment, including modulation of protein kinases, as well as compounds suitable for use in methods of treatment, including modulation of protein kinases.

[0004] According to some variants of implementation of the proposed connection, the structure of which corresponds to the following formula I:

or a salt, prodrug, tautomer or isomer,

where:

Ar represents optionally substituted heteroaryl;

R1in each case, independently selected from the group including halogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower quinil, optionally substituted cycloalkyl, optionally substituted heteroseksualci, optionally substituted aryl, optionally substituted heteroaryl, -NO2, -CN, -O-R5, -N(R5)-R6, -C(X)-N(R5)-R6, -C(X)-R7, -S(O)2-N(R5)-R6, -S(O)n-R7, -O-C(X)-R7, -C(X)-O-R5, -C(NH)-N(R8)-R9, -N(R5)-C(X)-R7, -N(R5)-S(O)2-R7, -N(R5)-C(X)-N(R5)-R6and-N(R5)-S(O)2-N(R5)-R6;

m represents 0, 1, 2, 3, 4 or 5;

n represents 0, 1 or 2;

R2isone hydrogen, lower alkyl or halogen;

L2selected from the group including-S(O)2-, -C(X)-, -C(X)-N(R10)- and-S(O)2-N(R10)-;

R3represents an optionally substituted lower alkyl, optionally substituted C3-6cycloalkyl, optionally substituted heteroseksualci, optionally substituted aryl or optionally substituted heteroaryl;

L1selected from the group comprising a bond, -N(R11)-, -O-, -S-, -C(X)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)-, -N(R11)-C(R12R13)-, -O-C(X)-, -C(X)-O-, -C(X)-N(R11)-, -N(R11)-C(X)-, -S(O)-, -S(O)2-, -S(O)2-N(R11)-, -N(R11)-S(O)2-, -C(NH)-N(R11)-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- and-N(R11)-S(O)2-N(R11)-;

X represents O or S;

each of R4, R10and R11represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, fluoro-substituted, monoalkylamines, dialkylamino, fluoro-substituted, dialkylamino and-NR14R15;

R5, R6, R8and R9in each case, independently selected from the group, including the setup portion of the hydrogen, optionally substituted lower alkyl, optionally substituted C3-6alkenyl, optionally substituted C3-6quinil, optionally substituted cycloalkyl, optionally substituted heteroseksualci, optionally substituted aryl and optionally substituted heteroaryl, or

R8and R9together with the nitrogen atom to which they are attached, form a 5-7 membered optionally substituted nitrogen containing heteroseksualci or 5 - or 7-membered optionally substituted nitrogen containing heteroaryl;

R7in each case, independently selected from the group comprising optionally substituted lower alkyl, optionally substituted C3-6alkenyl, optionally substituted C3-6quinil, optionally substituted cycloalkyl, optionally substituted heteroseksualci, optionally substituted aryl and optionally substituted heteroaryl;

R12and R13independently selected from the group comprising hydrogen, fluoro, -OH, -NH2, lower alkyl, lower alkoxy, lower alkylthio, monoalkylamines, dialkylamino and-NR14R15where the alkyl chain (chain) specified lower alkyl, lower alkoxy, lower alkylthio, monoalkylamines or dialkylamino optionally substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, the lower alcohol is si, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamino; or

R12and R13together with the carbon atom to which they are attached, form a 3-7-membered monocyclic cycloalkyl or a 5-7 membered monocyclic heteroseksualci, and specified monocyclic cycloalkyl or monocyclic heteroseksualci optionally substituted by one or more substituents selected from the group comprising halogen, -OH, -NH2, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamino; and

R14and R15together with the nitrogen atom to which they are attached, in each case, independently form a 5-7-membered heteroseksualci or substituted 5-7-membered heteroseksualci substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio,

however, provided that when L1represents a bond, -NR11-, -O-, -S-, -C(X)-, -S(O)- or-S(O)2-, Ar is not a 1H-pyrrolo[2,3-b]pyridine-3-yl, 1H-pyrazolo[3,4-b]p is ridin-3-yl, 5H-pyrrolo[2,3-b]pyrazin-7-yl, 7H-pyrrolo[2,3-d]pyrimidine-5-yl or 7H-pyrrolo[2,3-c]pyridazin-5-yl, i.e. is not a,or,

whereindicates the place of attachment to L1.

[0005] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Ia:

Formula Ia

or a salt, prodrug, tautomer or isomer,

where m, Ar, R1, R2, R3, R4and L1are as defined for formula I.

[0006] According to some variants of realization of the compounds of the formula I or Ia, L1represents a bond, -N(R11)-, -N(R11)-C(X)-, -N(R11)-S(O)2-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- or-N(R11)-S(O)2-N(R11)-, and-N(R11)-, -N(R11)-C(X) -, or-N(R11)-S(O)2-, and-N(R11)-C(O)-, with the left part of the L1(i.e.- N(R11)is linked to Ar and the right part of the L1linked to the phenyl ring according to formula I or Ia. According to some variants of realization, L1is a relationship

-N(R11)-, -N(R11)-C(X)-, -N(R11)-S(O)2-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- or-N(R11)-S(O)2-N(R11)-, and-N(R11), -N(R11)-C(X) -, or-N(R11)-S(O)2-, and-N(R11)-C(O)-, and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably each of R11and R4represents H.

[0007] According to some variants of realization of the compounds of the formula I or Ia, L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, with the left part of the L1associated with Ar, and the right part of the L1linked to the phenyl ring according to formula I or Ia. According to some variants of realization, L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, with a preference for the equipment each of R 11and R4represents H.

[0008] According to some variants of realization of the compounds of the formula I or Ia, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2represents fluorine or chlorine, and each of R11and R4represents H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine, and L1is a relationship

-N(R11)-, -N(R11)-C(X)-, -N(R11)-S(O)2-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- or-N(R11)-S(O)2-N(R11)-, and-N(R11)-, -N(R11)-C(X) -, or-N(R11)-S(O)2-, and-N(R11)-C(O)-, with the left part of the L1(i.e.- N(R11)is linked to Ar and the right part of the L1linked to the phenyl ring according to formula I or Ia. According to some variants of implementation, R2represents hydrogen, FPO is or chlorine, preferably fluorine or chlorine; L1represents a bond, -N(R11)-, -N(R11)-C(X)-, -N(R11)-S(O)2-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- or-N(R11)-S(O)2-N(R11)-, and-N(R11)-, -N(R11)-C(X) -, or-N(R11)-S(O)2-, and-N(R11)-C(O)-; and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably each of R11and R4represents H.

[0009] According to some variants of realization of the compounds of the formula I or Ia, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2represents fluorine or chlorine, and each of R11and R4 represents H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine, and L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, with the left part of the L1associated with Ar, and the right part of the L1linked to the phenyl ring according to formula I or Ia. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine; L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably each of R11and R4represents H.

[0010] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Ib:

The formula Ib

or a salt, prodrug, tautomer and the and the isomer,

where A represents-C(O)- or-C(R12R13)-; and

m, Ar, R1, R2, R3, R4, R11, R12and R13are as defined for formula I.

[0011] According to some variants of realization of the compounds of formula Ib, R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2represents fluorine or chlorine, and R4, R11, R12and R13represent H.

p> [0012] According to some variants of realization of the compounds of formula Ib, A is-C(O)-, and R4and R11are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4and R11represent H. According to some variants of implementation, A represents-C(O)-, and R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, A represents-C(O)-, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine, and R4and R11are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4and R11represent H.

[0013] According to some variants of realization of the compounds of formula Ib, A is-C(R12R13)-, and R4, R11, R12and R13are independently hydrogen or n is SSI alkyl, where lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H. According to some variants of implementation, A represents-C(R12R13)-, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R12and R13are H, and R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, A represents-C(R12R13)-; R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine; and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, which is preferably R 4, R11, R12and R13represent H.

[0014] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Ic:

Formula Ic

or a salt, prodrug, tautomer or isomer,

where m, Ar, R1, R2, R3and R4are as defined for formula I.

[0015] According to some variants of realization of the compounds of formula Ic, R4represents hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4represents H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, and R4represents hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2p is ecstasy a fluorine or chlorine, and R4represents H.

[0016] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Id:

Formula Id

or a salt, prodrug, tautomer or isomer,

where A represents-C(O)- or-C(R12R13)-; and

m, Ar, R1, R2, R3, R4, R11, R12, R13and L2are as defined for formula I.

[0017] According to some variants of realization of the compounds of formula Id, R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more Deputy what stitely, selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2represents fluorine or chlorine, and R4, R11, R12and R13represent H.

[0018] According to some variants of realization of the compounds of formula Id, A represents-C(O)-, and R4and R11are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4and R11represent H. According to some variants of implementation, A represents-C(O)-, and R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, A represents-C(O)-, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine, and R4and R11represent hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, if e is ω preferably R 4and R11represent H.

[0019] According to some variants of realization of the compounds of formula Id, A represents-C(R12R13)-, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H. According to some variants of implementation, A represents-C(R12R13)-, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R12and R13are H, and R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, A represents-C(R12R13)-; R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine; and R4, R11, R12and R13represent the independent is IMO hydrogen or lower alkyl, where lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H.

[0020] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Ie:

Formula Ie

or a salt, prodrug, tautomer or isomer,

where m, Ar, R1, R2, R3, R4and L2are as defined for formula I.

[0021] According to some variants of realization of the compounds of formula Ie, R4represents hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4represents H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, and R4represents hydrogen or lower ALK is l, where lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2represents fluorine or chlorine, and R4represents H.

[0022] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula If:

Formula If

or a salt, prodrug, tautomer or isomer,

where:

L3represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-; and

m, Ar, R1, R2, R3, R4, R11, R12, R13and X are as defined for formula I.

[0023] According to some variants of realization of the compounds of formula If, L3represents-C(O)-N(R11)-, -C(R12R13)-O-, -O-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, with the left part of the L3associated with Ar, and the right part of the L3linked to the phenyl ring according to formula If. According to some variants of realization, L3represents-C(O)-N(R11)-, -C(R12R13)-O-, -O-C(R12R13 )-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H.

[0024] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Ig:

Formula Ig

or a salt, prodrug, tautomer or isomer,

where:

L3represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-; and

m, Ar, R1, R2, R3, R4, R11, R12, R13X and L2are as defined for formula I.

[0025] According to some variants of realization of the compounds of formula Ig, L3represents-C(O)-N(R11)-, -C(R12R13)-O-, -O-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, with the left part of the L3associated with Ar, and the right part of the L3Vasanas phenyl ring according to formula Ig. According to some variants of realization, L3represents-C(O)-N(R11)-, -C(R12R13)-O-, -O-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H.

[0026] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Ih:

Formula Ih

or a salt, prodrug, tautomer or isomer,

where A represents-C(O)- or-C(R12R13)-; and

m, Ar, R1, R2, R3, R4, R11, R12and R13are as defined for formula I.

[0027] According to some variants of realization of the compounds of formula Ih, R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower ALK is XI, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2represents fluorine or chlorine, and R4, R11, R12and R13represent H.

[0028] According to some variants of realization of the compounds of formula Ih, A represents-C(O)-, and R4and R11are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4and R11are H. in some variations there of implementation, A represents-C(O)-, and R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, A represents-C(O)-, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine, and R4and R11are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4and R11represent H.

[0029] According to some variants of realization of the compounds of formula Ih, A represents-C(R12R13)-, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H. According to some variants of implementation, A represents-C(R12R13)-, R12and R13are independently hydrogen or lower alkyl, where lower alkyl is not battelino substituted by one or more substituents, selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R12and R13are H, and R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, A represents-C(R12R13)-; R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine; and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H.

[0030] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Ii:

Formula Ii

or a salt, prodrug, tautomer or isomer,

where A represents-C(O)- or-C(R12R13)-; and

m, Ar, R1, R2, R3, R4, R11, R12, R13and L2are as defined for formula I.

[0031] According to some is the option of implementation of the compounds of formula Ii, R4, R11,

R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2represents fluorine or chlorine, and R4, R11, R12and R13represent H.

[0032] According to some variants of realization of the compounds of formula Ii, A is-C(O)-, and R4and R11are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more of the Deputy is mi, selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4and R11represent H. According to some variants of implementation, A represents-C(O)-, and R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, A represents-C(O)-, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine, and R4and R11represent hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4and R11represent H.

[0033] According to some variants of realization of the compounds of formula Ii, A is-C(R12R13)-, and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4 , R11, R12and R13represent H. According to some variants of implementation, A represents-C(R12R13)-, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R12and R13are H, and R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, A represents-C(R12R13)-; R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine; and R4, R11, R12and R13are independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R4, R11, R12and R13represent H.

[0034] According to some variants of implementation, the structure of the compounds of formula I corresponds to the following private structural formula Ij:

Formula Ij

or a salt, prodrug, tautomer or isomer,

where:

m, Ar, R1, R2, R4and L1are as defined for formula I; and

R22choose from a group that includes monoalkylamines, dialkylamino, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted heteroseksualci, optionally substituted aryl and optionally substituted heteroaryl, where the alkyl chain (chain) specified monoalkylamines or dialkylamino may independently contain one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine.

[0035] According to some variants of realization of the compounds of the formula Ij, L1represents a bond, -N(R11)-, -N(R11)-C(X)-, -N(R11)-S(O)2-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- or-N(R11)-S(O)2-N(R11)-, and-N(R11)-, -N(R11)-C(X) -, or-N(R11)-S(O)2-, and-N(R11)-C(O)-, with the left part of the L1(i.e.- N(R11)is linked to Ar and the right part of the L1linked to the phenyl ring according to formula Ij. According to some variants of realization, L1is a relationship

-N(R11)-, -N(R11 )-C(X)-, -N(R11)-S(O)2-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- or-N(R11)-S(O)2-N(R11)-, and-N(R11)-, -N(R11)-C(X) -, or-N(R11)-S(O)2-, and-N(R11)-C(O)-, and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably each of R11and R4represents H.

[0036] According to some variants of realization of the compounds of the formula Ij, L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, with the left part of the L1associated with Ar, and the right part of the L1linked to the phenyl ring according to formula Ij. According to some variants of realization, L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising CFT is R, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably each of R11and R4represents H.

[0037] According to some variants of realization of the compounds of the formula Ij, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably R2represents fluorine or chlorine, and each of R11and R4represents H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine, and L1is a relationship

-N(R11)-, -N(R11)-C(X)-, -N(R11)-S(O)2-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- or-N(R11)-S(O)2-N(R11)-, and-N(R11)-, -N(R11)-C(X) -, or-N(R11)-S(O)2-, and-N(R11)-C(O)-, with the left part of the L1(i.e.- N(R11)is linked to Ar and the right part of the L1tie is on the phenyl ring according to formula Ij. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine; L1represents a bond, -N(R11)-, -N(R11)-C(X)-, -N(R11)-S(O)2-, -N(R11)-C(NH)-, -N(R11)-C(X)-N(R11)- or-N(R11)-S(O)2-N(R11)-, and-N(R11)-, -N(R11)-C(X) -, or-N(R11)-S(O)2-, and-N(R11)-C(O)-; and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably each of R11and R4represents H.

[0038] According to some variants of realization of the compounds of the formula Ij, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while predpochtitelno R 2represents fluorine or chlorine, and each of R11and R4represents H. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine, and L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, with the left part of the L1associated with Ar, and the right part of the L1linked to the phenyl ring according to formula Ij. According to some variants of implementation, R2represents hydrogen, fluorine or chlorine, preferably fluorine or chlorine; L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-; and each of R11and R4represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably each of R11and R4represents H.

[0039] According to some variants of realization of the compounds of the formula Ij, in addition to any of the above variants of realization of the formula Ij, R22represents the t of monoalkylamines, dialkylamino or optionally substituted heteroseksualci, with heteroseksualci preferably represents a 5 - or 6-membered nitrogen containing heteroseksualci, and in the specified heteroseksualci the nitrogen atom is linked to S(O)2according to the formula Ij. According to some variants of implementation, R22represents monoalkylamines, dialkylamino or 5 - or 6-membered nitrogen containing heteroseksualci, with the specified heteroseksualci contains one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkyl, lower alkoxy, lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, and lower alkyl or the alkyl chain (chain) specified lower alkoxy, lower alkylthio, monoalkylamines or dialkylamino optionally substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, while preferably specified 5 - or 6-membered nitrogen containing heteroseksualci optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkit is about and fluoro-substituted lower alkylthio.

[0040] According to some variants of realization of the compounds of formula I, Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii or Ij, in addition to any of the above variants of realization of formulas I, Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii or Ij, Ar represents a monocyclic or bicyclic nitrogen containing heteroaryl. According to some variants of realization, Ar is chosen from the group including

indicates the place of attachment of the specified ring Ar to L1in the formula I, Ia or Ij, L3in the formula If or Ig, to the nitrogen atom in the group Ar-N - in formula Ib or Id, to A in the formula Ih or Ii, or to the phenyl ring in formula Ic or Ie, when you do this:

T, U, X and Z in each case independently represent N or CH, provided that at least one, but not more than 2, X in any of the rings is an N, not more than 2 U in any of the rings are N, at least one T is a N, and not more than two T in any six-membered ring are N, at least one Z represents N, and not more than 2 Z in any bicyclic ring are N;

Y represents NH, O or S;

W in each case is independently N or CH;

V represents O, S or NH, provided that when V represents O or S, at least one U in any of the rings or W in any of the rings is a ; and

any R1associated with Ar on any available NH or CH, preferably any R1is an independent R16while R16in each case, independently selected from the group comprising-OH, -NH2, -CN, -NO2, -C(O)-OH, -S(O)2-NH2, -C(O)-NH2, -O-R17, -S-R17, -N(R19)-R17, -N(R19)-C(O)-R17, -N(R19)-S(O)2-R17, -S(O)2-R17, -C(O)-R17, -C(O)-O-R17, -C(O)-N(R19)-R17, -S(O)2-N(R19)-R17, halogen, lower alkyl, cycloalkyl, heteroseksualci, aryl and heteroaryl, and lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cycloalkyl, heteroseksualci, aryl and heteroaryl, with cycloalkyl, heteroseksualci, aryl and heteroaryl, speaking as R16or as deputies in the lower alkyl, optionally substituted by one or more substituents selected from the group comprising-OH, -NH2, -CN, -NO2, -C(O)-OH, -S(O)2-NH2, -C(O)-NH2, -O-R18, -S-R18, -N(R19)-R18, -N(R19)-C(O)-R18, -N(R19)-S(O)2-R18, -S(O)2-R18, -C(O)-R18, -C(O)-O-R18, -C(O)-N(R19)-R18, S(O) 2-N(R19)-R18, halogen, lower alkyl, fluorinated lower alkyl, cyclooctylamino;

R17in each case, independently selected from the group comprising lower alkyl, cycloalkyl, heteroseksualci, aryl and heteroaryl, where lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cycloalkyl, heteroseksualci, aryl and heteroaryl, and cycloalkyl, heteroseksualci, aryl and heteroaryl, speaking as R17or as deputies in the lower alkyl, optionally substituted by one or more substituents selected from the group comprising-OH, -NH2, -CN, -NO2, -C(O)-OH, -S(O)2-NH2, -C(O)-NH2, -O-R18, -S-R18, -N(R19)-R18, -N(R19)-C(O)-R18, -N(R19)-S(O)2-R18, -S(O)2-R18, -C(O)-R18, -C(O)-O-R18, -C(O)-N(R19)-R18, -S(O)2-N(R19)-R18, halogen, lower alkyl, fluorinated lower alkyl, cyclooctylamino;

R18in each case, independently selected from the group comprising lower alkyl, heteroseksualci and heteroaryl, where lower alkyl optionally substituted by one or more substituents selected from the group, including the ment fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamino; and

R19in each case represents independently hydrogen or lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio.

[0041] According to some variants of realization of the compounds of formula I, Ia, Ib, Id, If, Ig, Ih, Ii or Ij, in addition to any of the above variants of realization of formulas I, Ia, Ib, Id, If, Ig, Ih, Ii or Ij, when L1is different from the connection, Ar is chosen from the group including

,

whereindicates the place of attachment of the specified ring Ar to L1in the formula I, Ia or Ij, L3in the formula If or Ig, to the nitrogen atom in the group Ar-N - in formula Ib or Id, or to A in the formula Ih or Ii, with:

T1U1, W1X1and Z1in each case, independently represent N or CH, provided that no more than 1 of T1U1X1and Z1represents N;

T2in each case represents independently N or CH, provided that no more than 2 T2provide the amount of N;

Y and V1represent O, S or NH;

any R1associated with Ar on any available NH or CH, with preferably any R1is an independent R16as defined in paragraph [0040], while preferably R16in each case, independently selected from the group including halogen, -OH, -NH2, -CN, lower alkyl, lower alkoxy, lower alkylthio, monoalkylamines, dialkylamino and-NR20R21and lower alkyl and the alkyl chain (chain) specified lower alkoxy, lower alkylthio, monoalkylamines or dialkylamino may contain one or more, preferably 1, 2 or 3 substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines or cyclooctylamino; and

R20and R21together with the nitrogen atom to which they are attached, in each case, independently form a 5-7-membered heteroseksualci or a 5-7 membered heteroseksualci substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio.

[0042] According to some variants of realization of the compounds of the formula , Ia, Ib, Id, If, Ig, Ih, Ii or Ij, in addition to any of the above variants of realization of formulas I, Ia, Ib, Id, If, Ig, Ih, Ii or Ij, when L1is different from the connection, Ar is chosen from the group including

indicates the place of attachment of the specified ring Ar to L1in the formula I, Ia or Ij, L3in the formula If or Ig, to the nitrogen atom in the group Ar-N - in formula Ib or Id, or to A in the formula Ih or Ii, with:

W1in each case represents independently N or CH;

Y and V1represent O, S or NH;

p represents 0, 1, 2 or 3; and

R16contained as a substituent at any available CH or NH, is such, as defined in paragraph [0040], while preferably R16in each case, independently selected from the group including halogen, -OH, -NH2, -CN, lower alkyl, lower alkoxy, lower alkylthio, monoalkylamines, dialkylamino and-NR20R21and lower alkyl and the alkyl chain (chain) specified lower alkoxy, lower alkylthio, monoalkylamines or dialkylamino may contain one or more, preferably 1, 2 or 3 substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines or cyclooctylamino, the ri that R 20and R21are as defined in paragraph [0041].

[0043] According to some variants of realization of the compounds of formula I, Ia, Ib, Id, If, Ig, Ih, Ii or Ij, in addition to any of the above variants of realization of formulas I, Ia, Ib, Id, If, Ig, Ih, Ii or Ij, when L1is different from the connection, Ar is chosen from the group including

,

whereindicates the place of attachment of the specified ring Ar to L1in the formula I, Ia or Ij, L3in the formula If or Ig, to the nitrogen atom in the group Ar-N - in formula Ib or Id, or to A in the formula Ih or Ii, with:

p represents 0, 1, 2 or 3; and

R16contained as a substituent at any available CH or NH, is such, as defined in paragraph [0040].

[0044] According to some variants of realization of the compounds of formula Ic or Ie, in addition to any of the above variants of realization of the formula Ic or Ie, Ar is chosen from the group including

indicates the place of attachment of the specified ring Ar to the phenyl ring according to formula Ic or Ie, when you do this:

T1U1, W1and Z1in each case, independently represent N or CH, provided that no more than 1 of T1U1and Z1represents N;

T2represents N or CH, provided that < 2 T 2represent N;

V1represents O, S or NH; and

any R1associated with Ar on any available NH or CH, with preferably any R1is an independent R16as defined in paragraph [0040], while preferably R16in each case, independently selected from the group including halogen, -OH, -NH2, -CN, lower alkyl, lower alkoxy, lower alkylthio, monoalkylamines, dialkylamino and-NR20R21and lower alkyl and the alkyl chain (chain) specified lower alkoxy, lower alkylthio, monoalkylamines or dialkylamino may contain one or more, preferably 1, 2 or 3 substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines or cyclooctylamino, R20and R21are as defined in paragraph [0041].

[0045] According to some variants of realization of the compounds of formula Ic or Ie, in addition to any of the above variants of realization of the formula Ic or Ie, R1selected from the group including

and,

whereindicates the place of attachment of the specified ring Ar to phenyl to LCU according to the formula Ic or Ie, when you do this:

W1represents N or CH;

V1represents O, S or NH;

p represents 0, 1, 2 or 3; and

R16contained as a substituent at any available CH or NH, is such, as defined in paragraph [0040], while preferably R16in each case, independently selected from the group including halogen, -OH, -NH2, -CN, lower alkyl, lower alkoxy, lower alkylthio, monoalkylamines, dialkylamino and-NR20R21and lower alkyl and the alkyl chain (chain) specified lower alkoxy, lower alkylthio, monoalkylamines or dialkylamino may contain one or more, preferably 1, 2 or 3 substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines or cyclooctylamino, R20and R21are as defined in paragraph [0041].

[0046] According to some variants of realization of the compounds of formula I, Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ii, in addition to any of the above variants of realization of formulas I, Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ii, R3may contain as a substituent a lower alkyl or optionally substituted C3-6cycloalkyl. According to some variants of implementation, R3represents Nissi is alkyl or C 3-6cycloalkyl, where lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, fluoro-substituted, monoalkylamines, dialkylamino, fluoro-substituted, dialkylamino, cyclooctylamine and C3-5cycloalkyl, and C3-6cycloalkyl optionally substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, fluoro-substituted, monoalkylamines, dialkylamines and fluoro-substituted, dialkylamino. According to some variants of implementation, R3represents a lower alkyl or C3-6cycloalkyl, where lower alkyl or C3-6cycloalkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio. According to some variants of implementation, R3represents optionally fluoro-substituted lower alkyl or optionally fluoro-substituted C3-6cycloalkyl. According to some variants of implementation, R3represents the lowest Alki is, where lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, fluoro-substituted, monoalkylamines, dialkylamino, fluoro-substituted, dialkylamino, cyclooctylamine, and one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, fluoro-substituted, monoalkylamines, dialkylamines and fluoro-substituted, dialkylamino, and one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio. According to some variants of implementation, R3represents optionally fluoro-substituted lower alkyl.

[0047] According to some variants of realization of the compounds of formula I, Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ii, in addition to any of the above variants of realization of formulas I, Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ii, R3may contain as a substituent phenyl, and phenyl, monosubstituted in the para-position, and also phenyl, monosubstituted in the meta-position. According to some variants of implementation, R3is Soboh is phenyl, optionally substituted by one or more substituents selected from the group comprising halogen, -CN, -NO2, -OH, -NH2, lower alkyl, lower alkoxy, lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, and lower alkyl or the alkyl chain (chain) specified lower alkoxy, lower alkylthio, monoalkylamines or dialkylamino optionally substituted by one or more substituents selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, while preferably specified phenyl is monosubstituted or in the para-or meta-position. According to some variants of implementation, R3represents phenyl, optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio and fluoro-substituted lower alkylthio, while preferably specified phenyl is monosubstituted or in the para-or meta-position.

[0048] According to one implementation options of the compounds of formula I, the said compound is chosen from the group including:

6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-Piri is in 3-ylbenzene (P-0001),

N-(6-Acetylpiperidine-3-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (P-0002),

6-Chloro-2-fluoro-N-(6-methoxypyridine-3-yl)-3-(propane-1-sulfonylamino)-benzamide (P-0003),

N-(2-Acetylpiperidine-5-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (P-0004),

6-Chloro-2-fluoro-N-(6-isopropylaminomethyl-3-yl)-3-(propane-1-sulfonylamino)-benzamide (P-0005),

Pyrrolidin-1-carboxylic acid {5-[6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoylamine]-pyridine-2-yl}-amide (P-0006),

6-Chloro-N-(3,5-dimethylisoxazol-4-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (P-0007),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(propane-1-sulfonylamino)-benzamide (P-0008),

6-Chloro-N-(6-cyclopentenopyridine-3-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (P-0009),

6-Chloro-N-[5-(4-chlorophenyl)-2H-pyrazole-3-yl]-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (P-0010),

6-Chloro-2-fluoro-N-[6-(5-methylthiazole-2-ylamino)-pyridine-3-yl]-3-(propane-1-sulfonylamino)-benzamide (P-0011),

6-Chloro-N-[5-(4-chlorbenzyl)-[1,3,4]thiadiazole-2-yl]-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (P-0012),

6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-quinoline-3-ylbenzene (P-0013),

[2-[6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoylamine]-4H-[1,3,4]thiadiazin-(5E)-ilidene]-acetic acid ethyl ester (P-0014),

6-Chloro-N-(6-cyclopropylamino-3-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (P-0015),

6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-{6[(thiophene-2-ylmethyl)-amino]-pyridine-3-yl}-benzamide (P-0016),

N-(6-Benzylaminopurine-3-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (P-0017),

6-Chloro-2-fluoro-N-imidazo[1,2-a]pyridine-3-yl-3-(propane-1-sulfonylamino)-benzamide (P-0018),

Propane-1-sulfonic {2,4-debtor-3-[(5-methylisoxazol-3-ylamino)-methyl]-phenyl}-amide (P-0019),

N-{5-[2,6-Debtor-3-(propane-1-sulfonylamino)-benzylamino]-pyridine-2-yl}-ndimethylacetamide (P-0020),

Propane-1-sulfonic acids [2,4-debtor-3-(quinoline-3-illuminometer)-phenyl]-amide (P-0021),

Propane-1-sulfonic {3-[(6-chloropyridin-3-ylamino)-methyl]-2,4-differenl}-amide (P-0022),

Propane-1-sulfonic {2,4-debtor-3-[(6-methoxypyridine-3-ylamino)-methyl]-phenyl}-amide (P-0023),

The quinoline-3-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide (P-0024),

Propane-1-sulfonic {2,4-debtor-3-[(quinoline-3-ylmethyl)-amino]-phenyl}-amide (P-0025),

Propane-1-sulfonic acids [2,4-debtor-3-(quinoline-3-intoximeter)-phenyl]-amide (P-0026),

2,6-Debtor-3-(propane-1-sulfonylamino)-N-quinoline-3-ylbenzene (P-0027),

6-Acetylamino-N-[2,6-debtor-3-(2-forbindelseshandtering)-phenyl]-nicotinamide (P-0028),

6-Acetylamino-N-[2,6-debtor-3-(3-forbindelseshandtering)-phenyl]-nicotinamide (P-0029),

6-Acetylamino-N-[3-(2,6-differentialtopologie)-2,6-differenl]-nicotinamide (P-0030),

6-Acetylamino-N-[3-(2,4-differentialtopologie)-2,6-differenl]-nicotinamide (P-0031),

6-Acetylamino-N-[3-(2,5-differentialtopologie)-2,6-differeni the]-nicotinamide (P-0032),

6-Acetylamino-N-[2,6-debtor-3-(3-fluoro-4-methoxybenzenesulfonamide)-phenyl]-nicotinamide (P-0033),

6-Acetylamino-N-[2,6-debtor-3-(4-triftormetilfullerenov)-phenyl]-nicotinamide (P-0034),

6-Acetylamino-N-[3-(4-diftormetilirovaniya)-2,6-differenl]-nicotinamide (P-0035),

6-Acetylamino-N-[3-(3-diftormetilirovaniya)-2,6-differenl]-nicotinamide (P-0036),

6-Acetylamino-N-[2,6-debtor-3-(4-isopropylbenzenesulfonyl)-phenyl]-nicotinamide (P-0037),

6-Acetylamino-N-[3-(4-tert-butyl-benzosulfimide)-2,6-differenl]-nicotinamide (P-0038),

6-Acetylamino-N-[2,6-debtor-3-(4-propylbenzenesulfonyl)-phenyl]-nicotinamide (P-0039),

6-Acetylamino-N-[2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-nicotinamide (P-0040),

6-Acetylamino-N-[2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-nicotinamide (P-0041),

6-Acetylamino-N-[2,6-debtor-3-(dimethylaminomethylene)-phenyl]-nicotinamide (P-0042),

6-Acetylamino-N-[2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-nicotinamide (P-0043),

6-Acetylamino-N-[2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-nicotinamide (P-0044),

6-Acetylamino-N-[2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-phenyl]-nicotinamide (P-0045),

6-Acetylamino-N-(3-cyclopentanecarbonyl-2,6-differenl)-nicotinamide (P-0046),

6-Acetylamino-N-[2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-nicotinamide (P-0047),

6-ACET is a melamine-N-[2,6-debtor-3-(3,3,3-cryptochrome-1 sulfonylamino)-phenyl]-nicotinamide (P-0048),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(2-fluoro-benzosulfimide)-phenyl]-amide (P-0049),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(3-fluoro-benzosulfimide)-phenyl]-amide (P-0050),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,6-differentialtopologie)-2,6-differenl]-amide (P-0051),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,4-differentialtopologie)-2,6-differenl]-amide (P-0052),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,5-differentialtopologie)-2,6-differenl]-amide (P-0053),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(3-fluoro-4-methoxy-benzosulfimide)-phenyl]-amide (P-0054),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-trifluoromethyl-benzosulfimide)-phenyl]-amide (P-0055),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(4-deformedarse-benzosulfimide)-2,6-differenl]-amide (P-0056),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(3-deformedarse-benzosulfimide)-2,6-differenl]-amide (P-0057),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-isopropyl-benzosulfimide)-phenyl]-amide (P-0058),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(4-tert-butyl-benzosulfimide)-2,6-differenl]-amide (P-0059),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-propyl-benzosulfimide)-phenyl]-amide (P-0060),

1H-Pierre is lo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-amide (P-0061),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-amide (P-0062),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(dimethylaminomethylene)-phenyl]-amide (P-0063),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-amide (P-0064),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-amide (P-0065),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-phenyl]-amide (P-0066),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid (3-cyclopentanecarbonyl-2,6-differenl)-amide (P-0067),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-amide (P-0068),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(3,3,3-cryptochrome-1 sulfonylamino)-phenyl]-amide (P-0069),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(2-fluoro-benzosulfimide)-phenyl]-amide (P-0070),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(3-fluoro-benzosulfimide)-phenyl]-amide (P-0071),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,6-differentialtopologie)-2,6-differenl]-amide (P-0072),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,4-differentialtopologie)-2,6-debtor-phenyl]-amide (P-0073),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,5-debtor is solarthermie)-2,6-differenl]-amide (P-0074),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(3-fluoro-4-methoxy-benzosulfimide)-phenyl]-amide (P-0075),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-trifluoromethyl-benzosulfimide)-phenyl]-amide (P-0076),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(4-deformedarse-benzosulfimide)-2,6-differenl]-amide (P-0077),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(3-deformedarse-benzosulfimide)-2,6-differenl]-amide (P-0078),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-isopropyl-benzosulfimide)-phenyl]-amide (P-0079),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(4-tert-butyl-benzosulfimide)-2,6-differenl]-amide (P-0080),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-propyl-benzosulfimide)-phenyl]-amide (P-0081),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-amide (P-0082),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-amide (P-0083),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(dimethylaminomethylene)-phenyl]-amide (P-0084),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-amide (P-0085),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-amide (P-0086),

3H-Imidazo[4,5-b]pyridine-6-arbonboy acid [2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-phenyl]-amide (P-0087),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid (3-cyclopentanecarbonyl-2,6-differenl)-amide (P-0088),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-amide (P-0089),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(3,3,3-cryptochrome-1 sulfonylamino)-phenyl]-amide (P-0090),

N-{5-[2,6-Debtor-3-(propane-1-sulfonylamino)-benzyloxy]-pyridine-2-yl}-ndimethylacetamide (P-0091),

Propane-1-sulfonic acids [3-(2-aminopyridine-3-intoximeter)-2,4-differenl]-amide (P-0092),

Propane-1-sulfonic acids [2,4-debtor-3-(1H-pyrrolo[2,3-b]pyridine-5-intoximeter)-phenyl]-amide (P-0093),

N-{5-[2,6-Debtor-3-(4-triftormetilfullerenov)-benzyloxy]-pyridine-2-yl}-ndimethylacetamide (P-0094),

N-[3-(2-Aminopyridine-3-intoximeter)-2,4-differenl]-4-triftoratsetilatsetonom (P-0095),

N-[2,4-Debtor-3-(1H-pyrrolo[2,3-b]pyridine-5-intoximeter)-phenyl]-4-trifluoromethyl-benzosulfimide (P-0096),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(2-forbindelseshandtering)-benzamide (P-0097),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(3-forbindelseshandtering)-benzamide (P-0098),

N-(6-Acetylpiperidine-3-yl)-3-(2,6-differentialtopologie)-2,6-diflorasone (P-0099),

N-(6-Acetylpiperidine-3-yl)-3-(2,4-differentialtopologie)-2,6-diflorasone (P-0100),

N-(6-Acetylpiperidine-3-yl)-3-(2,5-differentialtopologie)-2,6-diflorasone (P-0101),

6-Acetylamino--[2,6-debtor-3-(3-fluoro-4-methoxybenzenesulfonamide)-phenyl]-nicotinamide (P-0102),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-triftormetilfullerenov)-benzamide (P-0103),

N-(6-Acetylpiperidine-3-yl)-3-(4-diftormetilirovaniya)-2,6-debtor-benzamide (P-0104),

N-(6-Acetylpiperidine-3-yl)-3-(3-diftormetilirovaniya)-2,6-debtor-benzamide (P-0105),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-isopropylbenzenesulfonyl)-benzamide (P-0106),

N-(6-Acetylpiperidine-3-yl)-3-(4-tert-butyl-benzosulfimide)-2,6-debtor-benzamide (P-0107),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-propylbenzenesulfonyl)-benzamide (P-0108),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyridine-2-sulfonylamino)-benzamide (P-0109),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyridine-3-sulfonylamino)-benzamide (P-0110),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(dimethylaminomethylene)-benzamide (P-0111),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(piperidine-1-sulfonylamino)-benzamide (P-0112),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(morpholine-4-sulfonylamino)-benzamide (P-0113),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-benzamide (P-0114),

N-(6-Acetylpiperidine-3-yl)-3-cyclopentanecarbonyl-2,6-diflorasone (P-0115),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-benzamide (P-0116),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(3,3,3-cryptochrome-1 sulfone is amino)-benzamide (P-0117),

6-Acetylamino-N-[2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-nicotinamide (P-0118),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide (P-0119),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide (P-0120), and

any salt, prodrug, tautomer or isomer of these compounds.

