Heterocyclic inhibitors of hh-sygnal cascade, based on them medicinal compositions and method of treating diseases induced by abbarant activity of hh-signal system

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel derivatives of 2,6-dihydro-7H- pyrazolo[3,4-d]pyradazin-7-one, 1,4-dihydropyrazolo[3,4-b]thiazin-5(6H)-one; N-acylated 4-imidazo[1,2-a]pyridin-2-yl- and 4-imidazo[1,2-a]pyrimidin-2-yl- anilines; amides of [(4H-thieno[3,2-b]pyrrol-5-yl)carbonyl]pyperidin-4-carboxylic acid; amides of 2-(4-carbamoylpyperidin-1-yl)isonicotinic acid; amides of N-sulfonyl-1,2,3,4-tetrahydrochinolin-6-carboxylic acid; as well as to N-acylated 3-azolyl derivatives of 2-amino-4,5,6,7-tetrahydtithieno[2,3-c]pyridine possessing properties of Hh-signal cascade inhibitors.

EFFECT: compounds can be applied for use in pharmaceutical compositions and medications for treating diseases induced by abberant activity of Hedgehog (Hh) signal system, in particular, oncological diseases, for instance, for pancreatic carcinoma treatment.

23 cl, 13 dwg, 11 tbl, 26 ex

 

The text descriptions are given in facsimile form.

1. Derivatives of 2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-ones of General formula I

in which n can take the values 0, 1 or 2;
R1 represents optionally substituted phenyl;
R2, R5 represents lower alkyl;
R3 represents H or lower alkyl;
R4a represents H, R4b represents lower alkyl, substituted 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen, or sulfur; C3-C7cycloalkyl; phenyl, optionally substituted by fluorine, isopropyl, C1-C2alkylenedioxy; or R4a and R4b together with the nitrogen atom to which they are bound, form an optionally substituted azaheterocyclic, such as morpholinyl; piperazinil, substituted by optionally substituted phenyl, optionally substituted by alkyl, cyclohexyl.

2. Derivatives 1.4-dihydropyrazolo[3,4-b][1,4]thiazin-5-onewebday formula II

in which m can take the values 0, 1 and 2;
R6 represents optionally substituted phenyl;
R7 represents lower alkyl;
R8 represents H or lower alkyl;
R9a represents H, R9b represents lower alkyl, possibly substituted 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen or sulfur, substituted phenyl, alkoxygroup; cyclopentyl; phenyl substituted by alkoxygroup, trifluoromethyl; or R9a and R9b together with the nitrogen atom to which they are bound, form an optionally substituted azaheterocyclic, such as pyrrolidinyl; morpholinyl; homopiperazine; piperazinil, replaced by pyridium, optionally substituted phenyl.

3. Derivatives of 4-imidazo[1,2-a]pyridine-2-yl-anilines of General formula III

in which each of R10a, R10b, R10c and R10d independently represents H or lower alkyl;
R11 represents an optionally substituted alkyl, C3-C7cycloalkyl,optionally substituted phenyl,
optionally substituted 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen and/or sulfur;
R12 represents H;
excluding compounds of General formula

R10a=R10b=R10c=R10d=Y=Z=H, X=2,4-dimethoxybenzamide; 3,4-dimethoxy what benzamido; 3,4,5-trimethoxybenzamide; 3-(dimethylamino)benzamide; 3-methoxy-4-(morpholinomethyl)benzamide;
R10a=R10b=R10c=R10d=X=Z=H, Y=3-methoxy-4-(morpholinomethyl)benzamido; acetamido; 3 methoxybenzamido;
R10a=R10b=R10c=R10d=Z=H, X=NO2Y=butanolide;
R10a=R10b=R10c=R10d=X=y=H, Z=2-methoxybenzamide; 2 nitrobenzamide; 2-chloro-5-nitrobenzamide; 1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide;
7-(benzo[b]thiophene-2-yl)-1H-indazol-5-carboxamide; acetamido; acetamido iodometric; acetamido methyl p-toluensulfonate; acetamido hydrochloride; acetamido salt with methyl-allyl;
R10a=R10b=R10c=R10d=X=H,Y=N02, Z=acetamido;
R10d=methyl, R10a=R10b=R10c=X=Y=H, Z=2-morpholinoethyl; 3-(piperidine-1-yl)propanamide; 2-(pyrrolidin-1-yl)acetamido; 3-(diethylamino)propanolamide:
R10d=methyl, R10a=R10b=R10c=X=Z=H, Y=3,4,5-trimethoxybenzamide;
R10c=methyl, R10a=R10b=R10d=X=Y=H, Z=acetamido; acetamido salt with methyl-allyl;
R10c=methyl, R10a=R10b=R10d=X=Z=H, Y=4 methoxybenzamido; 2,4-dimethoxybenzamide; 3,4,5-trimethoxybenzamide;
R10b=methyl, R10a=R10c=R10d=X=Y=H, Z=acetamido; atsetamidometil p-toluensulfonate; acetamido salt with methyl-allyl;
R10a=R10c=methyl, R10b=R10d=X=Y=H, Z=atsetamidometil p-toluensulfonate.

4. Derivatives of 4-imidazo[1,2-a]pyrimidine-2-yl-anilines of General formula IV,

in which R13a, R13b, R13c each independently represents H or lower alkyl;
R14 represents H, lower alkyl, alkoxygroup the u;
R15 represents optionally substituted alkyl, C3-C7cycloalkyl, substituted phenyl, 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen and/or sulphur, or tetrahydrofuranyl;
excluding compounds of General formula

in which R13a=R13c=Y'=Z'=H; X'=3-(dimethylamino)benzamide; benzo[d][1,3]dioxol-5-carboxamide; 3-methoxy-4-(morpholinomethyl)benzamide;
R13a=R13c=X'=Z'=H; Y'=1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide;
sqlopenconnection; 3,4,5-trimethoxybenzamide;
R13a=R13c=X'=Y'=H; Z'=acetamido;
R13c=X'=Y'=H, R13a=methyl, Z'=acetamido;
X'=Y'=H, R13a=R13c=methyl; Z'=acetamido.

5. Derivative [(4H-thieno[3,2-b]pyrrol-5-yl)carbonyl]piperidine-4-carboxylic acid of General formula V,

in which R16a represents H, R16b represents H; lower alkyl, substituted alkyl, methoxy group, dialkylamino, 5-6-membered saturated or unsaturated heterocyclyl, substituted phenyl; cyclopentyl; phenyl, substituted lower alkyl, alkoxygroup; or R16a and R16b together with the nitrogen atom to which they are bound, form an optionally substituted azaheterocyclic, such as pyrrolidinyl; indolin-1-yl; 1,4-dioxa-8 azaspiro[4,5]Decan-8-yl; morpholinyl; piperidinyl; piperazinil, substituted alkyl, optionally substituted phenyl, 5-6-clinimetrics, in which heteroatoms selected from nitrogen, oxygen, or sulfur;
R17 is an optionally substituted alkyl;
R18 represents H or lower alkyl, excluding compounds of General formula Va

where R171=methyl, W=1-ethoxycarbonylpyrimidine-4-ylamine; 2-(W.-butyl(cyclohexyl)amino); 4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazine-1-yl; 4-(furan-2-carbonyl)piperazine-1-yl; 2-(1H-indol-3-yl)ethylamine; 3-methyl-4-m-tailpipes-1-yl;
R171=ethyl, W=benzylamino; 3,4-dimethoxyphenethylamine; 1,4-dioxy-8 azaspiro[4,5]Decan-8-yl; 4-(pyridine-2-yl)piperazine-1-yl; benzo[d][1,3]dioxol-5-ylmethylamino; 2-(1H-indol-3-yl)ethylamine; 4-(furan-2-carbonyl)piperazine-1-yl; 3-(cyclohexylthio)propylamino.

6. Derivatives of 2-(4-carbamoylbiphenyl-1-yl)-isonicotinic acid of General formula VI

in which R19a represents H, R19b represents H; lower alkyl substituted optionally substituted by phenyl, heterocyclyl, benzo[d][1,3]dioxol-5-yl;
phenyl, substituted lower alkyl, methylmercapto, alkoxygroup, fluorine. the etoxycarbonyl; 2,3-dihydrobenzo[b][1,4]dioxin-6-yl; or R19a and R19b together with the nitrogen atom to which they are bound, form an optionally substituted azaheterocyclic, such as morpholinyl or pyrrolidinyl;
R20a represents H, when R20b pre who is a substituted phenyl; or R20a and R20b together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic, which may contain an additional heteroatom selected from nitrogen, oxygen.

7. Derivatives of N-sulfonyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid of General formula VII

in which R21 represents a lower alkyl, optionally substituted phenyl;
R22a represents H, R22b is a substituted alkyl, C3-C7cycloalkyl: optionally substituted phenyl; or R22a and R22b together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic, which may contain an additional heteroatom selected from nitrogen, oxygen.

