Cycloalkyl compounds - inhibitors of potassium channels function

FIELD: chemistry.

SUBSTANCE: compound of formula I , its diastereomers or salts, where dot line represents optional double bond, m and p independently stand for 0, 1, 2 or 3; R1 stands for H, -N(R8)-C(O)-NR6R7, -N(R8)-S(O)2-NR6R7, -N(R8)-C(O)-N(R8a)-S(O)2-NR6R7, etc.; R1a stands for H or group OH; or R1 or R1a together form oxo; or R1 and R1a together with carbon atom, to which they are bound, form optionally substituted oxo spiro-condensed heterocyclic group, representing fully saturated 5-member monocyclic group, containing 2 nitrogen atoms; R2 stands for heteroaryl, (heteroary)alkyl, representing 5-6-member aromatic ring, contaning 1 nitrogen atom and/or 1 atom of oxygen and/or sulphur, and optionally condensed with aryl ring; aryl, (aryl)alkyl, alkyl, alkenyl or cycloalkyl, representing partly or fully saturated C3-C6 monocyclic structure, any of which can be optionally, independently, substituted with one or more groups T1, T2 or T3; J stands for bond, C1-4 alkylene, R3 stands for -R5, -C(Z1)-R5, -N(R8a1)-C(Z1)-R5, -N(R8a1)-C(Z1)-O-R5, -N(R8a1)-S(O)2-R5; R4 stands for alkyl, halogenalkyl, cycloalkyl, aryl, which can be optionally condensed with heteroaryl 6-member ring, containing 1-2 heteroatoms, selected from group SO2, N, etc.; R5 stands for -NR6aR7a or heteroaryl, (heteroaryl)alkyl, representing 5-6-member aromatic ring, which contains 1-3 nitrogen atoms and/or 1 or 2 atoms of oxygen or sulphur, optionally condensed with heteroaryl ring, representing 6-member aromatic ring, containing 1 nitrogen atom, etc.; R6a, R7a independently represent H, alkyl, aryl, (aryl)alkyl, heteroaryl, representing 5-6-member aromatic ring, which contains 1-2 nitrogen atoms, optionally condensed with aryl or heteroaryl ring, representing 6-member aromatic ring with 1 nitrogen atom; any of which can be optionally, independently, substituted with one or more groups T1c, T2c or T3c; R6, R7, R8, R8a, R8a1 R8a2, and R9, independently, represent H, alkyl, hydroxy, alkoxy, (hydroxy)alkyl, (alkoxy)alkyl, (cyano)alkyl, (alkenyl)alkyl, -NR12R13, cycloalkyl, (cycloalkyl)alkyl, optionally condensed with aryl; aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, etc.; R10, R10a, R11 and R11a, independently, represent H, alkyl, aryl, (aryl)alkyl, , hydroxy, (hydroxy)alkyl; heteroaryl, (heteroaryl)alkyl, representing 5-member aromatic ring, which contains 2 nitrogen atoms, or R11 and R11a can together form oxogroup, or R10a can together with R11a form bond, or R10 can together with R9 form saturated 3-4-member cycle; R12 and R13, independently, represent H, alkyl; W represents =NR8a2, =N- CO2R8a2, =N- CN; X represents C(=O), C=N-CN; Z1represents =O, or =N-CN; RX represents one optional substituent, bound with any suitable carbon atom in cycle, independently selected from T1g, T2g or T3g. Compounds of formula I are applied for manufacturing medication for treatment of IKur-mediated disorders.

EFFECT: cycloalkyl compounds, useful as inhibitors of potassium channels function.

13 cl, 694 ex, 1 tbl

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

its diastereomers or salts, where

the dotted line represents an optional double bond, m and p independently represent 0, 1, 2 or 3;

R1denotes H,

,,,

,,

,

,,,

R1adenotes H or a group of IT;

or R1or R1atogether form oxo;

or R1and R1atogether with the carbon atom to which they are attached, form an optionally substituted exasperation heterocyclic group, which represents a fully saturated 5-membered monocyclic group containing 2 nitrogen atom;

R2indicates heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1 nitrogen atom and/or 1 oxygen atom and/or sulfur, and optionally condensed with aryl ring; aryl, (aryl)alkyl, alkyl, alkenyl or cycloalkyl, which is partially or fully saturated With3-C6monocyclic structure, any of which may be optionally independently substituted one or more groups T1T2or T3;

J denotes a bond, C1-4alkylen,

R3means

,,

,,,

R4denotes alkyl, halogenated, cycloalkyl, aryl that may be optionally condensed with a heteroaryl 6-membered ring containing 1-2 heteroatoms selected from the group of SO2N; heteroaryl, represents a 5-membered aromatic ring containing 1-2 nitrogen atom and/or 1 sulfur atom; any of which is optionally, independently, may be substituted by one or more groups T1b, T2bor T3b;

R5refers to-NR6aR7aor heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally fused with a heteroaryl ring, which represents a 6-membered aromatic ring containing 1 nitrogen atom; aryl, (aryl)alkyl, optionally condensed with cycloalkyl, heteroseksualnymi ring, which is fully or partially saturated 5-membered ring containing 1 nitrogen atom or 1-2 oxygen atom, or heteroaryl ring, which is a 5-6-membered aromatic ring containing 1-2 nitrogen atom and/or sulfur atom as a heteroatom; heterocycle, which represents a fully saturated or partially saturated 5-6-membered monocyclic system containing 1 atom of nitrogen or oxygen; alkyl cycloalkyl, (cycloalkyl)alkyl, optionally condensed with aryl, any of which may be optionally independently substituted one or more groups T1CT2Cor T3s;

R6a, R7aindependently represent H; alkyl; aryl; aryl(alkyl); heteroaryl, which represents a 5-6-membered aromatic ring containing 1-2 nitrogen atoms, optionally condensed with aryl or heteroaryl ring, which represents a 6-membered aromatic ring with 1 nitrogen atom; any of which may be optionally independently substituted one or more groups T1CT2Cor T3s;

R6, R 7, R8, R8a1, R8al, R8a2and R9independently represent H, alkyl, hydroxy, alkoxy, (hydroxy)alkyl, (alkoxy)alkyl, (cyano)alkyl, (alkenyl)alkyl, -NR12R13cycloalkyl, (cycloalkyl)alkyl, optionally condensed with aryl; aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally condensed with aryl or heteroaryl ring, which represents a 5-membered aromatic ring containing 2 nitrogen atom; heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur; any of which may be optionally independently substituted one or more groups T1dT2dor T3d;

or R6and R7or R6aand R7atogether with the nitrogen atom to which they are joined, can form a saturated 4-6 membered cycle which optionally contains 1 additional heteroatom selected from nitrogen and oxygen, and optionally, independently substituted with one or more groups T1d, T2dor T3d;

or one of R6and R7can connect with one of R8, R8Aor R9with the formation of saturated or unsaturated 5-8-membered cycle, optionally, independently substituted with one or more groups T1dT2dor T3d;

R10, R10a, R11and R11aindependently represent H, alkyl, aryl, (aryl)alkyl, hydroxy, (hydroxy)alkyl; heteroaryl, (heteroaryl)alkyl, represents a 5 - membered aromatic ring containing 2 nitrogen atom;

or R11and R11amay together form oxoprop;

or R10awith R11ato form the connection;

or R10with R9to form a saturated 3-4 membered cycle;

R12and R13independently represent H, alkyl;

W denotes =NR8a2, =N-CO2R8a2, =N-CN;

X denotes,,

Z1represents =O or =N-CN;