[0049] According to the present invention, unless expressly stated otherwise, when referring to the connection description connection or group of connections includes pharmaceutically acceptable salts of the compounds (compounds), pharmaceutically acceptable compositions based on the compounds (compounds), prodrugs and all stereoisomers of the compounds. In reference to compositions, kits, methods of use, etc. of compounds of formula I, proposed in the present invention, it is understood (unless otherwise stated)that the compound of formula I includes all private options for implementing the specified connection (for example, including formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii and Ij and all the embodiments mentioned above).

[0050] According to one aspect, the present invention methods of treatment mediated by protein kinase disease or condition in an animal, the methods include the introduction of a specified animal an effective amount of real the or more compounds of formula I. The terms "treat", "treatment (therapy)" and other similar terms refer to the introduction of substances subject being treated, for example, one or more compounds of formula I in an amount effective to prevent, alleviate or ameliorate one or more symptoms of a disease or condition, i.e. in accordance with the indications, and/or for increasing the life expectancy of the specified entity. The term "mediated by protein kinase disease or condition" refers to a disease or condition in which the biological function of protein kinase affects the development and/or course and/or symptoms of the disease or condition and/or in which modulation of the specified protein kinase alters the development, course and/or symptoms of the disease or condition. Mediated by protein kinase disease or condition includes a disease or condition in which this modulation provides a positive therapeutic effect, for example, when treatment with modulators of protein kinases, including compounds according to the present invention, provides a positive therapeutic effect for the subject suffering from the specified disease or condition or at risk of developing this disease or condition. According to the od of the WMD aspect, modulator protein kinase is an inhibitor of protein kinase. According to one aspect, the method includes the introduction of a specified subject an effective amount of one or more compounds of the formula I together with one or more other methods of treatment of the specified disease or condition.

[0051] According to one aspect, the present invention methods of treatment mediated by protein kinase disease or condition in an animal, comprising the introduction of a specified animal an effective amount of one or more compounds of formula I.

[0052] According to one aspect, the present invention methods of treating a disease or condition mediated by protein kinase Raf, the animal, the proposed methods include the introduction of a specified animal an effective amount of one or more compounds of formula I. the Terms "disease or condition mediated by protein kinase Raf, Raf-mediated disease or condition" and other similar terms refer to a disease or condition in which the biological function of Raf kinase, including any mutations specified kinase, affects the development and/or course and/or symptoms of the disease or state and/or in which modulation of proteinsin the PS Raf leads to a change in development course and/or symptoms of the disease or condition. The Raf protein kinase includes, but is not limited to, A-Raf mutations in A-Raf, B-Raf mutations in B-Raf, c-Raf-1 and mutations of c-Raf-1. According to some variants of implementation, the Raf protein kinase is a mutation of B-Raf V600E. According to some variants of implementation, the Raf protein kinase is a mutation of B-Raf V600E/T529I. According to some variants of realization of the specified disease or condition is a cancer susceptible to treatment with inhibitors of mutant B-Raf mutation V600E. According to some variants of realization of the specified disease or condition is a cancer susceptible to treatment with inhibitors of mutant B-Raf mutation V600E/T529I. Specified disease or condition mediated by protein kinase Raf, includes a disease or condition in which modulation of Raf provides a positive therapeutic effect, for example, where treatment with modulators Raf, including compounds according to the present invention, provides a positive therapeutic effect for the subject suffering from the specified disease or condition or at risk of developing this disease or condition. According to one aspect, the specified modulator Raf p is ecstasy a Raf inhibitor. According to one aspect, the method includes the introduction of a specified subject an effective amount of the compounds of formula I together with one or more other methods of treatment of the specified disease or condition. Similarly, the terms "disease or condition mediated by protein kinase A-Raf, B-Raf or c-Raf-1, A-Raf-, B-Raf or c-Raf-1-mediated disease or condition" and other similar terms refer to a disease or condition in which the biological function of the protein kinase A-Raf, B-Raf or c-Raf-1, respectively, including any mutations of these kinases, affects the development and/or course and/or symptoms of the specified disease or condition, and/or in which modulation of protein kinase A-Raf, B-Raf or c-Raf-1, respectively, leads to a change in the development, course and/or symptoms of the disease or condition.

[0053] According to some variants of implementation, the compound of formula I is characterized by the value of the IC50less than 500 nm, less than 100 nm, less than 50 nm, less than 20 nm, less than 10 nm, less than 5 nm, or less than 1 nm, as defined by generally accepted method for studying kinase activity. According to some variants of implementation, the compound of formula I is characterized by an IC50 value of less than 500 nm, less than 100 nm, less than 50 nm, less than 20 nm, less than 10 nm, less than 5 nm, or less than 1 nm is the compared to at least one kinase, selected from the group including Abl, Akt1, Akt2, Akt3, ALK, Alk5, A-Raf, B-Raf, Brk, Btk, Cdk2, CDK4, CDK5, CDK6, CHK1, c-Raf-1, Csk, EGFR, EphA1, EphA2, EphB2, EphB4, Erk2, Fak, FGFR1, FGFR2, FGFR3, FGFR4, Flt1, Flt3, Flt4, Fms, Frk, Fyn, Gsk3α, Gsk3β, HCK, Her2/Erbb2, Her4/Erbb4, IGF1R, IKK beta, Irak4, Itk, Jak1, Jak2, Jak3, Jnk1, Jnk2, Jnk3, Kdr, Kit, Lck, Lyn, MAP2K1, MAP2K2, MAP4K4, MAPKAPK2, Met, Mnk1, MLK1, p38, PDGFRA, PDGFRB, PDPK1, Pim1, Pim2, Pim3, PKC alpha, PKC beta, PKC theta, Plk1, Pyk2, Ret, ROCK1, ROCK2, Ron, Src, Stk6, Syk, TEC, Tie2, TrkA, TrkB, Yes, and Zap70, including any mutations of these kinases.

[0054] According to some variants of implementation, the compound of formula I is characterized by the value of the IC50less than 500 nm, less than 100 nm, less than 50 nm, less than 20 nm, less than 10 nm, less than 5 nm, or less than 1 nm with respect to at least one kinase selected from the group including Abl, Akt1, Akt2, Akt3, ALK, Alk5, A-Raf, B-Raf, Btk, Cdk2, CDK4, CDK5, CDK6, CHK1, c-Raf-1, Csk, EGFR, EphA1, EphA2, EphB2, EphB4, Erk2, Fak, Fms, Fyn, Gsk3α, Gsk3β, HCK, Her2/Erbb2, Her4/Erbb4, IGF1R, IKK beta, Irak4, Itk, Jak1, Jak2, Jak3, Jnk1, Jnk2, Jnk3, Kit, Lck, Lyn, MAP2K1, MAP2K2, MAP4K4, MAPKAPK2, Met, Mnk1, MLK1, p38, PDPK1, Pim1, Pim2, Pim3, PKC alpha, PKC beta, PKC theta, Plk1, Pyk2, Ron, Src, Stk6, Syk, TEC, Tie2, TrkA, TrkB, Yes, and Zap70, including any mutations these kinases.

[0055] According to some variants of implementation, the compound of formula I is characterized by the value of the IC50less than 500 nm, less than 100 nm, less than 50 nm, less than 20 nm, less than 10 nm, less than 5 nm, or less than 1 nm with respect to at least one kinase selected from the group including Abl, A-Raf, B-Raf, Btk, c-Raf-1, EGFR, EphB2, Erk2, Fak, FGFR1, Flt1, Flt3, Flt4, Fms, Irak4, Jnk1, Jnk2, Jnk3, Kdr, Kit, Lck, Lyn, MAP2K1, MAP4K4, MAPKAPK2, Met, p38, PDGFRB, Pim1, PKC theta, Pyk2, Ret, Src, Stk6, rkA, TrkB, Yes, and Zap70, including any mutations of these kinases.

[0056] According to some variants of implementation, the compound of formula I is characterized by the value of the IC50less than 500 nm, less than 100 nm, less than 50 nm, less than 20 nm, less than 10 nm, less than 5 nm, or less than 1 nm with respect to at least one kinase selected from the group including Abl, A-Raf, B-Raf, Btk, c-Raf-1, EGFR, EphB2, Erk2, Fak, Fms, Irak4, Jnk1, Jnk2, Jnk3, Kit, Lck, Lyn, MAP2K1, MAP4K4, MAPKAPK2, Met, p38, Pim1, PKC theta, Pyk2, Src, Stk6, TrkA, TrkB, Yes, and Zap70, including any mutations of these kinases.

[0057] According to some variants of implementation, the compound of formula I is characterized by the value of the IC50less than 500 nm, less than 100 nm, less than 50 nm, less than 20 nm, less than 10 nm, less than 5 nm, or less than 1 nm with respect to at least one kinase selected from the group including A-Raf, B-Raf mutation V600E B-Raf mutation V600E/T529I B-Raf, c-Raf-1, Fak, FGFR1, FGFR2, FGFR3, FGFR4, Jnk1, Jnk2, Jnk3, Lck, Lyn, Met, Pim1, Pim2, Pim3, Pyk2, Kdr Src and Ret, including any mutations of these kinases.

[0058] According to some variants of implementation, the compound of formula I is an inhibitor of Raf kinase and is characterized by the value of the IC50less than 500 nm, less than 100 nm, less than 50 nm, less than 20 nm, less than 10 nm, less than 5 nm, or less than 1 nm, as defined by generally accepted method of research activity of Raf kinase. According to some variants of implementation, the compound of formula I is characterized by the value of the IC50less than 500 nm, less than 100 nm, less than 50 is M, less than 20 nm, less than 10 nm, less than 5 nm, or less than 1 nm with respect to A-Raf, B-Raf, c-Raf-1, mutant B-Raf mutation V600E or mutant B-Raf mutation V600E/T529I. According to some variants of implementation, the compound of formula I selectively inhibits one of the kinases Raf relative to one or more other Raf kinases. According to some variants of implementation, the compound of formula I selectively inhibits mutation of Raf kinase relative to the specified kinase wild-type, for example a mutation V600E B-Raf relative to B-Raf wild-type.

[0059] In addition to any of the above variants of implementation, the compound of formula I also inhibit the effects of mutation of the indicated kinases, including, but not limited to it, a mutation associated with a disease state such as cancer. For example, mutant B-Raf V600E is present in high concentrations in certain types of cancer, such as melanoma, and compounds according to the invention inhibit the kinase activity of the indicated mutant.

[0060] In addition to any of the above variants of implementation, the compound of the formula I are able to selectively inhibit one of the kinases with respect to one or more other kinases, while preferably suppression is selective with respect to any of these other kinases, including kinases, referred to in the present description, and other kinases. According to the some variants of implementation, the specified connection can selectively suppress the effects of mutation of the kinase, relative to the specified kinase wild-type, for example a mutant B-Raf V600E relative to B-Raf wild type. Selective suppression of one kinase relative to other kinases is such that the value of the IC50for the specified one kinase may be at least about 2 times and 5 times, 10 times, 20 times, 50 times or at least about 100 times less than the value IC50for any of these other kinases, where the values of the IC50is determined using generally accepted methods of kinase activity.

[0061] According to another aspect, the present invention proposed a composition containing a therapeutically effective amount of one or more compounds of formula I and at least one pharmaceutically acceptable carrier, excipient and/or diluent, including combinations of any two or more compounds of formula I. the Composition according to the invention may additionally contain a variety of different pharmacologically active compounds, which may include many compounds of formula I. in another aspect, the composition may contain one or more compounds of the formula I together with one or more compounds, therapeutically effective in the actual use of the AI with the same disease. According to another aspect, the composition may contain one or more compounds of the formula I together with one or more compounds, therapeutically effective for the same disease, these compounds have a synergistic effect when applied at the specified disease. According to one aspect, the composition comprises one or more compounds of formula I are effective for the treatment of cancer, and one or more other compounds effective for the treatment of cancer, these compounds additionally have a synergistic effect in the treatment of cancer.

[0062] According to another aspect, the present invention methods of modulating activity of a protein kinase selected from the group including Abl, Akt1, Akt2, Akt3, ALK, Alk5, A-Raf, B-Raf, Brk, Btk, Cdk2, CDK4, CDK5, CDK6, CHK1, c-Raf-1, Csk, EGFR, EphA1, EphA2, EphB2, EphB4, Erk2, Fak, FGFR1, FGFR2, FGFR3, FGFR4, Flt1, Flt3, Flt4, Fms, Frk, Fyn, Gsk3α, Gsk3β, HCK, Her2/Erbb2, Her4/Erbb4, IGF1R, IKK beta, Irak4, Itk, Jak1, Jak2, Jak3, Jnk1, Jnk2, Jnk3, Kdr, Kit, Lck, Lyn, MAP2K1, MAP2K2, MAP4K4, MAPKAPK2, Met, Mnk1, MLK1, p38, PDGFRA, PDGFRB, PDPK1, Pim1, Pim2, Pim3, PKC alpha, PKC beta, PKC theta, Plk1, Pyk2, Ret, ROCK1, ROCK2, Ron, Src, Stk6, Syk, TEC, Tie2, TrkA, TrkB, Yes, and Zap70, including any mutations of these kinases, by bringing the specified protein kinase in contact with an effective amount of one or more compounds of formula I.

[0063] According to another aspect, the methods of treatment mediated proteinsin the zoé disease or condition in an animal, involving the introduction of a specified animal an effective amount of a composition containing one or more compounds of formula I.

[0064] According to one aspect, the methods of treatment of a disease or condition mediated by a protein kinase selected from the group including Abl, Akt1, Akt2, Akt3, ALK, Alk5, A-Raf, B-Raf, Brk, Btk, Cdk2, CDK4, CDK5, CDK6, CHK1, c-Raf-1, Csk, EGFR, EphA1, EphA2, EphB2, EphB4, Erk2, Fak, FGFR1, FGFR2, FGFR3, FGFR4, Flt1, Flt3, Flt4, Fms, Frk, Fyn, Gsk3α, Gsk3β, HCK, Her2/Erbb2, Her4/Erbb4, IGF1R, IKK beta, Irak4, Itk, Jak1, Jak2, Jak3, Jnk1, Jnk2, Jnk3, Kdr, Kit, Lck, Lyn, MAP2K1, MAP2K2, MAP4K4, MAPKAPK2, Met, Mnk1, MLK1, p38, PDGFRA, PDGFRB, PDPK1, Pim1, Pim2, Pim3, PKC alpha, PKC beta, PKC theta, Plk1, Pyk2, ROCK1, ROCK2, Ron, Src, Stk6, Syk, TEC, Tie2, TrkA, TrkB, Yes, and Zap70, including any mutations of these kinases, by introducing a specified animal an effective amount of a composition containing one or more compounds of formula I.

[0065] According to one aspect, the methods of treatment of a disease or condition mediated by a protein kinase selected from the group including Abl, Akt1, Akt2, Akt3, ALK, Alk5, A-Raf, B-Raf, Btk, Cdk2, CDK4, CDK5, CDK6, CHK1, c-Raf-1, Csk, EGFR, EphA1, EphA2, EphB2, EphB4, Erk2, Fak, Fms, Fyn, Gsk3α, Gsk3β, HCK, Her2/Erbb2, Her4/Erbb4, IGF1R, IKK beta, Irak4, Itk, Jak1, Jak2, Jak3, Jnk1, Jnk2, Jnk3, Kit, Lck, Lyn, MAP2K1, MAP2K2, MAP4K4, MAPKAPK2, Met, Mnk1, MLK1, p38, PDPK1, Pim1, Pim2, Pim3, PKC alpha, PKC beta, PKC theta, Plk1, Pyk2, Ron, Src, Stk6, Syk, TEC, Tie2, TrkA, TrkB, Yes, and Zap70, including any mutations of these kinases, by introducing a specified animal an effective amount of a composition containing one or more compounds formula.

[0066] According to one aspect, the methods of treatment of a disease or condition mediated by a protein kinase selected from the group including Abl, A-Raf, B-Raf, Btk, c-Raf-1, EGFR, EphB2, Erk2, Fak, FGFR1, Flt1, Flt3, Flt4, Fms, Irak4, Jnk1, Jnk2, Jnk3, Kdr, Kit, Lck, Lyn, MAP2K1, MAP4K4, MAPKAPK2, Met, p38, PDGFRB, Pim1, PKC theta, Pyk2, Ret, Src, Stk6, TrkA, TrkB, Yes, and Zap70, including any mutations of these kinases, by introducing a specified animal an effective amount of a composition containing one or more compounds of formula I.

[0067] According to one aspect, the methods of treatment of a disease or condition mediated by a protein kinase selected from the group including Abl, A-Raf, B-Raf, Btk, c-Raf-1, EGFR, EphB2, Erk2, Fak, Fms, Irak4, Jnk1, Jnk2, Jnk3, Kit, Lck, Lyn, MAP2K1, MAP4K4, MAPKAPK2, Met, p38, Pim1, PKC theta, Pyk2, Src, Stk6, TrkA, TrkB, Yes, and Zap70, including any mutations of these kinases, by introducing a specified animal an effective amount of a composition containing one or more compounds of formula I.

[0068] According to one aspect, the present invention methods of treating a disease or condition mediated by a protein kinase selected from the group including A-Raf, B-Raf, mutant B-Raf V600E mutant B-Raf V600E/T529I, c-Raf-1, Fak, FGFR1, FGFR2, FGFR3, FGFR4, Jnk1, Jnk2, Jnk3, Lck, Lyn, Met, Pim1, Pim2, Pim3, Pyk2, Kdr, Src and Ret, including any mutations of these kinases, by introducing a specified animal an effective amount of a composition containing one or more compounds of the forms of the crystals I.

[0069] According to one aspect, the present invention methods of treating a disease or condition mediated by A-Raf, B-Raf, c-Raf-1, a mutant B-Raf V600E or mutant B-Raf V600E/T529I, by introducing a specified animal an effective amount of a composition containing one or more compounds of formula I. According to one aspect, the present invention methods of treating a disease or condition mediated by A-Raf, B-Raf, c-Raf-1, a mutant B-Raf V600E or mutant B-Raf V600E/T529I, by introducing a specified animal an effective amount of a composition containing one or more compounds of the formula I, together with one or more other suitable methods of treatment of this disease. According to one aspect, the present invention methods of treating cancer, mediated by mutant B-Raf V600E or mutant B-Raf V600E/T529I, by introducing a specified animal an effective amount of a composition containing one or more compounds of the formula I, together with one or more other suitable methods of cancer treatment, such as applying one or more chemotherapeutic drugs.

[0070] According to one aspect of the present invention, a method for treating cancer by introducing a specified animal now what about the amount of the composition, containing one or more compounds of the formula I, together with one or more other therapies or medical procedures effective for the treatment of this cancer. These other treatments or medical procedures include appropriate types of anti-cancer therapy (e.g., drug therapy, vaccine therapy, gene therapy, phototherapy) or medical procedures (such as surgery, radiation therapy, hyperthermia heating, bone marrow transplantation or stem cells). According to one aspect mentioned one or more suitable types of cancer treatment or medical procedure selected from the group comprising treatment with a chemotherapeutic agent (e.g. drug for chemotherapy), radiation therapy (e.g., x-rays, γ-rays or electron, proton, neutron beams or beam of α-particles), hyperthermia (heating such as microwave, ultrasound, radiofrequency ablation), vaccine therapy (e.g., vaccines on the basis of AFP gene cell carcinoma of the liver, vaccines based on vector AFP adenovirus, AG-858, vaccines based on allogeneic GM-CSF-secreting breast cancer cells, peptide vaccines based on cell papillary cancer), gene therapy (e.g., vector Ad5CMV-p53,adenovector, coding MDA7, necrosis factor-dependent adenovirus 5 tumors alpha), phototherapy (e.g., aminolevulinic acid, motexafin lutetium), surgery and bone marrow transplantation and stem cells.

[0071] According to a preferred implementation variant, in the present invention, a method for treating cancer by introducing to the subject an effective amount of a composition containing one or more compounds of the formula I, in combination with one or more suitable chemotherapeutic agents. According to one aspect mentioned one or more chemotherapeutic agents selected from the group comprising an alkylating agent, including, but not limited to, adozelesin, altretamin, bizelesin, busulfan, carboplatin, carboquone, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, estramustine, fotemustine, HaSulam, ifosfamide, improsulfan, irofulven, lomustin, mechlorethamine, melphalan, oxaliplatin, piposulfan, semustine, streptozocin, temozolomide, thiotepa and treosulfan; an antibiotic including, but not limited to, bleomycin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubitsin menogaril, mitomycin, mitoxantrone, neocarzinostatin, pentostatin and plicamycin; an antimetabolite, including, but not limited to, azacytidine, capecitabine, cladribine, Clofarabine, CIT is the Abin, decitabine, floxuridine, fludarabine, 5-fluorouracil, Ftorafur, gemcitabine, hydroxyurea, mercaptopurine, methotrexate, nelarabine, pemetrexed, raltitrexed, tioguanin and trimetrexate; immunotherapy drug, including, but not limited to, alemtuzumab, bevacizumab, cetuximab, galiximab, gemtuzumab, panitumumab, pertuzumab, rituximab, tositumomab, trastuzumab and 90 Y ibritumomab tiuxetan; a hormone or hormone antagonist, including, but not limited to, anastrozole, androgens, buserelin, diethylstilbestrol, exemestane, flutamide, fulvestrant, goserelin, idoxifene, letrozole, leuprolide, megestrol, raloxifene, tamoxifen, and toremifene; taxan, including, but not limited to, DJ-927, docetaxel, TPI 287, paclitaxel and DHA-paclitaxel; a retinoid, including, but not limited to, alitretinoin, bexarotene, phenetidine, isotretinoin and tretinoin; alkaloid, including, but not limited to, etoposide, homoharringtonine, teniposide, vinblastine, vincristine, vindesine and vinorelbine; anti-angiogenic agent, including, but not limited to, AE-941 (GW786034, Neovastat), ABT-510, 2-methoxyestradiol, lenalidomide and thalidomide; a topoisomerase inhibitor, including, but not limited to, amsacrine, edotecarin, exatecan, irinotecan (also active metabolite SN-38 (7-ethyl-10-hydroxycamptothecin)), rubitecan, topotecan, and 9-aminocamptothecin; in hibitor kinase, including, but not limited to, erlotinib, gefitinib, flavopiridol, imatinib mesilate, lapatinib, sorafenib, sunitinib malate, AEE-788, AG-013736, AMG 706, AMN107, BMS-354825, BMS-599626, UCN-01 (7-hydroxy-staurosporine) and vatalanib; directed inhibitor of signal transduction, including, but not limited to, bortezomib, geldanamycin and rapamycin; biological response modifier, including, but not limited to, imiquimod, interferon-α and interleukin-2; and other chemotherapeutic drugs including, but not limited to, 3-AP (3-amino-2-carboxyaldehyde thiosemicarbazone), aminoglutetimid, asparaginase, bryostatin-1, cilengitide, E7389, ixabepilone, procarbazine, sulindac, temsirolimus, tipifarnib. Preferably, the said method of treating cancer includes the introduction of a specified subject an effective amount of a composition containing one or more compounds of the formula I, in combination with a chemotherapeutic agent selected from the group consisting of 5-fluorouracil, carboplatin, dacarbazine, gefitinib, oxaliplatin, paclitaxel, SN-38, temozolomide, vinblastine, bevacizumab, cetuximab and erlotinib.

[0072] According to another aspect of the present invention, a method for treatment or prevention of diseases or disorders in a mammal by introducing a specified mammal a therapeutically effective amount of one or the more of the compounds of formula I, prodrugs of the compounds, pharmaceutically acceptable salts of the compounds or prodrugs or pharmaceutically acceptable composition on the basis of the specified compound or prodrug. The specified connection can be used individually or in composition. According to another aspect of the present invention, a method for treatment or prevention of diseases or disorders in a mammal by introducing a specified mammal a therapeutically effective amount of one or more compounds of formula I, prodrugs of the compounds, pharmaceutically acceptable salts of the compounds or prodrugs or pharmaceutically acceptable composition on the basis of the compounds or prodrugs together with the use of one or more other suitable methods of treatment of the specified disease or condition.

[0073] According to a related aspect, the present invention proposed a set containing composition according to the present invention. According to some variants of implementation, the composition is packaged, for example, an ampoule, a vial or flask, which can be further packaged, for example, in a box, envelope or package; this composition is approved for administration to a mammal, such as man, Department of health Naz the ru food and drug administration (USA) or similar oversight body. This composition is approved for administration to a mammal, for example a person with the disease or condition mediated by protein kinase. Set according to the present invention contains written instructions for use and/or other indication that the composition is suitable and approved for administration to a mammal, for example a person with the disease or condition mediated by protein kinase. While this composition is packaged in a standard metered dose or single dose form, such as pills, capsules and the like, containing a single dose.

[0074] According to the aspects involving the treatment or prevention of a disease or condition with the compounds of the formula I, the disease or condition is, for example, but without limitation, neurological diseases, including, but not limited to, cerebrovascular ischemia, multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, dementia, senile horey and Huntington's disease; neoplastic diseases and associated complications, including, but not limited to, caused by chemotherapy hypoxia, gastrointestinal stromal tumors (GISO), tumors of the prostate, technicle the intramural tumors (including tuckaleechee tumors in dogs), acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, multiple myeloma, melanoma, mastocytosis, gliomas, glioblastoma, astrocytoma, neuroblastoma, sarcoma (e.g., sarcomas of neuroectodermal origin, leiomyosarcoma), carcinoma (e.g., carcinoma of lung, breast, pancreas, colon cancer, hepatic cell carcinoma, renal carcinoma, carcinoma of the female genital tract, squamous cell carcinoma, preinvasive cancer), lymphoma (e.g., histiocytoma lymphoma, nahodkinskuju lymphoma), multiple endocrine neoplasia type 2 (MEN2), neurofibromatosis (including neoplasia Schwann cells), myelodysplastic syndrome, leukemia, tumor angiogenesis, cancer of the thyroid gland, liver, bone, skin, brain, Central nervous system, pancreas, lung (e.g. small cell lung cancer, non-small cell lung cancer), breast, colon, bladder, prostate, gastrointestinal tract, endometrium, fallopian tubes, testes and ovaries and metastasis of tumors to other tissues; pain of neuropathic or inflammatory nature, including, but not limited to, acute pain, chronic pain, bone pain the pain associated with cancer, and migraine; Ardeche disease, including, but not limited to, heart failure, ischemic stroke, cardiac hypertrophy, thrombosis (e.g. thrombotic syndromes microangiopathy), atherosclerosis, reperfusion injury and ischemia (e.g. cerebrovascular ischemia, liver ischemia); inflammation including, but not limited to, age-related macular degeneration, rheumatoid arthritis, allergic rhinitis, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), systemic lupus erythematosus, Sjogren syndrome, Wegener's granulomatosis, psoriasis, scleroderma, chronic thyroiditis, graves ' disease, myasthenia gravis, multiple sclerosis, osteoarthritis, endometriosis, scarring (e.g., skin, tissue), vascular restenosis, fibrotic disorders, hypereosinophilia, inflammatory violation of the CNS, pancreatitis, nephritis, atopic dermatitis, and hepatitis; diseases associated with immune deficiency, including, but not limited to, severe combined immunodeficiency (SCID), rejection of an organ transplant and disease graft versus host disease; kidney disease or prostate cancer, including, but not limited to, diabetic nephropathy, polycystic kidney disease, nephrosclerosis, glomerulonephritis, interstitial nephritis, lupus nephritis, hyperplasia of the prostate, onicescu renal failure, tubular necrosis, diabetes-related renal complications, and hypertrophy; metabolic diseases, including, but not limited to, type 1 diabetes, type 2 diabetes, metabolic syndrome, obesity, fatty liver, insulin resistance, hyperglycemia, lipolysis and obesity; infection, including, but not limited to, viruses, Helicobacter pylori, Hepatitis and Influenza, fever, and sepsis; pulmonary diseases including, but not limited to, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), asthma, allergies, bronchitis, emphysema and pulmonary fibrosis; genetic defects, including, but not limited to, Noonan syndrome, syndrome Crouzon, acrocephalosyndactyly type 1 syndrome Pfeyffera, syndrome, Jackson-Weiss syndrome Costello (skin-facial-skeletal syndrome), a syndrome of "the Leopard", cardio-skin-facial syndrome (CFC) and the variance associated with the nervous scallops, causing cardiovascular diseases, skeletal, intestinal, skin, hair and endocrine diseases; disorders of bone structure, mineralization and re-formation and bone resorption, including, but not limited to, osteoporosis, increased risk of fractures, disease Paget, hypercalcemia and cancer metastases in bone tissue; graves disease; disease, Hirschsprung's disease; lymphoedema; selective T-cell D. the effect (STD); X linked agammaglobulinemia; diabetic retinopathy; alopecia; erectile dysfunction; tuberose sclerosis and diseases associated with muscle regeneration or degeneration, including, but not limited to, sarcopenia, degenerative disorders of muscle (including, but not limited to, muscular dystrophy Duchenne, Becker, emery-Dreyfus, enveloping myodystrophy limbs (limb-girdle), degeneration of Landuse-Dejerine (facioscapulohumeral), myotonias dystrophy, degeneration of the muscles of the eyeball and pharynx, distal and congenital muscular dystrophy), motor neuron disease (including, but not limited to, amyotrophic lateral sclerosis, progressive muscular atrophy of the spinal cord in children of early age, muscle atrophy of the spinal cord in children, transitional age youth muscular atrophy spinal muscular atrophy of the medulla oblongata and muscle atrophy of the spinal cord in adults), inflammatory myopathies (including, but not limited to, dermatomyositis, polymyositis, and myositis with inclusions Taurus), diseases of the neuromuscular junction (including, but not limited to, myasthenia gravis syndrome of Lambert-Eaton and congenital myasthenic syndrome), myopathies due to endocrine abnormalities (including, but not limited to, hyperthyroid myopathy and Hipotel aidou myopathy), diseases of peripheral nerve (including, but not limited to, disease Charcot-Maritata, disease Dejerine-Cotta and ataxia), other myopathies (including, but not limited to, congenital myotonia, congenital paramythia, congenital myopathy with lesions of the heart muscle fibers, nemalenkuyu myopathy, myotubular myopathy, and periodic paralysis), and metabolic diseases of muscle (including, but not limited to, phosphorylase failure, generalized glycogens, phosphofructokinase insufficiency, deficiency Devetashka enzyme, mitochondrial myopathy, carnitine deficiency, deficit carnitinelongevity deficit phosphoglycerides deficit phosphoglyceromutase, the lactate dehydrogenase deficiency, and the deficiency of myoadenylate deaminase).

[0075] According to some aspects, the compounds of formula I can be used for obtaining a medicinal product for the treatment of a disease or condition which is, for example, but without limitation, neurological diseases, including, but not limited to, cerebrovascular ischemia, multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, dementia, senile horey, and Huntington's disease; neoplastics is their disease and associated complications including, but not limited to, caused by chemotherapy hypoxia, gastrointestinal stromal tumors (GISO), tumors of the prostate, tuckaleechee tumors (including tuckaleechee tumors in dogs), acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, multiple myeloma, melanoma, mastocytosis, gliomas, glioblastoma, astrocytoma, neuroblastoma, sarcoma (e.g., sarcomas of neuroectodermal origin, leiomyosarcoma), carcinoma (e.g., carcinoma of lung, breast, pancreas, colon cancer, hepatic cell carcinoma, renal carcinoma, carcinoma of the female genital tract, squamous cell carcinoma, preinvasive cancer), lymphoma (e.g., histiocytoma lymphoma, nahodkinskuju lymphoma), multiple endocrine neoplasia type 2 (MEN2), neurofibromatosis (including neoplasia Schwann cells), myelodysplastic syndrome, leukemia, tumor angiogenesis, cancer of the thyroid gland, liver, bone, skin, brain, Central nervous system, pancreas, lung (e.g. small cell lung cancer, non-small cell lung cancer), breast, colon, bladder, prostate, gastrointestinal tract, endometrium, fallopian tubes the CoE is enikov and ovarian cancer, and metastasis of tumors to other tissues; pain of neuropathic or inflammatory nature, including, but not limited to, acute pain, chronic pain, bone pain, pain associated with cancer, and migraine; cardiovascular diseases including, but not limited to, heart failure, ischemic stroke, cardiac hypertrophy, thrombosis (e.g. thrombotic syndromes microangiopathy), atherosclerosis, reperfusion injury and ischemia (e.g. cerebrovascular ischemia, liver ischemia); inflammation including, but not limited to, age-related macular degeneration, rheumatoid arthritis, allergic rhinitis, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), systemic lupus erythematosus, Sjogren syndrome, Wegener's granulomatosis, psoriasis, scleroderma, chronic thyroiditis, graves ' disease, myasthenia gravis, multiple sclerosis, osteoarthritis, endometriosis, scarring (e.g., skin, tissue), vascular restenosis, fibrotic disorders, hypereosinophilia, inflammatory violation of the CNS, pancreatitis, nephritis, atopic dermatitis, and hepatitis; diseases associated with immune deficiency, including, but not limited to, severe combined immunodeficiency (SCID), rejection organ transplant and disease graft-versus-host; diseases of the soil is to or prostate cancer, including, but not limited to, diabetic nephropathy, polycystic kidney disease, nephrosclerosis, glomerulonephritis, interstitial nephritis, lupus nephritis, benign prostate hyperplasia, chronic renal failure, tubular necrosis, diabetes-related renal complications, and hypertrophy; metabolic diseases, including, but not limited to, type 1 diabetes, type 2 diabetes, metabolic syndrome, obesity, fatty liver, insulin resistance, hyperglycemia, lipolysis and obesity; infection, including, but not limited to, viruses, Helicobacter pylori, Hepatitis and Influenza, fever, and sepsis; pulmonary diseases including, but not limited to, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), asthma, allergies, bronchitis, emphysema, and pulmonary fibrosis; genetic defects, including, but not limited to, Noonan syndrome, syndrome Crouzon, acrocephalosyndactyly type 1 syndrome Pfeyffera, syndrome, Jackson-Weiss syndrome Costello, (skin-facial-skeletal syndrome), a syndrome of "the Leopard", cardio-skin-facial syndrome (CFC) and the variance associated with neural crest-inducing cardio-vascular diseases, skeletal, intestinal, skin, hair and endocrine diseases; disorders of bone structure, mineralization and reforming the of and bone resorption, including, but not limited to, osteoporosis, increased risk of fractures, disease Paget, hypercalcemia and cancer metastases in bone tissue; graves disease; disease, Hirschsprung's disease; lymphoedema; selective T-cell defect (STD); X linked agammaglobulinemia; diabetic retinopathy; alopecia; erectile dysfunction; tuberose sclerosis and diseases associated with muscle regeneration or degeneration, including, but not limited to, sarcopenia, degenerative disorders of muscle (including, but not limited to, muscular dystrophy Duchenne, Becker, emery-Dreyfus, enveloping myodystrophy limbs (limb-girdle), degeneration of Landuse-Dejerine (facioscapulohumeral), myotonias dystrophy, degeneration of the muscles of the eyeball and pharynx, distal and congenital muscular dystrophy), motor neuron disease (including, but not limited to, amyotrophic lateral sclerosis, progressive muscular atrophy of the spinal cord in children of early age, muscle atrophy of the spinal cord in children, transitional age youth muscular atrophy spinal muscular atrophy of the medulla oblongata and muscle atrophy of the spinal cord in adults), inflammatory myopathies (including, but not limited to, dermatomyositis, polymyositis, and myositis with inclusions Taurus), diseases of the neuromuscular junction (including,but not limited to, myasthenia gravis syndrome of Lambert-Eaton and congenital myasthenic syndrome), myopathies due to endocrine abnormalities (including, but not limited to, hyperthyroid myopathy and hypothyroid myopathy)diseases of peripheral nerve (including, but not limited to, disease Charcot-Maritata, disease Dejerine-Cotta and ataxia), other myopathies (including, but not limited to, congenital myotonia, congenital paramythia, congenital myopathy with lesions of the heart muscle fibers, nemalenkuyu myopathy, myotubular myopathy, and periodic paralysis), and metabolic diseases of muscle (including, but not limited to, phosphorylase failure, generalized glycogens, phosphofructokinase insufficiency, deficiency Devetashka enzyme, mitochondrial myopathy, carnitine deficiency, deficit carnitinelongevity deficit phosphoglycerides deficit phosphoglyceromutase, lactate dehydrogenase deficiency, and the deficiency of myoadenylate deaminase).