8. Derivatives of 3-benzazocin-2-amino-4,5,6,7-tetrahydrothieno[2,3-C]pyridines of General formula VIII

in which R23 is an optionally substituted alkyl, C3-C7cycloalkyl, substituted phenyl, annelirovannymi 5-6-membered azaheterocycles, 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen,oxygen or sulfur and which may be condensed with a benzene ring;
R24 is an optionally substituted alkyl, acyl, alkoxycarbonyl;
R25 represents H;
excluding compounds of General fo the mules D

where R24=methyl; R=diethylamino, di-(n)-propylamino, di-(n)-butylamino, methylbutylamine, ethylbutylamine, di-(2-propen-1-yl)amino, 1-pyrrolidinyl, 1-piperidinyl, 3-methyl-1-piperidinyl, 4-methyl-1-piperidinyl, 3,5-dimethyl-1-piperidinyl, 4-morpholinyl, di-(2-methoxyethyl)amino, methylphenylamine, (1,3 .3m-trimethyl-6-azabicyclo[3.2.1]Oct-6-yl)ethyl 4-piperidinecarboxylate;
R24=ethyl; R=diethylamino, ethyl-(n)-butylamino, di-(n)-propylamino, di-(2-propen-1-yl)amino, hexahydro-1H-azepin-1-yl, 4-methyl-1-piperazinil;
R24=ISO-propyl; R=diethylamino; ethyl-(n)-butylamino, di-(2-propen-1-yl)amino, 1-piperidinyl, 2-methyl-1-piperidinyl, 4-morpholinyl;
R24=benzyl; R=diethylamino;
R24=etoxycarbonyl; R=diethylamino; and N-[3-(2-benzothiazolyl)-4,5,6,7-tetrahydro-6-(1-methylethyl)thieno[2,3-C]pyridine-2-yl] - for 3,5-dimethoxybenzamide its hydrochloride.

9. Compounds according to claim 1, which represents the derivative of 2,6-dihydro-7H-pyrazolo[3,4-Oh!]pyridazin-7-ones of General formula 1-1,

in which i can take the values 0, 1 and 2;
R4a and R4b have the above meaning;
R26 represents H or methyl;
R27 represents H or methyl.

10. Compounds according to claim 2, representing derivatives of 1,4-dihydropyrazolo[3,4-d][1,4]thiazin-5-ones of General formula II-1,

in which K can take values 0, 1 and 2;
R9a and R9b have ieuconoe value;
R28 represents H;
R29 represents N.

11. Compounds according to claim 3, representing derivatives of 4-imidazo[1,2-a]pyridine-2-yl-anilines represented by the General formulas (III-1A and III-1b

in which R30a, R30b, R30c and R30d each independently represents H or methyl;
R31 is an optionally substituted methyl, optionally substituted benzyl, ethyl, isopropyl; phenyl substituted by fluorine, chlorine, bromine, methoxy group;
3 - and 4-pyridyl, 2-thienyl, 2-phenyl-4-methylthiazole-5-yl;
R32 represents N.

12. Compounds according to claim 4, representing derivatives of 4-imidazo[1,2-a]pyrimidine-2-yl-anilines represented by the General formula (IV-1a and IV-1b

in which R33a, R33b and R33c represent H or methyl;
R34 represents both, methyl, methoxy group;
R35 represents lower alkyl, optionally substituted by a methoxy group, a 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen and sulfur; optionally substituted phenyl; cyclopropyl; cyclopentyl;phenyl, substituted stands, a methoxy group; 2-furyl, 2-thienyl, 2-tetrahydrofuranyl, benzo[d][1,3]dioxol-5-yl.

13. Compounds according to claim 5, representing amides [(4H-thieno[3,2-b]pyrrol-5-yl)carbonyl]piperidine-4-carbon is th acid of General formula V-1

in which R16a and R16b are above value;
R18 have the above meaning;
R36 represents a methyl, ethyl, substituted benzyl.

14. Compounds according to claim 6, representing derivatives of 2-(4-carbamoylbiphenyl-1-yl)isonicotinic acid of General formula VI-1,

in which R19a and R19b are above value;
R37a represents H, R37b is a phenyl, substituted alkoxygroup
or fluorine; or R37a and R37b together with the nitrogen atom to which they are bound, form an optionally substituted azaheterocyclic, such as morpholinyl. pyrrolidinyl, piperidinyl.

15. Compounds according to claim,7, representing derivatives of N-sulfonyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid of General formula VII-1

in which R38 represents a methyl, ethyl; phenyl, optionally substituted stands, chlorine or bromine;
R39a represents H, R39b is an alkyl, substituted alkoxygroup, substituted phenyl, 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen and sulfur; cyclohexyl; phenyl,
substituted by alkyl, fluorine, alkoxygroup; or R39a and R39b together with the nitrogen atom to which they are attached, can form an optionally substituted azaheterocycle, such as, pyrrolidin, piperidin, morpholine.

16. Connection of claim 8, representing derivatives of 3-(benzothiazol-2-yl)-2-amino-4,5,6,7-tetrahydrothieno[2,3-C]pyridines of General formula VIII-1

in which R40 is an alkyl substituted by phenyl, p-tolylthiourea; cyclopropyl, cyclohexyl; phenyl substituted by chlorine, alkoxygroup, fluorine, trifluoromethyl, etoxycarbonyl; 2-thienyl, 2-furanyl, 2,3-dihydrobenzo[b][1,4]dioxin-6-yl, benzo[d]thiazol-6-yl;
R41 represents a methyl, ethyl, isopropyl, benzyl, acetyl, etoxycarbonyl.