RXdenotes one optional Deputy associated with any suitable carbon atom in the cycle, independently selected from T1g, T2gor T3g;

T1-1gT2-2gand T3-3geach independently represent

(1) hydrogen or T6where T6means

(i) alkyl, (hydroxy)alkyl, (alkoxy)alkyl,

cycloalkyl, (cycloalkyl)alkyl, aryl, (aryl)alkyl, optionally condensed 5-membered fully saturated heterocyclization, sod is Rasim 2 oxygen atom; heteroaryl, or (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; or

(iii) a group (i), which, independently, substituted by one or more (preferably 1-3) the following groups (2)to(9) to determine the T1-1g, T2-2gand T3-3g

(2) HE or-FROM6,

(3) -SH or ST6,

(4) -C(O)tT6or-O-C(O)T6where t denotes 1 or 2;

(5) -S(O)tT6,

(6) halogen,

(7) cyano,

-T4-NT7T8,

-T4-N(T10)-T5-T6,

(10) oxo,

T4and T5each independently represent a single bond, -T11-C(O)-T12-,

T7T8and T10, each independently, represent hydrogen, alkyl or aryl;

T11and T12each independently represent a single bond,

provided that

(i) R2is other thanwhen simultaneously met both conditions (a) and (b):

(a)- (J-R3does; and

(b) R1denotes H, -OC(=O)NR6*R7*, -N(R8)C(O)NR6*R7*, -OC(=O)R4or R1and R1atogether form oxoprop; or R1and R1atogether with the carbon atom to which which they are attached, form a Spiro-condensed heterologous,

where R6* and R7*each independently represent H, aryl, alkyl, or heterocycle, which represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur;

R5does;

R8a1denotes H or alkyl; and

u denotes 0, 1, 2 or 3;

(vi) R2has a different meaning than optionally substituted phenyl or pyridyl, when simultaneously met both conditions, (j) and (k)

(j) R1adenotes H, hydroxy, a R1denotes N;

or R1aand R1together form oxo,

(k) -J-R3refers to a group -(CR15R16)-NR8a1-C(O)-R5*, -(CR15R16)-(CR17R18)-(CR19R20)- R5*, - (CR15R16)-(CR17R18)-C(O)-R5*,

where

R5*doeswhere

T1c*denotes a hydroxy, alkyl, foralkyl, cycloalkyl, (cycloalkyl)alkyl, alkoxy, feralcode, (alkoxy)alkyl, (alkoxy)alkoxy, (feralcode)alkyl, cycloalkane, (cycloalkyl)alkoxy, phenoxy, cyano, halogen, -NT7T8where T7and T8have the value defined above, -SH, -ST6where T6is C Uchenie by definition above, -S(O)tT6where t is set as defined above, -C(O)tT6;

T2C*denotes H, halogen, alkyl or alkoxy;

T3C*denotes H, halogen, alkyl, foralkyl, alkoxy, feralcode, cycloalkyl, (cycloalkyl)alkyl, cyano, heteroaryl, -NT7T8, -SH, -ST6, -S(O)tT6, -C(O)tT6or alkyl substituted by cyano, CO2T;

and

R15, R16, R17, R18, R19and R20independently represent H;

or R15and R16together form-CH2CH2-;

or together form a-CH2CH2-;

or R19and R20together form-CH2CH2-.

2. The compound according to claim 1, wherein R1means

,,,

,,,

where R7denotes heteroaryl, which represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur.

3. The compound according to claim 1, characterized in that

J denotes the relationship or1-4alkylen

R1means

H,, ,,

,

R1arepresents hydroxy;

R2denotes alkyl, alkenyl, benzyl, phenyl, thienyl or sensational, any of which may be optionally independently substituted one or more groups T1T2or T3;

R3means

,,,

and R5denotes alkyl, cycloalkyl, optionally substituted aryl, heteroaryl, which represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, NR6aR7aany of which may be optionally independently substituted one or more groups T1CT2Cor T3s.

4. The compound according to claim 1, characterized in that

R1means

(a)-N(R8)-SO2-NR6R7or-N(R8)-C(W)-NR6R7,

where

R6and R7independently represent

(i) N or

(ii) alkyl, cycloalkyl, NR12R13, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or ser is, heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur, alkoxy, (aryl)alkyl, (cycloalkyl)alkyl, (alkoxy)alkyl, each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl,

or R6and R7together with the nitrogen atom to which they are connected, with the formation of a saturated 4-6 membered cycle which optionally contains 1 additional heteroatom selected from nitrogen and oxygen, optionally substituted by one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)4T6)alkyl, (NT7 T8)alkyl, (cyano)alkyl, (aryl)alkyl; and

R8means

(i) N or

(ii) alkyl, cycloalkyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, (cycloalkyl)alkyl, heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur, each of which may be optionally independently substituted one or more groups from the series: HE, SH, 6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl,

(b) -N(R8)-C(Z)-N(R8a)-SO2-OH,

where

R4means

(ii) alkyl, cycloalkyl, aryl, heteroaryl, represents a 5-membered aromatic ring containing 1-2 nitrogen atom and/or 1 sulfur atom, each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT 6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, (aryl)alkyl, optionally condensed 5-membered fully saturated heterocyclization containing 2 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; and

R8, R8adenote, independently

(i) H; or

(ii) alkyl, cycloalkyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, (heterocycle)alkyl, heterocycle, which represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur, (cycloalkyl)alkyl, each of which may be optionally independently substituted one or more groups from the series: HE, SH, 6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)t 6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl; or

(C) or a group

;

R1adenotes N;

R2denotes phenyl, (phenyl)alkyl, naphthyl, thienyl, benzothiazyl, alkyl or alkenyl, each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl; J represents a bond, methylene or ethylene;

R3means

(a) -R5where R5denotes heteroaryl, which represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, heterocycle, which represents a fully saturated or partially saturated 5-6-membered monocyclic system containing 1 atom of nitrogen or oxygen; or-NR6aR7a, each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl;

(b) -C(Z1)-R5,

where

R5denotes aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, or-NR6aR7a; and R6aand R7aindependently represent

(i) H; or

(ii) alkyl, aryl, (aryl)alkyl, heteroaryl, which represents a 5-6-membered aromatic ring containing 1-2 nitrogen atoms, optionally condensed with aryl or heteroaryl ring, which represents a 6-membered aromatic ring with 1 nitrogen atom; each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)4sup> 6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl; or

(s) -N(R8a1)-C(Z1)-R5or-N(R8a1)-SO2-R5,

where

R5denotes aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, heterocycle, which represents a fully saturated or partially saturated 5-6-membered monocyclic system containing 1 atom of nitrogen or oxygen; alkyl, cycloalkyl, each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl; and

R8a1means

(i) H; or

(ii) alkyl, cycloalkyl, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally condensed with aryl or heteroaryl ring, pre the excitation 5-membered aromatic ring, containing 2 nitrogen atom; heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur; (cycloalkyl)alkyl, (aryl)alkyl, each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl,

R5denotes alkyl, cycloalkyl, heteroaryl, which represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, or-NR6aR7aany of which may be optionally independently substituted one or more groups T1CT2Cor T3s; R6a, R7aindependently represent H, aryl, heteroaryl, which represents a 5-6-membered aromatic ring containing 1-2 nitrogen atom, (aryl)alkyl, alkyl, any of which may be optionally independently substituted one or more groups T1CT2Cor T3s;

R6, R7independently represent H, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally condensed with aryl or heteroaryl ring, which represents a 5-membered aromatic ring containing 2 nitrogen atom; cycloalkyl, heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur, (aryl)alkyl, alkyl, any of which may be optionally independently substituted with one or more groups T1dT2cor T3c,

or R6and R7or R6aand R7atogether with the nitrogen atom to which they are joined, can form a saturated 4-6 membered cycle.