[0076] According to the aspects involving the treatment or prevention of a disease or condition with the compounds of the formula I, in the present invention methods of treating a disease or condition mediated by A-Raf, B-Raf and/or c-Raf-1, an animal (e.g. a mammal such as a human is, other primates, hunting animals, animals of commercial interest such as cattle, farm animals such as horses, or Pets such as dogs and cats), with a specified disease or condition, for example, can be characterized by pathological activity of A-Raf, B-Raf and/or c-Raf-1 (e.g., kinase activity). The methods according to the present invention includes the introduction of a subject suffering from a disease or condition mediated by A-Raf, B-Raf and/or c-Raf-1, or at risk of developing such disease or condition an effective amount of the compounds of formula I. According to one implementation options, specified disease, mediated by A-Raf, B-Raf and/or c-Raf-1, selected from the group including neurological diseases, including, but not limited to, multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease; neoplastic diseases including, but not limited to, melanoma, glioma, sarcoma, carcinoma (e.g. colorectal, lung, breast, pancreatic, thyroid, renal, ovarian), lymphoma (e.g., histiocytoma lymphoma)neurofibromatosis, acute myeloid leukemia, myelodysplastic syndrome, leukemia, tumor angiogenesis, Narain okanye tumor, such as medullary thyroid cancer, carcinoid tumors, small cell lung cancer and pheochromocytoma; pain of neuropathic or inflammatory nature, including, but not limited to, acute pain, chronic pain, pain associated with cancer, and migraine; cardiovascular diseases including, but not limited to, heart failure, ischemic stroke, cardiac hypertrophy, thrombosis (e.g. thrombotic syndromes microangiopathy, atherosclerosis, and reperfusion injury; inflammation including, but not limited to, psoriasis, arthritis and autoimmune diseases and conditions, osteoarthritis, endometriosis, scarring, vascular restenosis, fibrotic disorders, rheumatoid arthritis, inflammatory bowel disease; diseases associated with immune deficiency, including, but not limited to, rejection of organ transplant, the disease is graft versus host disease; kidney disease or prostate cancer, including, but not limited to, diabetic nephropathy, polycystic kidney disease, nephrosclerosis, glomerulonephritis, prostate gland hyperplasia; metabolic disorders, including, but not limited to, obesity; infection, including, but not limited to, viruses, Helicobacter pylori, Hepatitis and Influenza, fever, and sepsis; pulmonary diseases including, but not about rancevas them chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS); genetic developmental defects, including, but not limited to, Noonan syndrome, Costello syndrome, (skin-facial-skeletal syndrome), a syndrome of "the Leopard", cardio-skin-facial syndrome (CFC) and the variance associated with the nervous scallops, causing cardiovascular diseases, skeletal, intestinal, skin, hair and endocrine diseases; and diseases associated with muscle regeneration or degeneration, including, but not limited to, sarcopenia degenerative disorders of muscle (including, but not limited to, muscular dystrophy Duchenne, Becker, emery-Dreyfus, enveloping myodystrophy limbs (limb-girdle), degeneration of Landuse-Dejerine (facioscapulohumeral), myotonias dystrophy, degeneration of the muscles of the eyeball and pharynx, distal and congenital muscular dystrophy), motor neuron disease (including, but not limited to, amyotrophic lateral sclerosis, progressive muscular atrophy of the spinal cord in children of early age, muscle atrophy of the spinal cord in children, transitional age youth muscular atrophy spinal muscular atrophy of the medulla oblongata and muscle atrophy of the spinal cord in adults), inflammatory myopathies (including, but not limited to, dermato isit, polymyositis and myositis with inclusions Taurus), diseases of the neuromuscular junction (including, but not limited to, myasthenia gravis syndrome of Lambert-Eaton and congenital myasthenic syndrome), myopathies due to endocrine abnormalities (including, but not limited to, hyperthyroid myopathy and hypothyroid myopathy)diseases of peripheral nerve (including, but not limited to, disease Charcot-Maritata, disease Dejerine-Cotta and ataxia), other myopathies (including, but not limited to, congenital myotonia, congenital paramythia, congenital myopathy with defeat core muscle fibers, nemalenkuyu myopathy, myotubular myopathy, and periodic paralysis), and metabolic diseases of muscle (including, but not limited to, phosphorylase failure, generalized glycogens, phosphofructokinase insufficiency, deficiency Devetashka enzyme, mitochondrial myopathy, carnitine deficiency, deficit carnitinelongevity deficit phosphoglycerides deficit phosphoglyceromutase, lactate dehydrogenase deficiency, and the deficiency of myoadenylate deaminase).

[0077] According to some aspects, the compounds of formula I can be used for obtaining a medicinal product for the treatment mediated by A-Raf, B-Raf and/or c-Raf-1 disease or is Oceania, selected from the group including neurological diseases, including, but not limited to, multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease; neoplastic diseases including, but not limited to, melanoma, glioma, sarcoma, carcinoma (e.g. colorectal, lung, breast, pancreatic, thyroid, renal, ovarian), lymphoma (e.g., histiocytoma lymphoma)neurofibromatosis, acute myeloid leukemia, myelodysplastic syndrome, leukemia, tumor angiogenesis, neuroendocrine tumors such as medullary thyroid cancer, carcinoid tumors, small cell lung cancer and pheochromocytoma; pain of neuropathic or inflammatory nature, including, but not limited to, acute pain, chronic pain, pain associated with cancer, and migraine; cardiovascular diseases including, but not limited to, heart failure, ischemic stroke, cardiac hypertrophy, thrombosis (e.g. thrombotic syndromes microangiopathy, atherosclerosis, and reperfusion injury; inflammation including, but not limited to, psoriasis, arthritis and autoimmune diseases and conditions, osteoarthritis, endometriosis, scarring, vascular restenosis, fibrotic disorders, rheumatoid arthritis, in Sporitelna bowel disease; diseases associated with immune deficiency, including, but not limited to, rejection of organ transplant, the disease is graft versus host disease; kidney disease or prostate cancer, including, but not limited to, diabetic nephropathy, polycystic kidney disease, nephrosclerosis, glomerulonephritis, prostate gland hyperplasia; metabolic disorders, including, but not limited to, obesity; infection, including, but not limited to, viruses, Helicobacter pylori, Hepatitis and Influenza, fever, and sepsis; pulmonary diseases including, but not limited to, chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS); genetic developmental defects, including, but not limited to, Noonan syndrome, Costello syndrome, (skin-facial-skeletal syndrome), a syndrome of "the Leopard", cardio-skin-facial syndrome (CFC) and the variance associated with the nervous scallops, causing cardiovascular diseases, skeletal, intestinal, skin, hair and endocrine diseases; and diseases associated with muscle regeneration or degeneration, including, but not limited to, sarcopenia, degenerative disorders muscle (including, but not limited to, muscular dystrophy Duchenne, Becker, emery-Dreyfus, enveloping myodystrophy limbs (limb-girdle), distro is July Landuse-Dejerine (facioscapulohumeral), myotonias dystrophy, degeneration of the muscles of the eyeball and pharynx, distal and congenital muscular dystrophy), motor neuron disease (including, but not limited to, amyotrophic lateral sclerosis, progressive muscular atrophy of the spinal cord in children of early age, muscle atrophy of the spinal cord in children, transitional age youth muscular atrophy spinal muscular atrophy of the medulla oblongata and muscle atrophy of the spinal cord in adults), inflammatory myopathies (including, but not limited to, dermatomyositis, polymyositis, and myositis with inclusions Taurus), diseases of the neuromuscular junction (including, but not limited to, myasthenia gravis syndrome of Lambert-Eaton and congenital myasthenic syndrome), myopathies due to endocrine abnormalities (including, but not limited to, hyperthyroid myopathy and hypothyroid myopathy)diseases of peripheral nerve (including, but not limited to, disease Charcot-Maritata, disease Dejerine-Cotta and ataxia), other myopathies (including, but not limited to, congenital myotonia, congenital paramythia, congenital myopathy with lesions of the heart muscle fibers, nemalenkuyu myopathy, myotubular myopathy, and periodic paralysis), and metabolic diseases of muscle (R is, but not limited to, phosphorylase failure, generalized glycogens, phosphofructokinase insufficiency, deficiency Devetashka enzyme, mitochondrial myopathy, carnitine deficiency, deficit carnitinelongevity deficit phosphoglycerides deficit phosphoglyceromutase, lactate dehydrogenase deficiency, and the deficiency of myoadenylate deaminase).

[0078] the compounds of formula I with kinase activity, characterized by the value of the IC50less than 10 μm, defined using the standard tests described in the present description, can be used to treat mediated by protein kinase diseases and conditions associated with the following protein kinases, including any mutations of these kinases, for example, but without limitation:

Abl associated with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML);

Akt1 associated with cancer of the stomach, prostate, colon, ovarian, pancreatic and breast cancer, glioblastoma and leukemia, as well as schizophrenia and bipolar disorder, also using in combination with other chemotherapeutic agents;

Akt2 associated with hyperglycemia due to peripheral insulin resistance and nosuppressive production of glucose by the liver, resistance is odumase insufficient compensatory hyperinsulinemia; and also associated with pancreatic cancer, ovarian and breast cancer;

Akt3 associated with melanoma, prostate cancer and breast cancer;

ALK-related non-Hodgkin's lymphomas, such as diffuse extensive b-cell lymphoma and anaplastic both lymphoma;

Alk5 associated with cancer of the pancreas and gall bladder and cutaneous T-cell lymphoma;

A-Raf associated with neurological diseases, including multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease; neoplastic diseases including, but not limited to, melanoma, glioma, sarcoma, carcinoma (e.g. colorectal, lung, breast, pancreatic, thyroid, renal, ovarian), lymphoma (e.g., histiocytoma lymphoma)neurofibromatosis, myelodysplastic syndrome, leukemia, tumor angiogenesis; pain of neuropathic or inflammatory nature, including acute pain, chronic pain, pain associated with cancer, and migraine; and diseases associated with muscle regeneration or degeneration, including, but not limited to, vascular restenosis, sarcopenia, degenerative disorders of muscle (including, but not limited to, muscular dystrophy Duchenne, Becker, emery-Dreyfus, enveloping Ministro is the s extremity (limb-girdle), dystrophy, Landuse-Dejerine (facioscapulohumeral), myotonias dystrophy, degeneration of the muscles of the eyeball and pharynx, distal and congenital muscular dystrophy), motor neuron disease (including, but not limited to, amyotrophic lateral sclerosis, progressive muscular atrophy of the spinal cord in children of early age, muscle atrophy of the spinal cord in children, transitional age youth muscular atrophy spinal muscular atrophy of the medulla oblongata and muscle atrophy of the spinal cord in adults), inflammatory myopathies (including, but not limited to, dermatomyositis, polymyositis, and myositis with inclusions Taurus), diseases of the nervous-muscle connection (including, but not limited to, myasthenia gravis syndrome of Lambert-Eaton and congenital myasthenic syndrome), myopathies due to endocrine abnormalities (including, but not limited to, hyperthyroid myopathy and hypothyroid myopathy)diseases of peripheral nerve (including, but not limited to, disease Charcot-Maritata, disease Dejerine-Cotta and ataxia), other myopathies (including, but not limited to, congenital myotonia, congenital paramythia, congenital myopathy with lesions of the heart muscle fibers, nemalenkuyu myopathy, myotubular myopathy and periodic paralysis) and metabolicheskie diseases of muscle (including, but not limited to, phosphorylase failure, generalized glycogens, phosphofructokinase insufficiency, deficiency Devetashka enzyme, mitochondrial myopathy, carnitine deficiency, deficit carnitinelongevity deficit phosphoglycerides deficit phosphoglyceromutase, lactate dehydrogenase deficiency, and the deficiency of myoadenylate deaminase);

B-Raf or c-Raf-1 associated with neurological zabolevanii, including, but not limited to, multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease; neoplastic diseases including, but not limited to, melanoma, glioma, sarcoma, carcinoma (e.g. colorectal, lung, breast, pancreatic, thyroid, renal, ovarian), lymphoma (e.g., histiocytoma lymphoma)neurofibromatosis, acute myeloid leukemia, myelodysplastic syndrome, leukemia, tumor angiogenesis, neuroendocrine tumors such as medullary thyroid cancer, carcinoid tumors, small cell lung cancer and pheochromocytoma; pain of neuropathic or inflammatory nature, including, but not limited to, acute pain, chronic pain, pain associated with cancer, and migraine; cardiovascular diseases including, but not limited to the mi, heart failure, ischemic stroke, cardiac hypertrophy, thrombosis (e.g. thrombotic syndromes microangiopathy, atherosclerosis, and reperfusion injury; inflammation including, but not limited to, psoriasis, arthritis and autoimmune diseases and conditions, osteoarthritis, endometriosis, scarring, vascular restenosis, fibrotic disorders, rheumatoid arthritis, inflammatory bowel disease; diseases associated with immune deficiency, including, but not limited to, rejection of organ transplant, the disease is graft versus host disease; renal disease or prostate cancer, including, but not limited to, diabetic nephropathy, polycystic kidney disease, nephrosclerosis, glomerulonephritis, prostate gland hyperplasia; metabolic disorders, including, but not limited to, obesity; infection, including, but not limited to, viruses, Helicobacter pylori, Hepatitis and Influenza, fever, and sepsis; pulmonary diseases including, but not limited to, chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS); genetic developmental defects, including, but not limited to, Noonan syndrome, Costello syndrome (skin-facial-skeletal syndrome), a syndrome Leopard"cardio-skin-facial syndrome (CFC) and deviation, is knitted with a nervous scallop, causing cardiovascular diseases, skeletal, intestinal, skin, hair and endocrine diseases;

Brk associated with breast cancer and colon cancer, and squamous cell cancer of the head and neck;

Btk associated with X-linked agammaglobulinemia, acute lymphocytic leukemia, autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis and graves ' disease, suppression of the immune response of an organ transplant and the susceptibility of b cells to drugs;

Cdk2 associated with prostate cancer, breast cancer, colon cancer and ovarian cancer;

Cdk4 associated with glioblastoma (for example, the multiform glioblastoma), with anaplastic astrocytoma and breast cancer;

Cdk5 associated with Alzheimer's disease, amyotrophic lateral sclerosis and disease with calves Levi;

Cdk6 associated with the multiform glioblastoma, non-Hodgkin lymphoma, lymphocytoma spleen, T-cell lymphoblastic lymphoma (T-LBL) and T-cell acute lymphoblastic leukemia (T-ALL);

CHK1 associated with the recovery of DNA damage; sencibilisiruet cells to the action of chemotherapeutic agents;

Csk associated with carcinoma of the colon and pancreas and autoimmune disorders such as type 1 diabetes, reumatoide the arthritis and systemic lupus erythematosus;

EGFR-related cancer of the breast, colon, bladder, prostate and non-small cell lung cancer, squamous cell cancer of the head and neck, oral cavity and esophagus, and multihormonal glio;

EphA1 associated with squamous head and neck cancer, hepatoma and lung cancer;

EphA2 associated with aberrant middle contact-mediated axonal guidance, bladder cancer, breast, prostate, colon, skin, cervical, ovarian, pancreatic and lung and metastatic melanoma;

EphB2 associated with impaired angiogenesis (for example, the angiogenic eye disease, such as retinopathy and cancer (e.g. glioblastoma, breast cancer and liver cancer);

EphB4, is associated with colorectal cancer (CRC), squamous cell cancer of the head and neck and prostate tumors, breast cancer, endometrial and bladder;

Erk2 associated with aberrant proliferation, differentiation, regulation and development of transciption, which may be suitable for the treatment of inflammation, for example, inflammation associated with Lyme neuroborreliosis, and also for the treatment of cancer such as cancer of the stomach;

Fak associated with tumors of the colon and breast cancer, and squamous cell esophageal cancer, melanoma, anaplastic the th astrocytoma, glio, preinvasive cancer of the ducts, prostate gland and hepatic cell carcinoma and metastatic tumors; may also provide synergistic effects with other chemotherapeutic agents;

FGFR1 associated with myeloproliferative syndrome 8p11;

FGFR2 associated with the syndrome Crouzon, syndrome, Jackson-Weiss syndrome Apert, craniosynostosis, syndrome Pfeyffera, acrocephalosyndactyly V type and syndrome Bira-Stevenson;

FGFR3-related angiogenesis, wound healing, achondroplasia, craniosynostosis the Director (Muenke), syndrome Crouzon, acanthocardia, thanatophoric dysplasia, carcinoma of the bladder and multiple myeloma;

FGFR4 associated with cancer of the breast, lung, colon cancer, medullary thyroid cancer, pancreatic cancer, ovarian, prostate, endometrium and fallopian tubes, squamous cell head and neck cancer and leiomyosarcoma;

Flt1 associated with non-small cell lung cancer, carcinoma of the prostate and cancer of the colon;

Flt3 associated with acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia;

Flt4 associated with the primary lymphedemas;

Fms-related immune disorders, including rheumatoid arthritis, systemic lupus erythematosus (SLE) and ottorini the graft, inflammatory diseases, including inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), chronic obstructive pulmonary disease (COPD), emphysema, and atherosclerosis, metabolic disorders, including type 1 diabetes and type 2 diabetes, insulin resistance, hyperglycemia, and lipolysis, disorders of bone structure, mineralization and re-formation and bone resorption, including osteoporosis, increased risk of fractures, disease Paget, hypercalcemia and cancer metastases in bone, kidney diseases, including nephritis (e.g. glomerulonephritis, interstitial nephritis, lupus nephritis), tubular necrosis, diabetes-related kidney complications (e.g. diabetic nephropathy) and hypertrophy, diseases of the Central nervous system, including multiple sclerosis, stroke, Alzheimer's disease and Parkinson's disease; inflammatory and chronic pain, including bone pain; and cancers, including multiple myeloma, acute myeloid leukemia, chronic myeloid leukemia (CML), prostate cancer, breast cancer, ovarian cancer, and metastasis of tumors to other tissues;

Frk-related acute myeloid leukemia and type 1 diabetes;

Fyn associated with Alzheimer's disease, schizophrenia and prevention of metastasis, for example, in melanoma and squamous cell cancer;

GSK3 (Gsk3α and/or Gsk3β), is associated with CNS disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, type 2 diabetes, bipolar disorder, stroke, cancer, chronic inflammatory disease, leukopenia, schizophrenia, chronic pain, neuropathic pain and trauma of the head;

HCK associated with chronic myelogenous leukemia and acute lymphocytic leukemia;

Her2/Erbb2 related cancer of the prostate and breast;

Her4/Erbb4 associated with medulloblastoma in children;

IGF1R associated with prostate cancer, hepatic cell carcinoma;

IKK beta associated with leukemia T cells, necrosis, insulin resistance and malignant neoplasms;

Irak4 associated with bacterial infections, immunodeficiency syndrome, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), asthma, chronic bronchitis, cardiac hypertrophy and renal hypertension;

Itk associated with allergic asthma;

Jak1-related viral infection hepatitis C;

Jak2, related to myeloproliferative disorders such as polycythemia Vera, myelofibrosis, essential thrombocythemia, myeloid metaplasia and leukemias, including acute lymphoblastic leukemia, chronic neutrophilic leukemia, juvenile is almanacmanny leukemia, chronic myelomonocytic leukemia (CMML), chronic myeloid leukemia, negative with respect to the chromosome "Philadelphia", megakaryocytic leukemia, and acute erythroid leukemia;

Jak3 associated with X-linked severe combined immune deficiency, myeloproliferative disorders, graft rejection and autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), systemic lupus erythematosus, psoriasis and multiple sclerosis;

Jnk (Jnk1, Jnk2, Jnk3), associated with metabolic diseases, including type 1 diabetes, type 2 diabetes, metabolic syndrome, obesity and fatty liver; cardiovascular diseases such as atherosclerosis, ischemia (e.g. cerebrovascular ischemia, liver ischemia), reperfusion injury, cardiac hypertrophy; renal diseases, such as chronic renal failure; neoplastic diseases and associated complications, including caused by chemotherapy hypoxia, prostate carcinoma, myeloid leukemia and cancers of the liver, bone, skin, brain, pancreas, lung, breast, colon, prostate and ovary; graft rejection; pain of neuropathic or inflammatory nature is, including acute and chronic pain; inflammatory and autoimmune diseases, including age-related macular degeneration, rheumatoid arthritis, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), systemic lupus erythematosus, Sjogren syndrome, psoriasis, scleroderma, chronic thyroiditis, graves ' disease, myasthenia gravis and multiple sclerosis, and inflammation of other organs, including inflammatory violation of the CNS, pancreatitis, nephritis, atopic dermatitis, and hepatitis; inflammatory diseases of the Airways such as asthma, Allergy, bronchitis, pulmonary fibrosis, chronic obstructive pulmonary disease; neurological diseases, including stroke, cerebrovascular ischemia, neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, dementia, senile chorea, brain and spinal cord and Huntington's disease. In particular, Jnk1 is associated with type 1 diabetes, type 2 diabetes, metabolic syndrome, obesity and fatty liver, Jnk2 is associated with atherosclerosis, and Jnk3 is associated with inflammatory diseases, including autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), systemic lupus erythematosus, syndrome Segr is on, psoriasis and multiple sclerosis, inflammatory respiratory diseases such as asthma, Allergy, pulmonary fibrosis and chronic obstructive pulmonary disease, inflammation of other organs, such as inflammatory violation of the CNS, pancreatitis, nephritis, and hepatitis; neurological diseases such as stroke, cerebrovascular ischemia, and neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and Huntington's disease; neoplastic diseases such as prostate carcinoma and myeloid leukemia;

Kdr associated with anti-angiogenesis for the treatment of growth of solid tumors (e.g., ovarian cancer, lung, breast, pancreas, prostate cancer, colon cancer, gastrointestinal stromal tumors, non-small cell lung cancer and squamous cell cancer), metastasis, psoriasis, rheumatoid arthritis, diabetic retinopathy and age-related macular degeneration;

Kit associated with malignant neoplasms, including tuckaleechee tumors, small cell lung cancer, testicular cancer, gastrointestinal stromal tumor (GISO), glioblastoma, astrocytoma, neuroblastoma, carcinomas of the female genital tract, sarcomas of neuroectodermal origin, carcinoma of the colon, preinvasive cancer, n is aplasia Schwann cells, associated with neurofibromatosis, acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, mastocytosis, melanoma, and tuckaleechee tumors in dogs, and inflammatory diseases, including asthma, rheumatoid arthritis, allergic rhinitis, multiple sclerosis, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), graft rejection, and hypereosinophilia;

Lck is associated with acute lymphoblastic leukemia, T-cell lymphoma, lymphopenia, carcinoma of the kidney, carcinoma of the colon, severe combined immunodeficiency, multiple sclerosis, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease (CD) and type 1 diabetes;

Lyn associated with cancer, such as glioblastoma;

MAP2K1 associated with acute myeloid leukemia, breast cancer, ovarian cancer and liver cancer;

MAP2K2 associated with cancer and inflammation;

MAP4K4 associated with metabolic indications, including re-sensitization of fat and muscle cells to insulin, alleviation of pathological processes in adipocytes, alleviation of pathological processes in muscle cells, metabolic syndrome and type 2 diabetes; a wide range of Oncology indications, including blocking migration, invasion, and metastasis to the large shopping Mall is the number of different types of tumors; and autoimmune disease mediated by T-cells;

MAPKAPK2 associated with cancer (e.g. prostate, breast), stroke, meningitis, and inflammatory disorders;

Met-related cancer of the kidney, breast, bladder, non-small cell lung cancer, colon cancer and bladder and hepatic cell carcinoma;

Mnk1-related conditions associated with thermal stress, lack of nutrients, oxidative or osmotic stress, and infection of mammalian cells (for example, viruses such as adenovirus (Ad) or influenza virus), and autoimmune diseases;

MLK1 associated with neurodegenerative diseases such as Alzheimer's and Parkinson's disease, and inflammatory disorders;

p38 associated with acute coronary syndrome, stroke, atherosclerosis, and inflammatory autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease);

DERIVED (PDGFRA, PDGFRB), associated with idiopathic syndrome hypereosinophilia, chronic eosinophilia leukemia, glioma, gastrointestinal stromal tumors (GISO), juvenile myelomonocytic leukemia, metastatic medulloblastoma, atherogenesis and restenosis. In particular, PDGFRA SV is related to idiopathic syndrome hypereosinophilia, chronic eosinophilia leukemia, glioma, gastrointestinal stromal tumors (GISO), juvenile myelomonocytic leukemia, metastatic medulloblastoma, atherogenesis and restenosis, and PDGFRB associated with idiopathic syndrome hypereosinophilia, chronic eosinophilia leukemia, juvenile myelomonocytic leukemia, and metastatic medulloblastoma;

PDPK1 associated with cancer and diabetes;

Pim1-related cancers, such as cancers of the blood (e.g., acute myeloid and acute lymphoid leukemia and cancers of the prostate, and non-Hodgkin's lymphoma;

Pim2-related lymphoma;

Pim3 associated with hepato-cellular carcinoma;

PKC alpha, associated with pituitary tumors and dysfunctions of the prefrontal cortex, such as pathologically increased otvlekaemost, impaired judgment, impulsivity, and thought disorder; which is also suitable for use to increase susceptibility to chemotherapy in breast cancer, colon cancer and non-small cell lung cancer;

PKC beta associated with diabetic retinopathy;

PKC-theta associated with insulin resistance, T-cell lymphoma;

Plk1 associated with cancer (e.g., lymphoma of the thyroid, non-Hodgkin lymphoma, cancer of the new diseases of the colon, various types of leukemia and melanoma), which is also suitable for use as a sensitizer chemotherapy;

Pyk2 associated with inflammation (e.g., osteoporosis, polycystic kidney disease, rheumatoid arthritis and inflammatory bowel disease), Central nervous system diseases (such as Parkinson's and Alzheimer's disease), stroke, and cancer (e.g., glioma, breast cancer and pancreatic cancer);

Ret associated with thyroid cancer, neuroblastoma, hereditary medullary thyroid cancer (FMTC), multiple endocrine neoplasia type IIA and IIB (MEN2A, MEN2B) and neurodegenerative disorders (e.g., disease, Hirschsprung's disease, Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis);

ROCK (ROCK-1, ROCK-2)associated with cancer (e.g. ovarian cancer, hepatic cell carcinoma, pancreatic cancer), diseases of the eye (e.g. glaucoma), cardiac hypertrophy, increased blood flow to the renal graft rejection and acute respiratory distress syndrome;

Ron associated with cancer and inflammation;

Src-related cancer and osteoporosis;

Stk6 associated with cancer of the stomach, bladder, breast, lung, CNS, ovarian, renal, colon Ki is Ki, prostate, pancreas and cervix, melanoma, leukemia, and neuroblastoma;

Syk-related lymphomas (e.g., lymphoma of the cells of the mantle zone);

TEC associated with sepsis, septic shock, inflammation, rheumatoid arthritis, Crohn's disease, irritable bowel syndrome (IBD) and ulcerative colitis;

Tie2 (TEK)that is associated with cancer, arthritis (such as rheumatoid arthritis and atherosclerosis;

TrkA-related pain (e.g. chronic pain, neuropathic pain), cancer (e.g. prostate cancer, lung cancer, pancreatic cancer), allergic disorders (e.g. asthma), arthritis, diabetic retinopathy, macular degeneration and psoriasis;

TrkB associated with obesity, hyperphagia, developmental delays, cancer (e.g. prostate cancer, lung cancer, Wilms ' tumors, neuroblastoma, pancreatic cancer, various diseases of the nervous system (e.g. stroke, multiple sclerosis, transverse myelitis, and encephalitis) and diabetes.

Yes that is associated with various cancers, including squamous cell carcinoma of the esophagus; and

Zap70, AIDS, systemic lupus erythematosus, myasthenia gravis, atherosclerosis, rejection of transplanted organs or tissues, the rejection of alltrans ntata, including acute and chronic allograft rejection, disease, graft versus host disease, rheumatoid arthritis, psoriasis, systemic sclerosis, atopic dermatitis, eczematous dermatitis, alopecia, and inflammation of the mucous membranes of the nose, including all forms of rhinitis.

[0079] Additional aspects and the embodiments of the present invention will become apparent from the following detailed description and claims.

A DETAILED DESCRIPTION of the PREFERRED VARIANTS of the INVENTION

[0080] In the present description, unless expressly noted otherwise, use the following definitions:

[0081] “Halogen” refers to all Halogens, i.e. chlorine (Cl), fluorine (F), bromine (Br) or iodine (I).

[0082] “Hydroxyl” or "hydroxy" refers to the group-OH.

[0083] “Thiol” refers to the group-SH.

[0084] the Term “lower alkyl”, used alone or in combination, means derived from alkane radical containing from 1 to 6 carbon atoms (unless otherwise noted), including linear alkyl and branched alkyl. Specified linear or branched alkyl group is valid from a chemical point of view and attached at any available position with the formation of stable compounds. According to many variants of implementation, lower alkyl represents a linear or branched what th alkyl group, containing from 1 to 6, 1 to 4 or 1 to 2 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, and others. "Optionally substituted lower alkyl" means lower alkyl, unless specified otherwise, may independently contain one or more substituents, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent attached at any available atom with the formation of stable compounds, and these substituents selected from the group comprising-F, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Ro, -S-Ro, -O-C(O)-Ro, -O-C(S)-Ro, -C(O)-Ro, -C(S)-Ro, -C(O)-O-Ro, -C(S)-O-Ro, -S(O)-Ro, -S(O)2-Ro, -C(O)-N(H)-Ro, -C(S)-N(H)-Ro, -C(O)-N(Ro)-Ro, -C(S)-N(Ro)-Ro, -S(O)2-N(H)-Ro, -S(O)2-N(Ro)-Ro, -C(NH)-N(H)-Ro, -C(NH)-N(Rp)-Rc, -N(H)-C(O)-Ro, -N(H)-C(S)-Ro, -N(Ro)-C(O)-Ro, -N(Ro)-C(S)-Ro, -N(H)-S(O)2-Ro, -N(Ro)-S(O)2-Ro, -N(H)-C(O)-N(H)-Ro, -N(H)-C(S)-N(H)-Ro, -N(Ro)-C(O)-NH2, -N(Ro)-C(S)-NH2, -N(Ro)-C(O)-N(H)-Ro, -N(Ro)-C(S)-N(H)-Ro, -N(H)-C(O)-N(Ro)-Ro, -N(H)-C(S)-N(Ro)-Ro, -N(Ro)-C(O)-N(Ro)-Ro, -N(Ro)-C(S)-N(Ro)-Ro , -N(H)-S(O)2-N(H)-Ro, -N(Ro)-S(O)2-NH2, -N(Ro)-S(O)2-N(H)-Ro, -N(H)-S(O)2-N(Ro)-Ro, -N(Ro)-S(O)2-N(Ro)-Ro, -N(H)-Ro, -N(Ro)-Ro, -Re, -Rfand Rg. In addition, possible substituents include private combinations of the above substituents, including combinations of substituents given in the present description, for example, for compounds of formula I, the substituents attached at any available atom with the formation of stable compounds. For example, fluoro-substituted lower alkyl” means a lower alkyl group containing as substituents one or more fluorine atoms, such as perfluoroalkyl, while preferably specified lower alkyl contains as substituents 1, 2, 3, 4 or 5 fluorine atoms and 1, 2 or 3 fluorine atom. This implies that these substituents are valid from a chemical point of view and attached at any available position with the formation of stable compounds.

[0085] the Term "lower alkenyl", used separately or in combination, means linear or branched hydrocarbon containing from 2 to 6 carbon atoms (unless otherwise specified) and at least one, preferably from 1 to 3, more preferably from 1 to 2, most preferably one to double the link "carbon-carbon". Double bond "carbon-carbon" may contain both linear and branched portions of the said hydrocarbon. Specified linear or branched Alchemilla group is valid from a chemical point of view and attached at any available position with the formation of stable compounds. Examples of the lower alkenylphenol groups include ethynyl, propenyl, Isopropenyl, butenyl and other "Optional substituted lower alkenyl" means the lowest alkenyl, which, if not specified otherwise, may independently contain one or more substituents, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent attached at any available atom with the formation of stable compounds, and these substituents selected from the group comprising-F, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Ro, -S-Ro, -O-C(O)-Ro, -O-C(S)-Ro, -C(O)-Ro, -C(S)-Ro, -C(O)-O-Ro, -C(S)-O-Ro, -S(O)-Ro, -S(O)2-Ro, -C(O)-N(H)-Ro, -C(S)-N(H)-Ro, -C(O)-N(Ro)-Ro, -C(S)-N(Ro)-Ro, -S(O)2-N(H)-Ro, -S(O)2-N(Ro)-Ro, -C(NH)-N(H)-Ro, -C(NH)-N(Rp)-Rc, -N(H)-C(O)-Ro, -N(H)-C(S)-Ro, -N(Ro)-C(O)-Ro, -N(Ro)-C(S)-Ro, -N(H)-S(O)2-Ro , -N(Ro)-S(O)2-Ro, -N(H)-C(O)-N(H)-Ro, -N(H)-C(S)-N(H)-Ro, -N(Ro)-C(O)-NH2, -N(Ro)-C(S)-NH2, -N(Ro)-C(O)-N(H)-Ro, -N(Ro)-C(S)-N(H)-Ro, -N(H)-C(O)-N(Ro)-Ro, -N(H)-C(S)-N(Ro)-Ro, -N(Ro)-C(O)-N(Ro)-Ro, -N(Ro)-C(S)-N(Ro)-Ro, -N(H)-S(O)2-N(H)-Ro, -N(Ro)-S(O)2-NH2, -N(Ro)-S(O)2-N(H)-Ro, -N(H)-S(O)2-N(Ro)-Ro, -N(Ro)-S(O)2-N(Ro)-Ro, -N(H)-Ro, -N(Ro)-Ro, -Rd, -Rfand Rg. In addition, possible substituents include private combinations of the above substituents, including combinations of substituents given in the present description, for example, for compounds of formula I, the substituents attached at any available atom with the formation of stable compounds. For example, fluoro-substituted lower alkenyl” means the lowest alkenylphenol group containing as substituents one or more fluorine atoms, while preferably specified lower alkenyl contains as substituents 1, 2, 3, 4 or 5 fluorine atoms and 1, 2 or 3 fluorine atom. “C3-6alkenyl” means the lowest alkenyl containing from 3 to 6 carbon atoms. “Optionally substituted C3-6alkenyl” means optionally substituted lower alkenyl containing from 3 to 6 carbon atoms. If this is m means, these deputies are valid from a chemical point of view and attached at any available position with the formation of stable compounds.

