Imidazochinolines with immunomodulating properties

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel derivatives of imidazo[4,5-c]chinoline of general formula or to its pharmaceutically acceptable salts, where R1 represents straight-chained C1-C6alkyl, possibly substituted with one substituent, selected from C1-C3alkoxy; Z1 represents C2-C6alkylene; X1 represents NR5 or >NCOR5; Y1 represents C1-C6alkylene; R3 represents C1-C6alkyl, possibly substituted with C1-C6alkoxy; R5 represents hydrogen, piperidinyl, possibly substituted by piperidinyl nitrogen with group R10, group C1-C6alkyl, where the last group is possibly substituted with one substituent, independently selected from NR7R8 or R9; or R5 represents C1-C6alkylene, which can be bound with carbon atom in C2-C6alkylene group Z1 with formation of piperidine ring; each of R7 and R8 independently represents tetrahydropyranyl, piperidinyl, possibly substituted by piperidinyl nitrogen atom with group R10a, C1-C6alkyl, where the last group is possibly substituted with one group, independently selected from OR12; or R7 and R8 together with nitrogen atom, to which they are bound, form 4-7-membered saturated heterocyclic ring, selected from asetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, 1,4-oxazepanyl and 1,4-diazepanyl, where heterocyclic ring is possibly substituted with one or two substituents, independently selected from S(O)qR15, OR15, CO2R15, COR15, CONR15R16, NR15CO2R16, pyrimidinyl and C1-C6alkyl, where the last group is possibly substituted with one group, independently selected from OR18 and CO2R18; R9 represents S(O)qR20; R10 and R10a independently represent COR2 or group C1-C6alkyl; each of R12, R15, R16, R18, R20 and R24 independently represents hydrogen or C1-C6alkyl; q equals 2; m and n both equal 0; and A represents phenyl. Invention also relates to method of obtaining formula (I) compound, based on it pharmaceutical composition, and to method of treating said pathological conditions.

EFFECT: obtained are novel derivatives of imidazo[4,5-c]chinoline, useful modulation of TLR7 activity.

17 cl, 18 dwg, 81 ex

 

The text descriptions are listed faxing

1. The compound of formula (I)
,
where R1represents remotemachine C1-C6alkyl, possibly substituted by one Deputy, selected from C1-C3alkoxy;
Z1represents a C2-C6alkylen;
X1represents NR5or >NCOR5;
Y1represents a C1-C6alkylen;
R3represents a C1-6alkyl, possibly substituted C1-6alkoxy;
R5represents hydrogen, piperidinyl, possibly substituted on the nitrogen atom of piperidine group, R10group C1-C6alkyl, where the latter group possibly substituted by one Deputy, is independently selected from NR7R8or R9;
or R5represents a C1-C6Alki the Yong, which can be linked to a carbon atom in the C2-C6alkalinous group Z1with the formation of piperidino ring;
each of R7and R8independently represents tetrahydropyranyl, piperidinyl, possibly substituted on the nitrogen atom of piperidine group, R10aC1-C6alkyl, where the latter group possibly substituted with one group independently selected from OR12;
or R7and R8together with the nitrogen atom to which they are attached, form a 4-7-membered saturated heterocyclic ring selected from azetidine, pyrrolidine, piperidine, piperazinil, morpholinyl, azepane, 1,4-oxazepine and 1,4-diazepine, where the heterocyclic ring may substituted by one or two substituents, independently selected from S(O)qR15, OR15, CO2R15, COR15, CONR15R16, NR15CO2R16, pyrimidinyl and C1-C6of alkyl, where the latter group possibly substituted with one group independently selected from OR18and CO2R18;
R9represents S(O)qR20;
R10and R10aindependently represent a COR24or group C1-C6alkyl;
each of R12, R15, R16, R18, R20and R24independently represents hydrogen or C1-C6 alkyl;
q is 2;
m and n are both equal to 0; and
Rather it represents a phenyl;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1 or its pharmaceutically acceptable salt, where R1represents methyl.

3. The compound according to claim 1 or 2, or its pharmaceutically acceptable salt, where Z1is a n-propylene.

4. The compound according to claim 1 or its pharmaceutically acceptable salt, where X1represents >NCOR5.

5. The compound according to claim 4 or pharmaceutically acceptable salt, where R5represents hydrogen or C1-C6alkyl, possibly substituted by one group NR7R8or R9where R7, R8and R9such as defined in claim 1.