5. The compound according to claim 1, characterized in that

R1means

(a) hydrogen;

(b) -O-C(O)-NR6R7, -N(R8)-SO2-NR6R7or-N(R8)-C(W)-NR6R7,

where R6and R7independently represent

(i) N or

(ii) alkyl, cycloalkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, obazatelno condensed with aryl or heteroaryl ring, represents a 5-membered aromatic ring containing 2 nitrogen atom; cycloalkyl, (cycloalkyl)alkyl, heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur; alkoxy, (alkoxy)alkyl or NR12R13, each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6, NR12R13, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl,

or R6and R7together with the nitrogen atom to which they are joined, can form a saturated 4-6 membered cycle which optionally contains 1 additional heteroatom selected from nitrogen and oxygen, optionally substituted by one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 atom sour is kind; (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl; and

R8means

(i) N or

(ii) alkyl, cycloalkyl, aryl, (cycloalkyl)alkyl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally condensed with aryl or heteroaryl ring, which represents a 5-membered aromatic ring containing 2 nitrogen atom; heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur; each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6With(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom, (OH)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl,

(C) or a group

;

R1adenotes N;

R2hereafter the denotes phenyl, (phenyl)alkyl, naphthyl, thienyl, benzothiazyl, alkyl or alkenyl, each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom, (OH)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(Oh)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl;

J represents a bond, methylene or ethylene;

R3means

(a) -R5where R5denotes heteroaryl, which represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally fused with a heteroaryl ring, which represents a 6-membered aromatic ring containing 1 nitrogen atom; heterocycle, which represents a fully saturated or partially saturated 5-6-membered monocyclic system containing 1 atom of nitrogen or oxygen; each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)Ala is l, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom, (OH)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl;

(b) -C(Z1)-R5,

where Z1represents =N-CN;

R5denotes aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally fused with a heteroaryl ring, which represents a 6-membered aromatic ring containing 1 nitrogen atom; or-NR6aR7a; and

R6aand R7aindependently represent

(i) H; or

(ii) alkyl, aryl, (aryl)alkyl, heteroaryl, which represents a 5-6-membered aromatic ring containing 1-2 nitrogen atoms, optionally condensed with aryl or heteroaryl ring, which represents a 6-membered aromatic ring with 1 nitrogen atom; each of which may be optionally independently substituted one or more groups from the series: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 13 nitrogen atom and/or 1 oxygen atom, (HE)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(Oh)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl; or (c)-N(R8a1)-C(Z1)-R5or-N(R8a1)-SO2-R5,

where Z1represents =N-CN;

R5denotes aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally fused with a heteroaryl ring, which represents a 6-membered aromatic ring containing 1 nitrogen atom; heterocycle, which represents a fully saturated or partially saturated 5-6-membered monocyclic system containing 1 atom of nitrogen or oxygen; alkyl, cycloalkyl, each of which may be optionally independently substituted one or more groups from a number of: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom, (OH)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl; and

R8a1means

(i) H; or

(ii) alkyl, cycloalkyl, aryl, (cyclea the keel)alkyl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally condensed with aryl or heteroaryl ring, which represents a 5-membered aromatic ring containing 2 nitrogen atom; heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur; each of which may be optionally independently substituted one or more groups of range: HE, SH,6ST6C(O)tT6NT7T8, cyano, halogen, oxo, alkyl, halogenated, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom, (OH)alkyl, (SH)alkyl, (FROM6)alkyl, (ST6)alkyl, (C(O)tT6)alkyl, (NT7T8)alkyl, (cyano)alkyl, (aryl)alkyl,

R5denotes alkyl, cycloalkyl, heteroaryl, which represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally fused with a heteroaryl ring, which represents a 6-membered aromatic ring containing 1 nitrogen atom; aryl, or-NR6aR7aeach of to the which can be, optionally, independently substituted with one or more groups T1CT2Cor T3s.

R6a, R7aindependently represent H, aryl, heteroaryl, which represents a 5-6-membered aromatic ring containing 1-2 nitrogen atom, (aryl)alkyl, alkyl, any of which may be optionally independently substituted one or more groups T1CT2Cor T3s;

R6, R7independently represent H, aryl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally condensed with aryl or heteroaryl ring, which represents a 5-membered aromatic ring containing 2 nitrogen atom; cycloalkyl, heterocycle, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur, (aryl)alkyl, alkyl, any of which may be optionally independently substituted with one or more groups T1d, T2dor T3d,

or R6and R7or R6Aand R7atogether with the nitrogen atom to which they are linked, form a saturated 4-6 membered cycle which optionally contains 1 additional heteroatom selected from nitrogen and oxygen, optional is entrusted, independently substituted by one or more groups T1dT2dor T3d.

6. The compound according to claim 1, characterized in that

m denotes 1;

p denotes 1 or 2;

R1denotes H,

,,,

,,,

R1adenotes H or a group of IT;

or R1or R1atogether form oxo;

or R1and R1atogether with the carbon atom to which they are attached, form an optionally substituted exasperation heterocyclic group, which represents a fully saturated 5-membered monocyclic group containing 2 nitrogen atom;

R2denotes heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1 nitrogen atom and/or 1 oxygen atom and/or sulfur, and optionally condensed with aryl ring; aryl, (aryl)alkyl, alkyl or cycloalkyl, which is partially or fully saturated With3-C6monocyclic structure, any of which may be optionally independently substituted one or more groups T1T2or T3;

J hereafter which includes communication, C1-4alkylen;

R3means

,,

,,,

R4denotes alkyl, halogenated, cycloalkyl, aryl that may be optionally condensed with a heteroaryl 6-membered ring containing 1-2 heteroatoms selected from the group of SO2N; or heteroaryl, represents a 5-membered aromatic ring containing 1-2 nitrogen atom and/or 1 sulfur atom; any of which is optionally independently, may be substituted by one or more groups T1bT2bor T3b;

R5refers to - NR6aR7aor heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally fused with a heteroaryl ring, which represents a 6-membered aromatic ring containing 1 nitrogen atom; aryl, (aryl)alkyl, optionally condensed with cycloalkyl, heteroseksualnymi ring, which is fully or partially saturated 5-membered ring containing 1 nitrogen atom or 1-2 oxygen atom, or heteroaryl ring, which is a 5-6-membered aromatic ring containing 1-2 atoms AZ is TA and/or sulfur atom as a heteroatom; heterocycle, which represents a fully saturated or partially saturated 5-6-membered monocyclic system containing 1 atom of nitrogen or oxygen; alkyl, cycloalkyl, (cycloalkyl)alkyl, any of which may be optionally independently substituted one or more groups T1CT2Cor T3c;

R6a, R7aindependently represent H; alkyl; aryl; aryl(alkyl); heteroaryl, which represents a 5-6-membered aromatic ring containing 1-2 nitrogen atoms, optionally condensed with aryl or heteroaryl ring, which represents a 6-membered aromatic ring with 1 nitrogen atom; any of which may be optionally independently substituted one or more groups T1CT2Cor T3c;

R6, R7, R8, R8a, R8a1, R8a2and R9independently represent H, alkyl, hydroxy, alkoxy, (hydroxy)alkyl, (alkoxy)alkyl, (alkenyl)alkyl, -NR12R13cycloalkyl, (cycloalkyl)alkyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-4 nitrogen atoms and/or 1 or 2 oxygen atom or sulfur, optionally condensed with aryl or heteroaryl ring, which represents a 5-membered aromatic ring containing 2 nitrogen atom; hetaeras the cyclo, (heterocycle)alkyl, a represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur, any of which may be optionally independently substituted one or more groups T1dT2dor T3d;

or R6and R7or R6aand R7atogether with the nitrogen atom to which they are joined, can form a saturated 4-6 membered cycle, optionally, independently substituted with one or more groups T1dT2dor T3d;

or one of R6or R7can connect with one of R8, R8aor R9with the formation of saturated or unsaturated 5-8-membered cycle, optionally, independently substituted with one or more groups T1dT2dor T3d.