[0086] the Term "lower quinil", used separately or in combination, means linear or branched hydrocarbon containing from 2 to 6 carbon atoms (unless otherwise specified) and at least one, preferably one triple bond "carbon-carbon". Specified linear or branched Alchemilla group is valid from a chemical point of view and attached at any available position with the formation of stable compounds. Examples etkinlik groups include ethinyl, PROPYNYL, butynyl and other "Optional substituted lower quinil" means the lowest quinil, which, if not specified otherwise, may independently contain one or more substituents, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent attached at any available atom with the formation of stable compounds, and these substituents selected from the group comprising-F, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Ro, -S-Ro, -O-C(O)-Ro, -O-C(S)-Ro, -C(O)-Ro, -C(S)-Ro, -C(O)-O-Ro, -C(S)-O-Ro, -S(O)-Ro, -S(O) 2-Ro, -C(O)-N(H)-Ro, -C(S)-N(H)-Ro, -C(O)-N(Ro)-Ro, -C(S)-N(Ro)-Ro, -S(O)2-N(H)-Ro, -S(O)2-N(Ro)-Ro, -C(NH)-N(H)-Ro, -C(NH)-N(Rp)-Rc, -N(H)-C(O)-Ro, -N(H)-C(S)-Ro, -N(Ro)-C(O)-Ro, -N(Ro)-C(S)-Ro, -N(H)-S(O)2-Ro, -N(Ro)-S(O)2-Ro, -N(H)-C(O)-N(H)-Ro, -N(H)-C(S)-N(H)-Ro, -N(Ro)-C(O)-NH2, -N(Ro)-C(S)-NH2, -N(Ro)-C(O)-N(H)-Ro, -N(Ro)-C(S)-N(H)-Ro, -N(H)-C(O)-N(Ro)-Ro, -N(H)-C(S)-N(Ro)-Ro, -N(Ro)-C(O)-N(Ro)-Ro, -N(Ro)-C(S)-N(Ro)-Ro, -N(H)-S(O)2-N(H)-Ro, -N(Ro)-S(O)2-NH2, -N(Ro)-S(O)2-N(H)-Ro, -N(H)-S(O)2-N(Ro)-Ro, -N(Ro)-S(O)2-N(Ro)-Ro, -N(H)-Ro, -N(Ro)-Ro, -Rd, -Reand Rg. In addition, possible substituents include private combinations of the above substituents, including combinations of substituents given in the present description, for example, for compounds of formula I, the substituents attached at any available atom with the formation of stable compounds. For example, fluoro-substituted lower quinil” means the lowest alkylamino group containing as substituents one or more fluorine atoms, while preferably specified lower quinil contains as mandated the indices 1, 2, 3, 4 or 5 fluorine atoms and 1, 2 or 3 fluorine atom. “C3-6quinil” means the lowest quinil containing from 3 to 6 carbon atoms. “Optionally substituted C3-6quinil” means optionally substituted lower quinil containing from 3 to 6 carbon atoms. This implies that these substituents are valid from a chemical point of view and attached at any available position with the formation of stable compounds.

[0087] the Term "cycloalkyl" refers to a saturated or unsaturated non-aromatic monocyclic, bicyclic or tricyclic systems carbon ring, containing from 3 to 10, and from 3 to 8, preferably from 3 to 6 atoms in the ring such as cyclopropyl, cyclopentyl, cyclohexyl, substituted and other "Optional substituted cycloalkyl" means cycloalkyl, which, if not specified otherwise, may independently contain one or more substituents, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent attached on any available atom with the formation of stable compounds, and these substituents selected from the group comprising halogen, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Ro, -S-Ro, -O-C(O)-Ro, -O-C(S)- o, -C(O)-Ro, -C(S)-Ro, -C(O)-O-Ro, -C(S)-O-Ro, -S(O)-Ro, -S(O)2-Ro, -C(O)-N(H)-Ro, -C(S)-N(H)-Ro, -C(O)-N(Ro)-Ro, -C(S)-N(Ro)-Ro, -S(O)2-N(H)-Ro, -S(O)2-N(Ro)-Ro, -C(NH)-N(H)-Ro, -C(NH)-N(Rp)-Rc, -N(H)-C(O)-Ro, -N(H)-C(S)-Ro, -N(Ro)-C(O)-Ro, -N(Ro)-C(S)-Ro, -N(H)-S(O)2-Ro, -N(Ro)-S(O)2-Ro, -N(H)-C(O)-N(H)-Ro, -N(H)-C(S)-N(H)-Ro, -N(Ro)-C(O)-NH2, -N(Ro)-C(S)-NH2, -N(Ro)-C(O)-N(H)-Ro, -N(Ro)-C(S)-N(H)-Ro, -N(H)-C(O)-N(Ro)-Ro, -N(H)-C(S)-N(Ro)-Ro, -N(Ro)-C(O)-N(Ro)-Ro, -N(Ro)-C(S)-N(Ro)-Ro, -N(H)-S(O)2-N(H)-Ro, -N(Ro)-S(O)2-NH2, -N(Ro)-S(O)2-N(H)-Ro, -N(H)-S(O)2-N(Ro)-Ro, -N(Ro)-S(O)2-N(Ro)-Ro, -N(H)-Ro, -N(Ro)-Ro, -Rd, -Re, -Rfand Rg. “C3-6cycloalkyl” means cycloalkyl containing from 3 to 6 carbon atoms. “C3-5cycloalkyl” means cycloalkyl containing from 3 to 5 carbon atoms. This implies that these substituents are valid from a chemical point of view and attached at any available position with the formation of stable compounds.

[0088] the Term “heteroseksualci” refers to a saturated or unsaturated, not the romantic cycloalkyl group, containing from 5 to 10 atoms, where from 1 to 3 carbon atoms in the ring are replaced by heteroatoms selected from the group comprising O, S and N, while the group may be condensed with a benzene group or heteroaryl group containing from 5 to 6 atoms in the ring. Heteroseksualci may also contain oxidized form S or N, such as sulfinil, sulfonyl and N-oxides of tertiary nitrogen atom in the ring. Heteroseksualci also includes compounds in which the carbon atom in the ring may be oxo-substituted, i.e. where the carbon atom in the ring represents a carbonyl group, such as lactones and lactams. Specified geteroseksualnoe ring attached on this carbon atom or nitrogen in the ring, joining which ensures the preservation of sustainable patterns of ring. Examples geteroseksualnoe groups include, but are not limited to, morpholino, tetrahydrofuranyl, dihydropyridines, piperidinyl, pyrrolidinyl, pyrrolidinyl, piperazinil, dihydrobenzofuranyl and dihydroindole. "Nitrogen containing heteroseksualci" refers to heteroseksualci, in which at least one heteroatom represents n "Optionally substituted heteroseksualci" means heteroseksualci, which, if not specified otherwise, may independently contain one or more Deputy who, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent attached at any available atom with the formation of stable compounds, and these substituents selected from the group comprising halogen, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Ro, -S-Ro, -O-C(O)-Ro, -O-C(S)-Ro, -C(O)-Ro, -C(S)-Ro, -C(O)-O-Ro, -C(S)-O-Ro, -S(O)-Ro, -S(O)2-Ro, -C(O)-N(H)-Ro, -C(S)-N(H)-Ro, -C(O)-N(Ro)-Ro, -C(S)-N(Ro)-Ro, -S(O)2-N(H)-Ro, -S(O)2-N(Ro)-Ro, -C(NH)-N(H)-Ro, -C(NH)-N(Rp)-Rc, -N(H)-C(O)-Ro, -N(H)-C(S)-Ro, -N(Ro)-C(O)-Ro, -N(Ro)-C(S)-Ro, -N(H)-S(O)2-Ro, -N(Ro)-S(O)2-Ro, -N(H)-C(O)-N(H)-Ro, -N(H)-C(S)-N(H)-Ro, -N(Ro)-C(O)-NH2, -N(Ro)-C(S)-NH2, -N(Ro)-C(O)-N(H)-Ro, -N(Ro)-C(S)-N(H)-Ro, -N(H)-C(O)-N(Ro)-Ro, -N(H)-C(S)-N(Ro)-Ro, -N(Ro)-C(O)-N(Ro)-Ro, -N(Ro)-C(S)-N(Ro)-Ro, -N(H)-S(O)2-N(H)-Ro, -N(Ro)-S(O)2-NH2, -N(Ro)-S(O)2-N(H)-Ro, -N(H)-S(O)2-N(Ro)-Ro, -N(Ro)-S(O)2-N(Ro)-Ro, -N(H)-Ro, -N(Ro)-Ro, -Rd, -Re, -Rfand Rg. This implies that these substituents are valid from a chemical point of view and attached at any available position with the formation of stable compounds.

[0089] the Term “aryl”used alone or in combination, refers to monocyclic or bicyclic ring system containing aromatic hydrocarbons, such as phenyl or naphthyl, which may be condensed with cycloalkyl, preferably containing from 5 to 7, more preferably from 5 to 6 atoms in the ring. "Optionally substituted aryl" is an aryl, which, if not specified otherwise, may independently contain one or more substituents, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent attached at any available atom with the formation of stable compounds, and these substituents selected from the group comprising halogen, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Ro, -S-Ro, -O-C(O)-Ro, -O-C(S)-Ro, -C(O)-Ro, -C(S)-Ro, -C(O)-O-Ro, -C(S)-O-Ro, -S(O)-Ro, -S(O)2-Ro, -C(O)-N(H)-Ro, -C(S)-N(H)-Ro, -C(O)-N(Ro)-Ro, -C(S)-N(Ro)-Ro, -S(O)2-N(H)-Ro, -S(O)2-N(Ro)-Ro, -C(NH)-N(H)-Ro, -C(NH)-N(Rp)-Rc, -N(H)-C(O)-Ro, -N(H)-C(S)-Ro, -N(Ro)-C(O)-Ro, -N(Ro)-C(S)-Ro, -N(H)-S(O)2-Ro, -N(Ro)-S(O)2-Ro, -N(H)-C(O)-N(H)-Ro, -N(H)-C(S)-N(H)-Ro, -N( o)-C(O)-NH2, -N(Ro)-C(S)-NH2, -N(Ro)-C(O)-N(H)-Ro, -N(Ro)-C(S)-N(H)-Ro, -N(H)-C(O)-N(Ro)-Ro, -N(H)-C(S)-N(Ro)-Ro, -N(Ro)-C(O)-N(Ro)-Ro, -N(Ro)-C(S)-N(Ro)-Ro, -N(H)-S(O)2-N(H)-Ro, -N(Ro)-S(O)2-NH2, -N(Ro)-S(O)2-N(H)-Ro, -N(H)-S(O)2-N(Ro)-Ro, -N(Ro)-S(O)2-N(Ro)-Ro, -N(H)-Ro, -N(Ro)-Ro, -Rd, -Re, -Rfand Rg. This implies that these substituents are valid from a chemical point of view and attached at any available position with the formation of stable compounds.

[0090] the Term “heteroaryl”, used separately or in combination, refers to a monocyclic aromatic ring structure containing 5 or 6 atoms in the ring, or a bicyclic aromatic system containing from 8 to 10 atoms, containing one or more, preferably from 1 to 4, more preferably from 1 to 3, even more preferably from 1 to 2 heteroatoms, independently selected from the group comprising O, S and N. Heteroaryl may also contain oxidized form S or N, such as sulfinil, sulfonyl and N-oxide of a tertiary atom nitrogen in the ring. Specified heteroaryl ring structure attached on this carbon atom or nitrogen, accession colormepretty to the formation of stable compounds. Examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, pyrazinyl, Minoxidil, indolinyl, benzo[b]thienyl, hintline, purinol, indolyl, chinoline, pyrimidinyl, pyrrolyl, pyrazolyl, oxazolyl, thiazolyl, tienilic, isoxazolyl, oxadiazolyl, isothiazolin, tetrazolyl, imidazolyl, triazolyl, furanyl, benzofuran and indolyl. "Nitrogen containing heteroaryl" refers to heteroaryl, in which at least one heteroatom represents n In some cases, for example, when the group R at the nitrogen atom together with the indicated nitrogen atom form a 5 - or 7-membered nitrogen containing heteroaryl, all heteroatoms in such 5 - or 7-membered heteroaryl represent N. "Optionally substituted heteroaryl" is heteroaryl, which, if not specified otherwise, may independently contain one or more substituents, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 Deputy, attached at any available atom with the formation of stable compounds, and these substituents selected from the group comprising halogen, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Ro, -S-Ro, -O-C(O)-Ro, -O-C(S)-Ro, -C(O)-Ro, -C(S)-Ro, -C(O)-O-Ro, -C(S)-O-Ro , -S(O)-Ro, -S(O)2-Ro, -C(O)-N(H)-Ro, -C(S)-N(H)-Ro, -C(O)-N(Ro)-Ro, -C(S)-N(Ro)-Ro, -S(O)2-N(H)-Ro, -S(O)2-N(Ro)-Ro, -C(NH)-N(H)-Ro, -C(NH)-N(Rp)-Rc, -N(H)-C(O)-Ro, -N(H)-C(S)-Ro, -N(Ro)-C(O)-Ro, -N(Ro)-C(S)-Ro, -N(H)-S(O)2-Ro, -N(Ro)-S(O)2-Ro, -N(H)-C(O)-N(H)-Ro, -N(H)-C(S)-N(H)-Ro, -N(Ro)-C(O)-NH2, -N(Ro)-C(S)-NH2, -N(Ro)-C(O)-N(H)-Ro, -N(Ro)-C(S)-N(H)-Ro, -N(H)-C(O)-N(Ro)-Ro, -N(H)-C(S)-N(Ro)-Ro, -N(Ro)-C(O)-N(Ro)-Ro, -N(Ro)-C(S)-N(Ro)-Ro, -N(H)-S(O)2-N(H)-Ro, -N(Ro)-S(O)2-NH2, -N(Ro)-S(O)2-N(H)-Ro, -N(H)-S(O)2-N(Ro)-Ro, -N(Ro)-S(O)2-N(Ro)-Ro, -N(H)-Ro, -N(Ro)-Ro, -Rd, -Re, -Rfand Rg. This implies that these substituents are valid from a chemical point of view and attached at any available position with the formation of stable compounds.

[0091] the Variables Ro, Rp, Rc, Rd, Re, Rfand Rgspecified in the description of possible substituents in the alkyl, alkenyl, quinil, cycloalkyl, heteroseksualci, aryl and heteroaryl, are as defined below:

each of Ro, Rpand Rcnez the performance is chosen from the group includes Rd, Re, Rfand Rgor Rpand Rctogether with the nitrogen atom to which they are attached, form a 5-7-membered heteroseksualci or 5 - or 7-membered nitrogen containing heteroaryl, with specified 5-7-membered heteroseksualci or 5 - or 7-membered nitrogen containing heteroaryl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising halogen, -NO2, -CN, -OH, -NH2, -O-Ru, -S-Ru, -N(H)-Ru, -N(Ru)-Ru, -Rxand Ry;

each Rdrepresents independently lower alkyl, with the specified lower alkyl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising fluorine, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Rk, -S-Rk, -O-C(O)-Rk, -O-C(S)-Rk, -C(O)-Rk, -C(S)-Rk, -C(O)-O-Rk, -C(S)-O-Rk, -S(O)-Rk, -S(O)2-Rk, -C(O)-N(H)-Rk, -C(S)-N(H)-Rk, -C(O)-N(Rk)-Rk, -C(S)-N(Rk)-Rk, -S(O)2-N(H)-Rk, -S(O)2-N(Rk)-Rk, -C(NH)-N(H)-Rk, -C(NH)-N(Rm)-Rn, -N(H)-C(O)-Rk, -N(H)-C(S)-Rk, -N(Rk)-C(O)-Rk, -N(Rk)-C(S)-Rk, -N(H)-S(O)2-Rk , -N(Rk)-S(O)2-Rk, -N(H)-C(O)-N(H)-Rk, -N(H)-C(S)-N(H)-Rk, -N(Rk)-C(O)-NH2, -N(Rk)-C(S)-NH2, -N(Rk)-C(O)-N(H)-Rk, -N(Rk)-C(S)-N(H)-Rk, -N(H)-C(O)-N(Rk)-Rk, -N(H)-C(S)-N(Rk)-Rk, -N(Rk)-C(O)-N(Rk)-Rk, -N(Rk)-C(S)-N(Rk)-Rk, -N(H)-S(O)2-N(H)-Rk, -N(Rk)-S(O)2-NH2, -N(Rk)-S(O)2-N(H)-Rk, -N(H)-S(O)2-N(Rk)-Rk, -N(Rk)-S(O)2-N(Rk)-Rk, -N(H)-Rk, -N(Rk)-Rk, -Riand Rj;

each Rerepresents independently lower alkenyl, with specified lower alkenyl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising fluorine, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Rk, -S-Rk, -O-C(O)-Rk, -O-C(S)-Rk, -C(O)-Rk, -C(S)-Rk, -C(O)-O-Rk, -C(S)-O-Rk, -S(O)-Rk, -S(O)2-Rk, -C(O)-N(H)-Rk, -C(S)-N(H)-Rk, -C(O)-N(Rk)-Rk, -C(S)-N(Rk)-Rk, -S(O)2-N(H)-Rk, -S(O)2-N(Rk)-Rk, -C(NH)-N(H)-Rk, -C(NH)-N(Rm)-Rn, -N(H)-C(O)-Rk, -N(H)-C(S)-Rk, -N(Rk)-C(O)-Rk, -N(Rk)-C(S)-Rk, -N(H)-S(O)2-Rk, -N(Rk)-S(O)2-Rk/sup> , -N(H)-C(O)-N(H)-Rk, -N(H)-C(S)-N(H)-Rk, -N(Rk)-C(O)-NH2, -N(Rk)-C(S)-NH2, -N(Rk)-C(O)-N(H)-Rk, -N(Rk)-C(S)-N(H)-Rk, -N(H)-C(O)-N(Rk)-Rk, -N(H)-C(S)-N(Rk)-Rk, -N(Rk)-C(O)-N(Rk)-Rk, -N(Rk)-C(S)-N(Rk)-Rk, -N(H)-S(O)2-N(H)-Rk, -N(Rk)-S(O)2-NH2, -N(Rk)-S(O)2-N(H)-Rk, -N(H)-S(O)2-N(Rk)-Rk, -N(Rk)-S(O)2-N(Rk)-Rk, -N(H)-Rk, -N(Rk)-Rk, -Rhand Rj;

each Rfrepresents independently lower quinil, with specified lower quinil may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising fluorine, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Rk, -S-Rk, -O-C(O)-Rk, -O-C(S)-Rk, -C(O)-Rk, -C(S)-Rk, -C(O)-O-Rk, -C(S)-O-Rk, -S(O)-Rk, -S(O)2-Rk, -C(O)-N(H)-Rk, -C(S)-N(H)-Rk, -C(O)-N(Rk)-Rk, -C(S)-N(Rk)-Rk, -S(O)2-N(H)-Rk, -S(O)2-N(Rk)-Rk, -C(NH)-N(H)-Rk, -C(NH)-N(Rm)-Rn, -N(H)-C(O)-Rk, -N(H)-C(S)-Rk, -N(Rk)-C(O)-Rk, -N(Rk)-C(S)-Rk, -N(H)-S(O)2-Rk, -N(Rk)-S(O)2-Rk, -N(H)-C(O)-N(H)-Rk, -N(H)-C(S)-N(H-R k, -N(Rk)-C(O)-NH2, -N(Rk)-C(S)-NH2, -N(Rk)-C(O)-N(H)-Rk, -N(Rk)-C(S)-N(H)-Rk, -N(H)-C(O)-N(Rk)-Rk, -N(H)-C(S)-N(Rk)-Rk, -N(Rk)-C(O)-N(Rk)-Rk, -N(Rk)-C(S)-N(Rk)-Rk, -N(H)-S(O)2-N(H)-Rk, -N(Rk)-S(O)2-NH2, -N(Rk)-S(O)2-N(H)-Rk, -N(H)-S(O)2-N(Rk)-Rk, -N(Rk)-S(O)2-N(Rk)-Rk, -N(H)-Rk, -N(Rk)-Rk, -Rhand Rj;

each Rgindependently selected from the group including cycloalkyl, heteroseksualci, aryl and heteroaryl, with the specified cycloalkyl, heteroseksualci, aryl and heteroaryl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising halogen, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Rk, -S-Rk, -O-C(O)-Rk, -O-C(S)-Rk, -C(O)-Rk, -C(S)-Rk, -C(O)-O-Rk, -C(S)-O-Rk, -S(O)-Rk, -S(O)2-Rk, -C(O)-N(H)-Rk, -C(S)-N(H)-Rk, -C(O)-N(Rk)-Rk, -C(S)-N(Rk)-Rk, -S(O)2-N(H)-Rk, -S(O)2-N(Rk)-Rk, -C(NH)-N(H)-Rk, -C(NH)-N(Rm)-Rn, -N(H)-C(O)-Rk, -N(H)-C(S)-Rk, -N(Rk)-C(O)-Rk, -N(Rk)-C(S)-Rk, -N(H)-S(O)2-Rk, -N(Rk/sup> )-S(O)2-Rk, -N(H)-C(O)-N(H)-Rk, -N(H)-C(S)-N(H)-Rk, -N(Rk)-C(O)-NH2, -N(Rk)-C(S)-NH2, -N(Rk)-C(O)-N(H)-Rk, -N(Rk)-C(S)-N(H)-Rk, -N(H)-C(O)-N(Rk)-Rk, -N(H)-C(S)-N(Rk)-Rk, -N(Rk)-C(O)-N(Rk)-Rk, -N(Rk)-C(S)-N(Rk)-Rk, -N(H)-S(O)2-N(H)-Rk, -N(Rk)-S(O)2-NH2, -N(Rk)-S(O)2-N(H)-Rk, -N(H)-S(O)2-N(Rk)-Rk, -N(Rk)-S(O)2-N(Rk)-Rk, -N(H)-Rk, -N(Rk)-Rk, -Rh, -Riand Rj;

thus Rk, Rmand Rnin each case, independently selected from the group comprising Rh, Riand Rjor Rmand Rntogether with the nitrogen atom to which they are attached, form a 5-7-membered heteroseksualci or 5 - or 7-membered nitrogen containing heteroaryl, and specified 5-7-membered heteroseksualci or 5 - or 7-membered nitrogen containing heteroaryl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising halogen, -NO2, -CN, -OH, -NH2, O-Ru, -S-Ru, -N(H)-Ru, -NRuRu, -Rxand Ry;

each Rhrepresents independently lower alkyl, optionally containing one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group including the cabbage soup fluorine, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Rr, -S-Rr, -O-C(O)-Rr, -O-C(S)-Rr, -C(O)-Rr, -C(S)-Rr, -C(O)-O-Rr, -C(S)-O-Rr, -S(O)-Rr, -S(O)2-Rr, -C(O)-N(H)-Rr, -C(S)-N(H)-Rr, -C(O)-N(Rr)-Rr, -C(S)-N(Rr)-Rr, -S(O)2-N(H)-Rr, -S(O)2-N(Rr)-Rr, -C(NH)-N(H)-Rr, -C(NH)-N(Rs)-Rt, -N(H)-C(O)-Rr, -N(H)-C(S)-Rr, -N(Rr)-C(O)-Rr, -N(Rr)-C(S)-Rr, -N(H)-S(O)2-Rr, -N(Rr)-S(O)2-Rr, -N(H)-C(O)-N(H)-Rr, -N(H)-C(S)-N(H)-Rr, -N(Rr)-C(O)-NH2, -N(Rr)-C(S)-NH2, -N(Rr)-C(O)-N(H)-Rr, -N(Rr)-C(S)-N(H)-Rr, -N(H)-C(O)-N(Rr)-Rr, -N(H)-C(S)-N(Rr)-Rr, -N(Rr)-C(O)-N(Rr)-Rr, -N(Rr)-C(S)-N(Rr)-Rr, -N(H)-S(O)2-N(H)-Rr, -N(Rr)-S(O)2-NH2, -N(Rr)-S(O)2-N(H)-Rr, -N(H)-S(O)2-N(Rr)-Rr, -N(Rr)-S(O)2-N(Rr)-Rr, -N(H)-Rr, -N(Rr)-Rr, -Riand Rj;

each Riindependently selected from the group comprising lower alkenyl and lower quinil, and the specified lower alkenyl or lower quinil may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent, wybranych group, comprising fluorine, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Rr, -S-Rr, -O-C(O)-Rr, -O-C(S)-Rr, -C(O)-Rr, -C(S)-Rr, -C(O)-O-Rr, -C(S)-O-Rr, -S(O)-Rr, -S(O)2-Rr, -C(O)-N(H)-Rr, -C(S)-N(H)-Rr, -C(O)-N(Rr)-Rr, -C(S)-N(Rr)-Rr, -S(O)2-N(H)-Rr, -S(O)2-N(Rr)-Rr, -C(NH)-N(H)-Rr, -C(NH)-N(Rs)-Rt, -N(H)-C(O)-Rr, -N(H)-C(S)-Rr, -N(Rr)-C(O)-Rr, -N(Rr)-C(S)-Rr, -N(H)-S(O)2-Rr, -N(Rr)-S(O)2-Rr, -N(H)-C(O)-N(H)-Rr, -N(H)-C(S)-N(H)-Rr, -N(Rr)-C(O)-NH2, -N(Rr)-C(S)-NH2, -N(Rr)-C(O)-N(H)-Rr, -N(Rr)-C(S)-N(H)-Rr, -N(H)-C(O)-N(Rr)-Rr, -N(H)-C(S)-N(Rr)-Rr, -N(Rr)-C(O)-N(Rr)-Rr, -N(Rr)-C(S)-N(Rr)-Rr, -N(H)-S(O)2-N(H)-Rr, -N(Rr)-S(O)2-NH2, -N(Rr)-S(O)2-N(H)-Rr, -N(H)-S(O)2-N(Rr)-Rr, -N(Rr)-S(O)2-N(Rr)-Rr, -N(H)-Rr, -N(Rr)-Rrand Rj;

each Rjindependently selected from the group including cycloalkyl, heteroseksualci, aryl and heteroaryl, and the specified cycloalkyl, heteroseksualci, aryl or heteroaryl may contain one or more, preferably 1, 2, 3, 4 ili, and also 1, 2 or 3 substituent selected from the group comprising halogen, -OH, -NH2, -NO2, -CN, -C(O)-OH, -C(S)OH, -C(O)-NH2, -C(S)-NH2, -S(O)2-NH2, -N(H)-C(O)-NH2, -N(H)-C(S)-NH2, -N(H)-S(O)2-NH2, -C(NH)-NH2, -O-Rr, -S-Rr, -O-C(O)-Rr, -O-C(S)-Rr, -C(O)-Rr, -C(S)-Rr, -C(O)-O-Rr, -C(S)-O-Rr, -S(O)-Rr, -S(O)2-Rr, -C(O)-N(H)-Rr, -C(S)-N(H)-Rr, -C(O)-N(Rr)-Rr, -C(S)-N(Rr)-Rr, -S(O)2-N(H)-Rr, -S(O)2-N(Rr)-Rr, -C(NH)-N(H)-Rr, -C(NH)-N(Rs)-Rt, -N(H)-C(O)-Rr, -N(H)-C(S)-Rr, -N(Rr)-C(O)-Rr, -N(Rr)-C(S)-Rr, -N(H)-S(O)2-Rr, -N(Rr)-S(O)2-Rr, -N(H)-C(O)-N(H)-Rr, -N(H)-C(S)-N(H)-Rr, -N(Rr)-C(O)-NH2, -N(Rr)-C(S)-NH2, -N(Rr)-C(O)-N(H)-Rr, -N(Rr)-C(S)-N(H)-Rr, -N(H)-C(O)-N(Rr)-Rr, -N(H)-C(S)-N(Rr)-Rr, -N(Rr)-C(O)-N(Rr)-Rr, -N(Rr)-C(S)-N(Rr)-Rr, -N(H)-S(O)2-N(H)-Rr, -N(Rr)-S(O)2-NH2, -N(Rr)-S(O)2-N(H)-Rr, -N(H)-S(O)2-N(Rr)-Rr, -N(Rr)-S(O)2-N(Rr)-Rr, -N(H)-Rr, -N(Rr)-Rrcyclooctylamino and Rx;

each of Rr, Rsand Rtin each case, independently selected from the group comprising lower alkyl, C3-6alkenyl, C3-6quinil, cycloalkyl, hetaeras cycloalkyl, aryl and heteroaryl, and the specified lower alkyl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising-Ry, fluoro, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, and with the specified C3-6alkenyl or C3-6quinil may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising-Ry, fluorine, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, and the specified cycloalkyl, heteroseksualci, aryl or heteroaryl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising halogen, -OH, -NH2, -NO2, -CN, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, or Rsand Rttogether with the nitrogen atom to which they are attached, form a 5-7-membered heteroseksualci or 5 - or 7-membered nitrogen containing heteroaryl, and is shown 5-7-membered heteroseksualci or 5 - or 7-membered nitrogen containing heteroaryl may contain one or more preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising halogen, -NO2, -CN, -OH, -NH2, O-Ru, -S-Ru, -N(H)-Ru, -N(Ru)-Ru, -Rxand Ry;

each Ruindependently selected from the group comprising lower alkyl, C3-6alkenyl, C3-6quinil, cycloalkyl, heteroseksualci, aryl and heteroaryl, and the specified lower alkyl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising-Ry, fluoro, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, and with the specified C3-6alkenyl or C3-6quinil may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising-Ry, fluoro, -OH, -NH2, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, and the specified cycloalkyl, heteroseksualci, aryl and heteroaryl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising halogen, -OH, -NH2, -NO2,-CN, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamino;

each Rxselected from the group comprising lower alkyl, lower alkenyl and lower quinil, and the specified lower alkyl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising-Ry, fluoro, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine, and with the specified lower alkenyl or lower quinil may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising-Ry, fluoro, -OH, -NH2, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamino;

each Ryselected from the group including cycloalkyl, heteroseksualci, aryl and heteroaryl, and the specified cycloalkyl, heteroseksualci, aryl and heteroaryl may contain one or more, preferably 1, 2, 3, 4 or 5, also 1, 2 or 3 substituent selected from the group comprising halogen, -OH, -NH2, -NO2, -CN, lower alkyl, fluorinated lower alkyl, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine.

[0092] According to some variants of implementation, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted C3-6alkenyl, optionally substituted lower quinil or optionally substituted C3-6quinil in each case optionally substituted by one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising fluorine, -NO2, -CN, -O-R1a, -S-R1a, -N(R1a)-R1a, -O-C(O)-R1a, -O-C(S)-R1a, -C(O)-R1a, -C(S)-R1a, -C(O)-O-R1a, -C(S)-O-R1a, -C(O)-N(R1a)-R1a, -C(S)-N(R1a)-R1a, -S(O)2-N(R1a)-R1a, -C(NH)-N(R1a)-R1a, -N(R1a)-C(O)-R1a, -N(R1a)-C(S)-R1a, -N(R1a)-S(O)2-R1a, -N(R1a)-C(O)-N(R1a)-R1a, -N(R1a)-C(S)-N(R1a)-R1a, -N(R1a)-S(O)2-N(R1a)-R1a, -S(O)-R1a, -S(O)2-R1acycloalkyl, heteroseksualci, aryl and heteroaryl; and cycloalkyl, heteroseksualci, aryl or heteroaryl optionally substituted by one or more substituents, as well as 1, 2 or 3 groups or Deputy shall, selected from the group comprising halogen, -NO2, -CN, -O-R1a, -S-R1a, -N(R1a)-R1a, -O-C(O)-R1a, -O-C(S)-R1a, -C(O)-R1a, -C(S)-R1a, -C(O)-O-R1a, -C(S)-O-R1a, -C(O)-N(R1a)-R1a, -C(S)-N(R1a)-R1a, -S(O)2-N(R1a)-R1a, -C(NH)-N(R1a)-R1a, -N(R1a)-C(O)-R1a, -N(R1a)-C(S)-R1a, -N(R1a)-S(O)2-R1a, -N(R1a)-C(O)-N(R1a)-R1a, -N(R1a)-C(S)-N(R1a)-R1a, -N(R1a)-S(O)2-N(R1a)-R1a, -S(O)-R1a, -S(O)2-R1a, -R1band lower alkyl, optionally containing one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines and R1b; optionally substituted cycloalkyl, optionally substituted heteroseksualci, optionally substituted 5-7-membered heteroseksualci, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted 5 - or 7-membered nitrogen containing heteroaryl optionally substituted by one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising halogen, -NO2, -CN, -O-R1a, -S-R1a, -N(R1a)-R1a, -O-C()-R 1a, -O-C(S)-R1a, -C(O)-R1a, -C(S)-R1a, -C(O)-O-R1a, -C(S)-O-R1a, -C(O)-N(R1a)-R1a, -C(S)-N(R1a)-R1a, -S(O)2-N(R1a)-R1a, -C(NH)-N(R1a)-R1a, -N(R1a)-C(O)-R1a, -N(R1a)-C(S)-R1a, -N(R1a)-S(O)2-R1a, -N(R1a)-C(O)-N(R1a)-R1a, -N(R1a)-C(S)-N(R1a)-R1a, -N(R1a)-S(O)2-N(R1a)-R1a, -S(O)-R1a, -S(O)2-R1a, -R1band lower alkyl, optionally containing one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines and R1b; R1aselected from the group comprising hydrogen, -R1band lower alkyl, optionally containing one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines and R1band R1bselected from the group including cycloalkyl, heteroseksualci, aryl and heteroaryl where cycloalkyl, heteroseksualci, aryl or heteroaryl optionally substituted by one or more substituents, as well as 1, 2 Il the 3 groups or Deputy, selected from the group comprising halogen, -CN, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine.

[0093] According to some variants of implementation, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted C3-6alkenyl, optionally substituted lower quinil or optionally substituted C3-6quinil in each case optionally substituted by one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising fluorine, -CN, -O-R1a, -S-R1a, -N(R1a)-R1a, -C(O)-R1a, -C(S)-R1a, -C(O)-O-R1a, -C(O)-N(R1a)-R1a, -C(S)-N(R1a)-R1a, -S(O)2-N(R1a)-R1a, -N(R1a)-C(O)-R1a, -N(R1a)-C(S)-R1a, -N(R1a)-S(O)2-R1a, -S(O)-R1a, -S(O)2-R1acycloalkyl, heteroseksualci, aryl and heteroaryl, with cycloalkyl, heteroseksualci, aryl or heteroaryl optionally substituted by one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising halogen, -CN, -O-R1a, -S-R1a, -N(R1a)-R1a, -C(O)-R1a, -C(S)-R1a, -C(O)-O-R1a, -C(O)-N(R1a)-R1a, -C(S)-N(R1a)-R1a, -S(O)2-N(R1a)-R 1a, -N(R1a)-C(O)-R1a, -N(R1a)-C(S)-R1a, -N(R1a)-S(O)2-R1a, -S(O)-R1a, -S(O)2-R1a, -R1band lower alkyl, optionally containing one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines and R1b; and optionally substituted cycloalkyl, optionally substituted heteroseksualci, optionally substituted 5-7-membered heteroseksualci, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted 5 - or 7-membered nitrogen containing heteroaryl in each case optionally substituted by one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising halogen, -CN, -O-R1a, -S-R1a, -N(R1a)-R1a, -C(O)-R1a, -C(S)-R1a, -C(O)-O-R1a, -C(O)-N(R1a)-R1a, -C(S)-N(R1a)-R1a, -S(O)2-N(R1a)-R1a, -N(R1a)-C(O)-R1a, -N(R1a)-C(S)-R1a, -N(R1a)-S(O)2-R1a, -S(O)-R1a, -S(O)2-R1a, -R1band lower alkyl, optionally containing one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising fluorine, -OH, -NH 2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines and R1b; R1aselected from the group comprising hydrogen, -R1band lower alkyl, optionally containing one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising fluorine, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines and R1band R1bselected from the group including cycloalkyl, heteroseksualci, aryl and heteroaryl, with cycloalkyl, heteroseksualci, aryl or heteroaryl optionally substituted by one or more substituents, as well as 1, 2 or 3 groups or a substituent selected from the group comprising halogen, -CN, -OH, -NH2, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines, cyclooctylamine.