6. The compound according to claim 1 or its pharmaceutically acceptable salt, where R3represents n-butyl, methoxyethyl or ethoxymethyl.

7. The compound according to claim 1 or its pharmaceutically acceptable salt, where Z1represents remotemachine2-C4alkylenes group.

8. The compound according to claim 1 or its pharmaceutically acceptable salt, where R5represents a C1-C3alkyl, possibly substituted by one group NR7R8where R7and R8such as defined in claim 1.

9. The compound according to claim 1 or its pharmaceutically acceptable salt, where Y1represents CH2

10. The compound according to claim 1 or its pharmaceutically acceptable salt, where R7and R8each independently represents tetrahydropyranyl, N-acetylpiperidine or1-C4alkyl, possibly substituted by a group OR12where R12such as defined in claim 1.

11. The compound according to claim 1 or its pharmaceutically acceptable salt, where:
R1represents methyl;
X1represents >NCOR5;
R3represents n-butyl, methoxyethyl or ethoxymethyl;
Z1represents remotemachine2-C4alkylenes group;
Y1represents CH2;
R5represents a C1-C3alkyl, possibly substituted by one group NR7R8;
R7and R8each independently represents tetrahydropyranyl, N-acetylpiperidine or1-C4alkyl, possibly substituted by a group OR12where R12such as defined in claim 1; and
m and n are both equal to 0.

12. The compound according to claim 1, chosen from:
Methyl-2-(4-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propylamino)methyl)phenyl)acetate,
Methyl-2-(3-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propylamino)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-Ninidze[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((4-((4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)methyl)piperidine-1-yl)methyl)phenyl)acetate di-triptoreline salt,
Methyl-[4-({[3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl][2-(dimethylamino)ethyl]amino}methyl)phenyl]acetate,
Methyl-2-(3-((N-(3-(4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(1-methylpiperidin-4-yl)amino)methyl)phenyl)acetate,
Methyl-2-(4-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(1-methylpiperidin-4-yl)amino)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methylpiperazin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-(dimethylamino)propyl)amino)methyl)phenyl)acetate,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-morpholinopropan)amino)methyl)phenyl)acetate,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-(ethyl(methyl)amino)propyl)amino)methyl)phenyl)acetate,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-(4-methylpiperazin-1-yl)propyl)amino)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(methylsulphonyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]hinali the-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-morpholinoethyl)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2-methoxyethyl)(methyl)amino)acetamido)methyl)phenyl)-acetate,
Methyl-2-(4-((2-(4-acetylpiperidine-1-yl)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
(R)-Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(3-hydroxypyrrolidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(pyrimidine-2-yl)piperazine-1-yl)acetamido)methyl)phenyl)acetate,
Ethyl-4-(2-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(4-(2-methoxy-2-oxoethyl)benzyl)amino)-2-oxoethyl)piperazine-1-carboxylate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(ethylsulfonyl)piperazine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(tert-butoxycarbonylamino)piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(tert-butoxycarbonyl(methyl)amino)piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Ethyl-2-(1-(2-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)PR who drank)(4-(2-methoxy-2-oxoethyl)benzyl)amino)-2-oxoethyl)piperidine-4-yl)acetate,
Methyl-1-(2-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(4-(2-methoxy-2-oxoethyl)benzyl)amino)-2-oxoethyl)piperidine-4-carboxylate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2-methoxyethyl)(methyl)amino)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-3-(piperidine-1-yl)propanamide)methyl)phenyl)acetate,
Methyl-2-(4-(((3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-morpholinopropan)amino)methyl)phenyl)acetate,
(S)-Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(2-(methoxymethyl)pyrrolidin-1-yl)acetamido)methyl)phenyl)acetate,
(R)-Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(2-(methoxymethyl)pyrrolidin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(pyrrolidin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]x is the nolin-1-yl)propyl)-2-((2-hydroxyethyl)(methyl)amino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2-methoxyethyl)(methyl)amino)acetamido)methyl)phenyl)-acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(butyl(methyl)amino)acetamido)methyl)phenyl)acetate,
Methyl-3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dipropylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(bis(2-hydroxyethyl)amino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(methyl(tetrahydro-2H-Piran-4-yl)amino)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(azetidin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(3-hydroxyazetidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(pyrrolidin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(3-hydroxypyrrolidine-1-yl)acetamido)methyl)phenyl)acetate,
(R)-Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(3-hydroxypyrrolidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N - (3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-hydroxypiperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methoxypiperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(dimethylcarbamoyl)piperidine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-morpholinoethyl)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2S,6R)-2,6-dimethylmorpholine)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methylpiperazin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-hydroxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-methoxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((2-(4-acetylpiperidine-1-yl)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(methylsulphonyl)piperazine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(azepin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(1,4-oxazepan-4-yl)acetamido)methyl)phenyl)ACE the ATA,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methyl-1,4-diazepan-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((2-(4-acetyl-1,4-diazepan-1-yl)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(ethylcarbamate)-1,4-diazepan-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(methylsulphonyl)-1,4-diazepan-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-methoxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(4-((2-(4-acetyl-1,4-diazepan-1-yl)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(methylsulphonyl)-1,4-diazepan-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((2-((1-acetylpiperidine-4-yl)(methyl)amino)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methylpiperazin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-methoxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-it is dazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methylpiperazin-1-yl)acetamido)methyl)phenyl)acetate and
Methyl-2-(3-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-methoxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate,
or pharmaceutically acceptable salt of any of them.