R10, R10a, R11and R11aindependently represent H, alkyl, aryl, (aryl)alkyl, hydroxy, (hydroxy)alkyl; heteroaryl, (heteroaryl)alkyl, represents a 5-membered aromatic ring containing 2 nitrogen atom;

or R10awith R11ato form the connection;

or R10with R9to form a saturated 3-4 membered cycle;

R12and R13independently represent H, alkyl,

W denotes =NR8a2, =N-CO2R8a2, =N-CN;

means

,,

Z1means =O, =N-CN;

RXdenotes one optional Deputy associated with any suitable carbon atom in the cycle, independently selected from T1g, T2gor T3g;

T1-1g, T2-2gand T3-3geach independently represent

(1) hydrogen or T6where T6means

(i) alkyl, (hydroxy)alkyl, (alkoxy)alkyl,

cycloalkyl, (cycloalkyl)alkyl, aryl, (aryl)alkyl, optionally condensed 5-membered fully saturated heterocyclization containing 2 oxygen atom; heteroaryl or (heteroaryl)alkyl, represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom;

or

(iii) a group (i), which, independently, substituted by one or more (preferably 1-3) the following groups (2)to(9) to determine the T1-1gT2-2gand T3-3g

(2) HE or-FROM6,

(3) -SH or-ST6,

(4) -C(O)tT6or-O-C(O)T6where t denotes 1 or 2;

(5) -S(O)tT6,

(6) halogen,

(7) cyano,

-T4-NT7T8,

-T4-N(T10)-T5-T6,

(10) oxo,

T4and T5, each independently, is oznachaet single bond, -T11-C(O)-T12-,

T7T8and T10each independently, represent hydrogen, alkyl or aryl;

T11and T12each independently represent a single bond, provided that

(i) R2is other thanwhen simultaneously met both conditions (a) and (b):

(a)- (J-R3does; and

(b) R1denotes H, -OC(=O)NR6*R7*, - N(R8)C(O)NR6*R7*, -OC(=O)R4or R1and R1atogether form oxoprop; or R1and R1atogether with the carbon atom to which they are attached, form a Spiro-condensed heterologous,

where

R6* and R7*each independently represent H, aryl, alkyl, or heterocycle, which represents a fully saturated or partially saturated 5-6 membered monocyclic system containing 1 nitrogen atom and/or sulfur;

R5does;

R8denotes H or alkyl; and

u denotes 0, 1, 2 or 3;

(vi) R2has a different meaning than optionally substituted phenyl or pyridyl, when simultaneously met both conditions, (j) and (k)

(j) R1adenotes H, hydroxy, a R1denotes N;

or R1a and R1together form oxo,

(k) -J-R3refers to a group -(CR15R16)-NR8a1-C(O)-R5*, -(CR15R16)-(CR17R18)-(CR19R20)-R5*, -(CR15R16)-(CR17R18)-C(O)-R5*,

where

R5* denoteswhere

T1C*denotes a hydroxy, alkyl, foralkyl, cycloalkyl, (cycloalkyl)alkyl, alkoxy, feralcode, (alkoxy)alkyl, (alkoxy)alkoxy, (feralcode)alkyl, cycloalkane, (cycloalkyl)alkoxy, phenoxy, cyano, halogen, -NT7T8where T7and T8have the value defined above, -SH, -ST6where T6is set as defined above, -S(O)tT6where t is set as defined above, -C(O)tT6;

T2C*denotes H, halogen, alkyl or alkoxy;

T3s* denotes H, halogen, alkyl, foralkyl, alkoxy, feralcode, cycloalkyl, (cycloalkyl)alkyl, cyano, heteroaryl, which represents a 5-6-membered aromatic ring containing 1-3 nitrogen atom and/or 1 oxygen atom; NT7T8, -SH, -ST6, -S(O)tT6, -C(O)tT6or alkyl substituted by cyano, CO2T6;

and

R15, R16, R17, R18, R19and R20independently represent H;

or R15/sup> and R16together form-CH2CH2-;

or R17and R18together form-CH2CH2-;

or R19and R20together form-CH2CH2-.

7. The use of at least one compound according to claim 1 for the manufacture of tools for the treatment of IKur-associated disorders.

8. The use according to claim 7, characterized in that the IKur-condition is an arrhythmia, gastrointestinal disorders or inflammatory or immunological disease.

9. The use of claim 8, wherein the atrial fibrillation is a supraventricular extrasystole.

10. The use according to claim 9, wherein the supraventricular arrhythmia is an atrial fibrillation or atrial flutter.

11. The use according to claim 7, wherein the gastrointestinal infringement is reflux esophagitis or motility disorders.

12. The use according to claim 7, wherein the inflammatory disease is a chronic obstructive pulmonary disease.

13. The use of at least one compound according to claim 1 for the manufacture of tools for the treatment of diabetes, cognitive impairment, or epilepsy.



 

Same patents:

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to agonist of receptor of glucagone-like peptide-1, which can be applied for treatment of diseases, caused by disturbance of glycometabolism, such as type II diabetes, insensibility to insulin or obesity. In structural formula each of Ar1 and Ar2 independently represents substituted phenyl, and group-substituents represent one, two or three groups selected from C1-C6alkoxyl, C1-C6-alkanoylamino, which is substituted with hydroxyl (which contains groups-substituents, including hydroxyl); C3-C6-cyclolkanoylamino, C2-C6-lkenoylamino; banzoylamino, banzyloxy C1-C6-alkanoylamino, thenoyloxy, tret-butoxyformamido, adamantanformamido; and mandeloylamino; X represents O; Y represents O. Invention also relates to method of obtaining agonist, and to its application for obtaining medication for treatment of diseases caused by disturbance of glycometabolism.

EFFECT: obtaining medication for treatment of diseases caused by disturbance of glycometabolism.