[0094] the Term “lower alkoxy” means the group-ORzwhere Rzrepresents lower alkyl. "Substituted lower alkoxy" denotes lower alkoxy in which Rzrepresents a lower alkyl containing one or more substituents as described in the present description, for example, to compounds of formula I, including the description of the s substituted cycloalkyl, geterotsiklicheskie, aryl and heteroaryl, attached at any available atom with the formation of stable compounds. Preferably, lower alkoxy contains 1, 2, 3, 4 or 5 substituents, 1, 2 or 3 substituent. For example, fluoro-substituted lower alkoxy" denotes lower alkoxy, wherein said lower alkyl contains as substituents one or more fluorine atoms, while preferably specified lower alkoxy contains as substituents 1, 2, 3, 4 or 5 fluorine atoms and 1, 2 or 3 fluorine atom. This implies that these substituents are valid from a chemical point of view and attached at any available atom with the formation of stable compounds.

[0095] the Term “lower alkylthio” means the group-SRaawhere Raarepresents lower alkyl. "Substituted lower alkylthio” means lower alkylthio, in which Raarepresents a lower alkyl containing one or more substituents as described in the present description, for example, to compounds of formula I, including descriptions of substituted cycloalkyl, geterotsiklicheskie, aryl and heteroaryl, attached at any available atom with the formation of stable compounds. Preferably, the lower alkylthio contains 1, 2, 3, 4 or 5 substituents, 1, 2 or 3 substituent. For example, "ptors the displaced lower alkylthio" means lower alkylthio, wherein said lower alkyl contains as substituents one or more fluorine atoms, while preferably specified lower alkylthio contains as substituents 1, 2, 3, 4 or 5 fluorine atoms and 1, 2 or 3 fluorine atom. This implies that these substituents are valid from a chemical point of view and attached at any available atom with the formation of stable compounds.

[0096] the Term “amino” or “amine” refers to the group-NH2. “Monoalkylamines” means the group-otherbbwhere Rbbrepresents lower alkyl. “Dialkylamino” means the group-NRbbRccwhere Rbband Rccare independently lower alkyl. “Cycloalkenyl” means the group-NRddReewhere Rddand Reetogether with the nitrogen atom form a 5-7-membered heteroseksualci, with the specified heteroseksualci may contain an additional heteroatom in the ring, such as O, N or S, and may optionally contain as a substituent a lower alkyl. Examples 5-7-membered geterotsiklicheskie include, but are not limited to, piperidine, piperazine, 4-methylpiperazine, morpholine and thiomorpholine. Assume that when monoalkylamines, dialkylamino or cyclooctylamino represent the substituents in the other fragments, the batch shall itali valid from a chemical point of view and attached at any available atom with the formation of stable compounds.

[0097] In the present description, the term "composition" refers to a composition suitable for injection for therapeutic purposes in a selected animal, while the composition contains at least one pharmaceutically active compound and at least one pharmaceutically acceptable carrier or excipient.

[0098] the Term "pharmaceutically acceptable" indicates that the indicated material has properties that might make careful reasonable physician to avoid the introduction of this material to a patient with a specific disease or condition being treated, and the appropriate way of introduction. For example, as a rule, it is necessary that this material was essentially sterile, as, for example, in the case of injectable drugs.

[0099] In the context of the present invention the term "therapeutically effective" or "effective amount" indicates that the material or the amount of material is effective to prevent, alleviate or ameliorate one or more symptoms of a disease or pathological condition and/or increasing the life expectancy of the subject being treated.

[0100] In the context of the present invention the term "synergistically effective" or "synergistic effect" indicates that two or more compounds, which is therapeutically effective when used in combination provide enhanced therapeutic effect beyond the expected cumulative effect that could be obtained with the introduction of each of these compounds separately.

[0101] In the present description, the terms "ligand" and "modulator" are used interchangeably to refer to compounds that alter (i.e. increasing or decreasing) the activity of a target biomolecule, for example, an enzyme such as a kinase. The term "inhibitor" refers to the modulator, downward activity for a specified target biomolecules. In General, the ligand or modulator is a small molecule size, where the term "small molecule size" refers to the compound with a molecular weight of 1500 daltons or less, preferably 1000 daltons or less, 800 daltons or less, or 600 daltons or less.

[0102] When applying in relation to compounds that bind to the target, the terms "higher activity" and "election" indicate that such compounds bind more strongly in comparison with the reference compound or compared with the same connection when the state selected as the reference, i.e. have a lower dissociation constant. According to some variants of implementation indicated a higher AF is innosti (i.e. selectivity is at least 2, 3, 4, 5, 8, 10, 50, 100, 200, 400, 500, 1000 or 10,000 times higher.

[0103] In the present description, if used in relation to compounds according to the present invention, the term "synthesizing" and other similar terms refer to the chemical synthesis of one or more precursor.

[0104] Under the "research" understanding the creation of experimental conditions and data collection specific to the specified experimental conditions. For example, the study of enzymes can be carried out on the basis of the ability of these enzymes to act as a detectable substrate. The study compound or ligand can be carried out on the basis of the ability of the compounds or ligand to bind to a specific molecule or molecules which target (the target).

[0105] In the present description, the term "modulating" or "modulate" refers to the action providing a change in biological activity, in particular, the biological activity associated with a specific biomolecule, such as a protein kinase. For example, agonist or antagonist of specific biomolecules modulates the activity specified biomolecules, for example, enzyme, either by increasing (for example, in the case of agonist, activator)or lower (for example, if antagonist, inhibitor) activity specified biomolecule such as an enzyme. Specified activity, usually expressed in terms of concentration inhibition (IC50or concentration of excitation (EC50) the specified connection, acting as an inhibitor or activator, respectively, compared to, for example, to the enzyme.

[0106] In the context of the application, testing or screening of compounds that are or may be modulators, the term "bringing into contact" means that ensure the presence of the indicated compounds (compounds) in sufficient proximity to a specific molecule, complex, cell, tissue, organism or other specified material, potentiating interaction, leading to the binding and/or chemical interaction between the specified connection, and other specified material.

[0107] In the present description, when applied to the amino acid or nucleic acid sequences, the term "isolate" indicates that this sequence is separated from at least part of the specified amino acids and/or sequences of nucleic acids with which it is usually associated.

[0108] When applied to the amino acid or nucleic acid sequences, the term "purified" indicates that the contents of this molecule in the composition C is acetelyne exceeds the specified content, observed in the original composition, for example, the cell culture. Specified a higher content can be in 2, 5, 10 or more times higher than the concentration found in the original composition.

[0109] the Present invention relates to compounds of the formula I and of all private formulas, which are modulators of protein kinases, for example, but without limitation, compounds which are modulators of at least one kinase selected from the group including Abl, Akt1, Akt2, Akt3, ALK, Alk5, A-Raf, B-Raf, Brk, Btk, Cdk2, CDK4, CDK5, CDK6, CHK1, c-Raf-1, Csk, EGFR, EphA1, EphA2, EphB2, EphB4, Erk2, Fak, FGFR1, FGFR2, FGFR3, FGFR4, Flt1, Flt3, Flt4, Fms, Frk, Fyn, Gsk3α, Gsk3β, HCK, Her2/Erbb2, Her4/Erbb4, IGF1R, IKK beta, Irak4, Itk, Jak1, Jak2, Jak3, Jnk1, Jnk2, Jnk3, Kdr, Kit, Lck, Lyn, MAP2K1, MAP2K2, MAP4K4, MAPKAPK2, Met, Mnk1, MLK1, p38, PDGFRA, PDGFRB, PDPK1, Pim1, Pim2, Pim3, PKC alpha, PKC beta, PKC theta, Plk1, Pyk2, Ret, ROCK1, ROCK2, Ron, Src, Stk6, Syk, TEC, Tie2, TrkA, TrkB, Yes, and Zap70, and any mutations of these kinases, and the use of such compounds for treating diseases or conditions.

Kinase targets and indications for use according to the invention

[0110] Protein kinases play a key role in the transmission of biochemical signals via different routes of transmission of biological signals. It was described more than 500 kinases were shown the relationship of specific kinases with a wide range of diseases and conditions (i.e. indications for use), including, for example, but without limitation, cancer, cardiovascular diseases, inflammatory diseases, never the logical diseases and other diseases. Kinase as such represent an important location for the regulation of therapeutic intervention with the use of molecules of small size. Specific protein kinase-target according to the present invention are known in the art and include, for example, but without limitation, protein kinase specified in the application for U.S. patent 11/473347 (see also international publication WO2007002433), the contents of which are hereby incorporated in the present description in its entirety by reference, including all drawings and tables, for any purpose, these protein kinases include the following:

[0111] A-Raf: Kinase-target A-Raf (i.e. viral oncogenic homolog 1 v-raf murine sarcoma 3611) is a serine/trionychinae weight of 67.6 kDa encoded by chromosome Xp11.4-p11.2 (designation: ARAF). The Mature protein contains RBD (i.e. Ras-binding domain) and the domain of "zinc fingers" phorbol-ester/DAG-type and involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Inhibitors of A-Raf may be suitable for treatment of neurological disorders, including multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease; neoplastic diseases including, but not limited to, melanoma, glioma, sarcoma, carcinoma (e.g. colorectal, lung, breast VC is SHL, pancreatic, thyroid, renal, ovarian), lymphoma (e.g., histiocytoma lymphoma)neurofibromatosis, myelodysplastic syndrome, leukemia, tumor angiogenesis; pain of neuropathic or inflammatory nature, including acute pain, chronic pain, pain associated with cancer, and migraine; and diseases associated with muscle regeneration or degeneration, including, but not limited to, vascular restenosis, sarcopenia, degenerative disorders of muscle (including, but not limited to, muscular dystrophy Duchenne, Becker, emery-Dreyfus, enveloping myodystrophy limbs (limb-girdle), degeneration of Landuse-Dejerine (facioscapulohumeral), myotonias dystrophy, degeneration of the muscles of the eyeball and pharynx, distal and congenital muscular dystrophy), motor neuron disease (including, but not limited to, amyotrophic lateral sclerosis, progressive muscular atrophy of the spinal cord in children of early age, muscle atrophy of the spinal cord in children, transitional age youth muscular atrophy spinal muscular atrophy of the medulla oblongata and muscle atrophy of the spinal cord in adults), inflammatory myopathies (including, but not limited to, dermatomyositis, polymyositis, and myositis with inclusions Taurus)diseases of the neuromuscular junction (including, but not limited is indeed them, myasthenia gravis syndrome of Lambert-Eaton and congenital myasthenic syndrome), myopathies due to endocrine abnormalities (including, but not limited to, hyperthyroid myopathy and hypothyroid myopathy)diseases of peripheral nerve (including, but not limited to, disease Charcot-Maritata, disease Dejerine-Cotta and ataxia), other myopathies (including, but not limited to, congenital myotonia, congenital paramythia, congenital myopathy with lesions of the heart muscle fibers, nemalenkuyu myopathy, myotubular myopathy, and periodic paralysis), and metabolic diseases of muscle (including, but not limited to, phosphorylase failure, generalized glycogens, phosphofructokinase insufficiency, deficiency Devetashka enzyme, mitochondrial myopathy, carnitine deficiency, deficit carnitinelongevity deficit phosphoglycerides deficit phosphoglyceromutase, lactate dehydrogenase deficiency, and the deficiency of myoadenylate deaminase).

[0112] B-Raf: Kinase-targeted B-Raf (i.e. viral oncogenic homolog B1 v-raf murine sarcoma) is a serine/trionychinae mass 84,4 kDa encoded by chromosome 7q34 (designation: a skin disease). The Mature protein contains RBD (i.e. Ras-binding domain), C1 (i.e. conserved region 1 protein kinase C) and STK (i.e., the Rin/trainingindustry) domains.

[0113] the Kinase-target B-Raf is involved in the transduction of mitogenic signals from the cell membrane to the nucleus and may affect the postsynaptic responses of hippocampal neurons. Genes of the RAF family as they encode kinases regulated Ras, and mediate cellular responses to signals from growth factor. In fact, the kinase B-Raf is a key component of the transmission signal kinase RAS->Raf-> MEK- > ERK/MAP, playing a pivotal role in the regulation of growth, division and proliferation of cells, and constitutive activation induces oncogenesis. Among several isoforms of the kinase Raf kinase B-type or B-Raf, is the strongest activator of the signal below the cascade of MAP kinase.

[0114] a skin disease Gene is frequently affected by mutations in various tumors in humans, particularly in malignant melanoma and carcinoma of the colon. The most frequently reported mutations, which are missense-transverse thymine (T) adenine at nucleotide 1796 (T1796A; amino acid change in the specified protein B-Raf is a replacement for Val<600> Glu<600>), observed in 80% of cases of malignant melanoma. Using functional analysis, it was found that the specified transverse is only installed mutation causing constitutive activation of B-Raf kinase activity by transformation of B-Raf dominantly transforming protein. In the course of the earlier research it has been established that human tumors have developed resistance to kinase inhibitors due to a mutation engine specific amino acids in the catalytic domain in the "gatekeeper" (gatekeeper) (Balak et. al., Clin Cancer Res. 2006, 12:6494-501). Thus, mutation of Thr-529 skin disease in Ile considered as a mechanism of emergence of resistance to inhibitors of skin disease that can be represented in the form of the transitions in codon 529 of the ACC ATC.

[0115] Niihari al. reported that among 43 individuals with cardio-skin-facial syndrome (CFC) identified two heterozygous KRAS mutations in three individuals and eight skin disease mutations in 16 individuals, suggesting that dysregulation of pathways RAS-RAF-ERK is a common molecular basis for three of these interrelated disorders (Niihori et al., Nat Genet. 2006, 38(3):294-6).

[0116] c-Raf-1 Kinase is a target of c-Raf-1 (i.e. viral oncogenic homolog of the v-raf murine sarcoma) STK weight 73,0 kDa encoded by chromosome 3p25 (designation: RAF1). c-Raf-1 can affect the mitochondria, acting as a target, under the influence of BCL-2 (i.e. with oncogenic b-cell leukemia 2), which is the regulator of apoptotic cell death. Active c-Raf-1 increases BCL2-mediated resistance to apoptosis, while c-Raf-1 phosphorylates BAD (i.e. BCL2-binding protein). c-Raf-1 is associated with carcinomas, including the th cell carcinoma of the colon, ovarian, lung and kidney. C-Raf-1 is also considered as an important mediator of tumor angiogenesis (Hood, J.D. et al., 2002, Science 296, 2404). Inhibitors of C-Raf-1 can also be suitable for the treatment of acute myeloid leukaemia and myelodysplastic syndromes (Crump, Curr Pharm Des 2002, 8(25):2243-8). Activators of Raf-1 may be suitable for the treatment of neuroendocrine tumors such as medullary thyroid cancer, carcinoid tumors, small cell lung cancer and pheochromocytoma (Kunnimalaiyaan et al., Antipak Drugs 2006, 17(2):139-42).

[0117] the Inhibitors of Raf (A-Raf and/or B-Raf and/or c-Raf-1) may be suitable for treatment of A-Raf-mediated, B-Raf-mediated or c-Raf-1-mediated disease or condition is selected from the group including neurological diseases, including, but not limited to, multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease; neoplastic diseases including, but not limited to, melanoma, glioma, sarcoma, carcinoma (e.g. colorectal, lung, breast, pancreatic, thyroid, renal, ovarian), lymphoma (e.g., histiocytoma lymphoma)neurofibromatosis, acute myeloid leukemia, myelodysplastic syndrome, leukemia, tumor angiogenesis, neuroendocrine tumors such as medullary thyroid cancer, carcinoid tumors, m is collocini lung cancer and pheochromocytoma; the pain of neuropathic or inflammatory nature, including, but not limited to, acute pain, chronic pain, pain associated with cancer, and migraine; cardiovascular diseases including, but not limited to, heart failure, ischemic stroke, cardiac hypertrophy, thrombosis (e.g. thrombotic syndromes microangiopathy, atherosclerosis, and reperfusion injury; inflammation including, but not limited to, psoriasis, arthritis and autoimmune diseases and conditions, osteoarthritis, endometriosis, scarring, vascular restenosis, fibrotic disorders, rheumatoid arthritis, inflammatory bowel disease (IBD); diseases associated with immune deficiency, including, but not limited to, rejection of organ transplant, the disease is graft versus host disease; kidney disease or prostate cancer, including, but not limited to, diabetic nephropathy, polycystic kidney disease, nephrosclerosis, glomerulonephritis, prostate gland hyperplasia; metabolic disorders, including, but not limited to, obesity; infection, including, but not limited to, viruses, Helicobacter pylori, Hepatitis and Influenza, fever, and sepsis; pulmonary diseases including, but not limited to, chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (the RDS); genetic defects, including, but not limited to, Noonan syndrome, Costello syndrome (skin-facial-skeletal syndrome), a syndrome of "the Leopard", cardio-skin-facial syndrome (CFC) and the variance associated with the nervous scallops, causing cardiovascular diseases, skeletal, intestinal, skin, hair and endocrine diseases.

The study of kinase activity

[0118] Determination of active modulators and/or specificity of the modulator with respect to a particular kinase or group of kinases can be performed using a number of different ways to study kinase activity. In addition to the methods of the studies referred to in the examples below, the person skilled in the art known in the art or other suitable methods, and the method of study may be modified by a person skilled in the technical field to suit the particular application. For example, suitable techniques are described in a large number of works devoted to the kinases.

[0119] Additional alternative research may provide the binding definition. For example, this type of research can be done either by using the method of resonance energy transfer fluorescence (FRET), or by using the method AlphaScreen (amplified luminescent proximity homogeneous assay, refined homogeneous study lumen santoy similarity), by varying the donor and acceptor reagents associated with streptavidin or phosphor-specific antibody.

Methods of organic synthesis

[0120] In the art there are many different methods of organic synthesis, suitable to facilitate designing potential modulators. Many of these methods of organic synthesis are described in detail in the classic reference materials used in the work of the specialist in the art. One example of such a reference is March, 1994, Advanced Organic Chemistry; Reactions, Mechanisms and Structure, New York, McGraw Hill. Thus, techniques, suitable for the synthesis of a potential modulator of kinase function, easily accessible for professionals in the field of organic synthesis.

Alternative forms of the compounds or derivatives

[0121] the Description of the compounds according to the present invention described with reference as to the General structural formulas, and specific compounds. In addition, the compounds according to the invention can exist in several different forms or derivatives, all of these forms and derivatives are within the scope of the present invention. Alternative forms or derivatives include, for example, (a) prodrugs and active metabolites, (b) the tautomers, the isomers (including stereoisomers and R is gosamaru) and racemic mixtures, (C) pharmaceutically acceptable salts and compositions, and (d) solid forms, including various crystalline forms, polymorphic or amorphous solids, including a hydrate and a solvate of such compounds, and other forms.

(a) Prodrugs and metabolites

[0122] in Addition to the proposed formulas and compounds described in the present description, the present invention also includes prodrugs of (in General, pharmaceutically acceptable prodrug, derivative active metabolites (active metabolites) and pharmaceutically acceptable salts of these prodrugs and derivatives.

[0123] Prodrugs are compounds or pharmaceutically acceptable salts of these compounds, which upon metabolism in the conditions of the organism or by solvolysis lead to the formation of the target active compounds. Prodrugs include, without limitation, esters, amides, carbamates, carbonates, ureides, solvate or hydrate active compounds. Typically, the prodrug is inactive or less active than the active connection, however, has one or more advantages from the standpoint of ease of handling, introduction, and/or metabolic properties. For example, some prodrugs are esters of active compounds during metabolism ester group atseps is carried out with the formation of the active compounds. Esters include, for example, esters of carboxylic acids or S-acyl or O-acyl derivatives tylenol, alcohol or phenol groups. In this context, a common example is an alkyl ether carboxylic acid. Some prodrugs are activated under the action of the enzyme with the formation of the active compound or compounds, which result in further chemical reactions leads to the formation of active compounds. Prodrugs can move in and out proletarienne form into the active form in one stage or may have one or more intermediate forms, which can be active or inactive.

[0124] As indicated in The Practice of Medicinal Chemistry, Ch. 31-32 (Ed. Wermuth, Academic Press, San Diego, CA, 2001), prodrugs can be conceptually divided into two newsamerica category - prodrugs-bioprecursor and prodrugs of the media. In General, prodrugs-bioprecursor are compounds that are inactive or have low activity compared to the corresponding active drug compound, contain one or more protective groups and become active during metabolism or solvolysis. At the same time as active pharmaceutical form and released during the metabolism of the product must have acceptable low current of what was mentioned. Typically, in the formation of the active medicinal compounds involved metabolic process or reaction that belong to one of the following types:

[0125] oxidation Reactions: Examples of oxidation reactions include without limitation such reactions as oxidation of alcohol, carbonyl, and acid functional groups, hydroxylation of aliphatic carbons, hydroxylation of alicyclic carbon atoms, oxidation of aromatic carbon atoms, oxidation of double bonds in the carbon-carbon bonds, oxidation of nitrogen-containing functional groups, oxidation of silicon, phosphorus, arsenic, and sulfur, oxidative N-dealkylation, oxidative O - and S-dealkylation, oxidative diaminononane, as well as other oxidation reactions.

[0126] the Reaction of recovery: Examples of reactions of recovery include without limitation such reactions as reduction of carbonyl functional groups, restoration of functional groups of alcohols and double bonds in the carbon-carbon recovery of nitrogen-containing functional groups and other reactions of recovery.

[0127] Reaction, do not result in a change in the degree of oxidation: Examples of reactions that do not result in a change in the degree of oxidation include without limitation such reactions as hydrolysis of esters and ethers, hydrolytic splitting of the single is Vasa "carbon-nitrogen", hydrolytic cleavage of non-aromatic heterocycles, hydration and dehydration on multiple bonds, new interatomic bonds formed by dehydration reactions, hydrolytic, dihalogenoalkane, the separation of molecules halogenated and other similar reactions.

[0128] the Prodrugs of the media are medicinal compounds containing transport fragment, for example, provides superior absorption and/or localized delivery to the place (places) actions. For these prodrugs vehicles it is desirable that the bridge between drug fragment and shipping fragment represented a covalent bond, but such prodrug would be inactive or less active than the drug connection, and the specified prodrug and released any shipping fragment was acceptable non-toxic. In the case of prodrugs, in which the transport segment should provide increased absorption, as a rule, it is necessary to release the specified shipping fragment was rapid. In other cases, it is desirable to use the snippet, providing slow release, for example, certain polymers and other fragments, such as cyclodextrins (see for example, Chen et al., publication of U.S. patent No. 20040077595, application No. 10/656838, the contents of which are fully incorporated into the present description by reference). Such prodrugs carriers often provide an advantage when the drug is designed for oral administration. In some cases, transport fragment provides targeted delivery of a drug; for example, the drug may be anywhereman with the antibody or antibody fragment. Prodrugs-carriers can be used, for example, to improve one or more of the following properties: high lipophilicity, increased duration of pharmacological activity, increased site-specificity, low toxicity and side effects and/or improve the characteristics of the pharmaceutical composition (e.g., stability, solubility in water, suppression of undesirable organoleptic or physico-chemical properties). For example, the lipophilicity can be increased by the esterification of hydroxyl groups of lipophilic carboxylic acid or the esterification of carboxyl groups, alcohols, for example aliphatic alcohols. Wermuth, see above.

[0129] the Metabolites, for example, active metabolites, partially coincide with the above described prodrugs, for example, prodrugs of bioprecursor. So, mentioned IU ability are pharmacologically active compound or compounds, additionally metabolized to a pharmacologically active compounds derived, formed in the body of the subject as a result of metabolic processes. Active metabolites are these pharmacologically active derivatives of compounds. In the case of prodrugs of the compound, which is a prodrug, as a rule, is inactive or has a lower activity compared with the product of metabolism. In the case of active metabolites of the parent compound may be both active and inactive prodrug. For example, in some compounds, one or more CNS groups during metabolism can turn into a hydroxyl group with retention of pharmacological activity, and/or carboxyl groups can be subjected to esterification, for example, glucuronidation. In some cases, not necessarily the existence of more than one metabolite, the intermediate metabolite (metabolite) is further metabolized to form the active metabolite. For example, in some cases, the derivative, resulting from metabolic glucuronidation may be inactive or have low activity and can be further metabolisation with the formation of the active metabolite.

[0130] the Metabolites joint may be identified using standard techniques, known in the art, the activity of these metabolites can be determined during testing, for example, in the present description. See, for example, Bertolini / Marian Fisher et al., 1997, J. Med. Chem., 40:2011-2016; Shan et al., 1997, J Pharm Sci 86(7):756-757; Bagshawe, 1995, Drug Dev. Res., 34:220-230; Wermuth, previously.

(b) the Tautomers, the stereoisomers and the regioisomers

[0131] it is evident that some compounds can be tautomerism. In such cases given in this description of the formula explicitly characterize only one of the possible tautomeric forms. It should be understood that in the present description of the formulas include all tautomeric forms of the proposed connections and are not restricted to one particular tautomeric form shown formulas.

[0132] Similarly, some compounds according to the present invention can exist as stereoisomers, i.e. with the same interatomic connection covalently linked atoms have different spatial orientation of the atoms. For example, connections can be a optical isomers containing one or more chiral centers and therefore may exist in two or more stereoisomeric forms (e.g., enantiomers or diastereomers). In addition, these compounds may be presented in the form of the individual stereoisomers (i.e. essentially not containing other stereoisomers), racemates, and/or mixtures of enantiomers and/or diastereomers. As another example, the stereoisomers include geometric isomers, such as isomers with CIS - or TRANS-orientation of the substituents at adjacent carbon atoms at the double bond. All these separate stereometry, racemates and mixtures thereof are also within the present invention. Unless otherwise provided in this formula include each of these stereoisomeric forms.

[0133] According to some variants of implementation, chiral compound according to the present invention can be in the form containing at least 80% of individual isomer (60%enantiomeric excess (enantiomeric excess, e.e.) or diastereomeric excess (diastereomeric excess, d.e.)) or at least 85% (70% e.e. or d.e.), 90% (80% e.e. or d.e.), 95% (90% e.e. or d.e.), 97,5% (95% e.e. or d.e.) or 99% (98% e.e. or d.e.). In the General case to a person skilled in the art it is obvious that the optically pure compound containing one chiral center, is a compound consisting of essentially one of the two possible enantiomers (i.e. which is enantiomerically pure), and optically pure compound containing more than one chiral center, is a compound, which is as diastereomers clean and Enan is yamarna clean. According to some variants of implementation, the specified connection is in optically pure form, with such optically pure form is received and/or allocate using methods known in the art (for example, a recrystallization method, a chiral method of synthesis (including the synthesis of optically pure starting compounds) and chromatographic separation using a chiral column.

(C) Pharmaceutically acceptable salts and formulations

[0134] Unless otherwise noted, the description of the compounds according to the present invention includes pharmaceutically acceptable salts of the compounds. Thus, the compounds of formula I can be in the form of pharmaceutically acceptable salts or can be introduced into the composition in the form of pharmaceutically acceptable salts. Pharmaceutically acceptable salt form according to the invention include, without limitation, mono-, bis-, Tris-, tetrakis -, and other similar forms. Pharmaceutically acceptable salts are non-toxic in the amounts and the concentrations at which carry out the introduction of these salts. The receipt of such salts may contribute to the pharmacological use by changing the physical properties of compounds without the need to take measures to prevent changes in the physiological activity of a compound. Appropriate changes in the physical properties include the lower the melting temperature to facilitate transmucosal introducing and increasing the solubility to facilitate the introduction of higher concentrations of the specified drug. The connection according to the present invention can possess a sufficiently acidic, a sufficiently basic, or contain both functional groups, and accordingly to interact with any number of inorganic or organic bases and inorganic or organic acids with the formation of pharmaceutically acceptable salts.

[0135] Pharmaceutically acceptable salts include salts of joining acids, for example, salts containing chloride, bromide, iodide, hydrochloride, acetate, phenyl acetate, acrylate, ascorbate, aspartate, benzoate, 2-phenoxybenzoic, 2-acetoxybenzoic, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, methylbenzoate, bicarbonate, Butin-1,4-diet, hexyne-1,6-diet, caproate, kaprilat, chlorobenzoate, cinnamate, citrate, decanoate, formate, fumarate, glycolate, gluconate, glucarate, glucuronate, glucose-6-phosphate, glutamate, heptanoate, hexanoate, isetionate, isobutyrate, gamma-hydroxybutyrate, phenylbutyrate, lactate, malate, maleate, hydroxymet, methylmaleic, malonate, mandelate, nicotinate, nitrate, isonicotinate, octanoate, oleate, oxalate, pamoate, phosphate, monohydratefast, dihydrophosphate, orthophosphate, metaphosphate, pyrophosphate, 2-phosphoglycerate, 3-phosphoglycerate, phthalate, propionate, phenylpropionate, propionate, pyruvate, hint, salicylate, 4-aminosalitsilata, sebacina, stearate, suberate, succinate, su is that, persulfate, bisulfate, sulpham, sulfonate, bansilalpet (i.e. besilate), econsultant (i.e. Eilat), ethane-1,2-disulfonate, 2-hydroxyethanesulfonic (i.e. isetionate), methanesulfonate (i.e. mesilate), naphthalene-1-sulfonate, naphthalene-2-sulfonate (i.e. napsylat), propanesulfonate, p-toluensulfonate (i.e. toilet), xylenesulfonate, cyclohexylsulfamate, tartratami and triptoreline. These pharmaceutically acceptable salt accession acids can be obtained by using the corresponding suitable acid.

[0136] In the case when there are acid functional groups such as carboxyl or phenol, and pharmaceutically acceptable salts also include salts of joining bases, for example, salts containing benzathine, chloroprocaine, choline, ethanolamine, diethanolamine, triethanolamine, tert-butylamine, dicyclohexylamine, Ethylenediamine, N,N'-dibenziletilendiaminom, meglumin, hydroxyethylpyrrolidine, piperidine, morpholine, piperazine, procaine, aluminum, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium, zinc, ammonium and mono-, di - or trialkylamine or salts derived from amino acids such as L-histidine, L-glycine, L-lysine and L-arginine. For example, see Remington's Pharmaceutical Sciences, 19thed., Mack Publishing Co., Easton, PA, Vol. 2, p. 1457, 1995. These pharmaceutically acceptable salt accession bases can be obtained with p the physical alteration of the corresponding right reasons.

[0137] Pharmaceutically acceptable salts may be obtained using standard methods. For example, a compound in free base form can be dissolved in a suitable solvent such as water or water-alcohol solution containing the appropriate acid and then extract by evaporation of the resulting solution. According to another example, salt can be obtained by the reaction of the specified free base and acid in an organic solvent. If a particular compound is an acid, the target pharmaceutically acceptable salt can be obtained using any suitable method, for example, by processing the free acid with a suitable inorganic or organic base.

[0138] Pharmaceutically acceptable salts of the various compounds may represent complexes. Examples of complexes include 8-horrifyingly complex (similar, for example, the complex dimenhydrinate: diphenhydramine 8-chlorotheophylline (1:1); Dramamine) and various inclusion complexes of cyclodextrin.

(d) Other forms of connections

[0139] In the case of agents which are solid substances to a person skilled in the art it is obvious that these compounds and salts may exist in different crystal or polymorphic forms which can be obtained in the form of co-crystals or may be in an amorphous form, or a combination of any of these forms (for example, to be partially crystalline, partially amorphous, or a mixture of polymorphs), with each of these forms is within the present invention and the following formulas. At that time, as a salt formed by the addition of acids/bases, i.e. consider the connection in the form of a free base or free acid becomes acidic/basic reaction with the corresponding attachable basis or attachable acid, respectively, which leads to the interactions of charged ions, co-crystals represent a new chemical species formed by the neutral compounds, leading to the formation of the specified connection and additional types of molecules in the same crystal structure.

[0140] in Addition, in the present description of the formulas also include hydrated or solvated and non hydrated or nonsolvated form prescribed patterns. For example, the patterns include both hydrated and non hydrated form. Other examples of the solvate include these structures in combination with a suitable solvent, such as isopropanol, ethanol, methanol, dimethylsulfoxide, etelaat is t, acetic acid, or ethanolamine.

Introduction

[0141] the methods and compounds in General is used to treat people. However, these methods and compounds can also be used to treat similar or identical States in other animals. The compounds of formula I can be administered in a number of ways, including injection (i.e. parenteral, including intravenous, intraperitoneal, subcutaneous, and intramuscular), oral, transdermal, transmucosal, rectal or inhalation methods. Such dosage forms should provide optionality achieve the connection of the target cells. Other factors well known in the art and include aspects such as toxicity, and dosage forms, slowing the manifestation of the activity of a compound or composition. Methods and compositions in the General case can be found in the work of Remington: The Science and Practice of Pharmacy, 21stedition, Lippincott, Williams and Wilkins, Philadelphia, PA, 2005 (the contents of which are incorporated into this description by reference).

[0142] According to some variants of implementation, the compositions contain carriers or fillers, which can be chosen in such a way as to facilitate the introduction of a connection in a particular way. Examples of carriers include calcium carbonate, calcium phosphate, various sugars, such as La the Tosa, glucose or sucrose, various types of starch, cellulose derivatives, gelatin, lipids, liposomes, nanoparticles, and other Media also include physiologically compatible fluid, such as solvents or liquid used for producing suspensions, including, for example, sterile solutions on the basis of water for injection (WFI), saline, dextrose, Hanks solution, ringer's solution, vegetable oils, animal oils, polyethylene glycols, liquid paraffin and other

[0143] According to some variants of implementation, it is possible to apply oral administration. Pharmaceutical preparations for oral use can be prepared in the form of traditional dosage forms for oral administration such as capsules, tablets and liquid preparations such as syrups, elixirs and concentrated drops. The compounds of formula I can be combined with solid fillers with the possibility of carrying out grinding the resulting mixture and, after adding suitable auxiliaries (when this is desirable), to process the obtained granulated mixture with obtaining, for example, tablets, tablets with shell, hard capsules, soft capsules, solutions (for example, water, alcohol or oil solutions) and other Suitable fillers are, for example, such fillers like sugar on the tea lactose, glucose, sucrose, mannitol or sorbitol; preparations of cellulose, for example, corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, methylcellulose, hypromellose, sodium carboxymethyl cellulose (CMC) and/or polyvinylpyrrolidone (PVP: povidone); oil fillers, including vegetable and animal oils, such as sunflower oil, olive oil or fish oil of cod liver oil. Dosed compounds for oral administration may also contain dezintegriruetsja agents, such as cross-linked polyvinylpyrrolidone, agar or Aleynikova acid or its salts, such as sodium alginate; a lubricating substance, such as talc or magnesium stearate; a plasticizer such as glycerol or sorbitol; a sweetener such as sucrose, fructose, lactose or aspartame; a natural or artificial flavoring, such as peppermint, oil of gaultheria or cherry flavoring, or dyes or pigments that can be used to identify or indicate different doses or combinations. The present invention also proposed a middle part (kernel) jar coated with suitable membranes. For this purpose you can use concentrated solutions of sugars, which can additionally contain, for example, gum Arabic, talc, polyvin pyrrolidon, carboloy gel, polyethylene glycol and/or titanium dioxide, solutions varnish and suitable organic solvents or solvent mixtures.

[0144] the Pharmaceutical preparations suitable for oral administration include capsules with a filler made of gelatin, and also soft sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. These capsules with the filler can contain active ingredients mixed with a filler, such as lactose, binders, such as starches, and/or lubricating agents such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols.