17. Compounds according to any one of claims 1-16, representing:
2-Phenyl-3,4-dimethyl-6-{2-[4-(3-methoxyphenyl)piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-C1]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{2-[4-(3-chlorophenyl)piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{2-[4-phenylpiperazin-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{2-[4-(2,3-dimetilfenil)piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-a]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{2-[4-(2,5-dimetilfenil)piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{2-[4-(4-forfinal)piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{2-[4-(2-forfinal)piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dim the Teal-6-{1-methyl-2-[4-phenylpiperazin-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{1-methyl-2-[4-(3-chlorophenyl)piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{1-methyl-2-[4-cyclohexylpiperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{1-methyl-2-[4-(2,3-dimetilfenil)piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{1-methyl-2-[4-benzylpiperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-{1-methyl-2-[4-(2-forfinal)-piperazine-1-yl]-2-oxoethyl}-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-[2-(2,4-dimetilfenil)-3,4-dimethyl-7-oxo-2,7-dihydro-6H-pyrazolo[3,4-d]pyridazin-6-yl]-N-(2-forfinal)ndimethylacetamide;
2-Phenyl-3,4-dimethyl-6-[1-(morpholine-4-ylcarbonyl)propyl]-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-[2-(4-Were)-3,4-dimethyl-7-oxo-2,7-dihydro-6H-pyrazolo[3,4-d]pyridazin-6-yl]-N-[(5-methylfuran-2-yl)methyl]ndimethylacetamide;
2-[2-(4-Were)-3,4-dimethyl-7-oxo-2,7-dihydro-6H-pyrazolo[3,4-d]pyridazin-6-yl)-N-(2-Tien-2-retil)propanamide;
2-[2-(4-Were)-3,4-dimethyl-7-oxo-2,7-dihydro-6H-pyrazolo[3,4-d]pyridazin-6-yl]-N-(cyclopropyl)butanamide;
3-(2-Phenyl-3,4-dimethyl-7-oxo-2,7-dihydro-6H-pyrazolo[3,4-d]pyridazin-6-yl)-N-(pyridine-3-ylmethyl)propanamide;
3-(2-Phenyl-3,4-dimethyl-7-oxo-2,7-dihydro-6N-pyrazolo[3,4-d]pyridazin-6-yl)-N-(furan-2-ylmethyl)propanamide;
2-Phenyl-3,4-dimethyl-6-(3-morpholine-4-yl-3-oxopropyl)-2,6-dihydro-7H-pyrazolo[3,4-d]paidin-7-he;
3-(2-Phenyl-3,4-dimethyl-7-oxo-2,7-dihydro-6H-pyrazolo[3,4-d]pyridazin-6-yl)-N-(Tien-2-ylmethyl)propanamide;
4-[2-(4-Were)-3,4-dimethyl-7-oxo-2,7-dihydro-6H-pyrazolo[3,4-d]pyridazin-6-yl]-N-(2-furan-2-retil)butanamide;
2-(4-Were)-3,4-dimethyl-6-[4-(4-ethylpiperazin-1-yl)-4-oxobutyl]-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
2-Phenyl-3,4-dimethyl-6-(4-(morpholine-4-yl-4-oxobutyl)-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-he;
4-(2-Phenyl-3,4-dimethyl-7-oxo-2,7-dihydro-6H-pyrazolo[3,4-d]pyridazin-6-yl)-N-[(1-methylethyl)phenyl]butanamide;
2-(2-Phenyl-3,4-dimethyl-7-oxo-2H-pyrazolo[4,3-d|pyridazin-6-yl)-N-[2-(4-benzylpiperidine-1-yl)ethyl]ndimethylacetamide;
2-Phenyl-3,4-dimethyl-2H-pyrazolo[4,3-d]pyridazin-6-[2-(4-benzylpiperazine-1-yl)-4-oxoethyl]-7-he;
4-(2-p-Tolyl-3,4-dimethyl-7-oxo-2H-pyrazolo[3,4-d]pyridazin-6-yl)-N-(benzo[d][1,3]-dioxol-5-ylmethyl)butanamide;
2-p-Tolyl-3,4-dimethyl-6-[4-oxo-4-(4-(pyridin-2-yl)piperazine-1-yl)butyl]-2H-pyrazolo[3,4-d]pyridazin-7-he;
3-Methyl-4-[2-(3-methyl-4-m-tailpipes-1-yl)-2-oxo-ethyl]-1-phenyl-1,4-dihydro-pyrazolo[3,4-b][1,4]thiazin-5-he;
2-(3-Methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)-N-(3-trifluoromethyl-phenyl)ndimethylacetamide;
2-(3-Methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-bb][1,4]thiazin-4-yl)-N-pyridin-2-ylmethylene;
N-Cyclopentyl-2-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)ndimethylacetamide;
N-[2-(3,4-Acid)-ethyl]-2-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b[1,4]thiazin-4-yl)ndimethylacetamide;
N-Furan-2-ylmethyl-2-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)-ndimethylacetamide;
N-(4-Methoxybenzyl)-2-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)ndimethylacetamide;
N-Isopropyl-2-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)ndimethylacetamide;
2-(3-Methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)-N-thiophene-2-ylmethylene;
2-(3-Methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)-N-(2-morpholine-4-yl-ethyl)ndimethylacetamide;
N-Methyl-2-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)ndimethylacetamide;
4-{2-[4-(4-Chlorophenyl)piperazine-1-yl]-2-oxoethyl}-3-methyl-1-phenyl-1,4-dihydropyrazolo[3,4-b][1,4]thiazin-5-he;
3-Methyl-4-(2-oxo-2-pyrrolidin-1-yl-ethyl)-1-phenyl-1,4-dihydropyrazolo[3,4-b][1,4]thiazin-5-he;
3-Methyl-4-(2-morpholine-4-yl-2-oxoethyl)-1-phenyl-1,4-dihydropyrazolo[3,4-b][1,4]thiazin-5-he;
N-(5-Methylfuran-2-ylmethyl)-2-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)ndimethylacetamide:
N-|3-Chlorobenzyl)-4-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)butyramide;
4-(3-Methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)-1H-pyridine-2-retibution;
N-(3-Methoxyphenyl)-4-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)butyramide;
N-Furan-2-ylmethyl-4-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)butyramide;
N-(2-Methoxyethyl)-4-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-piraso what about[3,4-b][1,4]thiazin-4-yl)butyramide;
N-Methyl-4-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)butyramide;
4-(4-Azepin-1-yl-4-oxobutyl)-3-methyl-1-phenyl-1,4-dihydropyrazolo[3,4-b][1,4]thiazin-5-he;
3-Methyl-4-[4-oxo-4-(4-phenylpiperazin-1-yl)butyl]-1-phenyl-1,4-dihydropyrazolo[3,4-b][1,4]thiazin-5-he;
3-Methyl-4-(4-(morpholine-4-yl-4-oxo-butyl)-1-phenyl-1,4-dihydropyrazolo[3,4-b][1,4]thiazin-5-he;
3-Methyl-4-[4-oxo-4-(4-pyridine-2-reparation-1-yl)butyl]-1-phenyl-1,4-dihydropyrazolo[3,4-b][1,4]thiazin-5-he;
N-(4-Methoxyphenyl)-4-(3-methyl-5-oxo-1-phenyl-5,6-dihydro-1H-pyrazolo[3,4-b][1,4]thiazin-4-yl)butyramide
N-(4-Imidazo[1,2-a]pyridine-2-ylphenyl)-3-methoxybenzamide;
N-(4-Imidazo[1,2-a]pyridine-2-ylphenyl)propionamide;
N-(4-Imidazo[1,2-a]pyridine-2-yl-phenyl)-ISO-nicotinamide;
N-[-(4-Imidazo[1,2-a]pyridine-2-ylphenyl)thiophene-2-carboxamide;
4-Chloro-N-(4-imidazo[1,2-a]pyridine-2-ylphenyl)benzamide;
N-(4-Imidazo[1,2-a]pyridine-2-ylphenyl)-4-methoxybenzamide;
N-(4-Imidazo[1,2-a]pyridine-2-ylphenyl)ndimethylacetamide;
N-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]ndimethylacetamide;
N-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]propionamide;
2-Methyl-N-[4-(8-methylimidazo[1,2-a]pyridine-2-yl)phenyl]propionamide;
2-Fluoro-N-[4-(8-methylimidazo[1,2-a]pyridine-2-yl)phenyl]benzamide;
2-Methoxy-N-[4-(8-methylimidazo[1,2-a]pyridine-2-yl)phenyl]benzamide;
N-[4-(8-Methylimidazo[1.2-a]pyridine-2-yl)-phenyl]-2-phenylacetamide:
N-(3-Imidazo[1.2-a]pyridine-2-ylphenyl)propionamide;
4-Fluoro-N-(3-imidazo[1,2-a]pyridine-2-yl-phenyl)benzamide
Thiophene-2-carboxylic acid(3-imidazo[1,2-a]pyridine-2-yl-phenyl)amide;
4-Methyl-2-phenylthiazol-5-carboxylic acid [3-(7-methylimidazo[1,2-a]pyridine-2-yl)phenyl]amide;
N-(3-Imidazo[1,2-a]pyridine-2-ylphenyl)-4-methoxybenzamide;
4-Methoxy-N-[3-(5-methylimidazo[1,2-a]pyridine-2-yl)phenyl]benzamide;
N-[3-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]nicotinamide;
N-[3-(5-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]ndimethylacetamide;
Thiophene-2-carboxylic acid[3-(5-tetriminos[1,2-a]pyridine-2-yl)phenyl]amide;
N-[3-(5-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]isobutyramide;
N-[3-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]ndimethylacetamide;
N-[3-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]propionamide;
Thiophene-2-carboxylic acid[3-(8-methylimidazo[1,2-a]pyridine-2-yl)phenyl]amide;
N-[3-(8-Methylimidazo[l,2-a]pyridine-2-yl)phenyl]-2-phenylacetamide;
N-[3-(7-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]propionamide;
M-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2-bromobenzene;
4-Methyl-2-phenylthiazol-5-carboxylic acid[3-(imidazo[1,2-a]pyridine-2-yl)phenyl]amide;
N-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2-methylbenzamide;
N-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2-chlorobenzamide;
N-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2,6-dimethylbenzamide;
N-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2,6-dichlorobenzamide;
N-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2,6-diflorasone;
N-[4-(imidazo[1,2-a]pyridine-2-yl)phenyl]-2-bromobenzene;
N-[4-(imidazo[1,2-a]is iridin-2-yl)phenyl]-2-chlorobenzamide;
N-[4-(imidazo[1,2-a]pyridine-2-yl)phenyl]-2-perbenzoic;
N-[4-(5-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2-perbenzoic;
N-[4-(5-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2-chlorobenzamide;
N-[4-(5-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2-bromobenzene;
N-[4-(8-Methylimidazo[1,2-a]pyridine-2-yl)phenyl]-2-bromobenzene;
N-[4-(3,8-Dimethylimidazo[1,2-a]pyridine-2-yl)phenyl]-2-bromobenzene;
N-(4-Imidazo[1,2-a]pyrimidine-2-ylphenyl)ndimethylacetamide;
Cyclopentanecarboxylic acid (4-imidazo[1,2-a]pyrimidine-2-ylphenyl)amide;
N-(4-Imidazo[1,2-a]pyrimidine-2-ylphenyl)-2-methoxyacetate;
N-(4-Imidazo[1,2-a]pyrimidine-2-ylphenyl)-2-methoxybenzamide;
N-(4-Imidazo[1,2-a]pyrimidine-2-ylphenyl)-2-thiophene-2-ylacetamide;
N-[4-(7-Methylimidazo[1,2-a]pyrimidine-2-yl)phenyl]ndimethylacetamide;
4-Methyl-N-[4-(7-methylimidazo[1,2-a]pyrimidine-2-yl)phenyl]benzamide;
2-(4-Methoxy-phenyl)-N-[4-(7-methylimidazo[1,2-a]pyrimidine-2-yl)-phenyl]ndimethylacetamide;
Thiophene-2-carboxylic acid[4-(7-methylimidazo[1,2-a]pyrimidine-2-yl)phenyl]amide;
Tetrahydrofuran-2-carboxylic acid[4-(7-methylimidazo[1,2-a]pyrimidine-2-yl)phenyl]amide;
N-(4-Imidazo[1,2-a]pyrimidine-2-yl-phenyl) - for 3,5-dimethoxybenzamide;
Benzo[1,3]dioxol-5-carboxylic acid(4-imidazo[1,2-a]pyrimidine-2-ylphenyl)amide;
Thiophene-2-carboxylic acid(4-imidazo[1,2-a]pyrimidine-2-ylphenyl)amide;
N-(3-Imidazo[1,2-a]pyrimidine-2-ylphenyl)-3-methylbenzamide;
N-(3-Imidazo[1,2-a]pyrimidine-2-ylphenyl)-2-thiophene-2-ylacetamide;br/> Cyclopentanecarbonyl acid(3-imidazo[1,2-a]pyrimidine-2-yl-phenyl)-amide;
Furan-2-carboxylic acid(3-imidazo[1,2-a]pyrimidine-2-ylphenyl)amide;
N-(5-Imidazo[1,2-a]pyrimidine-2-yl-2-were)isobutyramide;
N-(5-Imidazo[1,2-a]pyrimidine-2-yl-2-were)-4-methoxybenzamide;
N-(5-Imidazo[1,2-a]pyrimidine-2-yl-2-were)-2-m-tolylacetic;
Thiophene-2-carboxylic acid(5-imidazo[1,2-a]pyrimidine-2-yl-2-were)amide;
N-(5-Imidazo[1,2-a]pyrimidine-2-yl-2-methoxyphenyl)ndimethylacetamide;
Cyclopropanecarboxylic acid(5-imidazo[1,2-a]pyrimidine-2-yl-2-methoxyphenyl)amide;
N-(5-Imidazo[1,2-a]pyrimidine-2-yl-2-methoxyphenyl)-3-methoxybenzamide;
N-(5-Imidazo[1,2-a]pyrimidine-2-yl-2-methoxyphenyl)-2-phenylacetamide;
Furan-2-carboxylic acid(5-imidazo[1,2-a]pyrimidine-2-yl-2-methoxyphenyl)amide;
[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrol-5-yl][4-(morpholine-4-carbonyl)piperidine-1-yl]metano;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(3,5-dimethyl-phenyl)amide;
1-(4-Methyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylic acid amide;
1-(4-Ethyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylic acid cyclopentylamine;
1-(4-Ethyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylic acid(furan-2-ylmethyl)amide;
1-(4-Ethyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylic acid 2-methoxybenzylamine;
1-(4-Ethyl-4H-thieno[3,2-b]pyrrole-5-Carboni is)piperidine-4-carboxylic acid(3-pyrrolidin-1-ylpropyl)amide;
(4-Ethyl-4H-thieno[3,2-b]pyrrol-5-yl)[4-(4-phenyl-piperazine-1-carbonyl)piperidine-1-yl]metano;
(4-Ethyl-4H-thieno[3,2-b]pyrrol-5-yl)[4-(pyrrolidin-1-carbonyl)-piperidine-1-yl]metano;
1-(4-Methyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylic acid(pyridine-2-ylmethyl)amide;
1-(4-Methyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylic acid(furan-2-ylmethyl)amide;
1-(4-Methyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylic acid 4-methoxybenzylamine;
1-(4-Methyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylic acid(2-methoxyethyl)amide;
[4-(2,3-Dihydroindol-1-carbonyl)piperidine-1-yl][4-(4-terbisil)-4H-thieno[3,2-b]pyrrol-5-yl]-methanon;
[4-(4-Ethylpiperazin-1-carbonyl)-piperidine-1-yl]-[4-(4-terbisil)-4H-thieno[3,2-b]pyrrol-5-yl]metano;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid Isopropylamine;
[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)-piperidine-1-yl]metano;
[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl][4-(piperidine-1-carbonyl)-piperidine-yl]metano;