8 cl, 4 ex, 2 tbl, 2 dwg

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds of formula (I), its pharmaceutically acceptable salts, possessing qualities of chemokine receptor modulators. Compounds can be applied for asthma, allergic rhinitis, COLD, inflammatory intestinal disease, irritated intestine syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis or cancer. In compound of formula (I) , R1 represents group selected from C1-8alkyl, said group is possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4 , -NR5R6 , phenyl, phenyl is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4,-NR5R6,-SR10,C1-6alkyl and trifluoromethyl; R2 represents group selected from C1-8alkyl, said group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-(C1-6alkyl)-N-(phenyl)amino; R3 represents hydrogen, R4 represents hydrogen or group selected from C1-6alkyl and phenyl, R5 and R6, independently, represent hydrogen or group selected from C1-6alkyl and phenyl, said group being probably substituted with 1, 2 or 3 substituents, independently selected from -OR14, -NR15R16, -COOR14,-CONR15R16, or R5 and R6 together with nitrogen atom, to which they are bound, form 4-7-member saturated heterocyclic ring system, possibly containing additional heteroatom, selected from oxygen and nitrogen atoms, ring possibly being substituted with 1, 2 or 3 substituents, independently selected from -OR14, -COOR14,-NR15R16,CONR15R16 and C1-6alkyl; R10 represents hydrogen or group selected from C1-6alkyl or phenyl; and each from R7, R8, R9, R14, R15, R16 independently represents hydrogen, C1-6alkyl or phenyl; X represents hydrogen, halogeno; Rx represents trifluoromethyl, -NR5 R6 , phenyl, naphtyl, heteroaryl, heteroring can be partly or fully saturated, and one or more ring carbon atoms can form carbonyl group, each phenyl or heteroaryl group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR4, -NR5R6, -CONR5R6, -COR7, -COOR7, -NR8COR9, -SR10, -SO2R10, -SO2NR5R6, -NR8SO2R9, C1-6alkyl or trifluoromethyl; or Rx represents group selected from C1-6alkyl, said group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6, phenyl or heteroaryl, where heteroaryl represents monocyclic or bicyclic aryl ring, containing from 5 to 10 ring atoms, from which 1, 2 or 3 ring atoms are selected from nitrogen, sulfur or oxygen. Invention also relates to methods of obtaining compounds, versions, pharmaceutical composition and application for manufacturing medications using compounds of invention.

EFFECT: obtaining novel compounds of formula (I), its pharmaceutically acceptable salts, possessing properties of chemokine receptor moduators.

25 cl, 138 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to compounds of formula (I) or their pharmaceutically acceptable salts, where Q represents optionally substituted with 1-3 substituents, determined in formula, phenyl or pyridyl or pyrodazinyl; R2 represents C1-6alkyl or aminogroup, determined in item 1 of formula or C1-6alkyl, substituted with said aminogroup; bond between oxygen atom O* and adjacent carbon atom C1 or (i) is double bond, which determines carbonyl group [C(=O)], where R6 represents C1-6alkyl or cyclopropyl; or (ii) represents simple bond, where, in case of simple bond, said oxygen atom O*, is in addition bound to group R6 and, taken together with R6 and with adjacent nitrogen atom, determines optionally substituted with C1-6alkyl, oxadiazolyl ring, bond between C1 and adjacent nitrogen atom being double bond.

EFFECT: obtaining medications which are useful in obtaining medications for treatment of conditions connected with p38 kinase and/or in obtaining medications for treatment of inflammatory diseases or conditions in patient.

8 cl, 6 tbl, 88 ex

FIELD: medicine; pharmacology.

SUBSTANCE: presented are anilides of nicotinic acid of general formula I , where R means atom of hydrogen, halogen or benzyloxy-group, R' means atom of hydrogen or halogen, X means 2-furyl, 2-pyridyl, 3-pyridyl unsubstituted or substituted with phenyl halogen atom with fungicidal activity.

EFFECT: new compound are effective for hazardous fungi.

3 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: in pyridylmethylanilides of heterocyclic acids of general formula I R stands for atom of hydrogen halogen or benzyloxy-group, R' stands for atom of hydrogen or halogen, X stands for 2-phuryl or 2-pyridyl.

EFFECT: increase of compound efficiency against harmful fungi.

1 cl, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: in novel compounds of formula (I) X stands for C, N; R1 stands for H or (lower) alkyl, R2 stands for 9(lower) alkyl, -(CH2)n-R2a; R2a stands for C3-C8cycloalkyl, optionally and independently mono-, di-, tri- or tetrasubstituted with the following groups: OH, (lower)alkyl, (lower)alkoxy, 5- or 6-member single-valent saturated heterocyclic ring, containing from one to two heteroatoms, independently selected from nitrogen, oxygen and sulfur, said heterocyclic ring being optionally and independently mono-, di- or tri-substituted with the following groups: OH, (lower)alkyl, (lower)alkoxy, 5- or 6-member single-valent heteroaromatic ring, containing from one to two heteroatoms, independently selected from nitrogen, oxygen and sulfur, said heteroaromatic ring being optionally and independently mono-, di- or tri-substituted with the following groups: OH, (lower) alkyl, (lower)alkoxy, C3-C6cycloalkyl; R3 stands for C3-C6cycloalkyl, being optionally and independently mono-, di- or tri- or tetra-substituted with groups: OH, (lower) alkyl, (lower)alkoxy, phenyl, which optionally and independently is mono-, di- or tri- or tetra-substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, (lower)alkylamino, halogenated (lower)alkyl, halogenated (lower)alkoxy, nitro; R4 stands for 5- or 6-member single-valent heteroaromatic ring, containing from one to two nitrogen heteroatoms, said heteroaromatic ring being optionally and independently mono-, di- or tri- substituted with the following groups: OH, (lower) alkyl, (lower)alkoxy, halogen; naphtyl, which optionally and independently is mono-, di- or tri- substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, (lower)alkylamino, halogenated (lower)alkyl, halogenated (lower)alkoxy, nitro; or phenyl, which optionally and independently is mono-, di- or tri- substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, nitro, halogenated (lower)alkyl, halogenated (lower)alkoxy, cyano, (lower)alkylsulfonyl, -NR7R8; or two neighbouring substituents in said phenyl residue together represent -O-(CH2)p-O-, -(CH2)2-C(O)NH-; R5 and R6 each independently represent H, (lower)alkyl; R7 and R8 each independently represent hydrogen, (lower)alkyl, or R7 and R8 together with nitrogen atom, to which they are bound, form 5- or 6- member saturated or aromatic heterocyclic ring, which optionally contain nitrogen as additional heteroatom; said saturated or aromatic heterocyclic ring, being optionally substituted with the following groups: OH, (lower)alkyl, (lower)alkoxy; m equals 1 or 2, n equals 0 or 1, p equals 1, 2 or 3; or their pharmaceutically acceptable salts.

EFFECT: increased antagonistic activity of compounds.

19 cl

FIELD: chemistry.

SUBSTANCE: invention pertains to new compounds with general formula: , where R is -(CH2)n-A, where A: where each of B and C independently represent phenyl or phenyl substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, -OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NH-C(O)-(C1-C6alkyl) and -NO2; or n equals an integer from 0 to 3; n1 equals an integer from 1 to 3; n2 equals an integer from 0 to 4; n3 equals an integer from 0 to 3; n4 equals an integer from 0 to 2; X1 is chosen from a chemical bond -S-, -S(O)2-, -NH-, -NHC(O)- and -C=C-, R1 is chosen from C1-C6alkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, tetrahydropyranyl, CN, -N(C1-C6alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, naphtyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolydinyl, thiomopholinyl, tetrazolyl, benzoxazolyl, imidazolidine-2-thionyl, 7,7-dimethylbicyclo[2.2.1]heptane-2-onyl, benzo[1.2.5]oxadiazolyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and pyrrolyl, each of which can be optionally substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NO2, -SO2(C1-C3alkyl), -SO2NH2, -SO2N(C1-C3alkyl)2, -COOH, -CH2-COOH, pyridyl, 2-methylazolyl, morpholino, 1-chloro-2-methylpropyl, phenyl, (optionally substituted with one or more halogens), benzyloxy, and , X2 selected from -O-, -CH2-, -S-, -SO-, -SO2-, -NH- and , R2 represents a ring group, chosen from a phenyl or thienyl group. Each ring group is substituted with a group with formula -(CH2)n4-CO2H; and besides that, the ring group can optionally be substituted with 1 or 2 extra substitutes, independently chosen from halogen, - C1-C6alkyl and -C1-C6alkoxy; R3 is chosen from H, halogen and -NO2; R4 is chosen from H, halogen and morpholino; or its salt form, used in pharmaceuticals. The invention also relates to pharmaceutical compositions, to methods of treatment, and to compounds with formula (A).