[0145] According to some variants of implementation, it is possible to use injection (parenteral administration), for example, intramuscular, intravenous, intraperitoneal and/or subcutaneous. For administration by injection, the compounds of formula I can be prepared in the form of a sterile liquid solutions, preferably in physiologically compatible buffers or solutions, such as saline, Hanks solution or ringer's solution. It is also possible to prepare dispersions in non-aqueous solutions, such as CH is zerin, propylene glycol, ethanol, liquid polyethylene glycols, triacetin, and vegetable oil. The solutions may also contain a preservative, such as methylparaben, propylparaben, chlorobutanol, phenol, sorbic acid, thimerosal, etc. in Addition, these compounds may be prepared in the form of solid dosage forms, including, for example, lyophilized form, and can be re-dissolved or suspended before use.

[0146] According to some variants of implementation, it is possible to apply transmucosal, topical or transdermal administration. In such formulations based on the compounds of formula I using agents that increase the permeability, suitable for concrete barrier through which you want to provide. Such agents generally known in the art and include, for example, in the case transmucosal introduction, bile salts and derivatives of fuseboy acid. In addition, for increasing the permeability can be applied detergents. Transmucosally introduction, for example, can be accomplished using nasal sprays or suppositories (rectal or vaginal). Compositions based on compounds of the formula I for the topical injection can be prepared in the form of oils, creams, lotions, ointments, etc. by choosing the appropriate media known in the art. Suitable carrier materials including the Ute vegetable or mineral oils, medical petrolatum (soft white paraffin), fats or oils with a branched alkyl chain, animal fats, and alcohols with high molecular weight (>C12). According to some variants of implementation, the media is chosen so that the active ingredient was soluble. Also the composition can be incorporated emulsifiers, stabilizers, moisturizers and antioxidants, and agents, to give the color and smell, when this is desirable. Cream for topical application is preferably prepared from a mixture of mineral oils, offering self-emulsifying beeswax and water to this mixture add the active ingredient, dissolved in a small amount of solvent (e.g., oil). In addition, the introduction of using transdermal means may include applying a transdermal patch or dressing such as a bandage impregnated with active ingredient, and, optionally, one or more carrier or diluent known in the art. With the introduction in the form of a transdermal delivery system, the dose of exercise more continuously than periodically throughout the course of treatment.

[0147] According to some variants of implementation, the compounds administered in the form of inhalants. The compounds of formula I can be prepared in the form of a dry powder sludge is a suitable solution, suspension or aerosol. Powders and solutions can be prepared using suitable additives known in the art. For example, the powders may include a suitable powder base such as lactose or starch, and the solutions may contain propylene glycol, sterile water, ethanol, sodium chloride and other additives, such as acids, bases and buffer salts. Such solutions or suspensions can be administered by Invalidovna using the spray, pump spray inhaler or nebulizer, and other Compounds of formula I can also be used in combination with other medicines for inhalation, for example, corticosteroids, such as fluticasone propionate, beclomethasone dipropionate, triamcinolone acetonide, budesonide, and mometasone furoate; beta-agonists such as albuterol, salmeterol and formoterol; anticholinergic agents such as ipratropium bromide or Tiotropium; vasodilator means, such as treprostinil and iloprost; enzymes, such as Tnkase; therapeutic proteins; immune proteins; oligonucleotides such as single - or double-stranded DNA or RNA, small interfering RNA; antibiotics, such as tobramycin; antagonists of muscarinic receptor; leukotriene antagonists; antagonists of cytokines; inhib the tori protease; kromolin-sodium; nadarrel sodium and kromoglikatom sodium.

[0148] the number of in which impose a variety of compounds can be determined using standard methods taking into account such factors as the potency of the compound (activity in vitro, for example, IC50connection to the target, or in vivo in models assessing the effectiveness of the animal), the pharmacokinetic results of animal studies (for example, the biological half-life or bioavailability), age, composition and weight of the subject, as well as disorders associated with the specified subject. The importance of these and other factors known to a person skilled in the art. In General, the dose is in the range from about 0.01 to 50 mg/kg, about 0.1 to 20 mg/kg weight of the subject being treated. Optional use of multiple doses.

[0149] the compounds of formula I can also be used in combination with other therapeutic agents for treatment of the same disease. This combined use includes the introduction of these compounds and one or more other therapeutic drugs at different times or co-administration of the compounds and one or more other therapeutic agents. According to some variants of implementation, the dosage of one or more compounds according to us is oasea the invention and other therapeutic drugs, used in combination, can be modified; for example, the dosing amount can be reduced compared with the number of connections or therapeutic drug when applied separately, but such modification may be performed in accordance with methods known in the art.

[0150] it is evident that the use in combination involves the combined use with other therapeutic drugs, drugs, medical procedures and other, with other specified therapeutic drug can be administered or the other procedure is to exercise at different times (for example, within a short period of time, for example, for some number of hours (e.g. 1, 2, 3, 4-24 hours) or over a longer period of time (e.g., 1-2 days 2-4 days, 4-7 days, 1-4 weeks) relative to the compound of formula I or one and the same time with a compound of formula I. Use in combination also includes the combined use of therapeutic or medical procedure carried out once or infrequently, such as surgical procedure, along with the use of the compounds of formula I, administered over a short or longer period of time before or after conducting other specified therapy or procedure. According to some the eye options implementation in the present invention proposed delivery of the compounds of formula I and one or more other therapeutic drugs that are delivered through different routes of administration or the same way of introduction. Use in combination with any route of administration includes delivery of the compounds of formula I and one or more other therapeutic drugs, which are delivered via the same route of administration, together in the form of any composition, including the composition, in which the two compounds are chemically bound in such a way that with the introduction of these compounds retain their therapeutic activity. According to one aspect, other specified therapeutic drug can be administered together with a compound of formula I. Use in combination by joint injection involves the introduction of joint compounds or compositions on the basis of chemically-related compounds, or the introduction of two or more compounds in a separate compositions within a short period of time one after another (for example, within one hour, 2 hours, 3 hours, up to 24 hours), enter the same or different ways. Co-administration of separate compositions includes co-administration by delivery via a single device, for example, the same inhalation device, one and t the th same syringe and others, or introduction using different devices one after another within a short period of time. Getting joint formulations based on the compounds of formula I and one or more drugs delivered in different ways, includes the preparation of these substances in combination in such a way as to ensure the requirement of delivery of these substances using the same device, including consolidation into a single composition of individual compounds, or obtaining compounds modified with providing chemical binding of these compounds, while maintaining the biological activity of these compounds. Such chemically related compounds may contain a bridge, which essentially is saved in vivo or may break down in vivo to form two separate active components.

EXAMPLES

[0151] examples relating to the present invention. In most cases, the optional use of alternative methods. The examples given are illustrative and in no way limit the present invention. Some examples are provided to connect the results of the mass spectrometry can have more than one value due to the distribution of the isotopes of an atom in a molecule, for example, in the case of compounds containing K is the number of Deputy bromine or chlorine.

[0152] Unless specifically stated otherwise, the numbering of the formulas and the numbering of the groups R, used in the examples below, not associated with similar numbers in other sections of this description. Reagents and solvents used in the above examples, you can easily substitute a suitable alternative reagents and solvents known in the art, and the selection of products can be easily accomplished using methods known in the art, including, but not limited to, extraction, crystallization and chromatographic methods.

Example 1: Synthesis of compounds of formula Ib or Id, where A represents-C(O)-.

[0153] the compounds of formula Ib or Id specified in sections [0010] and [0016]accordingly, where A represents-C(O)-, can be obtained in five stages as shown in figure 1.

Scheme 1

Step 1 - Synthesis of compound 2:

[0154] the Compound 1 (R2and R4are as defined in paragraph [0004]) was dissolved in anhydrous solvent (e.g. tetrahydrofuran) under nitrogen atmosphere. The resulting solution was cooled in a bath of dry ice and acetone. To this solution was added a base (for example, n-utility) followed by the addition of 1,2-bis-(chlorodimethylsilyl)ethane at low temperatures (usually below -70°C). The resulting mixture is eremetical at low temperature for 1-2 hours. To this solution was added a base (for example, n-utility) followed by the addition of chloroformate. After the resulting mixture was heated to room temperature, this mixture was stirred at room temperature for 1-3 days. The reaction mixture was extinguished acidic solution was stirred at room temperature for a couple of hours and then podslushivaet. The mixture was extracted with organic solvent (e.g. dichloromethane or ethyl acetate). The target compound 2 was purified using chromatography.

Stage 2 - Synthesis of compound 3:

[0155] the compound 2 in an organic solvent (e.g. dichloromethane) was added pyridine followed by the addition of a suitable Alliluyeva reagent, isocyanate or sulphonylchloride, such as propane-1-sulphonylchloride. The reaction mixture was stirred at room temperature for 12 hours, and then the mixture was poured into water. The organic layer was separated, and the aqueous layer was extracted with a suitable organic solvent (e.g. dichloromethane). The target compound 3 (L2and R3are as defined in paragraph [0004], or L2represents S(O)2for formula Ib) was purified using chromatography.

Stage 3 - Synthesis of compound 4:

[0156] the compound 3 in a mixture of solvents (such as tetrahydrofuran and water) EXT is ulali base (for example, the lithium hydroxide or sodium hydroxide). The resulting suspension was stirred in a heated oil bath for 10 hours. The reaction mixture was cooled to room temperature and then acidified with a solution of acid such as concentrated hydrochloric acid. The aqueous layer was separated and was extracted with a suitable organic solvent (e.g. ethyl acetate). The target compound 4 was purified using chromatography.

Stage 4 - Synthesis of compound 5:

[0157] To a suspension of compound 4 in anhydrous solvent (e.g. dichloromethane), cooled in a bath of ice water was slowly added oxalicacid followed by the addition of dimethylformamide. The reaction mixture was stirred at room temperature for several hours. After removal of solvent and excess oxalicacid the obtained residue was used in the next stage without additional purification.

Stage 5 - Synthesis of compounds of formula Ib or Id:

[0158] To a suitable amine 6 (Ar, m, R1and R11are as defined in paragraph [0004]) in an anhydrous solvent (e.g. tetrahydrofuran) was added a base (such as triethylamine). To the resulting mixture, cooled in a bath of ice water, was slowly added a solution of compound 5 in anhydrous solvent (e.g. tetrahydrofuran). The resulting mixture was stirred PR the room temperature for 12 hours. The target compound of formula Ib (L2represents S(O)2or Id was purified using chromatography.

Example 2: Synthesis of compounds of formula Ic or Ie.

[0159] the compounds of formula Ic or Ie, as specified in sections [0014] and [0020]accordingly, can be obtained in four stages, as shown in Scheme 2.

Scheme 2

Step 1 - Synthesis of compound 8:

[0160] the Compound 7 (R2are as defined in paragraph [0004]) was dissolved in a suitable solvent (e.g. methanol). To the resulting solution was added the catalyst (e.g. palladium on coal). The resulting suspension was then placed in an atmosphere of hydrogen and shaken at room temperature for 12 hours. The catalyst was removed by filtration through zletovo plate and washed with a suitable solvent (e.g. methanol). The filtrate was concentrated under reduced pressure with the formation of compound 8, which was used in the next stage without additional purification.

Stage 2 - Synthesis of compound (9):

[0161] the compound 8 in an organic solvent (e.g. dichloromethane) was added a base (such as pyridine) followed by the addition of a suitable Alliluyeva agent, isocyanate or sulphonylchloride. The reaction mixture was stirred at room temperature for 12 hours. React the mixture was then poured into water. The organic layer was collected and the aqueous layer was extracted with a suitable organic solvent (e.g. dichloromethane). The organic solvents were then combined. The target compound 9 (L2and R3are as defined in paragraph [0004], or L2represents S(O)2for formula Ic) was purified using chromatography.

Stage 3 - Synthesis of compound 10:

[0162] the compound 9 in an organic solvent (such as tetrahydrofuran or dichloromethane) was added a base (e.g. sodium hydride) at low temperature followed by the addition of a suitable alkylating agent (e.g., halide). The reaction mixture was stirred at room temperature or heated in the oil bath to the desired temperature for several hours. The reaction mixture was then poured into water. The organic layer was collected and the aqueous layer was extracted with a suitable organic solvent (e.g. ethyl acetate or dichloromethane). The organic solvents were then combined. The target compound 10 (R4are as defined in paragraph [0004]) was purified using chromatography.

Stage 4 - Synthesis of compounds of formula Ic or Ie:

[0163] a Mixture of compound 10, a suitable Bronevoy acid 11 (Ar, m, and R1are as defined in paragraph [0004]) and a catalyst is a (for example, tetrakis(triphenylphosphine)palladium) in a mixture of bases (for example, an aqueous solution of potassium carbonate ) and an appropriate organic solvent (e.g. acetonitrile) was heated on an oil bath or exposed to radiation in the microwave system at a temperature of over 100°C for a suitable period of time depending on the starting materials. The reaction mixture was poured into water and then extracted with a suitable organic solvent (e.g. dichloromethane or ethyl acetate). The organic solvents were then combined. The target compound of the formula Ic (L2represents S(O)2or Id was purified using chromatography.

Example 3: Synthesis of compounds of formula I, where L1represents-CH2NR11-.

[0164] the compounds of formula I, which is as defined in paragraph [0004], where L1represents-CH2NR11-can be obtained in three stages, as shown in figure 3 - Method A, or in one stage, as shown in figure 3 - Method B.

Figure 3 - Method A

Step 1 - Synthesis of compound 12:

[0165] the Compound 4 (obtained as shown in Scheme 1, step 3 in Example 1) was dissolved in a suitable solvent (e.g. tetrahydrofuran). To the resulting solution was added a suitable reducing agent (e.g. the measures tetrahydroaluminate lithium) at low temperature (typically below -30°C). The reaction mixture was then stirred at room temperature for 2-24 hours. Was added sodium sulfate and the mixture was stirred at room temperature for 30 minutes. The mixture was filtered through zletovo plate and washed with a suitable solvent (e.g. ethyl acetate). The filtrate was concentrated under reduced pressure with the formation of compound 12, which was used in the next stage without additional purification.

Stage 2 - Synthesis of compound 13:

[0166] Compound 13 (LG represents a suitable leaving group) was obtained by transformation of compound 12 in mesilate or triflate by interacting with the corresponding sulphonylchloride in a suitable organic solvent. The specified connection can also be converted into the corresponding bromide by reacting with a suitable agent (e.g., tribromide phosphorus) in the presence of a suitable base (e.g. pyridine).

Stage 3 - the Synthesis of the compounds of formula I, where L1represents-CH2NR11is:

[0167] To a mixture of compound 13 and base (e.g. cesium carbonate) in a suitable organic solvent (e.g. acetonitrile) was added amine 6. The reaction mixture was stirred at room temperature or heated on oil is Noah bath, if it is necessary, for 2-24 hours. The reaction mixture was poured into water and then extracted with a suitable organic solvent (e.g. dichloromethane or ethyl acetate). The organic solvents were then combined. The target compound of formula I is purified using chromatography.

Figure 3 - Method B

Stage 1 - Getting connection 63:

[0168] It replaced the phenylamine 1 (R2and R4are as defined in paragraph [0004]) in a suitable solvent (e.g. tetrahydrofuran) was added a base (e.g. triethylamine) and an acid chloride (for example, acylchlorides or sulphonylchloride) in a suitable organic solvent under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2-24 hours. The reaction mixture was then poured in an acid solution and was extracted with a suitable organic solvent (e.g. dichloromethane or ethyl acetate). The obtained organic layers were then combined. The target compound 63 (L2and R3are as defined in paragraph [0004]) was purified by means of crystallization or chromatography.

Stage 2 - Getting connection 64:

[0169] Compound 63 in a suitable solvent (e.g. tetrahydrofuran) under nitrogen atmosphere was cooled in a bath of acetone/dry ice. It is received from the at to the solution was added a base (for example, diisopropylamide lithium) and then a suitable reagent (for example, N,N-dimethylformamide). The reaction mixture was stirred for 0.5 to 3 hours at low temperature (<50°C) and then left to warm to room temperature. The reaction mixture was poured into water and was extracted with a suitable organic solvent (e.g. dichloromethane or ethyl acetate). The target compound 64 was purified using chromatography.

Stage 3 - the Synthesis of the compounds of formula I, where L1represents-CH2NR11is:

[0170] To a mixture of compound 64 in a suitable organic solvent (e.g. acetonitrile) was added amine 6 (Ar, m, R1and R11are as defined in paragraph [0004]) and reducing agent (for example, triethylsilane and triperoxonane acid). The reaction mixture was heated on an oil bath for 2-24 hours. The reaction mixture was concentrated, poured into water and then extracted with a suitable organic solvent (e.g. dichloromethane or ethyl acetate). The obtained organic layers were then combined. The target compound of formula I is purified using chromatography.

[0171] Alternatively, the compounds of formula I, where L1represents-CH2NR11-can be obtained by the reduction of compounds of formula Ib or Id, where A represents-C(O)- (e.g., received the AK shown in Example 1) with a suitable reducing agent (for example, borane or diisobutylaluminium).

Example 4: Synthesis of 6-chloro-2-fluoro-N-[6-(5-methyl-thiazol-2-ylamino)-pyridine-3-yl]-3-(propane-1-sulfonylamino)-benzamide P-0011.

[0172] 6-Chloro-2-fluoro-N-[6-(5-methylthiazole-2-ylamino)-pyridine-3-yl]-3-(propane-1-sulfonylamino)-benzamide P-0011 synthesized in six stages from 4-chloro-2-foronline 14, as shown in figure 4.

Scheme 4

Stage 1 - Getting 3-amino-6-chloro-2-fermenting acid ethyl ester (15):

[0173] 4-Chloro-2-ftoranila (14, 12 ml) was dissolved in 200 ml of anhydrous tetrahydrofuran under nitrogen atmosphere in a 3-necked round-bottom flask with a capacity of 1 L. the Mixture was cooled to -78°C (bath of ice/acetone) and slowly was added dropwise n-utility (2.5 M, 45 ml), keeping the temperature below -70°C. the Mixture was stirred at -70°C for 30 minutes. 1,2-Bis(chlorodimethylsilyl)ethane (24,80 g) was dissolved in 80 ml of anhydrous tetrahydrofuran and slowly dropwise added to the reaction mixture, keeping the temperature below -70°C. the resulting mixture was stirred at -78°C for 1 hour, then slowly dropwise added n-utility (2.5 M, 45 ml), keeping the temperature below -70°C. the Mixture then was stirred for 30 minutes at -78°C, then heated to 15°C for 1 hour. The reaction mixture was cooled to -78°C and slowly was added dropwise n-utility (2.5 M, 50 ml), keeping the temperature below -70 the C. The mixture was stirred at -70°C for 90 minutes, then slowly dropwise added 13,40 ml ethylchloride, keeping the temperature below -70°C. the Reaction mixture was slowly heated to room temperature and was stirred at room temperature for 64 hours. The reaction was suppressed by careful addition of a solution of 50 ml of concentrated hydrochloric acid in 160 ml of water while cooling in a water bath with ice. The resulting mixture was stirred at room temperature for 2 hours, then was podslushivaet by adding potassium carbonate. The mixture was extracted with 3×100 ml ethyl acetate and the combined organic extracts were washed with 50 ml of saturated saline and dried with magnesium sulfate. After removal of solvent, the obtained residue was purified by column chromatography on silica gel using as eluent ethyl acetate in hexane with the formation of the target compounds (15, 17 g, 72%).

Stage 2 - Getting 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoic acid ethyl ester (17):

[0174] 3-Amino-6-chloro-2-fermenting acid ethyl ester (15, 17 g) was dissolved in 785 ml of dichloromethane, to which was added 13,2 ml of pyridine, followed by addition of propane-1-sulphonylchloride (16, 12.8 g). The reaction mixture was stirred at room temperature for 18 hours, then was poured into 400 ml of water. The PR is anceschi layer was separated, and the aqueous layer was extracted with 200 ml dichloromethane. The combined organic extracts were dried over magnesium sulfate with the formation of orange oil (41 g). Rubbing in 150 ml of diethyl ether resulted in the receipt of pyridinium salts in a solid white color. The ether filtrate was concentrated with the formation of orange oil, which was purified by column chromatography on silica gel using as eluent ethyl acetate in hexane with the formation of the target compound in the form of a solid orange (17, 20 g, 57%).

Stage 3 - Getting 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoic acid (18):

[0175] 6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoic acid ethyl ester (17, 20 g) was dissolved in a mixture of 500 ml of tetrahydrofuran and 150 ml of water. Was added lithium hydroxide (12,95 g) and the resulting suspension was stirred at 90°C for 17 hours. The mixture was cooled to room temperature, then brought to pH 1 with concentrated hydrochloric acid (~36 ml). The aqueous layer was separated and was extracted with 3×400 ml of ethyl acetate. The combined organic extracts were dried over magnesium sulfate and concentrated with the formation of solid beige color (25 g). The obtained solid is triturated in 100 ml of diethyl ether for 30 minutes, filtered, washed with 50 ml of diethyl ether and the left the house taking with the formation of the target compound in a solid white color (18, 16 g, 87%).

Stage 4 - Obtain 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (19):

[0176] 6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoic acid 18 suspended in anhydrous dichloromethane (30 ml/g). Added dimethylformamide (2 drops) and the resulting suspension was cooled in a water bath with ice. Was slowly added dropwise oxalicacid (5 EQ). Then the bath was removed and the reaction mixture was stirred at room temperature for 2 to 3 hours, the precipitated solids gradually disappeared. Dichloromethane and excess oxalicacid was removed under reduced pressure and the resulting residue was used without further purification in the next stage.

Stage 5 - Obtaining N-(6-bromopyridin-3-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (21):

[0177] 6-Bromopyridin-3-ylamine (20, 3,16 g, 18,26 mmol) was dissolved in 55 ml of anhydrous tetrahydrofuran. Was added triethylamine (1.85 g, 2.55 ml, 18,26 mmol) and the mixture was cooled in an ice bath salt. A solution of 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (19, 3.8 g, 12,17 mmol) in 55 ml of anhydrous tetrahydrofuran was slowly added dropwise into the reaction mixture. The resulting mixture was stirred at room temperature for 18 hours, then diluted with 180 ml of ethyl acetate, washed 2×70 ml water and once - 110 ml of saturated salt solution, dried over sulfate mA the of and centered with the formation of brown residue. The obtained residue was purified using flash chromatography on silica gel using as eluent 1% methanol with the formation of the target compound in a solid yellow color (21, 6,9 g, 66%).

Step 6 - Obtain 6-chloro-2-fluoro-N-[6-(5-methylthiazole-2-ylamino)-pyridine-3-yl]-3-(propane-1-sulfonylamino)-benzamide (P-0011):

[0178] N-(6-bromopyridin-3-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide (21, 250 mg, 0,555 mmol) was placed in a vessel for microwave systems together with palladium acetate (12.5 mg, by 0.055 mmol), BINAP (2,2'-bis(diphenylphosphino)-1,1'-binaphtyl) (69 mg, 0,111 mmol), tert-piperonyl potassium (124 mg, 1.11 mmol) and 2-amino-5-methylthiazole (22, 190 mg of 1.66 mmol). Added dimethylformamide (2.5 ml) and hermetically closed vessel. Then the mixture was heated at 150°C in a microwave for 3 hours. The mixture of black color was diluted with 50 ml ethyl acetate and washed with 15 ml of water, then 15 ml of 0.67 M solution of hydrochloric acid, 15 ml of water and, finally, 15 ml of saturated salt solution. The organic phase was dried over magnesium sulfate. After removal of solvent, the obtained residue was purified using preparative TLC and then HPLC with the formation of the target compound in a solid white color (P-0011, 10 mg). MS (IER) [M+H+]+= 483,8.

Example 5: Synthesis of 6-chloro-2-fluoro-N-(6-isopropylaminomethyl-3-yl)-3-(propane-1-sulfonylamino)-Bentham is Yes P-0005.

[0179] 6-Chloro-2-fluoro-N-(6-isopropylaminomethyl-3-yl)-3-(propane-1-sulfonylamino)-benzamide P-0005 synthesized in three steps from 2-bromo-5-nitropyridine 23, as shown in figure 5.

Scheme 5

Stage 1 - Getting 6 isopropylamino-3-nitropyridine (25):

[0180] 2-Bromo-5-nitropyridine (23, 400 mg) was placed in a vessel for a microwave system. Added Isopropylamine (24, 3 ml) and hermetically closed vessel. Then the mixture was heated at 120°C for 30 minutes using microwave system Biotage Initiator EXP. The crude mixture was then absorbed on the column and was purified by chromatography on silica gel. The fractions containing the target compound were combined and concentrated with the formation of the target compound in a solid yellow color.

Stage 2 - Getting N*2*-isopropylpyridine-2,5-diamine (26):

[0181] 6-Isopropylamino-3-nitropyridine 25 was dissolved in methanol (35 ml/g). Added a catalyst comprising a palladium on coal (10%, wet, ~100 mg)and the resulting suspension was placed in an atmosphere of hydrogen at room temperature overnight (~18 hours). The catalyst was removed by filtration through zletovo plate and were rinsed 2×10 ml of methanol. The filtrate was concentrated under reduced pressure with the formation of the target compound, which was used without further purification inherit the stage.

Stage 3 - Getting 6-chloro-2-fluoro-N-(6-isopropylaminomethyl-3-yl)-3-(propane-1-sulfonylamino)-benzamide (P-0005):

[0182] N*2*-isopropylpyridine-2,5-diamine (26, 155 mg, 1.01 mmol) was dissolved in 4 ml of anhydrous tetrahydrofuran. Was added triethylamine (103 mg, 142 μl, 1.01 mmol) and the mixture was cooled in an ice bath salt. Then slowly added dropwise 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (19, 200 mg of 0.68 mmol) in 4 ml of anhydrous tetrahydrofuran. The resulting mixture was stirred at room temperature for 20 hours, then diluted with 30 ml ethyl acetate, washed 3×10 ml water and 15 ml of saturated salt solution. After removal of solvent, the obtained residue was purified by chromatography on silica gel with the formation of the target compound in a solid white color (P-0005, 35 mg). MS (IER) [M+H+]+= 429,0.

[0183] 6-Chloro-N-(6-cyclopentenopyridine-3-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0009, 6-Chloro-N-(6-cyclopropylamino-3-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0015, 6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-{6-[(thiophene-2-ylmethyl)-amino]-pyridine-3-yl}-benzamide P-0016 and N-(6-Benzylaminopurine-3-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0017,

were obtained in accordance with the methodology described in Scheme 5, where Isopropylamine 24 was replaced by the CEC shall pentylamine, cyclopropylamine, thiophene-2-yl-methylamine and benzylamine, respectively, in Stage 1. MS (IER) [M+H+]+P-0009 = to 455.2, P-0015 = 427,0, P-0016 = 483,2 and P-0017 = 477,2.

Example 6: Synthesis of N-(2-acetylpiperidine-5-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0004.

[0184] N-(2-Acetylpiperidine-5-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0004 synthesized in three steps from 2-amino-5-nitropyrimidine 27, as shown in figure 6.

Scheme 6

Stage 1 - Getting N-(5-nitropyrimidin-2-yl)-ndimethylacetamide (28):

[0185] 2-Amino-5-nitropyrimidin (27, 500 mg) suspended in 5 ml of acetic anhydride. The mixture was heated at 160°C for two hours, then cooled to room temperature. The solids were filtered and washed with 5 ml of water, then suspended in 10 ml of water, and brought the pH to 8-9 by addition of 25% ammonium hydroxide solution. The solids were filtered off, washed with 2×10 ml of cold water and recrystallized from ethyl acetate with the formation of the target compound in the form of needle crystals beige (28, 382 mg, 58%).

Stage 2 - get N-(5-amino-pyrimidine-2-yl)-ndimethylacetamide (29):

[0186] N-(5-Nitropyrimidin-2-yl)-ndimethylacetamide (28, 620 mg) suspended in 31 ml of methanol. Added a catalyst comprising a palladium on coal (10%, wet, 60 mg)and the resulting suspension was placed in the atmosphere is odorata for 17 hours. The catalyst was filtered through zletovo plate and washed 2×30 ml of methanol. The filtrate was concentrated under reduced pressure with the formation of the target compound in the form of needle crystals of light-yellow color (29, 520 mg, 100%).

Stage 3 - Getting N-(2-acetylpiperidine-5-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0004:

[0187] N-(5-aminopyridin-2-yl)-ndimethylacetamide (29, 154 mg, 1.01 mmol) was dissolved in 3 ml of anhydrous tetrahydrofuran. Was added triethylamine (103 mg, 142 μl, 1.01 mmol)and the mixture was cooled in an ice bath salt. Then slowly added dropwise 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (19, 200 mg of 0.68 mmol) in 3 ml of anhydrous tetrahydrofuran. The resulting mixture was stirred at room temperature for 18 hours, then diluted with 20 ml ethyl acetate, washed 2×10 ml water and 10 ml of saturated salt solution. The organic layer was dried over magnesium sulfate. After removal of solvent, the obtained residue was purified by chromatography on silica gel with the formation of the target compound in a solid white color (P-0004, 55 mg, 19%). MS (IER) [M+H+]+= 430,2.

Example 7: Synthesis of N-(6-acetylpiperidine-3-yl)-2,6-debtor-3-(propane-1-sulfonylamino)-benzamide P-0008.

[0188] N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(propane-1-sulfonylamino)-benzamide P-0008 synthesized in three hundred the AI from 2,6-debtor-3-nitrobenzoic acid 30 and N-(5-amino-pyridin-2-yl)-ndimethylacetamide 31, as shown in Scheme 7.

Scheme 7

Stage 1 - Getting N-(6-acetylpiperidine-3-yl)-2,6-debtor-3-nitro-benzamide (32):

[0189] 2,6-Debtor-3-nitrobenzoic acid (30, 500 mg) was dissolved in 15 ml of anhydrous dichloromethane. Then was added N,N-dimethylformamide (1 drop) and the mixture was cooled to 5°C in a water bath with ice. Was slowly added dropwise oxalicacid (1.1 ml, 5 EQ). The reaction mixture was stirred at room temperature for two hours, then concentrated under reduced pressure with the formation of the solid yellow residue, which was dissolved in 5 ml of anhydrous tetrahydrofuran and slowly added dropwise to a solution of N-(5-aminopyridine-2-yl)-ndimethylacetamide (31, 558 mg, 1.5 EQ) and triethylamine (0,52 ml) in 10 ml of anhydrous tetrahydrofuran. The resulting suspension was stirred at room temperature overnight. The mixture was diluted with 50 ml ethyl acetate, washed 2×25 ml water, then with 25 ml of saturated salt solution, dried over magnesium sulfate and concentrated with the formation of the crude target compound in a solid brown color (32, 980 mg, 84%)which was used in the next stage without additional purification.

Stage 2 - get N-(6-acetylpiperidine-3-yl)-3-amino-2,6-differentated (33):

[0190] N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-nitrobenzamide (32, 90 mg) suspended in 15 ml of methanol. Added a catalyst comprising a palladium on coal (10%, wet, 100 mg)and the resulting suspension was placed in an atmosphere of hydrogen for 17 hours. The catalyst was filtered through zletovo plate and washed 2×20 ml of methanol. The filtrate was concentrated under reduced pressure with the formation of the target compound in a solid black color (33, 750 mg, 86%).

Stage 3 - Getting N-(6-acetylpiperidine-3-yl)-2,6-debtor-3-(propane-1-sulfonylamino)-benzamide (P-0008):

[0191] N-(6-Acetylpiperidine-3-yl)-3-amino-2,6-diflorasone (33, 700 mg) was dissolved in 35 ml of pyridine. Added 4-dimethylaminopyridine (1 EQ) followed by addition of propane-1-sulphonylchloride (16, 0,80 g, 2.3 EQ). The resulting mixture was stirred at room temperature for 3 days, then at 70°C for 18 hours. The pyridine was removed under reduced pressure and the resulting residue was purified by column chromatography on silica gel using as eluent ethyl acetate in hexane with the formation of the target compound in a solid yellow color (P-0008, 10 mg, 1%). MS (IER) [M+H+]+= 412,9.

[0192] According to the method presented in Scheme 7 can be obtained additional connections by replacing propane-1-sulphonylchloride 16 suitable sulphonylchloride on Stage 3. According to this method can be obtained follow what their connection is:

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(2-forbindelseshandtering)-benzamide (P-0097),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(3-forbindelseshandtering)-benzamide (P-0098),

N-(6-Acetylpiperidine-3-yl)-3-(2,6-differentialtopologie)-2,6-diflorasone (P-0099),

N-(6-Acetylpiperidine-3-yl)-3-(2,4-differentialtopologie)-2,6-diflorasone (P-0100),

N-(6-Acetylpiperidine-3-yl)-3-(2,5-differentialtopologie)-2,6-diflorasone (P-0101),

6-Acetylamino-N-[2,6-debtor-3-(3-fluoro-4-methoxybenzenesulfonamide)-phenyl]-nicotinamide (P-0102),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-triftormetilfullerenov)-benzamide (P-0103),

N-(6-Acetylpiperidine-3-yl)-3-(4-diftormetilirovaniya)-2,6-debtor-benzamide (P-0104),

N-(6-Acetylpiperidine-3-yl)-3-(3-diftormetilirovaniya)-2,6-debtor-benzamide (P-0105),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-isopropylbenzenesulfonyl)-benzamide (P-0106),

N-(6-Acetylpiperidine-3-yl)-3-(4-tert-butylbenzenesulfonamide)-2,6-debtor-benzamide (P-0107),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-propylbenzenesulfonyl)-benzamide (P-0108),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyridine-2-sulfonylamino)-benzamide (P-0109),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyridine-3-sulfonylamino)-benzamide (P-0110),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(dimethylaminoethyl is arylamino)-benzamide (P-0111),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(piperidine-1-sulfonylamino)-benzamide (P-0112),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(morpholine-4-sulfonylamino)-benzamide (P-0113),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-benzamide (P-0114),

N-(6-Acetylpiperidine-3-yl)-3-cyclopentanecarbonyl-2,6-diflorasone (P-0115),

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-benzamide (P-0116) and

N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(3,3,3-cryptochrome-1 sulfonylamino)-benzamide (P-0117).

In the table below in column 1 the number of connections specified in column 2 specific sulphonylchloride used in Stage 3, and in column 3 - the final connection:

Example 8: Synthesis of pyrrolidin-1-carboxylic acid {5-[6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoylamine]-pyridine-2-yl}-amide P-0006.

[0193] Pyrrolidin-1-carboxylic acid {5-[6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoylamine]-pyridine-2-yl}-amide P-0006 synthesized in four steps from 2-amino-5-nitropyridine 34, as shown in figure 8.

Scheme 8

Stage 1 - Getting isopropanolamide ether (5-nitropyridine-2-yl)-carbamino acid (35):

[0194] 2-Amino-5-nitropyridine (34, 500 mg) of restora and 5 ml of anhydrous tetrahydrofuran. Was added N-methylmorpholine (436 mg, 1.2 EQ) and the mixture was cooled to -10°C in a bath of ice/acetone with salt. Then slowly added dropwise a solution of isopropylcarbamate (520 mg) in 5 ml of tetrahydrofuran, maintaining the temperature below -10°C. the Reaction mixture was stirred at room temperature overnight, then diluted with 25 ml ethyl acetate and 20 ml of water. The aqueous layer was separated and was extracted with 2×25 ml ethyl acetate. The combined organic extracts were washed with 25 ml Polynesians salt solution and dried over magnesium sulfate. After removal of solvent, the obtained residue was purified by column chromatography on silica gel using as eluent ethyl acetate in hexane with the formation of the target compound in a solid white color (35, 0.52 g, 65%).

Stage 2 - Getting pyrrolidin-1-carboxylic acid (5-nitropyridine-2-yl)-amide (37):

[0195] Isopropanolamine ether (5-nitropyridine-2-yl)-carbamino acid (35, 160 mg) was dissolved in 2 ml of anhydrous tetrahydrofuran. Was added N-methylpyrrolidine (6 mg, 0.1 EQ) followed by the addition of pyrrolidine (36, 51 mg, 1 EQ). The mixture was stirred at room temperature overnight, it was formed precipitate. The precipitate was filtered off, washed with 1 ml of tetrahydrofuran and dried with formation of a solid white color. Additional number is the number of compounds was obtained by concentrating the filtrate under reduced pressure and trituration of the resulting residue in diethyl ether (~5 ml) with the formation of the target compounds in a solid beige color (37, 0.12 g, 71%).