13. The compound according to claim 1, chosen from:
Methyl-2-(4-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propylamino)methyl)phenyl)acetate,
Methyl-2-(3-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propylamino)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((4-((4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)methyl)piperidine-1-yl)methyl)phenyl)acetate di-triptoreline salt,
Methyl-[4-({[3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl][2-(dimethylamino)ethyl]amino}methyl)phenyl]acetate,
Methyl-2-(3-((N-(3-(4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)-acetate,
Methyl-2-(3(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(1-methylpiperidin-4-yl)amino)methyl)phenyl)acetate,
Methyl-2-(4-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(1-methylpiperidin-4-yl)amino)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methylpiperazin-1-yl)acetamido)methyl)phenyl)AC is Tata,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-(dimethylamino)propyl)amino)methyl)phenyl)acetate,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-morpholinopropan)amino)methyl)phenyl)acetate,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-(ethyl(methyl)amino)propyl)amino)methyl)phenyl)acetate,
Methyl-2-(3-(((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-(4-methylpiperazin-1-yl)propyl)amino)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(methylsulphonyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-morpholinoethyl)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2-methoxyethyl)(methyl)amino)acetamido)methyl)phenyl)-acetate,
Methyl-2-(4-((2-(4-acetylpiperidine-1-yl)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
(R)-Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(3-hydroxypyrrolidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(pyrimidine-2-yl)piperazine-1-yl)acetamido)methyl)phenyl)acetate,
Ethyl-4-(2-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)who ropyl)(4-(2-methoxy-2-oxoethyl)benzyl)amino)-2-oxoethyl)piperazine-1-carboxylate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(ethylsulfonyl)piperazine-1-yl)acetamido)methyl)phenyl)-acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(tert-butoxycarbonylamino)piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(tert-butoxycarbonyl(methyl)amino)piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Ethyl-2-(1-(2-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(4-(2-methoxy-2-oxoethyl)benzyl)amino)-2-oxoethyl)piperidine-4-yl)acetate,
Methyl-1-(2-((3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(4-(2-methoxy-2-oxoethyl)benzyl)amino)-2-oxoethyl)piperidine-4-carboxylate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(piperidine-1-yl)acetamido)methyl)phenyl)acetate some saccharine salts,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2-methoxyethyl)(methyl)amino)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-3-(piperidine-1-yl)propanamide)methyl)phenyl)acetate,
Methyl-2-(4-(((3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)(3-morpholinopropan)amino)methyl)phenyl)acetate,
(S)-Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(2-(methoxymethyl)pyrrolidin-1-yl)acetamido)methyl)phenyl)acetate disharmony salt,
(R)-Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(2-(methoxymethyl)pyrrolidin-1-yl)acetamido)methyl)phenyl)acetate disharmony salt,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(pyrrolidin-1-yl)acetamido)methyl)phenyl)acetate disharmony salt,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2-hydroxyethyl)(methyl)amino)acetamido)methyl)phenyl)acetate disharmony salt,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2-methoxyethyl)(methyl)amino)acetamido)methyl)phenyl)-acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(butyl(methyl)amino)acetamido)methyl)phenyl)acetate,
Methyl-3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dipropylamino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(bis(2-hydroxyethyl)amino)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(methyl(tetrahydro-2H-Piran-4-yl)amino)acetamido)-
IU who yl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(azetidin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(3-hydroxyazetidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(pyrrolidin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(3-hydroxypyrrolidine-1-yl)acetamido)methyl)phenyl)-acetate,
(R)-Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(3-hydroxypyrrolidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(piperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-hydroxypiperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methoxypiperidine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(dimethylcarbamoyl)piperidine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-morpholinoethyl)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-((2S,6R)-2,6-dimethylmorpholine)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methylpiperazin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-hydroxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-methoxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((2-(4-acetylpiperidine-1-yl)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(methylsulphonyl)piperazine-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(azepin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(1,4-oxazepan-4-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methyl-1,4-diazepan-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((2-(4-acetyl-1,4-diazepan-1-yl)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(ethylcarbamate)-1,4-diazepan-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(methylsulphonyl)-1,4-diazepan-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-methoxyethyl)piperazine--yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(4-((2-(4-acetyl-1,4-diazepan-1-yl)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(methylsulphonyl)-1,4-diazepan-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((2-((1-acetylpiperidine-4-yl)(methyl)amino)-N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate dimethanesulfonate salt,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate monosaharidov salt,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate disharmony salt,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate di-1-hydroxy-2-naftemporiki salt,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate dibenzoylresorcinol salt,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate mentalemotional salt,
Methyl-2-(4-((N-(3-(4-amino-2-butyl-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(dimethylamino)acetamido)methyl)phenyl)acetate is umarovatitle salt,
Methyl-2-(4-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methylpiperazin-1-yl)acetamido)methyl)phenyl)acetate,
Methyl-2-(4-((N-[-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-methoxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate,
Methyl-2-(3-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-methylpiperazin-1-yl)acetamido)methyl)phenyl)acetate, and
Methyl-2-(3-((N-(3-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-C]quinoline-1-yl)propyl)-2-(4-(2-methoxyethyl)piperazine-1-yl)acetamido)-methyl)phenyl)acetate.