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on them, which have inhibiting effect on cytosolic phospholipase A2.

45 cl, 300 ex

FIELD: medicine; pharmacology.

SUBSTANCE: subjects of invention are also pharmaceutical drugs or agents for prophylaxis and treatment of neuropathy, increase of production and treatment of the neurotrophic factor, for pain relief, for nerve protection, for prophylaxis and treatment of the neuropathic pain containing compound of the formula or of the formula . In the compounds of the formulas (I) and (II) symbols and radicals have the meanings mentioned in the invention formula. The specified agents have an excellent effect and low toxicity. There are also proposed ways of treatment and prophylaxis of the abovementioned conditions by means of the compounds of the formula (I) or (II) and application of these compounds for production of the abovementioned agents. Besides, one has proposed methods for production of the specified compounds and intermediate pyrazol compounds.

EFFECT: compound has an effect increasing production and secretion of the neurotrophic factor.

46 cl, 1 tbl, 233 ex

Carbonyl compounds // 2337099

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to novel compounds of general formula(I) , where D represents phenyl, pyridyl or tienyl, each of which is single-substituted or double-substituted with Hal; R1 represents H, =O, COOR3, OH, OA, NH2, alkyl, which has 1, 2, 3, 4, 5 or 6 carbon atoms, N3, ethinyl, vinyl, allyloxy, -OCOR3, NHCOA or NHSO2A; R2 represents H, =O, OH, OA or alkyl, which has 1, 2, 3, 4, 5 or 6 carbon atoms; R1 and R2 together alternatively represent spirocyclically linked 3-6-member carbocyclic ring, R3 represents H or A, R4 represents H or A; represents pyrrolidine-1,2-diyl, piperidine-1,2-diyl, oxazolidine-3,4 or 3,5-diyl, thiazolidine-3,4-diyl, 2,5-dihydro-1H-pyrrol-1,5-diyl, 1,3-dioxolane-4,5-diyl; G represents (CH2)n or (CH2)nNH-; X represents CONH; Y represents 1,3- or 1,4-phenylene, which is not substituted or is single-substituted with methyl, trifluoromethyl, ethyl, propyl, Cl or F; T represents morpholine-4-yl, which is single-substituted or double-substituted with carbonyl oxygen; A represents non-branched or branched alkyl, which has 1-10 carbon atoms and in which 1-7 hydrogen atoms can be substituted with F; Hal represents F, CI, Br or I, n represents 0, 1 or 2; and their pharmaceutically acceptable derivatives, solvates, salts or sterioisomers, including their mixtures in all ratios. Invention also relates to method of obtaining formula I compounds, to medication based on formula I compound and application of formula I compounds for preparation of medication, which has inhibiting activity with respect to coagulation factors Xa and VIla.

EFFECT: obtained novel compounds have inhibiting activity with respect to said coagulation factors.

11 cl, 1 tbl, 14 ex

Amid derivative // 2336273

FIELD: chemistry.

SUBSTANCE: invention relates to amid derivatives of formula (I), method of disease treatment and pharmaceutical composition based on them. Compounds can be applied in treatment of different herpes virus infections. In general formula (I) , Z: 1,2,4-oxydiazol-3-yl, 4-oxazolyl, 1,2,3-triazol-2-yl or 2-pyridyl, A: phenyl, which can have a substitute (substitutes) selected from group, including lower alkyl, halogen, halogen-substituted lower alkyl, O-lower alkyl, O-lower alkylene -OH, CN, OH, O-lower alkylene-phenyl, O-lower alkylene-O-lower alkyl, NH2, NH-lower alkyl, N-(lower alkyl)2 ,NH-lower alkylene-OH, NH-lower alkylene-O-lower alkyl, O-lower alkylene- NH2, O-lower alkylene-NH-lower alkyl and O-lower alkylene-N(lower alkyl)2; heteroaryl, representing monocyclic 6-member ring, which contains nitrogen atom as heteroatom or bicyclic 9-member ring, containing 1-2 heteroatoms selected from nitrogen and/or sulfur, which can have a substitute (substitutes), selected from lower alkyl; or phenyl group, condensed with saturated 5-member hydrocarbon cycle; or phenyl group, condensed with saturated 5-member heterocyclic cycle, which contains 1-2 heteroatoms, selected from nitrogen and/or oxygen, which can have a substitute (substitutes), selected from group, including lower alkyl, halogen, -C(O)-lower alkyl, lower alkylene-O-lower alkyl, on condition, that aryl group, condensed with saturated hydrocarbon cycle or aryl group, condensed with saturated heterocyclic cycle is bound with nitrogen atom through carbon atom in aromatic cycle, X: CO, R3: C3-C6cycloalkyl, which can have a substitute (substitutes), selected from group, which includes oxo, OH, halogen, CN, O-lower alkyl, -C(O)-NH2, -C(O)-NH-lower alkyl, -C(O)-N(lower alkyl)2, lower alkylene-OH, lower alkylene-O-lower alkyl; aryl, selected from phenyl, naphtyl, which can have a substitute (substitutes), selected from halogen; pyridyl; 9-member bicyclic heteroaryl, containing 1-3 heteroatoms, selected from S, N, O; or saturated heterocyclic group, representing monocyclic 6-member group, which contains 1-2 heteroatoms selected from S, SO, SO2, N, O, which can have a substitute (substitutes), selected from halogen.

EFFECT: obtaining amid derivatives that can be applied for treating various herpes virus infections.

17 cl, 26 tbl, 125 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds of formula (I), its pharmaceutically acceptable salts, possessing qualities of chemokine receptor modulators. Compounds can be applied for asthma, allergic rhinitis, COLD, inflammatory intestinal disease, irritated intestine syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis or cancer. In compound of formula (I) , R1 represents group selected from C1-8alkyl, said group is possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4 , -NR5R6 , phenyl, phenyl is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4,-NR5R6,-SR10,C1-6alkyl and trifluoromethyl; R2 represents group selected from C1-8alkyl, said group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-(C1-6alkyl)-N-(phenyl)amino; R3 represents hydrogen, R4 represents hydrogen or group selected from C1-6alkyl and phenyl, R5 and R6, independently, represent hydrogen or group selected from C1-6alkyl and phenyl, said group being probably substituted with 1, 2 or 3 substituents, independently selected from -OR14, -NR15R16, -COOR14,-CONR15R16, or R5 and R6 together with nitrogen atom, to which they are bound, form 4-7-member saturated heterocyclic ring system, possibly containing additional heteroatom, selected from oxygen and nitrogen atoms, ring possibly being substituted with 1, 2 or 3 substituents, independently selected from -OR14, -COOR14,-NR15R16,CONR15R16 and C1-6alkyl; R10 represents hydrogen or group selected from C1-6alkyl or phenyl; and each from R7, R8, R9, R14, R15, R16 independently represents hydrogen, C1-6alkyl or phenyl; X represents hydrogen, halogeno; Rx represents trifluoromethyl, -NR5 R6 , phenyl, naphtyl, heteroaryl, heteroring can be partly or fully saturated, and one or more ring carbon atoms can form carbonyl group, each phenyl or heteroaryl group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR4, -NR5R6, -CONR5R6, -COR7, -COOR7, -NR8COR9, -SR10, -SO2R10, -SO2NR5R6, -NR8SO2R9, C1-6alkyl or trifluoromethyl; or Rx represents group selected from C1-6alkyl, said group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6, phenyl or heteroaryl, where heteroaryl represents monocyclic or bicyclic aryl ring, containing from 5 to 10 ring atoms, from which 1, 2 or 3 ring atoms are selected from nitrogen, sulfur or oxygen. Invention also relates to methods of obtaining compounds, versions, pharmaceutical composition and application for manufacturing medications using compounds of invention.