Stage 3 - Getting pyrrolidin-1-carboxylic acid (5-aminopyridine-2-yl)-amide (38):

[0196] Pyrrolidin-1-carboxylic acid (5-nitropyridine-2-yl)-amide (37, 115 mg) was dissolved in 10 ml of methanol. Added a catalyst comprising a palladium on charcoal, and the resulting suspension was placed in an atmosphere of hydrogen for 64 hours. The catalyst was filtered through zletovo plate and washed 2×10 ml of methanol. The filtrate was concentrated under reduced pressure with the formation of the target compound in the form of a solid gray (38, 0.1 g, 100%).

Stage 4 - Getting pyrrolidin-1-carboxylic acid {5-[6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoylamine]-pyridine-2-yl}-amide (P-0006):

[0197] Pyrrolidin-1-carboxylic acid (5-aminopyridine-2-yl)-amide (38, 100 mg, 0.48 mmol) was dissolved in 2 ml of anhydrous tetrahydrofuran. Was added triethylamine (49 mg, 67 μl, 0.48 mmol) and the mixture was cooled in an ice bath salt. Then slowly added dropwise 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (19, 100 mg, 0.34 mmol) in 1 ml anhydrous tetrahydrofuran. The resulting mixture was stirred at room temperature for 60 hours, then diluted with 20 ml ethyl acetate, washed 2×10 ml water and 10 ml of saturated salt solution. The organic layer was dried over magnesium sulfate. After removal of solvent, the obtained residue ocialis by column chromatography on silica gel using as eluent ethyl acetate in hexane with the formation of the target compound in a solid white color (P-0006, 5 mg, 3%). MS (IER) [M+H+]+= 484,0.

Example 9: Synthesis of 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-quinoline-3-yl-benzamide P-0013.

[0198] 6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-quinoline-3-yl-benzamide P-0013 synthesized in one stage of the 3-aminoquinoline 39, as shown in Scheme 9.

Scheme 9

Stage 1 - Getting 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-quinoline-3-yl-benzamide (P-0013):

[0199] 3-Aminoquinoline (39, 172 mg, 1,19 mmol) was dissolved in 5 ml of anhydrous tetrahydrofuran. Was added triethylamine (120 mg, 170 μl, 1,19 mmol) and the mixture was cooled in an ice bath salt. Was slowly added dropwise 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (19, 250 mg, 0.80 mmol) in 5 ml of anhydrous tetrahydrofuran. The resulting mixture was stirred at room temperature for 20 hours, then diluted with 30 ml ethyl acetate, washed 3×10 ml water and 15 ml of saturated salt solution. The organic layer was dried over magnesium sulfate and concentrated with the formation of the remainder pale yellow (400 mg), which is then triturated in ethyl acetate with the formation of the target compound in a solid white color (P-0013, 110 mg, 32%). MS (IER) [M+H+]+= 421,9.

[0200] N-(6-Acetylpiperidine-3-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0002, 6-Chloro-2-fluoro-N-(6-methoxypyridine-3-yl)-3-(propane-1-sulfonylamino)-b is same P-0003, 6-Chloro-N-(3,5-dimethylisoxazol-4-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0007, 6-chloro-N-[5-(4-chlorophenyl)-2H-pyrazole-3-yl]-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0010, 6-chloro-N-[5-(4-chlorbenzyl)-[1,3,4]thiadiazole-2-yl]-2-fluoro-3-(propane-1-sulfonylamino)-benzamide P-0012, [2-[6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoylamine]-4H-[1,3,4]thiadiazin-(5E)-ilidene]-acetic acid ethyl ester P-0014 and 6-Chloro-2-fluoro-N-imidazo[1,2-a]pyridine-3-yl-3-(propane-1-sulfonylamino)-benzamide P-0018,

received according to the method presented in Scheme 9, substituting 3-aminoquinoline 39 N-(5-aminopyridine-2-yl)-ndimethylacetamide; 6-methoxypyridine-3-aluminum; 3,5-dimethylisoxazol-4-aluminum; 5-(4-chlorophenyl)-2H-pyrazole-3-aluminum; 5-(4-chlorbenzyl)-[1,3,4]thiadiazole-2-aluminum; [2-amino-4H-[1,3,4]thiadiazin-(5E)-ilidene]-acetic acid ethyl ester and imidazo[1,2-a]pyridine-3-aluminum, respectively. MS (IER) [M+H+]+P-0002 = 429,2, P-0003 = 402,2, P-0007 = 389,9, P-0010 = 471,2, P-0012 = 503,0, P-0014 = 478,9 and P-0018 = 411,0.

Example 10: Synthesis of 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-pyridin-3-yl-benzamide P-0001.

[0201] 6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-pyridin-3-ylbenzene P-0001 synthesized in two steps from 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoic acid 18 as shown in Scheme 10.

Scheme 10

Stage 1 - Getting 6-chloro-2-CFT is R-3-(propane-1-sulfonylamino)-benzoyl chloride (19):

[0202] To 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoic acid (18, 502 mg, 1.70 mmol, obtained, as shown in Stage 3 Scheme 4, Example 4) in 35 ml of dichloromethane was added oxalicacid (5 ml, 2.0 M in dichloromethane) and N,N-dimethylformamide (100 μl, 0.001 mol). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated with the formation of compound 19, which was used without further purification.

Stage 2 - Getting 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-pyridin-3-yl-benzamide (P-0001):

[0203] To 6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (19, 0,200 g, 0.64 mmol) in 10.0 ml of dichloromethane was added pyridine-3-ylamine (40, 0.126 g of 1.34 mmol) and 4-dimethylaminopyridine (7.8 mg, 0,064 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was poured into water and was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and was purified by column chromatography on silica gel using as eluent 5% methanol in dichloromethane with the formation of the target compounds P-0001, 0.15 g, 63%). MS (IER) [M+H+]+= 371,1.

Example 11: Synthesis of propane-1-sulfonic {2,4-debtor-3-[(5-methyl-isoxazol-3-ylamino)-methyl]-phenyl}-amide P-0019.

[0204] Propane-sulfonic {2,4-debtor-3-[(5-methylisoxazol-3-ylamino)-methyl]-phenyl}-amide P-0019 synthesized in three steps from 2,4-dipertanyakan 41, as shown in Scheme 11.

Scheme 11

Stage 1 - Getting propane-1-sulfonic acids (2,4-differenl)-amide (42):

[0205] To 2,4-dipertanyakan (41, 3.0 ml, to 29.8 mmol) in 50 ml of tetrahydrofuran was added in an atmosphere of nitrogen triethylamine (9,13 ml, 65,5 mmol) and propane-1-sulphonylchloride (16, 2,90 ml of 25.8 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was poured into 1 M HCl and was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated with the formation of the target compound (42, 2.0 g, 28%)which was used without further purification in the next stage.

Stage 2 - Getting propane-1-sulfonic acids (2,4-debtor-3-formylphenyl)-amide (43):

[0206] To propane-1-sulfonic acids (2,4-differenl)-amide (42, 1.5 g, 6.38 mmol) in 10 ml of tetrahydrofuran, cooled in a bath of acetone/dry ice with a temperature of -78°C under nitrogen atmosphere was added diisopropylamide lithium (0,80 M in tetrahydrofuran, 24 ml, freshly prepared from n-utility and Diisopropylamine). After 30 minutes the reaction mixture was added dropwise N,N-dimethylformamide (542 μl, 7,018 mmol). The reaction mixture was stirred for 30 minutes at -78°C and then left to warm to room temperature over 40 minutiae the mixture was poured into water and was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and was purified by column chromatography on silica gel using as eluent 5% ethyl acetate in hexane with the formation of solid light yellow (43, 300 mg, 18%). MS(ESI)[M-H+]-= 262,3.

Stage 3 - Getting propane-1-sulfonic {2,4-debtor-3-[(5-methylisoxazol-3-ylamino)-methyl]-phenyl}-amide (P-0019):

[0207] To 5-methylisoxazol-3-ylamine (44, of 0.13 g, 1.3 mmol) in 20 ml of acetonitrile was added propane-1-sulfonic acids (2,4-debtor-3-formylphenyl)-amide (43, 0.35 g, 1.3 mmol), triethylsilane (1 ml, 7 mmol) and triperoxonane acid (0.5 ml, 7 mmol). The reaction mixture was stirred at 80°C during the night. The reaction mixture was concentrated, then was poured into aqueous potassium carbonate solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. After removal of the drying agent and then the solvent, the obtained residue was purified by column chromatography on silica gel with the formation of the target compound in a solid white color (P-0019, 0,22 g, 48%). MS (IER) [M-H+] = 346,95.

[0208] N-{5-[2,6-Debtor-3-(propane-1-sulfonylamino)-benzylamino]-pyridine-2-yl}-ndimethylacetamide P-0020, propane-1-sulfonic acids [2,4-debtor-3-(quinoline-3-illuminometer)-phenyl]-amide P-0021, prop the n-1-sulfonic {3-[(6-chloro-pyridine-3-ylamino)-methyl]-2,4-debtor-phenyl}-amide P-0022 and propane-1-sulfonic {2,4-debtor-3-[(6-methoxypyridine-3-ylamino)-methyl]-phenyl}-amide P-0023,

received according to the method presented in Scheme 11, substituting 5-methylisoxazol-3-ylamine 44 N-(5-aminopyridine-2-yl)-ndimethylacetamide, quinoline-3-ylamine, 6-chloro-pyridine-3-ylamine and 6-methoxypyridine-3-ylamine, respectively. MS (IER) [M+H+]+P-0020 = 399,35, P-0021 = 392,40, P-0022 = 376,95 and P-0023 = 372,55.

Example 12: Synthesis of quinoline-3-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide P-0024 and propane-1-sulfonic {2,4-debtor-3-[(quinoline-3-ylmethyl)-amino]-phenyl}-amide P-0025.

[0209] Quinoline-3-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide P-0024 and propane-1-sulfonic {2,4-debtor-3-[(quinoline-3-ylmethyl)-amino]-phenyl}-amide P-0025 synthesized in three stages of propane-1-sulfonic acids (2,4-debtor-3-formyl-phenyl)-amide 43, as shown in Scheme 12.

Scheme 12

Stage 1 - Getting 2,6-debtor-3-(propane-1-sulfonylamino)-benzoic acid (45):

[0210] In a reaction flask under nitrogen atmosphere was added propane-1-sulfonic acids (2,4-debtor-3-formylphenyl)-amide (43, 3.00 g, to 11.4 mmol) and axon (9,10 g of 14.8 mmol) and 30 ml of anhydrous N,N-dimethylformamide. The mixture was stirred at room temperature overnight, then put 250 ml of 1 M hydrochloric acid and was extracted with 250 ml ethyl acetate. The organic layers were washed 3×100 ml of 1M hydrochloric acid and dried over magnesium sulfate. the donkey removal of the desiccant and solvent the obtained residue was dried under vacuum with the formation of the target compound (45, 2.9 g, 91%).

Stage 2 - Getting propane-1-sulfonic acids (3-amino-2,4-differenl)-amide (46):

[0211] In a reaction flask under nitrogen atmosphere was added 2,6-debtor-3-(propane-1-sulfonylamino)-benzoic acid (45, 2,88 g of 10.3 mmol), triethylamine (2,09 g of 20.6 mmol) and diphenylphosphoryl (3,21 g, 11.7 mmol), and 84 ml of anhydrous tert-butanol. The reaction mixture was heated on an oil bath at 105°C overnight, then cooled to room temperature and was diluted with ethyl acetate. The organic layer was washed 3×250 ml water, 250 ml of saturated salt solution, dried over magnesium sulfate, filtered and concentrated under vacuum to obtain 4.1 g of the crude amine containing protective group Boc, which was purified by column chromatography on silica gel using as eluent hexane:ethyl acetate to obtain 3.3 g of the Boc-protected amine. Specified substance was dissolved in 50 ml of dichloromethane and was added 16 ml triperoxonane acid, and the reaction mixture was stirred at room temperature until disappearance of the traces of the original compounds according to TLC. The reaction mixture is neutralized, pouring into a cooled saturated sodium bicarbonate solution and was extracted with 3×150 ml dichloromethane. The combined organic extracts were washed with 50 ml of saturated salt solution, dried over magnesium sulfate, filter is Ali and concentrated under vacuum with the formation of the target compound (46, 1,94 g, 75%).

Stage 3a - Receiving quinoline-3-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide (P-0024):

[0212] In a reaction vessel under nitrogen atmosphere was added 3-quinoline-carboxylic acid (47, 39,1 mg, 0.23 mmol), 1.5 ml of anhydrous tetrahydrofuran, 1 drop of anhydrous N,N-dimethylformamide and oxalicacid (86 mg, of 0.68 mmol). The reaction mixture was stirred at room temperature for 1.5 hours, then concentrated to obtain a dry residue, and the obtained residue was diluted with 2 ml of anhydrous tetrahydrofuran. To the resulting solution were added triethylamine (15.8 mg, 0.16 mmol) and propane-1-sulfonic acids (3-amino-2,4-differenl)-amide (46, 100 mg, 0.40 mmol)and the reaction mixture was stirred at room temperature over a weekend. The reaction mixture was diluted with 5 ml water and was extracted with 3×10 ml of ethyl acetate. The organic extracts were dried over magnesium sulfate, filtered and concentrated under vacuum, then purified by column chromatography on silica gel (gradient hexane:ethyl acetate) with the formation of the target compound (P-0024, 33 mg, 36%). MS (IER) [M+H+]+= 406,1.

Stage 3b - Getting propane-1-sulfonic {2,4-debtor-3-[(quinoline-3-ylmethyl)-amino]-phenyl}-amide (P-0025):

[0213] In a reaction vessel under nitrogen atmosphere was added propane-1-sulfonic acids (3-amino-2,4-differenl)-amide (46, 155 mg of 0.62 mmol) in 2 ml of anhydrous acetonitrile, 3-hyalinobatrachium (48, 100 mg, 0.64 mmol), triperoxonane acid (431 mg, of 3.78 mmol) and triethylsilane (425 mg, 3.65 mmol). The reaction mixture was heated at 80°C overnight, then cooled to room temperature and concentrated under vacuum; then added 10 ml of aqueous 10% potassium carbonate. The resulting mixture was extracted with 3×15 ml of ethyl acetate. The combined organic extracts washed with 15 ml saturated brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The obtained residue was purified by column chromatography on silica gel (gradient hexane:ethyl acetate) with the formation of the target compound (P-0025, 70 mg, 29%). MS (IER) [M+H+]+= 392,0.

Example 13: Synthesis of propane-1-sulfonic acids [2,4-debtor-3-(quinoline-3-intoximeter)-phenyl]-amide P-0026.

[0214] Propane-1-sulfonic acids [2,4-debtor-3-(quinoline-3-intoximeter)-phenyl]-amide P-0026 synthesized in three stages of propane-1-sulfonic acids (2,4-debtor-3-formylphenyl)-amide 43, as shown in figure 13.

Scheme 13

Stage 1 - Getting propane-1-sulfonic acids (2,4-debtor-3-hydroxymethylene)-amide (49):

[0215] In a reaction vessel under nitrogen atmosphere was added propane-1-sulfonic acids (2,4-debtor-3-formylphenyl)-amide (43, of 1.00 g of 3.80 mmol), 20 ml of methanol and sodium borohydride (0.29 grams, of 7.60 mmol). The reaction mixture is PE is amasyali at room temperature for 1 hour, then was poured into 50 ml of aqueous 10% solution of sodium dihydrophosphate. The mixture was extracted with 3×50 ml of dichloromethane, and the combined organic extracts were dried over magnesium sulfate, filtered and concentrated under vacuum with the formation of the target compound (49, 0.97 g, 96%)used in the next stage without additional purification.

Stage 2 - Getting propane-1-sulfonic acids (3-methyl bromide-2,4-differenl)-amide (50):

[0216] Into a reaction vessel containing triphenylphosphine on a polymer substrate (2,45 g, to 4.41 mmol) in 5 ml of acetonitrile, was added in nitrogen atmosphere bromine (0,70 g, to 4.41 mmol) followed by a solution of propane-1-sulfonic acids (2,4-debtor-3-hydroxymethyl-phenyl)-amide (49, 0.97 g, to 3.67 mmol) in 5 ml of acetonitrile. The reaction mixture was stirred at 60°C for approximately 3 hours. The reaction mixture was filtered and the polymer washed with 5 ml of ethyl acetate. The filtrate and washing liquid were concentrated under vacuum with the formation of the target compound (50, 0,91 g, 76%)used in the next stage without additional purification.

Stage 3 - Getting propane-1-sulfonic acids [2,4-debtor-3-(quinoline-3-intoximeter)-phenyl]-amide (P-0026):

[0217] In a reaction vessel under nitrogen atmosphere was added 3-hydroxyquinolin (51, 442 mg of 3.05 mmol) and 5 ml of anhydrous N,N-dimethylformamide. Sodium hydride (60% dispersion in mineral oil, 183 mg of 4.57 mmol) to allali parts. The reaction mixture was stirred at room temperature for 30 minutes, then was added propane-1-sulfonic acids (3-methyl bromide-2,4-differenl)-amide (50, 500 mg, of 1.52 mmol) and the reaction mixture was stirred at room temperature overnight. The reaction mixture was neutralized with acetic acid and was extracted with 3×20 ml ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated under vacuum. The obtained residue was purified by column chromatography on silica gel (gradient hexane:ethyl acetate) followed by a second purification using column chromatography on silica gel with the formation of the target compound (P-0026, 50 mg, 8%). MS (IER) [M+H+]+= 393,0.

[0218] According to the method illustrated in figure 13, can be obtained for more connection with optional replacement propane-1-sulfonic acids (2,4-debtor-3-formylphenyl)-amide 43 N-(2,4-debtor-3-formylphenyl)-4-triftoratsetilatsetonom (obtained according to Scheme 11, Example 11, stage 1 and 2, using 4-trifluoromethyl-benzosulfimide in Stage 1 instead of propane-1-sulphonylchloride 16) in Stage 1 and 3-hydroxyquinoline solution 51 with a suitable alcohol in Stage 3. According to the method shown can be obtained the following compounds:

N-{5-[2,6-Debtor-3-(propane-1-sulfonylamino)-benzyloxy]-PI is one-2-yl}-ndimethylacetamide (P-0091),

Propane-1-sulfonic acids [3-(2-aminopyridine-3-intoximeter)-2,4-differenl]-amide (P-0092),

Propane-1-sulfonic acids [2,4-debtor-3-(1H-pyrrolo[2,3-b]pyridine-5-intoximeter)-phenyl]-amide (P-0093),

N-{5-[2,6-Debtor-3-(4-triftormetilfullerenov)-benzyloxy]-pyridine-2-yl}-ndimethylacetamide (P-0094),

N-[3-(2-Aminopyridine-3-intoximeter)-2,4-differenl]-4-trifluoromethyl-benzosulfimide (P-0095),

and

N-[2,4-Debtor-3-(1H-pyrrolo[2,3-b]pyridine-5-intoximeter)-phenyl]-4-trifluoromethyl-benzosulfimide (P-0096).

In the table below in column 1 lists a number of compounds in column 2 indicates the specific aldehyde used in Stage 3, is specified in column 3 of the alcohol used in Stage 3, and in column 4 - the final connection:

Example 14: Synthesis of 2,6-debtor-3-(propane-1-sulfonylamino)-N-quinoline-3-ilasamaja P-0027.

[0219] 2,6-Debtor-3-(propane-1-sulfonylamino)-N-quinoline-3-yl-benzamide P-0027 synthesized in one stage of 2,6-debtor-3-(propane-1-sulfonylamino)-benzoic acid 45, as shown in figure 14.

Scheme 14

Stage 1 - Getting 2,6-debtor-3-(propane-1-sulfonylamino)-N-quinoline-3-ilasamaja (P-0027):

[0220] In a reaction vessel under nitrogen atmosphere was added 2,6-debtor-3-(propane-1-sulfonylamino)-benzoic acid (45, 250 mg, 0.90 mmol), 5 ml of anhydrous dichloromethane and Bezbog the CSO N,N-dimethylformamide (6,54 mg, 0.09 mmol). The reaction mixture was cooled to 0°C was added dropwise oxalicacid (568 mg, 4,48 mmol). The resulting mixture was stirred at room temperature for 3 hours, then concentrated under vacuum. The obtained residue was diluted with 5 ml of anhydrous tetrahydrofuran and triethylamine (136 mg, of 1.34 mmol) and 3-aminoquinoline (39, 194 mg of 1.34 mmol). The reaction mixture was stirred at room temperature over a weekend, then concentrated under vacuum. The obtained residue was purified by column chromatography on silica gel (gradient hexane:ethyl acetate) with the formation of the target compound (P-0027, 163 mg, 45%). MS (IER) [M+H+]+= 406,1.

Example 15: Synthesis of additional compounds

[0221] Additional compounds can be synthesized in six stages according to the Diagram below 15 or in four stages according to Scheme 16.

Scheme 15

Stage 1 - Receipt methyl ester (2,4-differenl)-carbamino acid (52):

[0222] To 2,4-diptiranjan 41 was slowly added dropwise potassium carbonate, water and methylchloroform 51. The reaction mixture was stirred at 0°C and then waited until the temperature of the mixture becomes equal to room temperature. The reaction mixture was extracted with ethyl acetate and washed with dilute HCl (pH 2), washed twice with saturated solution of bicarbonate, twice washed with saturated saline and dried over magnesium sulfate. After removal of the solvent was obtained target compound in the form of crude solid.

Stage 2 - Getting 2,6-debtor-3-methoxycarbonylaminophenyl acid (53):

[0223] To methyl ether (2,4-differenl)-carbamino acid 52 in tetrahydrofuran at -78°C was added 2.5 EQ. diisopropylamide lithium. After 15 minutes, was added solid carbon dioxide and leaving the reaction mixture to warm to room temperature. The reaction mixture was extracted with ethyl acetate and washed with dilute HCl (pH 2). The target compound was isolated by column chromatography on silica gel.

Stage 3 - getting the methyl ester (3-amino-2,4-differenl)-carbamino acid (54):

[0224] To 2,6-debtor-3-methoxycarbonylaminophenyl acid 53 was added anhydrous tert-butanol, triethylamine and diphenylphosphoryl. The reaction mixture was heated on an oil bath at 105°C during the night. The reaction mixture was cooled to room temperature and was diluted with ethyl acetate. The organic layer was washed 3× with water, then 1× with saturated saline, dried over magnesium sulfate and filtered and concentrated under vacuum to obtain Boc-protected amine, which was purified by column chromatography on silica gel. The purified Boc-protection of the military amine was dissolved in dichloromethane, added triperoxonane acid and stirred the reaction mixture at room temperature, checking with TLC a lack of basic substances. Upon completion the reaction mixture was neutralized, pouring into a cooled saturated solution of sodium bicarbonate, and then extracted 3× with dichloromethane. The combined organic extracts were washed with saturated salt solution, dried over magnesium sulfate, filtered and concentrated under vacuum with the formation of the target compounds.

Stage 4 - Getting connection 56:

[0225] In a reaction vessel under nitrogen atmosphere was added carboxylic acid 55 (Ramay contain heteroaryl), anhydrous tetrahydrofuran, 1 drop of anhydrous DMF (dimethylformamide) and oxalicacid. The reaction mixture was stirred at room temperature for 1.5 hours, then concentrated to obtain a dry residue. The obtained residue was diluted with anhydrous tetrahydrofuran, then added triethylamine and methyl ester of (3-amino-2,4-differenl)-carbamino acid 54 and stirred at room temperature overnight. The reaction mixture was diluted with water and was extracted 3× with ethyl acetate. The organic extracts were dried over magnesium sulfate, filtered and concentrated under vacuum with the formation of the target compound in the form of untreated solids, the cat who PoE was purified column chromatography on silica gel (gradient hexane:ethyl acetate).

Stage 5 - connection 57:

[0226] To the connection 56 in dioxane was added an equivalent amount of 1 n lithium hydroxide. The reaction mixture was stirred at 60°C and monitored by TLC. Upon completion the reaction mixture was extracted with 1 N. aqueous HCl and ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated volatile solvents with the formation of the target compound in the form of a crude solid.

Stage 6 - Getting connection 59:

[0227] compound 57 was added tetrahydrofuran followed by the addition of compound 58 (Rbrepresents dialkylamino, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted heteroseksualci, optionally substituted aryl or optionally substituted heteroaryl) in the form of a solution in tetrahydrofuran, then added pyridine. Stirred the mixture at room temperature. After 23 hours, the reaction mixture was poured into water and 1 N. aqueous HCl and was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and was purified by column chromatography on silica gel (gradient hexane:ethyl acetate) with the formation of the target compounds.

Scheme 16

Stage 1 - Getting 2,6-debtor-3-nitrophenylamino (61):

[0228] 2,6-Debtor-3-nitrobenzoic acid 60 was converted into 2,6-debtor-3-nitro-phenylamine 61 according to the method shown in Scheme 15, the Stage 3.

Stage 2 - Getting connection 62:

[0229] 2,6-Debtor-3-nitrophenylamino 61 was subjected to interaction with the connection 55 according to the method shown in Scheme 15, Stage 4, with the formation of the target compound 62.

Stage 3 - Getting connection 57:

[0230] To the connection 62 in ethanol and tetrahydrofuran was added ~3 cc of a suspension of Raney Nickel in water. The reaction mixture was placed in Hydrator Parra in the atmosphere of hydrogen at 35 psi and with TLC monitored the consumption of raw materials. The reaction mixture was filtered and all volatile solvents were removed with the formation of the target compound in the form of a crude solid.

Stage 4 - Getting connection 59:

[0231] Compound 57 was subjected to interaction with the connection 58 according to the method shown in Scheme 15, Stage 6, with the formation of the target compound 59.

[0232] the Following compounds can be obtained according to Scheme 15 or figure 16:

6-Acetylamino-N-[2,6-debtor-3-(2-fluoro-benzosulfimide)-phenyl]-nicotinamide (P-0028),

6-Acetylamino-N-[2,6-debtor-3-(3-fluoro-benzosulfimide)-phenyl]-nicotinamide (P-0029),

6-Acetylamino-N-[3-(2,6-differentialtopologie)-2,6-debtor-enyl]-nicotinamide (P-0030),

6-Acetylamino-N-[3-(2,4-differentialtopologie)-2,6-debtor-phenyl]-nicotinamide (P-0031),

6-Acetylamino-N-[3-(2,5-differentialtopologie)-2,6-debtor-phenyl]-nicotinamide (P-0032),

6-Acetylamino-N-[2,6-debtor-3-(3-fluoro-4-methoxy-benzosulfimide)-phenyl]-nicotinamide (P-0033),

6-Acetylamino-N-[2,6-debtor-3-(4-trifluoromethyl-benzosulfimide)-phenyl]-nicotinamide (P-0034),

6-Acetylamino-N-[3-(4-diftormetilirovaniya)-2,6-differenl]-nicotinamide (P-0035),

6-Acetylamino-N-[3-(3-diftormetilirovaniya)-2,6-differenl]-nicotinamide (P-0036),

6-Acetylamino-N-[2,6-debtor-3-(4-isopropylbenzenesulfonyl)-phenyl]-nicotinamide (P-0037),

6-Acetylamino-N-[3-(4-tert-butylbenzenesulfonamide)-2,6-differenl]-nicotinamide (P-0038),

6-Acetylamino-N-[2,6-debtor-3-(4-propylbenzenesulfonyl)-phenyl]-nicotinamide (P-0039),

6-Acetylamino-N-[2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-nicotinamide (P-0040),

6-Acetylamino-N-[2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-nicotinamide (P-0041),

6-Acetylamino-N-[2,6-debtor-3-(dimethylaminomethylene)-phenyl]-nicotinamide (P-0042),

6-Acetylamino-N-[2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-nicotinamide (P-0043),

6-Acetylamino-N-[2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-nicotinamide (P-0044),

6-Acetylamino-N-[2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-phenyl]-nicotinamide (P-0045),

p> 6-Acetylamino-N-(3-cyclopentanecarbonyl-2,6-differenl)-nicotinamide (P-0046),

6-Acetylamino-N-[2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-nicotinamide (P-0047),

6-Acetylamino-N-[2,6-debtor-3-(3,3,3-Cryptor-propane-1-sulfonylamino)-phenyl]-nicotinamide (P-0048),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(2-fluoro-benzosulfimide)-phenyl]-amide (P-0049),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(3-fluoro-benzosulfimide)-phenyl]-amide (P-0050),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,6-debtor-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0051),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,4-debtor-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0052),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,5-debtor-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0053),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(3-fluoro-4-methoxy-benzosulfimide)-phenyl]-amide (P-0054),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-trifluoromethyl-benzosulfimide)-phenyl]-amide (P-0055),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(4-deformedarse-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0056),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(3-deformedarse-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0057),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-isopropyl-benzene is sulfonylamino)-phenyl]-amide (P-0058),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(4-tert-butyl-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0059),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-propyl-benzosulfimide)-phenyl]-amide (P-0060),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-amide (P-0061),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-amide (P-0062),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(dimethylaminomethylene)-phenyl]-amide (P-0063),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-amide (P-0064),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-amide (P-0065),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(tetrahydro-Piran-4-sulfonylamino)-phenyl]-amide (P-0066),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid (3-cyclopentanecarbonyl-2,6-debtor-phenyl)-amide (P-0067),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-amide (P-0068),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(3,3,3-Cryptor-propane-1-sulfonylamino)-phenyl]-amide (P-0069),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(2-fluoro-benzosulfimide)-phenyl]-amide (P-0070),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3(3-fluoro-benzosulfimide)-phenyl]-amide (P-0071),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,6-debtor-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0072),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,4-debtor-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0073),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,5-debtor-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0074),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(3-fluoro-4-methoxy-benzosulfimide)-phenyl]-amide (P-0075),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-trifluoromethyl-benzosulfimide)-phenyl]-amide (P-0076),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(4-deformedarse-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0077),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(3-deformedarse-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0078),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-isopropyl-benzosulfimide)-phenyl]-amide (P-0079),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(4-tert-butyl-benzosulfimide)-2,6-debtor-phenyl]-amide (P-0080),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-propyl-benzosulfimide)-phenyl]-amide (P-0081),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-amide (P-0082),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-amide (P-0083),

3H-Imides the[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(dimethylaminomethylene)-phenyl]-amide (P-0084),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-amide (P-0085),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-amide (P-0086),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(tetrahydro-Piran-4-sulfonylamino)-phenyl]-amide (P-0087),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid (3-cyclopentanecarbonyl-2,6-debtor-phenyl)-amide (P-0088),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-amide (P-0089),

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(3,3,3-Cryptor-propane-1-sulfonylamino)-phenyl]-amide (P-0090),

6-Acetylamino-N-[2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-nicotinamide (P-0118),

1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide (P-0119) and

3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide (P-0120).

[0233] These compounds in the following table, where column 1 is the connection number, in column 2 connection 55, which represents a carboxylic acid, used either in Stage 4 schemes of 15 or Stage 2 Scheme 16, in column 3 connection 58, representing sulphonylchloride used either at the Stage of 6 schemes of 15 or Stage 4 Circuit 16, and in column 4 - the final connection 59.

Example 12: a Study of kinase activity

[0234] Methods of the research activity of kinases, including, but not limited to, Fms, Kit, B-Raf, B-Raf V600E, B-Raf V600E/T529I and c-Raf-1, known in the art and described, for example, in the publication of U.S. patent US20070032519 and U.S. patent 11/473347 (see also international publication WO2007002433), the content of these documents are fully incorporated in the present description by reference, including all sections of the description, drawings, and tables, for any purpose.

[0235] Representative compounds which research conducted at least one of the above methods or similar methods, with the value of the IC50less than 10 microns in terms of the research presented in tables 2a (A-Raf), 2b (B-Raf), 2c (B-Raf V600E), 2d (c-Raf-1), 2e (Brk), 2f (Btk), 2g (Csk), 2h (Fak), 2i (Fms), 2j (Kdr), 2k (Kit), 2l (Lck), 2m (Lyn), 2n (Src), 2o (TrkA) and 2p (Yes).

Table 2a
Representative compounds with activity toward kinase A-Raf with IC50< 10 μm in terms of research
A-RafP-0001, P-0002, P-0004, P-0005, P-006, P-0008, P-0009, P-0010, P-0011, P-0012, P-0013, P-0015, P-0016, P-0017, P-0020, P-0021, P-0025, P-0026, P-0027
Table 2b
Representative compounds with activity toward kinase B-Raf with IC50< 10 μm in terms of research
B-RafP-0002, P-0004, P-0008, P-0011, P-0013, P-0015, P-0016, P-0017, P-0018, P-0027
Table 2c
Representative compounds with activity toward kinase B-Raf V600E with IC50< 10 μm in terms of research
B-Raf V600EP-0001, P-0002, P-0004, P-0005, P-0008, P-0011, P-0013, P-0015, P-0016, P-0017, P-0018, P-0020, P-0021, P-0025, P-0026, P-0027
Table 2d
Representative compounds with activity toward kinase c-Raf-1 with IC50< 10 μm in terms of research
c-Raf-1:P-0001, P-0002, P-0004, P-0008, P-0009, P-0011, P-0013, P-0015, P-0016, P-0017, P-0020, P-0021, P-0027

Table 2e
Representative compounds with activity toward kinase Brk with IC50< 10 μm in terms of research
Brk: P-0002
Table 2f
Representative compounds with activity toward kinase Btk with IC50< 10 μm in terms of research
Btk:P-0011
Table 2g
Representative compounds with activity toward kinase Csk with IC50< 10 μm in terms of research
Csk:P-0002
Table 2h
Representative compounds with activity toward kinase Fak with IC50< 10 μm in terms of research
Fak:P-0002
Table 2i
Representative compounds with activity toward kinase Fms with IC50< 10 μm in terms of research
Fms:P-0010, P-0026

Table 2j
Representative compounds with activity toward kinase Kdr with IC50< 10 μm in terms of research
Kdr:P-0011
Table 2k
Representative compounds with activity toward kinase Kit with IC50< 10 μm in terms of research
Kit:P-0011
Table 2l
Representative compounds with activity toward kinase Lck with IC50< 10 μm in terms of research
Lck:P-0002
Table 2m
Representative compounds with activity toward kinase Lyn with IC50< 10 μm in terms of research
Lyn:P-0002
Table 2n
Representative compounds with activity toward kinase Src with IC50< 10 μm in terms of research
Src:P-0002, P-0011

Table 2o
Representative compounds with activity toward kinase TrkA with IC50< 10 μm in terms of conducting the research is of
TrkA:P-0002, P-0011
Table 2p
Representative compounds with activity toward kinase Yes with IC50< 10 μm in terms of research
Yes:P-0002

Example 13: effect of compounds in combination with chemotherapeutic agents in four human cell lines cancer

[0236] the Compounds according to the present invention, such as compound of the formula I, in combination with standard chemotherapeutic agents such as 5-fluorouracil, carboplatin, dacarbazine, gefitinib, oxaliplatin, paclitaxel, SN-38, temozolomide or vinblastine can be explored for their ability to kill human cancer cells. Such studies are known in the art and described, for example, in the patent application U.S. 11/473347.

[0237] Additional examples of methods according to the invention can be found in the following applications: publication of patent applications U.S. 2006/058339; 2006/058340; 2007/0032519 and 11/473347, filed June 21, 2006 (equivalent to international publication WO 2007/002433), the content of these documents are fully incorporated in the present description by reference, including all sections of the description, boundaries and and tables, for all purposes.

[0238] the Contents of all patents and other documents referred to in the present description, included in the present description by reference, including any drawings and tables, to the same extent as if the reference to each of these documents was presented separately and all such documents available to the person skilled in the technical field.

[0239] To a person skilled in the art it is evident that the present invention can be subjected to various modifications provide benefits as specified in the present description and obvious. Methods, options and composition proposed in the present invention, illustrate the preferred implementations of the invention and do not limit the scope of the present invention. All possible modifications, obvious to those skilled in the art, are also within the present invention, described in paragraphs appended claims.