14. The method of obtaining the compounds of formula (I) or its pharmaceutically acceptable salt according to claim 1, comprising,
when X1represents >N-COR5the interaction of the compounds of formula (I), where X1represents NR5where R5represents hydrogen, with a compound of formula (X)

where L4represents a leaving group, such as halogen, for example chloro, and R5is such as defined in claim 1;
and then, if desirable or necessary, perform one or more of the following stages:
remove any protective groups
getting a pharmaceutically acceptable salt of the compound.

15. Pharmaceutical composition for treating or reducing the risk of the disease or condition under which the useful modulation of the activity of TLR7, with whom containing a series connection of the formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 13, together with a pharmaceutically acceptable auxiliary substance, diluent or carrier.

16. A method of treating or reducing the risk of the disease or condition under which the useful modulation of TLR7 activity, comprising the administration to a patient in need, a therapeutically effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 13.

17. A method of treating asthma, allergic rhinitis, atopic dermatitis or cancer, comprising the administration to a patient in need, a therapeutically effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 13.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a novel heterocyclic amide compound of formula I: or a pharmaceutically acceptable salt thereof. Described also is a pharmaceutical composition containing said compound, having protein kinase inhibitor, regulator or modulator properties, which is acceptable in treating or preventing a proliferative disease, an anti-proliferative disorder, inflammation, arthritis, neurologic or neurodegenerative disease, cardiovascular disease, hair loss, neural disease, ischemic disorder, viral disease or fungal disease.

EFFECT: high efficiency of using the compounds.

2 cl, 20 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrole nitrogen-containing heterocyclic derivatives of formula (I) or their pharmaceutically acceptable salts:

,

wherein: X means C, N; each R1,R2 means H; R3 means C1-10alkyl; R4 means -[CH2CH(OH)]rCH2NR9R10, -(CH2)nNR9R10; provided X means N, R5 is absent, each R6, R7, R8 means H, halogen; provided X means C, each R5, R6, R7, R8 means H, halogen, hydroxyC1-10alkyl, C1-10alkyl, phenyl, 6-member heteroaryl with one N, -OH, -OR9, -NR9R10, -(CH2)nCONR9R10, -NR9COR10, -SO2R9 and -NHCO2R10, wherein said phenyl is unsubstituted or additionally substituted by one or more group C1-10alkyl, C1-10alkoxyl, halogen; each R9, R10 means H, C1-10alkyl wherein C1-10alkyl is unsubstituted or additionally substituted by one or more group C1-10alkyl, phenyl, halogenophenyl, -OH, C1-10alkoxy, OH- C1-10alkyl; or R9 and R10 together with an attached atom form a 5-6-member heteroring which may contain one O; n is equal to 2- 6; z is equal to 1-2; r is equal to 1-6;.