EFFECT: obtaining novel compounds of formula (I), its pharmaceutically acceptable salts, possessing properties of chemokine receptor moduators.

25 cl, 138 ex

FIELD: chemistry.

SUBSTANCE: in compound of general formula I or its pharmaceutically acceptable salts or N-oxides R1 stands for , R2 stands for R3 stands for C0-4alkyl.

EFFECT: possibility to use compounds in elaboration of anti-cancer pharmaceutical preparations.

11 cl, 1 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: compounds of formula (I) can be efficient with respect to diseases, in which phosphorylation of Tau protein takes place. , R3 stands for CONR1R2, where R1 and R2 can be substituted with heterocycle; R5, R6, R7 independently on each other are selected from halogen and phenyl; R1, R2 independently on each other stand for hydrogen, (C1-C6)alkyl or together with nitrogen of group CONR1R can form heterocycle.

EFFECT: obtaining novel biologically active compounds.

4 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: in novel compounds of formula (I) X stands for C, N; R1 stands for H or (lower) alkyl, R2 stands for 9(lower) alkyl, -(CH2)n-R2a; R2a stands for C3-C8cycloalkyl, optionally and independently mono-, di-, tri- or tetrasubstituted with the following groups: OH, (lower)alkyl, (lower)alkoxy, 5- or 6-member single-valent saturated heterocyclic ring, containing from one to two heteroatoms, independently selected from nitrogen, oxygen and sulfur, said heterocyclic ring being optionally and independently mono-, di- or tri-substituted with the following groups: OH, (lower)alkyl, (lower)alkoxy, 5- or 6-member single-valent heteroaromatic ring, containing from one to two heteroatoms, independently selected from nitrogen, oxygen and sulfur, said heteroaromatic ring being optionally and independently mono-, di- or tri-substituted with the following groups: OH, (lower) alkyl, (lower)alkoxy, C3-C6cycloalkyl; R3 stands for C3-C6cycloalkyl, being optionally and independently mono-, di- or tri- or tetra-substituted with groups: OH, (lower) alkyl, (lower)alkoxy, phenyl, which optionally and independently is mono-, di- or tri- or tetra-substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, (lower)alkylamino, halogenated (lower)alkyl, halogenated (lower)alkoxy, nitro; R4 stands for 5- or 6-member single-valent heteroaromatic ring, containing from one to two nitrogen heteroatoms, said heteroaromatic ring being optionally and independently mono-, di- or tri- substituted with the following groups: OH, (lower) alkyl, (lower)alkoxy, halogen; naphtyl, which optionally and independently is mono-, di- or tri- substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, (lower)alkylamino, halogenated (lower)alkyl, halogenated (lower)alkoxy, nitro; or phenyl, which optionally and independently is mono-, di- or tri- substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, nitro, halogenated (lower)alkyl, halogenated (lower)alkoxy, cyano, (lower)alkylsulfonyl, -NR7R8; or two neighbouring substituents in said phenyl residue together represent -O-(CH2)p-O-, -(CH2)2-C(O)NH-; R5 and R6 each independently represent H, (lower)alkyl; R7 and R8 each independently represent hydrogen, (lower)alkyl, or R7 and R8 together with nitrogen atom, to which they are bound, form 5- or 6- member saturated or aromatic heterocyclic ring, which optionally contain nitrogen as additional heteroatom; said saturated or aromatic heterocyclic ring, being optionally substituted with the following groups: OH, (lower)alkyl, (lower)alkoxy; m equals 1 or 2, n equals 0 or 1, p equals 1, 2 or 3; or their pharmaceutically acceptable salts.

EFFECT: increased antagonistic activity of compounds.

19 cl

FIELD: chemistry.

SUBSTANCE: in novel substituted aryl ketones of formula (I) Z stands for groupings and A1, A2, A3, R1, R2, R3, R4, R5, R6, R7, X and Y and m are such as given in formula of invention. In substituted aryl carboxylic acid of formula (II) and derivative of aryl carboxylic acid of formula (III) A1, A2, A3, R1, R2, X and Y are such as given in item 1 of invention formula, R12 stands for allyl, which are intermediate products. Also described is means to fight undesirable plants based on formula (I) compound.

EFFECT: increased herbicidal activity.

7 cl, 3 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to acidylated heteroarylcondensed cycloalkenylamines with formula I in any of their stereoisomeric form or in form of their mixtures in any ratio, or their pharmaceutical salts, where in formula I: ring A represents an aromatic 6-member ring, containing 1 nitrogen atom, or a 5-member aromatic ring, containing 1 sulphur atom; one or two of R1, R2, R3 and R4 is independently chosen from a group consisting of hydrogen, halogen or C1-C4-alkyl, and the other R1, R2, R3 and R4 represent hydrogen; R5 represents an Ar group or Hetar group. Description is also given of a pharmaceutical composition based on compound with formula I and use of the latter.

EFFECT: regulation of the expression of the enzyme endothelial NO-synthesis.

10 cl, 31 ex

FIELD: medicine; pharmacology.

SUBSTANCE: present invention is referred to the method of obtaining of glycopyrroniumbromide stereoisomers or an iodide-formula: from an admixture where A- = Br or I, R means phenyl or thienyl.

EFFECT: obtaining with high output of biologically active diastereoisomer glycopyrroniumbromide or iodide.

1 cl, 17 ex

Amid derivative // 2336273

FIELD: chemistry.

SUBSTANCE: invention relates to amid derivatives of formula (I), method of disease treatment and pharmaceutical composition based on them. Compounds can be applied in treatment of different herpes virus infections. In general formula (I) , Z: 1,2,4-oxydiazol-3-yl, 4-oxazolyl, 1,2,3-triazol-2-yl or 2-pyridyl, A: phenyl, which can have a substitute (substitutes) selected from group, including lower alkyl, halogen, halogen-substituted lower alkyl, O-lower alkyl, O-lower alkylene -OH, CN, OH, O-lower alkylene-phenyl, O-lower alkylene-O-lower alkyl, NH2, NH-lower alkyl, N-(lower alkyl)2 ,NH-lower alkylene-OH, NH-lower alkylene-O-lower alkyl, O-lower alkylene- NH2, O-lower alkylene-NH-lower alkyl and O-lower alkylene-N(lower alkyl)2; heteroaryl, representing monocyclic 6-member ring, which contains nitrogen atom as heteroatom or bicyclic 9-member ring, containing 1-2 heteroatoms selected from nitrogen and/or sulfur, which can have a substitute (substitutes), selected from lower alkyl; or phenyl group, condensed with saturated 5-member hydrocarbon cycle; or phenyl group, condensed with saturated 5-member heterocyclic cycle, which contains 1-2 heteroatoms, selected from nitrogen and/or oxygen, which can have a substitute (substitutes), selected from group, including lower alkyl, halogen, -C(O)-lower alkyl, lower alkylene-O-lower alkyl, on condition, that aryl group, condensed with saturated hydrocarbon cycle or aryl group, condensed with saturated heterocyclic cycle is bound with nitrogen atom through carbon atom in aromatic cycle, X: CO, R3: C3-C6cycloalkyl, which can have a substitute (substitutes), selected from group, which includes oxo, OH, halogen, CN, O-lower alkyl, -C(O)-NH2, -C(O)-NH-lower alkyl, -C(O)-N(lower alkyl)2, lower alkylene-OH, lower alkylene-O-lower alkyl; aryl, selected from phenyl, naphtyl, which can have a substitute (substitutes), selected from halogen; pyridyl; 9-member bicyclic heteroaryl, containing 1-3 heteroatoms, selected from S, N, O; or saturated heterocyclic group, representing monocyclic 6-member group, which contains 1-2 heteroatoms selected from S, SO, SO2, N, O, which can have a substitute (substitutes), selected from halogen.