[0240] the Present invention characterized in the present description may be implemented in the absence of one element or several elements, limitation or limitations, not mentioned explicitly in the present description. For example, in each case, the term "comprising", "consisting essentially of" and "consisting of" may is be replaced by another or two other terms. So, if in a variant implementation of the invention uses one of these terms, the invention also includes other embodiments, where the term replaced by other terms. For example, one embodiment may include a way to "contain" the sequence of stages, and another embodiment may include a method, "essentially consisting of" the same sequence of stages, while the third embodiment can include a method, "consisting of" the same stages. Thus, it should be understood that although the present invention is characterized by involving a specific implementation options and possible additional features, all possible modifications and changes are described inventive concept are also within the present invention are described in the paragraphs included in the formula.

[0241] furthermore, if the characteristics or aspects of the invention described in terms of Markush groups or other groups of alternative structures for specialists in this field will be obvious that the invention thus also described from the point of view of the individual member or subgroup of members of the Markush group or other group.

[0242] Also, unless specified to the contrary, in case of carrying out the invention are provided by various numerical the values, additional implementations of the invention can be described in two different values at the end points of the range. Such ranges are also included in the scope of claims of the present invention.

[0243] Thus, the embodiments are also within the present invention and the following claims.

1. The compound having a chemical structure of formula I

or its salt, where
Ar represents optionally substituted heteroaryl;
R1in each case, independently selected from the group including halogen, lower alkyl, optionally substituted by one or more substituents selected from fluorine, lower alkoxy, fluoro-substituted lower alkoxy, monoalkylamines, dialkylamines,
-O-R5, -N(R5)-R6and-N(R5)-C(X)R7;
m represents 0 or 1;
n represents 0, 1 or 2;
R2represents hydrogen or halogen;
L2represents-S(O)2-;
R3represents lower alkyl, optionally substituted by fluorine, C3-6cycloalkyl, optionally substituted lower alkyl, 5 - or 6-membered nitrogen containing heteroseksualci, optionally substituted by one or more substituents selected from fluorine, lower alkyl, fluoro-substituted lower alkyl lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio or fluoro-substituted lower alkylthio, aryl, optionally substituted with halogen, lower alkyl, optionally substituted with halogen or lower alkoxy, optionally substituted with halogen, or heteroaryl, optionally substituted with halogen or lower alkyl;
L1selected from the group comprising-O-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)-, -(R11)-C(R12R13)-, -C(X)-N(R11)-, -N(R11)-C(X);
X represents O;
R11represents hydrogen;
R4represents hydrogen or lower alkyl;
R5and R6in each case, independently selected from the group including hydrogen, lower alkyl, cycloalkyl, heteroseksualci, aryl and heteroaryl, where each of which is optionally substituted by one or more substituents selected from fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines;
R7in each case, independently selected from the group comprising lower alkyl;
in each case, the term "lower alkyl", alone or in combination, means derived from alkane radical containing from 1 to 6 carbon atoms;
in each case, the term "lower alkoxy", alone or in combination, the means-O-lower alkyl, where the lower alkyl contains from 1 to 6 carbon atoms;
in each case, the term "lower alkylthio", separately or in combination, refers to-S-lower alkyl, where the lower alkyl contains from 1 to 6 carbon atoms;
in each case, the term "monoalkylamines", separately or in combination, refers to-NH-lower alkyl, where the lower alkyl contains from 1 to 6 carbon atoms;
in each case, the term "dialkylamino", separately or in combination, refers to-N(Rbb)(Rcc), where Rbband Rcceach independently represents a lower alkyl containing from 1 to 6 carbon atoms;
in each case, the term "cycloalkyl" refers to a saturated or unsaturated non-aromatic monocyclic, bicyclic or tricyclic systems carbon rings containing from 3 to 10 atoms in the ring;
in each case, the term "heteroseksualci" refers to a saturated or unsaturated non-aromatic cycloalkyl group containing from 5 to 10 atoms, where from 1 to 3 carbon atoms in the ring are replaced by heteroatoms selected from O, S and N, and optionally condensed with a benzene group or heteroaryl group containing from 5 to 6 atoms in the ring;
in each case, the term "aryl", alone or in combination, refers to monocyclic or bicyclic ring system containing aromatic hydrocarbons such as phenyl is whether naphthyl;
in each case, the term "heteroaryl", separately or in combination, refers to a monocyclic aromatic ring structure containing 5 or 6 atoms in the ring, or a bicyclic aromatic system containing from 8 to 10 atoms, containing from 1 to 4 heteroatoms, independently selected from the group comprising O, S and N.

2. The compound according to claim 1, where L1represents-N(R11)-C(X)and R2represents hydrogen, fluorine or chlorine.

3. The compound according to claim 2, where L1represents-N(R11)-C(O)-.

4. The compound according to claim 1, where L1represents-C(X)-N(R11)-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)- or-N(R11)-C(R12R13)-, a R2represents hydrogen, fluorine or chlorine.

5. The compound according to any one of claims 1, 2 and 3-4, whereselected from the group including,,,andwhereindicates the place of attachment of the specified ring Ar to L1;
p represents 0, 1, 2 or 3;
R16in each case, independently selected from the group including
-OH, -NH2, -CN, -NO2, -C(O)-NH2, -O-R17, -N(R19)-R17, -N(R19)-C(O)-R17, -C(O)-N(R19)-R7 ,
halogen, lower alkyl, where the lower alkyl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines;
R17in each case, independently selected from the group comprising lower alkyl, cycloalkyl, heteroseksualci, aryl and heteroaryl, where lower alkyl, cycloalkyl, heteroseksualci, aryl or heteroaryl optionally substituted by one or more substituents selected from the group comprising fluorine, lower alkoxy, fluoro-substituted lower alkoxy, lower alkylthio, fluoro-substituted lower alkylthio, monoalkylamines, dialkylamines;
R19in each case represents independently hydrogen or lower alkyl.

6. The compound according to claim 1, where the compound is chosen from the group including
6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-pyridin-3-ylbenzene,
N-(6-Acetylpiperidine-3-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-2-fluoro-N-(6-methoxypyridine-3-yl)-3-(propane-1-sulfonylamino)-benzamide,
N-(2-Acetylpiperidine-5-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-2-fluoro-N-(6-isopropylaminomethyl-3-yl)-3-(propane-1-sulfonylamino)-benzamide,
Pyrrolidin-1-carboxylic acid {5-[6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzo is ylamino]-pyridine-2-yl}-amide,
6-Chloro-N-(3,5-dimethylisoxazol-4-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-N-(6-cyclopentenopyridine-3-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-N-[5-(4-chlorophenyl)-2H-pyrazole-3-yl]-2-fluoro-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-2-fluoro-N-[6-(5-methylthiazole-2-ylamino)-pyridine-3-yl]-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-N-[5-(4-chlorbenzyl)-[1,3,4]thiadiazole-2-yl]-2-fluoro-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-quinoline-3-ylbenzene,
[2-[6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzoylamine]-4H-[1,3,4]thiadiazin-(5E)-ilidene]-acetic acid ethyl ester,
6-Chloro-N-(6-cyclopropylamino-3-yl)-2-fluoro-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-2-fluoro-3-(propane-1-sulfonylamino)-N-{6-[(thiophene-2-ylmethyl)-amino]-pyridine-3-yl}-benzamide,
N-(6-Benzylaminopurine-3-yl)-6-chloro-2-fluoro-3-(propane-1-sulfonylamino)-benzamide,
6-Chloro-2-fluoro-N-imidazo[1,2-and]pyridine-3-yl-3-(propane-1-sulfonylamino)-benzamide,
Propane-1-sulfonic {2,4-debtor-3-[(5-methylisoxazol-3-ylamino)-methyl]-phenyl}-amide,
N-{5-[2,6-Debtor-3-(propane-1-sulfonylamino)-benzylamino]-pyridine-2-yl}-acetamide", she
Propane-1-sulfonic acids [2,4-debtor-3-(quinoline-3-illuminometer)-phenyl]-amide,
Propane-1-sulfonic {3-[(6-chloropyridin-3-ylamino)-methyl]-2,4-differenl}-the Ministry of foreign Affairs,
Propane-1-sulfonic {2,4-debtor-3-[(6-methoxypyridine-3-ylamino)-methyl]-phenyl}-amide,
The quinoline-3-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide,
Propane-1-sulfonic {2,4-debtor-3-[(quinoline-3-ylmethyl)-amino]-phenyl}-amide,
Propane-1-sulfonic acids [2,4-debtor-3-(quinoline-3-intoximeter)-phenyl]-amide,
2,6-Debtor-3-(propane-1-sulfonylamino)-N-quinoline-3-ylbenzene,
6-Acetylamino-N-[2,6-debtor-3-(2-forbindelseshandtering)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(3-forbindelseshandtering)-phenyl]-nicotinamide,
6-Acetylamino-N-[3-(2,6-differentialtopologie)-2,6-differenl]-nicotinamide,
6-Acetylamino-N-[3-(2,4-differentialtopologie)-2,6-differenl]-nicotinamide,
6-Acetylamino-N-[3-(2,5-differentialtopologie)-2,6-differenl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(3-fluoro-4-methoxybenzenesulfonamide)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(4-triftormetilfullerenov)-phenyl]-nicotinamide,
6-Acetylamino-N-[3-(4-diftormetilirovaniya)-2,6-differenl]-nicotinamide,
6-Acetylamino-N-[3-(3-diftormetilirovaniya)-2,6-differenl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(4-isopropylbenzenesulfonyl)-phenyl]-nicotinamide,
6-Acetylamino-N-[3-(4-tert-butyl-benzosulfimide)-2,6-differenl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(4-propylen is azulfidinee)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(dimethylaminomethylene)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-phenyl]-nicotinamide,
6-Acetylamino-N-(3-cyclopentanecarbonyl-2,6-differenl)-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-nicotinamide,
6-Acetylamino-N-[2,6-debtor-3-(3,3,3-cryptochrome-1 sulfonylamino)-phenyl]-nicotinamide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(2-fluoro-benzosulfimide)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(3-fluoro-benzosulfimide)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,6-differentialtopologie)-2,6-differenl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,4-differentialtopologie)-2,6-differenl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(2,5-differentialtopologie)-2,6-differenl]-amide,
1H-Pyrrolo [2,3-b] pyridine-5-carboxylic acid [2,6-debtor-3-(3-fluoro-4-methoxy-benzosulfimide)-phenyl]-amide,
1H-Pirro is about[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-trifluoromethyl-benzosulfimide)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(4-deformedarse-benzosulfimide)-2,6-differenl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(3-deformedarse-benzosulfimide)-2,6-differenl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-isopropyl-benzosulfimide)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [3-(4-tert-butyl-benzosulfimide)-2,6-differenl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(4-propyl-benzosulfimide)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(dimethylaminomethylene)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-phenyl]-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid (3-cyclopentanecarbonyl-2,6-differenl)-amide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-amide,
1H-Pyrrolo[2,3-b]is iridin-5-carboxylic acid [2,6-debtor-3-(3,3,3-cryptochrome-1 sulfonylamino)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(2-fluoro-benzosulfimide)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(3-fluoro-benzosulfimide)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,6-differentialtopologie)-2,6-differenl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,4-differentialtopologie)-2,6-debtor-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(2,5-differentialtopologie)-2,6-differenl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(3-fluoro-4-methoxy-benzosulfimide)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-trifluoromethyl-benzosulfimide)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(4-deformedarse-benzosulfimide)-2,6-differenl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(3-deformedarse-benzosulfimide)-2,6-differenl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-isopropyl-benzosulfimide)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [3-(4-tert-butyl-benzosulfimide)-2,6-differenl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(4-propyl-benzosulfimide)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyridine-2-sulfonylamino)-phenyl]-the ID,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyridine-3-sulfonylamino)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(dimethylaminomethylene)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(piperidine-1-sulfonylamino)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(morpholine-4-sulfonylamino)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid (3-cyclopentanecarbonyl-2,6-differenl)-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(3,3,3-cryptochrome-1 sulfonylamino)-phenyl]-amide,
N-{5-[2,6-Debtor-3-(propane-1-sulfonylamino)-benzyloxy]-pyridine-2-yl}-acetamide", she
Propane-1-sulfonic acids[3-(2-aminopyridine-3-intoximeter)-2,4-differenl]-amide,
Propane-1-sulfonic acids[2,4-debtor-3-(1H-pyrrolo[2,3-b]pyridine-5-intoximeter)-phenyl]-amide,
N-{5-[2,6-Debtor-3-(4-triftormetilfullerenov)-benzyloxy]-pyridine-2-yl}-acetamide", she
N-[3-(2-Aminopyridine-3-intoximeter)-2,4-differenl]-4-triftoratsetilatsetonom,
N-[2,4-Debtor-3-(1H-pyrrolo[2,3-b]pyridine-5-intoximeter)-phenyl]-4-trifluoromethyl-benzosulfimide,
N-(6-Acetylpiperidine-3-yl-2,6-debtor-3-(2-forbindelseshandtering)-benzamid,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(3-forbindelseshandtering)-benzamid,
N-(6-Acetylpiperidine-3-yl)-3-(2,6-differentialtopologie)-2,6-diflorasone,
N-(6-Acetylpiperidine-3-yl)-3-(2,4-differentialtopologie)-2,6-diflorasone,
N-(6-Acetylpiperidine-3-yl)-3-(2,5-differentialtopologie)-2,6-diflorasone,
6-Acetylamino-N-[2,6-debtor-3-(3-fluoro-4-methoxybenzenesulfonamide)-phenyl]-nicotinamide,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-triftormetilfullerenov)-benzamid,
N-(6-Acetylpiperidine-3-yl)-3-(4-diftormetilirovaniya)-2,6-debtor-benzamid,
N-(6-Acetylpiperidine-3-yl)-3-(3-diftormetilirovaniya)-2,6-debtor-benzamid,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-isopropylbenzenesulfonyl)-benzamid,
N-(6-Acetylpiperidine-3-yl)-3-(4-tert-butyl-benzosulfimide)-2,6-debtor-benzamid,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(4-propylbenzenesulfonyl)-benzamid,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyridine-2-sulfonylamino)-benzamide,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyridine-3-sulfonylamino)-benzamide,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(dimethylaminomethylene)-benzamid,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(piperidine-1-sulfonylamino)-benzamide,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(morpholine-4-sulfonylamino)-benzo the Ministry of foreign Affairs,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(tetrahydropyran-4-sulfonylamino)-benzamide,
N-(6-Acetylpiperidine-3-yl)-3-cyclopentanecarbonyl-2,6-diflorasone,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(pyrrolidin-1 sulfonylamino)-benzamide,
N-(6-Acetylpiperidine-3-yl)-2,6-debtor-3-(3,3,3-cryptochrome-1 sulfonylamino)-benzamide,
6-Acetylamino-N-[2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-nicotinamide,
1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide,
3H-Imidazo[4,5-b]pyridine-6-carboxylic acid [2,6-debtor-3-(propane-1-sulfonylamino)-phenyl]-amide, and any salt of these compounds.

7. Pharmaceutical composition for treating diseases mediated by Raf kinase, containing a pharmaceutically acceptable carrier and a compound according to any one of claims 1 to 6.

8. Set for the treatment of diseases mediated by Raf kinase, containing a compound according to any one of claims 1 to 6 or a composition according to claim 7.

9. The use of compounds according to any one of claims 1 to 6 or a pharmaceutical composition according to claim 7 to obtain drugs for the treatment of a disease or condition mediated by the Raf.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new polycyclic compounds, pharmaceutically acceptable salts thereof of general formula wherein R1 -phenyl, pyridyl, optionally substituted, or C3-7-cycloalkyl; R2 -H, -CH2R3, -C(=O)R3, -C(=O)N(R4)R3, and -SO2-pyridyl, wherein R3-H, C1-6 alkyl, C2-6 alkenyl, C3-7-cycloalkyl, -(CH2)m-phenyl -(CH2)m-(5-, 6- or 9-member heterocyclyl with 1-3 heteroatoms N, O or S); m is equal to 0-6; R4 -H; X represents O or S; the alkyl, alkenyl, cycloalkyl, phenyl and heterocyclyl groups may be substituted by one or more substitutes. A together with atoms whereto attached forms phenyl or heteroaryl with 1 or 2 nitrogen atoms, optionally substituted; B-C means -CH2-(CH2)z-, wherein z is equal to 1 or 2; D represents -CRIIIRIV-, wherein RIII and RIV are identical, and mean CH3 or H; or RIII and RIV together with the atom C whereto attached form a 3-member cycloalkyl ring, a pharmaceutical composition containing them, and the use of the above compounds for treating viral RSV infections.

EFFECT: new polycyclic compounds are described.

24 cl, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to azaindole-indole derivatives and pharmaceutically acceptable salts thereof of general formula: Y=Z (G), wherein Y means a group of azaindole of formula (Yl) Z means a group of indole of formula (Z1) or (Z2) wherein the values "=", R, R1, R1', R2, R3, R4, R2', R3, R4', R5' are presented in cl. 1 of the patent claim.

EFFECT: compounds inhibit cycline-dependent kinase that enables using them in a pharmaceutical composition.

6 cl, 3 dwg, 9 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely to new 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives of formula I or pharmaceutically acceptable salts thereof, wherein R1 represents H; R2 represents (C1-3)alkyl; R3 represents (C1-4)alkyl optionally substituted by three halogen atoms; R4 represents H; X represents O; n is equal to 1 or 2 or 3; Y is specified in OH, NR5R6 and Z, wherein Z represents a saturated 5- or 6-member heterocyclic ring containing 1 heteroatom specified in NR7, wherein the ring can be substituted by oxo(C1-3)alkyl, hydroxy(C1-3)alkyl; or wherein Z represents an aromatic 5- or 6-member heterocyclic ring containing 1-2 heretoatoms specified in N wherein the ring can be substituted by (C1-3)alkyl; R5 and R6 optionally represent H, (C3-8)cycloalkyl or (C1-6)alkyl optionally substituted 1-2 times by halogen, OH, (C1-6)alkyloxy, CONR14R15, NR14R15 or a 6-member saturated heterocyclic group containing a heteroatom specified in NR8; or R5 and R6 together with a nitrogen atom whereto attached form a 5-10-member saturated heterocyclic ring optionally additionally containing 1, 3 heteroatoms specified in NR9, with the ring optionally substituted by OH, oxo, (C1-4)alkyl, hydroxy(C1-3)alkyl, CONR10R11 or NR10R11; R7 represents H; R8 represents (C1-3)alkyl; R9 represents H, (C1-3)alkyl, hydroxy(C1-3)alkyl, (C1-3)alkoxy(C1-3)alykl, (C1-6)alkylcarbonyl, (C1-6)alkyloxycarbonyl, CONR12R13 or a 6-member heteroaryl group containing 1-2 heteroatoms specified in N; R10 and R11 optionally represent H or (C1-3)alkyl; R12 and R13 optionally represent (C1-3)alkyl; or R14 and R15 optionally represent (C1-3)alkyl. Also, the invention refers to the use of 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivative of formula I and a pharmaceutical composition thereof.

EFFECT: there are prepared new 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives effective for treating osteoporosis, atherosclerosis, inflammation and immune disorders, such as rheumatoid arthritis, psoriasis and chronic pain, such as neuropathic pain .

9 cl, 31 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline compounds of formula (I) and physiologically acceptable acid addition salts and N oxides thereof, wherein R denotes a polycyclic group of formula (R) wherein * indicates the quinolinyl radical binding site; A denotes (CH2)a, where a equals 0, 1, 2 or 3; B denotes (CH2)b, where b equals 0, 1, 2 or 3; X' denotes (CH2)x where x equals 0, 1, 2 or 3; Y denotes (CH2)y where y equals 0, 1, 2 or 3; provided that a+b=1, 2, 3 or 4, x+y=1, 2, 3 or 4, and a+b+x+y=3, 4, 5, 6 or 7; Q denotes N; R1 denotes hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, phenyl-C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, phenoxycarbonyl or benzyloxycarbonyl, where phenyl rings in last two said groups are unsubstituted or carry 1, 2 or 3 substitutes selected from halogen, C1-C4-alkyl or C1-C4-halogenalkyl; R2 denotes hydrogen; R3 denotes hydrogen; p=0, 1 or 2; R4, if present, denotes C1-C4-alkyl and is bonded with X and/or Y, if p=2, two radicals R4, which are bonded with adjacent carbon atoms of X or Y, together can also denote a straight C2-C5-alkylene; q=0; n=0; m=0; X denotes S(O)2; which is located in position 3 of quinoline; Ar denotes a radical Ar1, wherein Ar1 is a phenyl, wherein the phenyl can be unsubstituted or can carry 1 substitute Rx wherein Rx denotes halogen, CN, C1-C6-alkyl, C1-C6-halogenalkyl, C1-C6-alkoxy, C1-C6-halogenalkoxy, C1-C6-alkylthio, C1-C6-halogenalkylthio, NRx1 Rx2, wherein Rx1 and Rx2 independently denote hydrogen, C1-C6-alkyl, or Rx1 and Rx2 together with a nitrogen atom form an N-bonded 5-, 6- or 7-member saturated heteromonocyclic ring or an N-boned 7-, 8-, 9- or 10-member saturated heterobicyclic ring, which are unsubstituted or carry 1, 2, 3 or 4 radicals selected from C1-C4-alkyl. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of treatment using the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel quinoline derivatives are obtained, which respond to modulation of the serotonin 5-HT6 receptor.

23 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(5-isopropoxy-1H-pyarazol-3-yl)-3H-imidazo[4,5-b]pyridine-5-amine or pharmaceutically acceptable salt thereof, having inhibiting activity with respect to Trk (tropomyosin-related kinase). The compounds can be used as a medicinal agent for treating cancer. The invention also relates to use of said compound of pharmaceutically acceptable salt thereof to produce a medicinal agent for treating cancer in a warm-blooded animal and a pharmaceutical composition containing said compound or pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, a solvent or an inert filler.

EFFECT: high efficiency of using the compound.

4 cl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: given invention refers to a compound of formula I, wherein W and Z represent CH; Y represents CH2; wherein R1 and R2 independently represent H, halogen, CH2F, CHF2, CF3, CF2CF3, or C1-C6alkyl; R' represents H; R3 and R4 independently represent H, or C1-C3alkyl, all mentioned C1-C3alkyl groups and mentioned C1-C6alkyl groups are independently substituted by one or two groups independently substituted by one or two groups independently specified in OH, halogen, C1-C3alkyl, OC1-C3alkyl or trifluoromethyl; q=1 or 0; R5 represents C1-C6alkyl; and to pharmaceutically acceptable salts thereof. Furthermore, the invention refers to a composition, a tablet and pharmaceutical syrup having potassium channel modulation activity and containing the compound of formula I, to a method of preventing and treating diseases that are affected by the activation of potentially opened potassium channels.

EFFECT: there are prepared and described the new biologically active compounds which may be effective in the prevention or treatment of diseases or disorders that are affected by potassium channel activity.

21 cl, 2 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), where A is C-R1b; R1a, R1b, R1c, R1d, R1e, R2, R3, R4, R5 and n are as described in claim 1 of the invention, as well as pharmaceutically acceptable salts thereof. Described also is a pharmaceutical composition having activity as glucocorticoid receptor modulators.

EFFECT: novel compounds are obtained and described, which are glucocorticoid receptor antagonists and useful for treating and/or preventing diseases such as diabetes, dyslipidaemia, obesity, hyptension, cardiovascular diseases, adrenal gland malfunction or depression.

24 cl, 210 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) or to its stereoisomers, or to a pharmaceutically acceptable salt, wherein Ra represents H or (C1-C6)alkyl; Rb is specified in an optionally substituted group consisting of -(CH2)n-aryl, -CH(CH3)-aryl, -(CH2)n-arylaryl, -(CH2)n-arylheteroaryl, -(CH2)n-(C3-C8) cycloalkyl, -(CH2)n-heteroaryl, -(CH2)n-heterocyclyl and -(C3-C8) cycloalkylaryl; or Ra and Rb taken together with a nitrogen atom form 2,3-dihydro-1H-isoindolyl, decahydroisoquinolinyl, optionally substituted piperidinyl or optionally substituted pyrrolidinyl; Y is specified in an an optionally substituted group consisting of 5,6,7,8-tetrahydro[1,6]naphthyridinyl, -NH-(CH2)n-heterocyclyl, wherein NH is attached to carbonyl, and -heterocyclylaryl, wherein heterocyclyl is attached to carbonyl; and n is equal to 0, 1 or 2; wherein each heterocyclyl represents an independent non-aromatic ring system containing 3 to 12 ring atoms, and at least one ring atom specified in a group consisting of nitrogen, oxygen and sulphur; wherein each heteroaryl represents an independent non-aromatic ring system containing 3 to 12 ring atoms and at least one ring atom specified in a group consisting of nitrogen, oxygen and sulphur; and wherein the optional substitutes are independently specified in a group consisting of C1-C6-alkyl, C1-C6-alkoxy, halogen, CN, CF3, OCF3, NH2, NH(CH3), N(CH3)2, hydroxy, cyclohexyl, phenyl, pyrrolidinyl, -C(O)-piperidinyl, -N(H)-C(O)-C1-C6-alkyl and N(H)-S(O)2-C1-C6-alkyl. The invention also describes a pharmaceutical composition having chemokine receptor antagonist activity and a method of treating such diseases, such as rheumatoid arthritis, psoriasis, lupus, etc.

EFFECT: there are prepared and described new chemical compounds that can be used as chemokine receptor antagonists and, as such, may be used in treating certain pathological conditions and diseases, particularly inflammatory pathological conditions and diseases and proliferative disorders and conditions, eg rheumatoid arthritis, osteoarthritis, multiple sclerosis and asthma.

23 cl, 59 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel crystalline modification of para-methoxyanilide of 6-hydroxy-4-oxo-2,4-dihydro-1H-pyrrolo-[3,2,1-ij]quinoline-5-carboxylic acid of formula: (I) , which is obtained by crystallisation from ethyl acetate, where values of interplanar distance (d) and relative reflection intensities (Irel) are given in claim 1.

EFFECT: novel crystalline modification exhibits a high diuretic effect.

2 dwg, 9 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

where: A is CA1; E is CE1; W is (CH2)n; Y is (CH2)P; n and p are independently equal to 0 or 1; R1 is a phenyl which is substituted with a phenyl {which is optionally substituted with a halogen, hydroxy, CH(O), CO2H, C1-4alkyl, C1-4alkyl-(N(C1-4alkyl)2), C1-4alkyl(NH2), C1-4alkyl(NH(C1-4alkyl)), C1-4hydroxyalkyl, CF3, C1-4alkylthio, C1-4alkyl(heterocyclyl) or C1-4alkylNHC(O)O(C1-4alkyl)} or a heterocyclyl; and the heterocyclyl is optionally substituted with C1-6alkyl; R2 is NHC(O)R3; and R3 is C1-4alkyl {substituted with NR7R8 or a heterocyclyl}, C3-7cycloalkyl (optionally substituted with a NR43R44 group) or a heteroaryl; where R7, R8, R43 and R44 are as defined in claim 1; wherein the heteroaryl is optionally substituted with a halogen, C1-4alkyl, CF3, C1-4alkoxy, OCF3, heterocyclyl or an amino(C1-4alkyl) group; R7 and R8 are independently C1-6alkyl; A1, E1 and G1 are independently hydrogen or halogen; unless otherwise stated, the heterocyclyl is optionally substituted with C1-6alkyl; R25 is C1-6alkyl; R50 is hydrogen or C1-6alkyl (optionally substituted with a NR51R52 group); R30, R36, R40, R42 or R44 is independently hydrogen, C1-6alkyl(optionally substituted with hydroxy, C1-6alkoxy, C1-6alkylthio, C3-7cycloalkyl (which is optionally substituted with hydroxy) or NR45R46), C3-7cycloalkyl (optionally substituted with a hydroxy(C1-6alkyl) group) or a heterocyclyl (optionally substituted with C1-6alkyl); R29, R35, R39, R41, R43, R45, R46 and R51 are independently hydrogen or C1-6alkyl; where the heterocyclyl is a non-aromatic 5- or 6-member ring containing one or two heteroatoms selected from a group comprising nitrogen and oxygen; and where the aryl is phenyl or naphthyl; and where the heteroaryl is an aromatic 5- or 6-member ring, optionally condensed with another ring (which can be carbocyclic and aromatic or non-aromatic), having one or two heteroatoms selected from a group comprising nitrogen, or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine to treat a PDE4-mediated disease state.

10 cl, 81 dwg, 15 tbl, 375 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: application describes prodrugs being 2-amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}thio)-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitryl derivatives, and a method for preparing them.

EFFECT: invention can find application in treating and/or preventing cardiovascular diseases.

8 cl, 4 tbl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of general formula III which possess the properties of JAK pathway inhibitors and JAK-kinase inhibitors. In formula III: X is specified in a group consisting of C1-C10alkyl, amino, halogen, carboxyl, carboxylic acid ester, C2alkynyl, substituted tri-C1-C6alkylsilyl; R represents hydrogen; the cycle A is specified in a group consisting of C6aryl, bicycloheptene, five-and sis-member mono- or 10-member bicyclic heteroaryl including 1 to 3 heteroatoms specified in a group of heteroatoms, including N, O or S, and five- or six-member mono- or 10-member bicyclic heterocycle, including 1 to 2 heteroatoms specified in a group of heteroatoms, including N or O; p means 0, 1, 2 or 3; each of R2 is independently specified in a group consisting of C1-C6alkyl, C1-C4alkyl substituted by 1 to 3 substitutes. The other substitute and radical values are specified in the patent claim.

EFFECT: compounds may be used in preparing a therapeutic agent for T-cell mediated autoimmune disease, for treating or preventing allograft rejection in a recipient, for treating or preventing a type IV hypersensitivity reactions, which includes administering the above agent containing the compound according to cl 1-11, in an amount effective to treat the autoimmune disease or the allograft rejection or the type IV hypersensitivity.

23 cl, 7 dwg, 12 tbl, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely to new 1,2-dihydroquinoline derivatives of general formula , or to a pharmaceutically acceptable salt thereof, wherein R1 represents a lower alkyl group; R2 represents a hydrogen atom; each of R3 and R4 represents a lower alkyl group; R5 represents a lower alkyl group; R6 represents a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group; X represents -CO-, -C(O)NR8 - or -S(O)2-; each of R7 and/or R8 may be identical or different, and represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower cycloalkyl group, a phenyl or naphthyl group, a saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, a lower alkoxy group, a phenoxy group; provided R7 and/or R8 represent a lower alkyl group, a lower alkoxy group, the mentioned lower alkyl group and lower alkoxy group may contain one or three groups specified in a halogen atom, a phenyl group, an unsubstituted monocyclic 6-member heterocyclyl with one heteroatom specified in a nitrogen atom, and 5 carbon atoms in a cycle, a lower alkoxy group, and -NRaRb as a substitute (substitutes); provided R7 and/or R8 represent a phenyl group, a saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, a phenoxy group, the mentioned phenyl group, saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, phenoxy group may contain one or two groups specified in a halogen atom, a lower alkyl group, a halogen-substituted lower alkyl group, a phenyl group, a hydroxyl group, a lower alkoxy group, a halogen-substituted lower alkoxy group, a lower alkylthio group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a lower alkylcarbonyloxy group, -NRaRb, a nitro group and a cyano group as a substitute (substitutes); Ra and Rb may be identical or different, and each of them represents a hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group; Y represents a lower alkylene group; Z represents an oxygen atom; p is equal to 2, provided p is equal to 2, R6 may be identical or different. The invention also relates to a pharmaceutical composition and a glucocorticoid receptor modulator of the compound of formula (1).

EFFECT: there are produced new 1,2-dihydroquinoline derivatives possessing glucocorticoid receptor binding activity.

7 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyrrol derivatives of formula (1): or a pharmaceutically acceptable salt thereof wherein the values A, R1-R3, n are specified in clause 1 of the patent claim.

EFFECT: compounds (1) inhibit activity against the interleukin IL-6 production that allows using them both in pharmaceutical compositions, and in a prophylactic drug for ocular inflammatory disease.

23 cl, 2 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted pyrimidin-5-yl carboxylic acids of formula I and can be used in organic chemistry. The method is realised by reacting N-substituted guanidines and hetarylamidines with ethoxymethylene derivatives of 1,3-ketoesters according to a scheme given below (where the substitutes are as defined in the claim).

EFFECT: improved method of producing substituted pyrimidin-5-yl carboxylic acids of formula I.

2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to a method of producing M-(1,5,3-dithiazepan-3-yl)amides of general formula (1) where R = p-C5H4N (a), (CH3)3CO (b), o-CH3OC6H4 (c), which involves reaction of N1,N1,N6,N6-tetramethyl-2,5-dithiahexane-1,6-diamine with a hydrazide of general formula RC(O)NHNH2 [R is as described above] in the presence of a samarium nitrate crystalline hydrate Sm(NO3)3·6H2O catalyst with molar ratio N1,N1,N6,N6-tetramethyl-2,5-dithiahexane-1,6-diamine:RC(O)NHNH2:Sm(NO3)3·6H2O=10:10:(0.3-0.7) at temperature of 65-75°C and atmospheric pressure in the mixture of solvents - ethyl alcohol and chloroform for 20-28 hours.

EFFECT: method of producing N-(1,5,3-dithiazepan-3-yl)amides with high selectivity and output, which can be used as biologically active compounds, selective sorbents and extractants of noble and precious metals.

1 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds for treating cell-proliferative disorders having formula (II): wherein the values R1,R2, X, A, B, R6, R7, R9 are specified in cl. 1 of the patent claim with the exception of the compound of formula: .

EFFECT: there are presented compounds possessing anticancer activity.

95 cl, 27 dwg, 11 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to a method of producing N-(1,5,3-dithiazepinan-3-yl)amides of general formula (1): where R = p-C5H4N (a), (CH3)3CO (b), o-CH3OC6H4 (c) which involves reaction of t-butyl-1,5,3-dithiazepinane with a hydrazide of general formula RC(O)NHNH2 [R is as described above] in the presence of an iron chloride crystalline hydrate catalyst FeCl3-6H2O in molar ratio t-butyl-1,5,3-dithiazepinane:RC(O)NHNH2:FeCl3-6H2O=10:10:(0.3-0.7) at temperature of 65-75°C and atmospheric pressure of a mixture of solvents - ethyl alcohol-chloroform for 40-48 hours.

EFFECT: novel method of producing N-(1,5,3-dithiazepinan-3-yl)amides with high selectivity and output, which can be used as biologically active compounds, selective sorbents and extractants of noble and precious metals.

1 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound selected from a group consisting of: 4-[(2-{[(2S)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-[(2-{[(2R)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-{[(6-{[(2R)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl} benzoic acid, 4-[(5-chlor-2-{[(2S)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-4-methylphenoxy)methyl]benzoic acid, 4-[(5-chlor-2-{[(2R)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-4-methylphenoxy)methyl]benzoic acid, 4-[(2-{[(2R)-3-fluor-2- methylpropyl](pyridin-2-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-[(2-{[(2S)-3-fluor-2- methylpropyl](pyridin-2-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-{[(6-{[(2R)-2-fluorobutyl](pyridin-2-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl} benzoic acid, 4-{[(6-{[(2S)-2-fluorobutyl](pyridin-2-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl}benzoic acid, 4-[(5-chlor-2-{[(2R)-2-fluoropropyl] (pyridin-3-ylsulfonyl)amino}-4-methylphenoxy)methyl]benzoic acid, 4-[(5-chlor- 2-{[(2S)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-4-methylphenoxy)methyl] benzoic acid, 4-[(2-{[(2S)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-[(2-{[(2R)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl] benzoic acid, 4-{[(6-{[(2S)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl} benzoic acid and 4-{[(6-{[(2R)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl}benzoic acid, or a pharmaceutically acceptable salt thereof. These compounds have an EP1 receptor antagonist effect and may be used for treating the dysfunction pollakiuria.

EFFECT: preparing the sulfonamide compounds with a strong EP1 receptor antagonist effect.

23 cl, 24 tbl, 31 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, specifically to novel 3-(trinitromethyl-ONN-azoxy)-4-nitraminofurazans of general formula I . In formula I, R is Me, or . The invention also relates to methods of producing compounds of formula I.

EFFECT: obtaining compounds which can be used as oxidants for rocket fuel and explosive compositions.

3 cl, 1 tbl, 3 ex

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