EFFECT: compounds may be used as protein kinase inhibitors.

14 cl, 2 tbl, 67 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of 2-heteroaryl-substituted benzothiophene and benzofuran, precursors thereof and therapeutic use of said compounds, having structural formula (1a) where R1, R2, X9 and Q assume values given in the description, and pharmaceutically acceptable salts thereof, which are suitable for imaging amyloid deposits in living patients. The invention also relates to pharmaceutical compositions based on compounds of formula 1a, use and methods of producing said compounds. More specifically, the present invention relates to a method of imaging brain amyloid deposits in vivo for intravital diagnosis of Alzheimer's disease, and measuring clinical efficiency of therapeutic agents against Alzheimer's disease.

EFFECT: high efficiency of using said compounds.

15 cl, 1 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (IX) wherein radicals and symbols have values given in the claim, and pharmaceutically acceptable salts or tautomers thereof. Said compounds are inhibitors of poly(ADP-ribose)polymerase (PARP) and can be used to treat cancer, inflammatory diseases, reperfusion injuries, ischaemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, retroviral infections, retinal damage, skin senescence and UV-induced skin damage, and as chemo- or radiosensitisers for cancer treatment. The invention also relates to a pharmaceutical composition containing said compounds, use of said compounds and a method of treating said diseases.

EFFECT: high efficiency of using the compounds.

10 cl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 3-aza-bicyclo[3.3.0]octane derivatives of formula , where R1 and R2 are hydrogen, C1-4alkyl or fluorine; R3 is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl, trifluoromethoxy group and halogen; 2,3-dihydrobenzofuranyl; 2,3-dihydrobenzo[1,4]dioxynyl; or isoxazolyl, pyridyl, indazolyl, benzofuranyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, pyrrolo[2,1b]thiazolyl, imidazo[ 1,2-a]pyridinyl or imidazo[2,1-b]thiazolyl, where said groups are unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, halogen and trifluoromethyl; A is or ; R4 is C1-4alkyl or -NR6R7; R6 is hydrogen or C1-4alkyl; R7 is hydrogen or C1-4alkyl; and D is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl and halogen; or a pharmaceutically acceptable salt of such a compound. 3-aza-bicyclo[3.3.0]octane derivatives or a pharmaceutically acceptable salt thereof are used as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: novel 3-aza-bicyclo[3,3,0]octane derivatives as nonpeptide antagonists of human orexin receptors.

9 cl, 1 tbl, 85 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new antibacterial compounds of formula I

wherein R1 represents halogen or alkoxy group; each U and W represents N; V represents CH, and R2 represents H or F, or each U and V represents CH; W represents N, and R2 represents H or F, or U represents N; V represents CH; W represents CH or CRa, and R2 represents H, or also when W represents CH, may represent F; Ra represents CH2OH or alkoxycarbonyl; A represents group CH=CH-B, a binuclear heterocyclic system D, phenyl group which is mono-substituted in the position 4 by C1-4 alkyl group, or phenyl group which is di-substituted in positions 3 and 4 wherein each of two substitutes is optionally specified in a group consisting of C1-4 alkyl and halogen; B represents mono- or di-substituted phenyl group wherein each substitute is a halogen atom; D represents group

wherein Z represents CH or N, and Q represents O or S; or to salts of such compounds.

EFFECT: compounds are used for treating bacterial infections.