EFFECT: obtaining amid derivatives that can be applied for treating various herpes virus infections.

17 cl, 26 tbl, 125 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I) , where R1 represents phenyl group, containing 1-3 substitutes, selected from halogen and cyano group; R2 represents pyridyl group, which has 1-3 substitutes, selected from monocyclic or polycyclic heterocyclic group, which can have 1-3 substitutes, selected from halogen atoms, cyanogroup, as well as other values of R2 radical, given in formula of invention, R3 represents phenyl group or pyridyl group, which has 1-2 substitutes, selected from halogen and trihalogenmethyl group; R4 represents hydrogen atom; and X represents -SO2-; its salt or its solvate. As well as to medication and pharmaceutical composition, inhibiting production or secretion of β-amyloid protein, and containing compound of formula (I), and to application of compound of pt.1 in order to obtain medication.

EFFECT: obtaining novel compounds, inhibiting production or secretion of β-amyloid protein.

14 cl, 1 tbl, 296 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula I , where A is S(O)2 or C1-6alkylene possibly substituted by one or more fluorine atoms; R1 is (a) C1-10alkyl possibly substituted by one or more substitutes of aryl and Het1, (b) aryl possibly substituted by one or two substitutes selected out of halogeno, C1-4alkyl, CF3 and C1-4alkoxy, or (c) Het3; R2a, R2b, R3a and R3b are independently H or C1-3alkyl; R4 is (a) H, (b) C1-6alkyl; R5 and R6 are independently H, F or methyl; G is (a) -C(O)N(R8a)-[CH(C(O)R9)]0-1-C0-3alkylene-(Q1)a-, (b) -C(O)N(R8b)-C2-3alkenylene-(Q1)a-, R9 is H; Q1 is O; a is 0 or 1; L is (a) C0-6alkylene-Ra, (b) or , (c) ; Ar is phenyl or naphthyl; Het is 5-10-member heterocyclic group including one or two rings and one sulfur or oxygen and/or nitrogen atom as heteroatom; R11a is H or one or more substitute selected out of halogeno, OH, CN, C1-6alkyl and C1-6alkoxy (the last two groups are possibly substituted by one or more substitutes selected out of halogeno, OH, C1-4alkoxy); R11c is independently H or one or more substitute selected out of halogeno, OH, CN, C1-6alkyl, C1-6alkoxy; Ra, Rb and Rd are independently (a) , (b) , (c) , or (d) or Rb and Rd also can be H; Q3 is O; Q4 is O or CH2; a is 0 or 1; R13a-R13b are independently (a) H, (b) C(O)OR16; R16 is C1-10alkyl; R8a-R8b and R14a-R14d are independently (a) H or (b) C1-4alkyl (the last group is possibly substituted by one or more substitutes selected out of halogeno and OH), or R14a and R14b are independently C(O)O-C1-6alkyl, or R14c is (a) C3-7cycloalkyl, (b) C(O)O-C1-6alkyl, or R14c and R14d together are C3-6n-alkylene possibly interrupted by O, S, N(H) or N(C1-4alkyl) and/or substituted by one or more C1-4alkyl groups; each aryl is independently C6-10carbocyclic aromatic group which can contain one or two rings and be possibly substituted by one or more substitutes selected out of (a) halogeno, (b) C1-10alkyl, (c) OR17a, R17a is (a) H, (b) C1-10alkyl; Het1 and Het3 are independently 4-9-member heterocyclic groups including one or more heteroatom selected out of oxygen, nitrogen and/or sulfur, so that heterocyclic groups can contain one, two or three rings and be possibly substituted by one or more substitutes selected out of (a) halogeno, (b) C1-10alkyl, (c) =O, (d) OR19a, R19a is (a) H, (b) C1-10alkyl; n, p and q are independently 0, 1 or 2; or its pharmaceutically acceptable salts. Invention also concerns pharmaceutical composition; application; treatment method; method of obtaining compounds of the formula I; and compounds of the formula II, IV, V, VI.

EFFECT: new biologically active compounds with thrombin inhibition effect.

12 cl, 11 ex

Amid derivative // 2336273

FIELD: chemistry.

SUBSTANCE: invention relates to amid derivatives of formula (I), method of disease treatment and pharmaceutical composition based on them. Compounds can be applied in treatment of different herpes virus infections. In general formula (I) , Z: 1,2,4-oxydiazol-3-yl, 4-oxazolyl, 1,2,3-triazol-2-yl or 2-pyridyl, A: phenyl, which can have a substitute (substitutes) selected from group, including lower alkyl, halogen, halogen-substituted lower alkyl, O-lower alkyl, O-lower alkylene -OH, CN, OH, O-lower alkylene-phenyl, O-lower alkylene-O-lower alkyl, NH2, NH-lower alkyl, N-(lower alkyl)2 ,NH-lower alkylene-OH, NH-lower alkylene-O-lower alkyl, O-lower alkylene- NH2, O-lower alkylene-NH-lower alkyl and O-lower alkylene-N(lower alkyl)2; heteroaryl, representing monocyclic 6-member ring, which contains nitrogen atom as heteroatom or bicyclic 9-member ring, containing 1-2 heteroatoms selected from nitrogen and/or sulfur, which can have a substitute (substitutes), selected from lower alkyl; or phenyl group, condensed with saturated 5-member hydrocarbon cycle; or phenyl group, condensed with saturated 5-member heterocyclic cycle, which contains 1-2 heteroatoms, selected from nitrogen and/or oxygen, which can have a substitute (substitutes), selected from group, including lower alkyl, halogen, -C(O)-lower alkyl, lower alkylene-O-lower alkyl, on condition, that aryl group, condensed with saturated hydrocarbon cycle or aryl group, condensed with saturated heterocyclic cycle is bound with nitrogen atom through carbon atom in aromatic cycle, X: CO, R3: C3-C6cycloalkyl, which can have a substitute (substitutes), selected from group, which includes oxo, OH, halogen, CN, O-lower alkyl, -C(O)-NH2, -C(O)-NH-lower alkyl, -C(O)-N(lower alkyl)2, lower alkylene-OH, lower alkylene-O-lower alkyl; aryl, selected from phenyl, naphtyl, which can have a substitute (substitutes), selected from halogen; pyridyl; 9-member bicyclic heteroaryl, containing 1-3 heteroatoms, selected from S, N, O; or saturated heterocyclic group, representing monocyclic 6-member group, which contains 1-2 heteroatoms selected from S, SO, SO2, N, O, which can have a substitute (substitutes), selected from halogen.

EFFECT: obtaining amid derivatives that can be applied for treating various herpes virus infections.

17 cl, 26 tbl, 125 ex

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