1-[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]-piperidine-4-carboxylic acid(pyridine-3-ylmethyl)amide;
(4-Ethyl-4H-thieno[3,2-b]pyrrol-5-yl)-[4-(4-methylpiperazin-1-carbonyl)-piperidine-1-yl]metano;
[4-(1,4-Dioxa-8-Aza-Spiro[4.5]decane-8-carbonyl)piperidine-1-yl]-(4-ethyl-4H-thieno[3,2-b]pyrrol-5-yl)methanon;
(4-Methyl-4H-thieno[3,2-b]pyrrol-5-yl)-[4-(4-FeNi is piperazine-1-carbonyl)piperidine-1-yl]metano;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(pyridine-2-ylmethyl)amide:
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid cyclopentylamine;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(4-ethyl-phenyl)amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]-piperidine-4-carboxylic acid(2-morpholine-4-yl-ethyl)-amide;
[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl]-[4-(pyrrolidin-1-carbonyl)piperidine-1-yl]metano;
1-[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(2-methoxy-ethyl) - amide;
1-[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]-piperidine-4-carboxylic acid(thiophene-2-ylmethyl)amide;
1-[4-(2,4-Diferensial)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid[(pyridine-2-yl)methyl]amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(pyridine-3-ylmethyl)amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid 3-(diethylamino)propylamide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid[(4-were)methyl]amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(2,4-dimetilfenil)amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(3,4-dimetilfenil)amide;
1-[4-(4-CFT is benzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(2-methoxyethyl)amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid[(4-forfinal)methyl]amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid[(1-ethylpyrrolidin-2-yl)methyl]amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(3-ethoxypropan)amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(3-methoxypropyl)amide;
1[4-(2,4-Diferensial)-4H-thieno[3.2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(2-N-morpholinoethyl)amide;
1-[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(3-N-pyrrolidinyl)amide;
1-[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid hexamethylene;
1-[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid tetramethylene;
1-[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid[(pyridine-2-yl)methyl]amide;
1-[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid[(tetrahydrofuran-2-yl)methyl]amide;
1-[4-(4-Chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid(3-methoxypropyl)amide;
[4-(4-Terbisil)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(3-Chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]meta is he;
[4-(3-Terbisil)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(2-Terbisil)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(2-Chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(4-Methoxybenzyl)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(4-Dimethylaminobenzoyl)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(3,4-Methylenedioxybenzyl)-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(4-Chlorobenzyl)-2-methyl-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(4-Chlorobenzyl)-2,3-dimethyl-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(4-Chlorbenzyl)-2,3,6-trimethyl-4H-thieno[3,2-b]pyrrol-5-yl][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
(4-Pyridin-4-ylmethyl-4H-thieno[3.2-b]pyrrol-5-yl)[4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
(4-Cyclohexylmethyl-4H-thieno[3,2-b]pyrrol-5-yl)[4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[(4-Hydroxybenzyl-4H-thieno[3,2-b]pyrrol-5-yl)][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
(4-Pyridine-3-ylmethyl-4H-thieno[3,2-b]pyrrol-5-yl)[4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(2,4-Dichlorobenzyl-4H-thieno[3,2-b]pyrrole-5-is)][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(2,4-Dimethoxybenzyl-4H-thieno[3,2-b]pyrrol-5-yl)][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(2,4-Diferensial-4H-thieno[3,2-b]pyrrol-5-yl)][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
4-(Benzyl-4H-thieno[3,2-b]pyrrol-5-yl)[4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[4-(3,5-Dichlorobenzyl-4H-thieno[3,2-b]pyrrol-5-yl)][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
[(4-Bromobenzyl-4H-thieno[3,2-b]pyrrol-5-yl)][4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
{4-[4-(2-Hydroxyethoxy)benzyl]-4H-thieno[3,2-b]pyrrol-5-yl}[4-(4-methylpiperazin-1-carbonyl)piperidine-1-yl]metano;
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-(4-ethoxy-phenyl)-amide]4-[(3-phenylpropyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4-(3,4-dimethyl-phenyl)-amide]4'-[(4-ethoxyphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4-[(3, 5dimethylphenyl)amide]4'-[(4-ethoxyphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-[(4-ethoxyphenyl)amide]4-[(3-methylsulfinylphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-[(4-ethoxyphenyl)amide]4-[(4-isopropylphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-[(4-ethoxyphenyl)amide]4-[(2-methoxyphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-[(4-ethoxyphenyl)amide]4-[(4-forfinal)amide];
4-(IOE is Olin-4-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-carboxylic acid(4-ethoxyphenyl)amide;
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4-(4-chlorobenzylamino)4'-[(3-methoxyphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-[(3-methoxyphenyl)amide]4-[(thiophene-2-ylmethyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4-cyclopentenone 4'-[(3-methoxyphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-[(3-methoxyphenyl)amide]4-(ventilated);
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-[(2-forfinal)amide]4-[(4-isopropylphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4'-[(2-forfinal)amide]4-(3-methoxybenzylamine);
4'-(Morpholine-4-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid 4-forbindelse;
4'-(Morpholine-4-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)amide;
4'-(Pyrrolidin-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid 2-methoxy-benzylamine;
4'-(Pyrrolidin-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid (2,4-dimetilfenil)amide;
4'-(Pyrrolidin-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid (4-ethoxyphenyl)amide;
4'-(Pyrrolidin-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid (3-methoxyphenyl)amide;
4'-(piperidine-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid phenyl am is d;
4'-(piperidine-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid 4-bromobenzylamine;
4-{[4'-(piperidine-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl]amino}benzoic acid methyl ester
3,4,5,6-Tetrahydro-2H-[1,.2']bipyridinyl-4.4'-carboxylic acid 4-(2-methoxybenzylamine) 4'-[(2-methoxyphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 4-[(2,4-dimetilfenil)amide]4'-[(2-methoxyphenyl)amide];
3,4,5,6-Tetrahydro-2H-[1,2']bipyridinyl-4,4'-carboxylic acid 44(2,3-dihydrobenzo[1,4]dioxin-6-yl)amide]4'-[(2-methoxyphenyl)amide];
1-(Toluene-4-sulfonyl)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid(2,4,6-trimetilfenil)amide;
1-Methanesulfonyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid of methylamide;
1-Methanesulfonyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid 4-methoxybenzylamine;
1-Methanesulfonyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid (pyridine-2-ylmethyl)amide;
1-Methanesulfonyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid benzo[1,3]dioxol-5-alamid;
(1-Methanesulfonyl-1,2,3,4-tetrahydroquinolin-6-yl)morpholine-4-ylmethanone;
[4-(4-Forfinal)-piperazine-1-yl]-(1-Methanesulfonyl-1,2,3,4-tetrahydroquinolin-6-yl)methanon;
1-Benzazolyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid ethylamide;
1-Benzazolyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid 4-methylbenzylamine;
1-Benzazolyl-1,2,3,4-then it is carbonated shall rhinolin-6-carboxylic acid [2-(3,4-acid)ethyl]amide;
1-Benzazolyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid(pyridine-3-ylmethyl)amide;
1-Benzazolyl-1,2,3,4-tetrahydroquinolin-6-carboxylic acid(4-forfinal)amide;
(1-Benzazolyl-1,2,3,4-tetrahydroquinolin-6-yl)pyrrolidin-1-ylmethanone;
1-(Toluene-4-sulfonyl)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid(4-methoxyphenyl)amide;
1-(4-Chlorobenzenesulfonyl)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid ethylamide;
1-(4-Chlorobenzenesulfonyl)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid(furan-2-ylmethyl)amide;
1-(4-Chlorobenzenesulfonyl)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid(3,4-dimetilfenil)amide;
[1-(4-Chlorobenzenesulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl]piperidine-1-ylmethanone;
1-(4-Chlorobenzenesulfonyl)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid(2-morpholine-4-retil)amide;
1-(4-Brabanthallen)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid p-tailed;
1-(4-Brabanthallen)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid 4-methyl-benzylamine;
1-(4-Brabanthallen)-1,2,3,4-tetrahydroquinolin-6-carboxylic acid cyclohexylamine;
1-Econsultancy-1,2,3,4-tetrahydroquinolin-6-carboxylic acid (2-methoxyethyl)amide;
1-Econsultancy-1,2,3,4-tetrahydroquinolin-6-carboxylic acid (pyridine-3-ylmethyl)amide;
1-Econsultancy-1,2,3,4-tetrahydroquinolin-6-carboxylic acid (2-forfinal)amide;
(1-Econsultancy-1,2,3,4-tetr hydrochinon-6-yl)-morpholine-4-ylmethanone;
Cyclohexanecarboxylic acid (3-benzothiazol-2-yl-6-methyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
N-(3-Benzothiazol-2-yl-6-methyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)propionamide;
Cyclopropanecarboxylic acid (3-benzothiazol-2-yl-6-methyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
N-(3-Benzothiazol-2-yl-6-methyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)terephthalic acid methyl ester;
N-(3-Benzothiazol-2-yl-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)-4-chlorobenzamide;
Thiophene-2-carboxylic acid(3-benzothiazol-2-yl-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
N-(3-Benzothiazol-2-yl-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)-4-methoxybenzamide;
N-(3-Benzothiazol-2-yl-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-2-yl)ndimethylacetamide;
N-(3-Benzothiazol-2-yl-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)isobutyramide;
Furan-2-carboxylic acid (3-benzothiazol-2-yl-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
N-(3-Benzothiazol-2-yl-6-isopropyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)-4-perbenzoic;
N - (3-Benzothiazol-2-yl-6-isopropyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)ndimethylacetamide;
Thiophene-2-carboxylic acid (3-benzothiazol-2-yl-6-isopropyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
2,3-Dihydro-benzo[1,4]dioxin-6-carboxylic acid (6-acetyl-3-benzothiazol-2-yl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
Furan-2-carboxylic sour is s (6-acetyl-3-benzothiazol-2-yl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
Cyclohexanecarboxylic acid (6-acetyl-3-benzothiazol-2-yl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
N-(6-Acetyl-3-benzothiazol-2-yl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)-2-phenylacetamide;
Benzothiazole-6-carboxylic acid (6-acetyl-3-benzothiazol-2-yl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)amide;
N-(6-Acetyl-3-benzothiazol-2-yl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)-2-(4-perpenicular)ndimethylacetamide;
2-Acetylamino-3-benzothiazol-2-yl-4,7-dihydro-5H-thieno[2,3-C]pyridine-6-carboxylic acid ethyl ester;
3-Benzothiazol-2-yl-2-(4-methoxybenzylamine)-4,7-dihydro-5H-thieno[2,3-C]pyridine-6-carboxylic acid ethyl ester;
3-Benzothiazol-2-yl-2-propionamido-4,7-dihydro-5H-thieno[2,3-C]pyridine-6-carboxylic acid ethyl ester;
3-Benzothiazol-2-yl-2-(3-methoxybenzylamine)-4,7-dihydro-5H-thieno[2,3-C]pyridine-6-carboxylic acid ethyl ester;
3-Benzothiazol-2-yl-2-[(thiophene-2-carbonyl)amino]-4,7-dihydro-5H-thieno[2,3-C]pyridine-6-carboxylic acid ethyl ester;
N-(3-Benzothiazol-2-yl-6-isopropyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)-terephthalic acid methyl ester;
N-(3-Benzothiazol-2-yl-6-methyl-4,5,6,7-tetrahydrothieno[2,3-C]pyridine-2-yl)-3-cryptomelane, or their pharmaceutically acceptable salts.