13 cl, 2 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel tricyclic derivative of chemical formula 1 or pharmaceutically acceptable salts thereof: formula 1, where Y1, Y2 and Y3 independently denote H, C1-C10 alkyl with a straight or branched chain, hydroxy, C1-C10 alkoxy, -CCOR1, -NR2R3 or -A-B; A denotes -O-, -CH2-, -CH(CH3)-, -CH-N- or -CONH-; B denotes -(CH2)n1-Z, -(CH2)n2-NR2R3 or -(CH2)n3-OR1; Z denotes C5-C20 aryl, unsubstituted or substituted with R5 and selectively R6, C3-C10 cycloalkyl, unsubstituted or substituted with R5 and selectively R6, C1-C20 heterocyclic compound, unsubstituted or substituted with R5 and selectively R6; R1 denotes H or C1-C10 alkyl with a straight or branched chain; R2 and R3 independently denote H, C1-C10 alkyl with a straight or branched chain or -(CH2)n4R7; R5 denotes H, C1-C10 alkyl with a straight or branched chain, C5-C20 aryl or C1-C20 heterocyclic compound; R6 denotes H or C1-C10 alkyl with a straight or branched chain; R7 denotes -NR8R9, -COOR1, -OR1, -CF3, -CN, halogen or Z; R8 and R9 independently denote H or C1-C10 alkyl with a straight or branched chain; n1-n4 respectively denote an integer from 0 to 15; Y denotes H or C1-C10 alkyl with a straight or branched chain. The invention also relates to methods of producing a compound of formula 1, compositions containing the described compound and with effective inhibiting activity on poly(ADP-ribose)polymerase (PARP).

EFFECT: obtaining and describing novel compounds which can be suitable for preventing or treating diseases caused by excess PARP activity, especially neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis and cancer.

23 cl, 123 ex, 7 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 4-aryl-1,4-dihydro-1,6-naphthyridine-3-carboxamides, method for production thereof, use thereof to produce a medicinal agent which inhibits MR activity.

EFFECT: improved method.

11 cl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) where values of substituents are given in description, possessing inhibiting activity with respect to cathepsin K as well as to pharmaceutical compositions for treating diseases, associated with cysteine protease activity and to methods of inhibiting cathepsin K in mammals, requiring such treatment by introduction of efficient amount of compound to mammal.

EFFECT: claimed is application of formula (I) compound or its pharmaceutically acceptable salt in manufacturing medication for application in cathepsin K inhibition in a warm-blooded animal.

10 cl, 45 ex, 5 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to derivatives of antibiotics, which represent compounds of formula (I) and their pharmaceutically acceptable salts, where U, V, W, X, R1, R2, R3, R4, R5, R6, A, B, D, E, G, m and n are determined in description. Invention also relates to pharmaceutical composition, containing said compounds and their application for obtaining medication for prevention or treatment of bacterial infections.

EFFECT: obtaining useful antimicrobial agents, efficient against various pathogens of people and animals.

23 cl, 1 tbl, 186 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and concerns an ergogenic formulation possessing adaptogenic, hepatoprotective and immunomodulatory action, and may be used in hepatic diseases, in decreases in immunity and increase in performance efficiency and tolerance. The composition contains burnut extract, zinc aspartate, magnesium aspartate, vitamin B6, water in certain proportions of the ingredients.

EFFECT: composition possess higher pharmacological activity and bioavailability.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely immunology and may be used for treating rheumatoid arthritis. That is ensured by the use of a pharmaceutical composition containing an active principle presented by a monoclonal antibody which recognises a CD6 human leukocyte differentiation antigen and produced by secreting hybridoma IOR-TIA with deposition No. ECACC 96112640, and an applicable excipient. What is also presented is a method for the use of the pharmaceutical composition in the form of injections, as well as the use of a monoclonal antibody which recognises the CD6 human leukocyte differentiation antigen, for preparing a therapeutic agent.

EFFECT: group of inventions provides a prolonged therapeutic effect in the patients suffering rheumatoid arthritis after a short period of administration.

3 cl, 3 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: bacterial Lactobacillus casei CNNM 1-1518 strain is used for preparing an oral composition for increasing humoral immunity induced in influenza vaccination, preferentially in patients aged 65 years and older. The composition is found in the form of an enzyme milk product, in the form of a foodstuff or a food additive, and with the content Lactobacillus casei CNNM 1-1518, preferentially 1x108 to 1x109 CFU/ml.

EFFECT: intensified humoral response induced by influenza vaccination.

10 dwg, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, specifically pharmacology, and may be used for correction of immune disorders in pathological conditions associated with Th1-dependent type of immune response (chronic, smoldering and recurrent infectious, as well as oncological diseases).

EFFECT: water-soluble polysaccharides of molecular weight 310 and 490 kDa recovered from compendial raw calendula are macrophage inflammatory properties activators, and Th-dependent type of immune response, and may extend the range of herbal products able to stimulate immune response in infectious-inflammatory processes and oncological disease.