18. Inhibitors of Hh-signalling cascade, which are compounds of General formula I-VIII, for the production of pharmaceutical compositions of the medicinal product






where X represents an oxygen atom or a sulfur atom; type can take the values 0, 1, 2;
R1 represents optionally substituted phenyl;
R2, R5 represents lower alkyl;
R3 represents H or lower alkyl;
R4a represents H, when R4b represents a substituted alkyl; optionally substituted phenyl, C3-C7cycloalkyl, or R4a and R4b together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic, which may contain additional heteroatoms selected from nitrogen,oxygen, and whether sulfur;. R6 represents optionally substituted phenyl;
R7 represents lower alkyl;
R8 represents H or lower alkyl;
R9a represents H, when R9b represents a possibly substituted alkyl, C3-C7cycloalkyl, substituted phenyl; or R9a and R9b together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic, which may contain additional heteroatoms selected from nitrogen, oxygen, or sulfur;. R10 represents H or Nissi is alkyl;
R11 represents an optionally substituted alkyl, C3-C7-cycloalkyl, optionally substituted phenyl, optionally substituted 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen and/or sulfur;
R12 represents H;
R13 represents H or lower alkyl;
R14 represents H, lower alkyl, alkoxygroup;
R15 represents optionally substituted alkyl, C3-C7cycloalkyl, substituted phenyl, 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen and/or sulphur, or tetrahydrofuranyl;
R16a represents H, when R16b represents H, possibly substituted alkyl, C3-C7cycloalkyl, substituted phenyl, or R16a and R16b together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic, which may contain additional heteroatoms selected from nitrogen, oxygen, or sulfur;. R17 is an optionally substituted alkyl;
R18 represents H or lower alkyl;
R19a represents H, when R19b represents H, possibly substituted alkyl, possibly substituted phenyl; 2,3-dihydrobenzo[b][1,4]dioxin-6-yl; or R19a and R19b together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic which could contain additional heteroatoms, selected from nitrogen, oxygen, or sulfur;.
R20a represents H, when R20b represents a substituted phenyl; or R20a and R20b together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic, which may contain additional heteroatoms selected from nitrogen, oxygen, or sulfur;
R21 represents a lower alkyl, optionally substituted phenyl;
R22a represents H, when R22b is a substituted alkyl; cycloalkyl; optionally substituted phenyl; or R22a and R22b together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic, which may contain additional heteroatoms selected from nitrogen,oxygen, or sulfur;
R23 represents a substituted alkyl, C3-C7cycloalkyl; optionally substituted phenyl; 5-6-membered 5-6-membered aromatic heterocyclyl, in which the heteroatoms are selected from nitrogen, oxygen or sulfur, and which may be condensed with a benzene ring;
R24 is an optionally substituted alkyl, acyl, alkoxycarbonyl;
R25 represents H.

19. Pharmaceutical composition having the properties of inhibitors of Hh-signalling cascade, containing as an active ingredient the compound according p in an effective amount.

20. Drug among the society in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing for the treatment and prevention of diseases associated with abberant activity of Hh-signalling cascade, comprising as an active ingredient an inhibitor for p or pharmaceutical composition according to claim 19.

21. Method for the treatment and prevention of diseases associated with abberant activity of Hh-signalling cascade, through the introduction of drugs in claim 20.

22. The method of treatment and prevention according to item 21, where the disease is cancer.

23. The method of treatment and prevention according to item 22, where the disease is pancreatic carcinoma.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention relates to new annelated azaheterocyclic amides, including a pyrimidine fragment, with the general formula 1, method of obtaining them and their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of P13K kinase, in compounds with the general formula 1: , where: X represents an oxygen atom, sulphur atom or not necessarily substituted at the nitrogen NH group, where the substitute is selected from lower alkyls and possibly a substituted aryl; Y represents an atom of nitrogen or substituted at the carbon atom CH group, where the substitute is selected from lower alkyls; Z represents an oxygen atom; R1 represents a hydrogen atom or not necessarily substituted C1-C6alkyl, or Z represents a nitrogen atom, which is together with a carbon atom, with which it is joined, form through Z and R1 annelated imidazole cycle; R2 and R3 independently from each other represent hydrogen, not necessarily substituted with C1-C6alkyl, C3-C6cycloalkyl, not necessarily substituted with phenyl, not necessarily substituted with 6-member aza-heteroaryl, under the condition, when Y represents a nitrogen atom, or R2 and R3 independently from each other represent not necessarily substituted C1-C6alkyl, not necessarily substituted with phenyl, not necessarily substituted with 5-7-member heterocycle with 1-2 heteroatoms, selected from nitrogen and oxygen, and possibly annelated with a phenyl ring, under the condition, when Y does not necessarily represent a substituted carbon atom at the CH group, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents a substituted aminoC1-C6alkyl and not necessarily substituted 5-6-member aza-heterocycloalkyl, under the condition, when Y represents a group which is substituted at the CH atom, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents phenyl which is not necessarily substituted, pyridyl which is not necessarily substituted, pyrimidinyl which is not necessarily substituted, under the conditions, when R1 represents a substituted aminoC1-C6alkyl, substituted C2-C3hydroxyalkyl and aza-heterocycloalkyl not necessarily substituted, Y represents a group with CH substituted, and X represents an oxygen atom, sulphur, and the substitute of the above indicated substituted alkyl, phenyl, heterocycle, pyridyl, pyrimidyl are selected from groups of hydroxyl-, cyano-groups, hydrogen, lower alkyls, possibly mono- or di-substituted lower alkyl sulfamoyl, carbamoyl, C1-C6alkoxycarbonyl, amino, mono- or di-lower alkyl-amine, N-(lower alkyl), N-(phenylC1-C6alkyl)amine, phenyl, possibly substituted with a halogen atom, C1-C6alkyl, haloid-C1-C6alkyl; phenylC1-C6alkyl, saturated or non-saturated 5-6-member heterocycle containing 1-2-heteroatoms, selected from nitrogen, oxygen and sulphur, and possible condensation with a benzene ring R4 represents hydrogen or a lower alkyl.

EFFECT: obtaining new annelated aza-heterocyclic amides, including a pyrimidine fragment, with the general formula with the possibility of their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of PI3K kinase.

16 cl, 5 tbl, 5 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: present invention relates to mono-sodium salt 5-[[(2,3-difluorophenyl)methyl]thio]-7-[[2-hydroxy-1-(hydroxymethyl)-1-methylethyl]amino]thiazole[4,5-d]pyrimidine-2(3H)-on as a modulator of the activeness of chemokine receptors, method of obtaining it and pharmaceutical composition on its basis, and also its application in production of medicinal agents.

EFFECT: obtaining compounds, which can find application in treatment of diseases mediated by chemokine receptors, such as asthma, allergic rhinitis, COPD (chronic obstructive pulmonary disease), inflammatory bowel disease, osteoarthritis, and rheumatoid arthritis.

10 cl, 2 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: present invention relates to new condensed dicyclic nitrogen-containing heterocycles with the general formula (I), their pharmaceutically accepted salts and stereoisomers, possessing DGAT inhibiting action. In the compound of formula (I): , X is selected from a group, which consists of C(R1) and N; Y is selected from a group, which consists of C(R1), C(R2)(R2), N and N(R2); Z is selected from a group, which consists of O; W1 is selected from cyclo(C3-C6)alkyl, aryl and 5- or 6-member heteroaryl, containing 1-2 heteroatoms, selected from a group, which comprises of nitrogen and sulphur, W2 selected from cyclo(C3-C8)alkyl, (C5-C6)heterocycloalkyl, containing 1 or 2 heteroatoms, selected from groups, consisting of nitrogen or oxygen, benzol and 5-or 6-member heteroaryl, containing 1-2 nitrogen atoms as heteroatoms, L1 is the link; L2 is selected from a group consisting of links, 0, (C1-C4)alkylene and (C1-C4)oxyalkylene; m denotes 0 or 1; its not a must that when m denotes 1 and L2 denotes a link, the substitute for W2 can be integrated with the substitute for W1 forming a 5-or 6-member ring, condensed with c W1 forming a spiro-system or condensed with W2, where specified ring could be saturated or unsaturated and has 0 or 1 atom O, as a member of the ring R1 is H; R2 is H; R3 and R4 are independently selected from groups consisting of H and (C1-C8) alkyl; optionally, R3 and R4 can together form 3-, 4-, 5- or 6-member spirorings, R5 and R6 are independently H; optionally, when Y includes the group R1 or R2, R5 or R6 can be joined with R1 and R2 forming a 5- or 6-member condensate ring, containing a nitrogen atom, to which R5 or R6 are joined, and optionally containing an oxo-group; R7 is selected from a group, composed of H, (C1-C8) alkyl, halogen(C1-C4)alkyl, 0Ra and NRaRb ; Ra selected from groups composed of H and (C1-C8)alkyl; and Rb selected from groups consisting of H and (C1-C8)alkyl; a dotted line indicates a possible bond. The invention also relates to pharmaceutical compositions and applications of the compounds.

EFFECT: obtaining compounds which can be used for getting medicinal agents to treat or prevent diseases or a mediated action state of DGAT, such as obesity, diabetes, syndrome X, resistance of insulin, hyperglycemia, hyperinsulinemia, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, disease of non-alcoholic fatty infiltration of the liver, atherosclerosis, arteriosclerosis, coronary artery disease and myocardial infarction.

33 cl, 17 dwg, 11 tbl, 391 ex

FIELD: chemistry.

SUBSTANCE: in general formula (I) , R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 can be similar or different and represent, each independently, hydrogen, halogen, hydroxyl, unsubstituted (C1-C6)alkyl, (C1-C6)alkoxy, or neighbouring groups R2 and R3 together with carbon atoms to which they are bound, can form benzol ring; R13 and R14 can be similar or different and represent each independently, hydrogen, unsubstituted (C1-C6)alkyl, optionally, R13 and R14 together with nitrogen atom can form 5-, 6-member heterocyclic ring, where heterocycle also can be substituted (C1-C6)alkyl, and it can have "additional heteroatoms", selected from O, N; "n" is an integer in interval from 1 to 4, and carbon chain, to which it relates is linear.

EFFECT: compound possess the characteristic of activity modulators 5-HT and can be applied for treatment of such diseases as anxiety, depression, convulsive syndromes, migraine.

15 cl, 67 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new derivatives of 2-pyridinecarboxamide and their pharmaceutical salts, which have glucokinase activating properties. In formula (I): D represents O or S; R2 and R3 each represents a hydrogen atom; formula (II) represents triazole group, imidazole group, thiazole group and pyridine group, which can have in the ring, 1 or 2 substitutes; formula (III) represents a thiazole group, thiadiazole group, isoxazolyl group, pyrazine group, pyridothiazolyl group or pyridyl group, ring B can have 1 or 2 substitutes. The invention also relates to pharmaceutical compositions based on the invented compounds.