2 ex, 4 tbl

Liquid formulations // 2470631

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine and describes a pharmaceutical concentration for dissolution before oral introduction, containing S1P receptor modulator or agonist specified in a group involving 2-amino-2-[2-(4-octylphenylethyl)]propane-1,3-diol, 2-amino-2-[4-(benzyloxyphenylthio)-2-chlorophenyl]ethyl-1,3-propanediol or proper phosphate, and 1-{4-[1-(4-cyclohexyl-3-trifluoromethylbenzyloxyimino)ethyl]-2-ethylbenzyl}azetidine-3-carboxylic acid, or their pharmaceutically acceptable salts, respectively, and 65 to 99 wt % propylene glycol, and optionally one or more other solvents, one or more aromatisers and/or one or more preserving agents; all the ingredients are added up to 100 wt %. What is also described is a pharmaceutical solution containing the concentrate, the use of the concentrate and the method for treating an individual in need of immune system suppression with the use of said concentrate.

EFFECT: invention provides physical stability over long periods of time.

9 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biologically active peptide complexes with immunomodulating and antiviral activity. The disclosed peptide complexes have a three-dimensional structure wherein X1 is absent or contains at least 1 amino acid; R1 and R2 are peptide chains which contain amino acid residues, His or Cys, capable of reacting with transition metal ions, wherein R1 contains up to 5 amino acid residues or is absent; R2 contains up to 3 amino acid residues or is absent.

EFFECT: peptide complexes rich in histidine and, primarily alloferon peptides with Zn ions, enable to produce preparations with a directed mechanism of action and enable their design in accordance with the understanding of the structure of the medicinal target.

3 cl, 7 dwg, 2 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: complex therapy, including introduction of antibiotics, is performed. Additionally carried out is immunomodulating therapy 2 ml of 0.2% superlimf during and for 5-7 days after operation 2 times per day.

EFFECT: reduction of treatment terms due to normalisation of functional state of immune and antioxidant systems in said category of patients.

7 tbl

FIELD: medicine.

SUBSTANCE: for the purpose of treating allergy in an individual characterised by cytokine Th1 and Th2 imbalance, β-hydroxy-β-methylbutyrate (HMB) is introduced into the individual in an amount effective to reduce cytokine Th1 and Th2 production imbalance. What is also presented is a method of treating allergy in the individual belonging to a risk group of developing allergy.

EFFECT: elimination, delay and reduction of the rate of the onset or severity of allergy-related symptoms due to increase of the cytokine Th1 content with no increase of the cytokine Th2 content.

11 cl, 5 dwg, 8 tbl, 14 ex

FIELD: medicine.

SUBSTANCE: what is produced is a recombinant protein created by gene shuffling possessing higher antiviral and antiproliferative activities as compared with existing human interferon-alpha-2b (HulFN-α2b). The prepared polypeptide is used in a composition as an antiviral, antiproliferative, anticancer or immunomodulatory agent.

EFFECT: invention enables using the prepared high-active interferon-like protein for treating a condition sensitive to interferon therapy, cancer or viral disease.

49 cl, 9 dwg, 8 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention described immunomodulatory compounds of oligonucleotides individually providing unique profiles of cytokines and chemokines by relation as TLR agonists. The TLP9 agonists aim at modulation of immune responses mediated by Toll-like receptor (TLR). There are also described a composition containing an immunomodulatory compound and a physiologically acceptable carrier and enables producing an immune response in a patient, a method for producing the immune response in the patient with the use of the immunomodulatory compound, methods of therapeutic and preventive treatment in the patient in need of modulation of the immune response, particularly in cancer, autoimmune and inflammatory disorders, an infectious disease, allergy, asthma and other diseases. The immunomodulatory compounds may be used in a combination with other therapeutic agents and chemotherapeutic compounds used in specific diseases or disorders.

EFFECT: compounds under the invention create such specific modulations of the immune response different from modulations created by non-methylated dinucleotides CpG.

9 cl, 35 dwg, 2 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition for local application containing a therapeutic compound of an immune response modifier, sterilisation-resistant and applicable for local application immediately on tissue regions with skin damages wherein said composition is sterilised by electron-beam irradiation, and the therapeutic compound represents 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline-4-amine (imiquimod). Also, the invention refers to a packed composition for local application containing a packing material and said pharmaceutical composition.

EFFECT: invention provides the sterilisation-resistant pharmaceutical composition.

26 cl, 5 tbl, 1 ex

Up!