EFFECT: new derivatives can be used for treating such diseases as sugar diabetes.

19 cl, 5 tbl, 165 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula II as neuropeptide FF receptor antagonist, their pharmaceutically acceptable acid-additive salts, medication based on them, as well as their application. Compounds can be applied for treatment and prevention of diseases mediated by activity of neuropeptide FF receptor, such as pain, hyperalgesia, enuresis, for elimination of syndromes arising in case of alcohol, psychotropic and nicotine addiction, for regulation of insulin release, digestion, memory functions, blood pressure or electrolytic and energy exchange. In general formula II , A together with thiazole ring forms 4,5,6,7-tetrahydrobenzothiazole, 5,6,7,8-tetrahydro-4H-cycloheptathiazole, 5,6-dihydro-4H-cyclopentathiazole fragments; R1 represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tret-butyl, 1,1-dimethylpropyl or phenyl; R2-R6 each represents hydrogen or methyl.

EFFECT: obtaining solutions, which ca be used for treatment and prevention of diseases, mediated by activity of neuropeptide FF receptor.

6 cl, 4 tbl, 106 ex

FIELD: chemistry.

SUBSTANCE: invention was targeted at obtaining crystals of acetonitrile solvate of 6-fluor-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolene-4-yl)methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (compound B), which is an intermediate compound in obtaining crystals of 6-fluor-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolene-4-yl)methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid of III type (compound A). Compound B crystals are mostly precipitated by regulation of super-saturation during crystallisation involving acetonitrile as a solvent. Then compound A crystals of III type are obtained crystal desolvation.

EFFECT: increased efficiency of compounds.

6 cl, 4 dwg, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention refers to cyclic sulphonamide derivatives of general formula I where bonds indicated with wavy lines represent mutually cis- in relation to cyclohexane ring; R3 represents H or hydrocarbon group having up to 10 carbon atoms; Ar1 and Ar2 independently represent phenyl which carries 0-3 substitutes independently selected from halogen, CF3, CHF2; or its pharmaceutically acceptable salt. Besides, invention refers to technology of compounds of general formula I and to pharmaceutical composition based on compounds of general formula I and applied as gamma-secretase inhibitor.

EFFECT: new derivatives of cyclic sulphonamide, activating gamma-secretase inhibition and suitable for treatment and prevention of Alzheimer's disease.

9 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to the obtaining of the new derivatives of benzamide of the formulas (I), which possess the activating influence on glucokinase, which can be used for treating of diabetes and obesity: where X1 and X2 represent oxygen, R1 represents alkylsufonyl, alkaneyl, halogen or hydroxyl; R2 represents alkyl or alkenyl, R3 represents alkyl or hydroxyalkyl, ring A represents phenyl or pyridyl, the ring B represents thiazolyl, thiadiazolil, isoxazoleyl, pyridothiazolyl or pyrazolyl, in which the atom of carbon of ring B, which is connected with the atom of nitrogen of the amide group of the formula(I), forms C=N bond with ring B.

EFFECT: obtaining new bioactive benzamides.

12 cl, 166 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention is related to the compound of general formula 1 or its tautomer or pharmaceutically acceptable salt, where W selected from N and CR4; X is selected from CH(R8), O, S, N(R8), C(=O), C(=O)O, C(=O)N(R8), OC(=O), N(R8)C(=O), C(R8)-CH and C(=R8); G1 - bicyclic or tricyclic condensed derivative of azepin, selected from general formulas 2-9 , or derivative of aniline of common formula 10 , where A1, A4, A7 and A10 are independently selected from CH2, C=O, O and NR10; A2, A3, A9, A11, A13, A14, A15, A19 and A20 are independently selected from CH and N; or A5 stands for covalent connection, and A6 represents S; or A5 stands for N=CH, and A6 represents covalent connection; A8 , A12 , A18 and A21 are independently selected from CH=CH, NH, NCH3 and S; A16 and A17 both represent CH2, or one from A16 and A17 represents CH2, and the one another is selected from C=O, CH(OH), CF2, O, SOc and NR10; Y is selected from CH=CH or S; R1 and R2 are independently selected from H, F, Cl, Br, alkyl, CF3 and group O-alkyl; R3 is selected from H and alkyl; R4-R7 are independently selected from H, F, Cl, Br, alkyl, CF3, OH and group O-alkyl; R8 is selected from H, (CH2)bR9 and (C=O)(CH2)bR9; R9 is selected from H, alkyl, possibly substituted aryl, possibly substituted heteroaryl, OH, groups O-alkyl, OC(=O)alkyl, NH2, NHalkyl, N(alkyl)2, CHO, CO2H, CO2alkyl, CONH2, CONHalkyl, CON(alkyl)2 and CN; R10 is selected from H, alkyl, group COalkyl and (CH2)dOH; R11 is selected from alkyl, (CH2)dAr, (CH2)dOH, (CH2)dNH2, group (CH2)aCOOalkyl, (CH2)dCOOH and (CH2)dOAr; R12 and R13 are independently selected from H, alkyl, F, CI, Br, CH(OCH3)2, CHF2, CF3, groups COOalkyl, CONHalkyl, (CH2)dNHCH2Ar, CON(alkyl)2, CHO, COOH, (CH2)dOH, (CH2)dNH2, N(alkyl)2, CONH(CH2)dAr and Ar; Ar is selected from possibly substituted heterocycles or possibly substituted phenyl; a is selected from 1, 2 and 3; b is selected from 1, 2, 3 and 4; c is selected from 0, 1 and 2; and d is selected from 0, 1, 2 and 3. Besides, the invention is related to pharmaceutical compound and to method for activation of vasopressin receptors of type 2.

EFFECT: compounds according to invention represent agonists of receptor of vasopressin V2, which stipulates for their application (another object of invention) for preparation of medicine for treatment of condition selected from polyuria, including polyuria, which is due to central diabetes insipidus, nocturnal enuresis of nocturnal polyurea, for control of enuresis, to postpone bladder emptying and for treatment of disorders related to bleeds.

21 cl, 228 ex

FIELD: medicine.

SUBSTANCE: invention offers analogues of quinazoline of the formula I

where A is bound at least with one of atoms of carbon in position 6 or 7 of the dicyclic ring; X represents N. A represents the group Q or Z including tautomeric group Z form where Q and Z, have the formulas resulted more low in which symbols and radicals, have the value specified in item 1 of the formula of the invention. R1 represents phenyl, substituted -(G)nOAr or -O(G)nAr and where phenyl is unessentially replaced by halogen or C1-C10alkyl; where G represents C1-C4alkylene, n is peer 0 or 1. And Ar represents phenyl either pyridyl or thiazolyl where Ar is unessentially substituted by 1-2 substituents chosen from halogen or C1-C10alkyl; R2 and R3 represent N. The bonds of the formula I are inhibitors of the receptor tyrosine kinases of type 1. The invention includes also a way of treatment of hyperproliferative diseases, such as a cancer, application of bonds of the formula 1 in manufacture of medical products and pharmaceutical composition on the basis of these bonds.

EFFECT: rising of efficiency of a composition and the method of treatment.

14 cl, 6 dwg, 63 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new annelated azaheterocyclic amides, including a pyrimidine fragment, with the general formula 1, method of obtaining them and their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of P13K kinase, in compounds with the general formula 1: , where: X represents an oxygen atom, sulphur atom or not necessarily substituted at the nitrogen NH group, where the substitute is selected from lower alkyls and possibly a substituted aryl; Y represents an atom of nitrogen or substituted at the carbon atom CH group, where the substitute is selected from lower alkyls; Z represents an oxygen atom; R1 represents a hydrogen atom or not necessarily substituted C1-C6alkyl, or Z represents a nitrogen atom, which is together with a carbon atom, with which it is joined, form through Z and R1 annelated imidazole cycle; R2 and R3 independently from each other represent hydrogen, not necessarily substituted with C1-C6alkyl, C3-C6cycloalkyl, not necessarily substituted with phenyl, not necessarily substituted with 6-member aza-heteroaryl, under the condition, when Y represents a nitrogen atom, or R2 and R3 independently from each other represent not necessarily substituted C1-C6alkyl, not necessarily substituted with phenyl, not necessarily substituted with 5-7-member heterocycle with 1-2 heteroatoms, selected from nitrogen and oxygen, and possibly annelated with a phenyl ring, under the condition, when Y does not necessarily represent a substituted carbon atom at the CH group, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents a substituted aminoC1-C6alkyl and not necessarily substituted 5-6-member aza-heterocycloalkyl, under the condition, when Y represents a group which is substituted at the CH atom, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents phenyl which is not necessarily substituted, pyridyl which is not necessarily substituted, pyrimidinyl which is not necessarily substituted, under the conditions, when R1 represents a substituted aminoC1-C6alkyl, substituted C2-C3hydroxyalkyl and aza-heterocycloalkyl not necessarily substituted, Y represents a group with CH substituted, and X represents an oxygen atom, sulphur, and the substitute of the above indicated substituted alkyl, phenyl, heterocycle, pyridyl, pyrimidyl are selected from groups of hydroxyl-, cyano-groups, hydrogen, lower alkyls, possibly mono- or di-substituted lower alkyl sulfamoyl, carbamoyl, C1-C6alkoxycarbonyl, amino, mono- or di-lower alkyl-amine, N-(lower alkyl), N-(phenylC1-C6alkyl)amine, phenyl, possibly substituted with a halogen atom, C1-C6alkyl, haloid-C1-C6alkyl; phenylC1-C6alkyl, saturated or non-saturated 5-6-member heterocycle containing 1-2-heteroatoms, selected from nitrogen, oxygen and sulphur, and possible condensation with a benzene ring R4 represents hydrogen or a lower alkyl.

EFFECT: obtaining new annelated aza-heterocyclic amides, including a pyrimidine fragment, with the general formula with the possibility of their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of PI3K kinase.

16 cl, 5 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: novel chemical compounds of formula (I) or their pharmaceutically acceptable salts possess inhibiting activity with respect to kinase p-38 MAP and kinase FGFR, and can be used in treatment of such diseases as arthritis, obstructive lung disease, Alzheimer's disease or oncological and other diseases. In general formula (I) , R1 is hydrogen, R2 is 6-member oxygen-containing heterocyclyl, aryl, selected from unsubstituted phenyl or phenyl substituted with aliphatic acyl group which contains 1-6 carbon atoms, halogen cyano, hydroxyl, C1-6alkylsulfinyl, C1-6alkylsulfonyloxy, C1-6alkylsulfonyl, C1-6alkylsulfanyl, tret-butydimethylsilanyloxy, 6-member heterocyclyl, containing 1-2-heteroatoms, selected from nitrogen and oxygen, R3 is C1-6alkyl, Ar1 is phenyl, substituted with 1-2 substituents, selected from atoms of halogen, C1-6alkyl, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, X1 is oxygen and X2 is chemical bond.

EFFECT: efficient application of invention compounds in pharmaceutical composition.

13 cl, 1 tbl, 64 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: invention relates to application of the substituted esters of 1,2,3,7-tetrahydro-pyrrolo [3,2-f][1,3]benzoxazine-5-carboxylic acid of general formula 1 or their racemoids, or their pharmaceutically acceptable and/or hydrates as substances of pharmaceutical compositions having anti-influenza virus activity: , where: R1 and R4 independently represent amines substitute selected from hydrogen, optionally substituted by liner or branched alkyl, containing 3-12 carbon atoms, optionally substituted cycloalkyl containing 3-10 carbon atoms, optionally substituted aryl, and probably, annelated heterocyclyl, which can be aromatic or non-aromatic and contains from 3 to 10 atoms in the ring, with one or several heteroatoms selected from nitrogen, oxygen or sulphur or their oxides; R2 represents alkyl substitute selected from hydrogen, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl; R5 represents substitute of the cyclic system selected from hydrogen, optionally substituted linear or branched alkyl, containing 3-12 carbon atoms, optionally substituted cycloalkyl containing 3-10 carbon atoms optionally substituted aryl or optionally substituted and optionally substituted annelated heterocyclyl, which can be aromatic or non-aromatic and contains from 3 to 10 atoms in the ring with one or several heteroatoms selected from nitrogen, hydrogen or sulphur or their oxides; R6 represents substitute of cyclic system selected from hydrogen, halogen atom, cyano group, optionally substituted aryl or optionally substituted annelated heterocycle, which can be aromatic or non-aromatic and contains from 3 to 10 atoms in the ring with one or several heteroatoms selected from nitrogen, hydrogen or sulphur or their oxides.

EFFECT: production of the pharmaceutical compositions having anti-influenza virus activity.

12 cl, 2 dwg, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to non-peptide antagonists GnRH, with general formula 1 , where each of A1, A2 and A3 are independently chosen from A5 and A6; and A4 represents either a covalent bond, or A5; under the condition that, if A4 is a covalent bond, then one of A1-A3 represent A6, and the other two represent A5, and that, if A4 represents A5, then all of A1-A3 represent A5; A5 is chosen from C-R13 and N; A6 is chosen from N-R14, S and O; R1 is chosen from H, NHY1 and COY2, and R2 represents H; or and R1, and R2 represents methyl or together represent =O; each of R3, R4 and R5 independently represents H or low alkyl; each of R6, R7, R8, R9, R10, R11 and R12 are independently chosen from H, NH2, F, CI, Br, O-alkyl and CH2NMe2; R13 is chosen from H, F, CI, Br, NO2, NH2, OH, Me, Et, OMe and NMe2; R14 is chosen from H, methyl and ethyl; W is chosen from CH and N; X is chosen from CH2, O and NH; Y1 is chosen from CO-low alkyl, CO(CH2)bY3, CO(CH2)bCOY3 and CO(CH2)bNHCOY3; Y2 is chosen from OR15, NRI6R17 and NH(CH2)cCOY3; Y3 is chosen from alkyl, OR15 and NR16R17; R15 represents H; each of R16 and R17 is independently chosen from H, low alkyl and (CH2)aR18, or together represent -(CH2)2-Z-(CH2)2-; R18 is chosen from OH, pyridyl, pyrizinyl and oxadiazolyl; Z represents NH; a represents 0-4; and b and c represent 1-3. The invention also relates to use of formula 1 a compound as a therapeutic agent and pharmaceutical composition, with antagonistic effect to GnRH receptor. Description is also given of the method of obtaining compounds with the given formula.

EFFECT: obtaining new compounds, with useful biological properties.

27 cl, 70 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of the formula (1a) or its pharmaceutically acceptable salt, esters or imides where A is a thiophenyl group containing, probably, substitution, the thiophenyl group A containing, probably, substitution with one or several groups as follows: alkyl, halo or arylalkyl, Y is O, S or NR2 where R2 is hydrogen or alkyl group containing 1 to 6 carbon atoms, and R1 is an non-ramified alkyl group containing 6 to 25 carbon atoms, ramified alkyl group containing 6 to 25 carbon atoms, aryl alkyl group where the alkyl group contains 2 to 25 carbon atoms or phenyl group containing substitution with one or several groups as follows: phenyloxy, phenylthio, SO2-phenyl, alkylphenyl, CO-phenyl, CONR16- phenyl, NR16CO-phenyl or NR16 -phenyl containing, probably, substitution where R16 is hydrogen or alkyl group containing 1 to 4 carbon atoms, the groups phenyloxy, phenylthio, SO2-phenyl, alkylphenyl, CO-phenyl, CONR-phenyl or NR-phenyl containing, probably, substitution with one or several groups as follows: halo, alkyl, alkylhalo or phenyl group containing substitution with one or several groups or alkyl groups provided the above compound is not 5-methyl-2-(4-metoxyphenyl)amino-4H-thieno[2,3-d][1,3]oxazine-4-on, 6-amyl-2-(4-chlorophenyl)amino-4H-thieno[2,3-d][1,3]oxazine-4-on or 6-amyl-2-(4-metoxyphenyl)amino-4H-thieno[2,3-d][1,3]oxazine-4-on Invention also relates to method of obtaining compounds of the formula (Ia) or (IIa), to pharmaceutical compound and application, as well as cosmetic technique.

EFFECT: obtaining of new biologically active compounds and pharmaceutical compounds based on them.

27 cl, 4 ex, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): , wherein X represents heteroatom, such as oxygen (O) or sulfur (S) atoms; X and Z mean independently of one another one or some identical or different substitutes bound any available carbon atom and they can represent hydrogen atom or halogen atom; R1 represents a substitute of the formula (II): , wherein R2 and R3 can represent simultaneously or independently of one another hydrogen atom or (C1-C4)-alkyl, or R1 can represent hydrogen, halogen atom, (C1-C7)-alkyl, -CHO, -(CH2)2COOH, -(CH2)2CO2Et, (CH2)mL wherein L means -OH or bromine atom (Br); m represents a whole number from 1 to 3; n represents a whole number from 0 to 3; Q1 and Q2 represent independently of one another oxygen atom or group of the formula: wherein substitutes y1 and y2 represent hydrogen atom, and to their pharmacologically acceptable salts. Also, invention relates to use of these compounds as intermediate substances used in synthesis of novel compounds of dibenzoazulene class, and to their using for preparing drugs.

EFFECT: valuable medicinal properties of compounds.

9 cl, 4 tbl, 13 ex

FIELD: organic chemistry, medicine, pharmacy, chemical technology.

SUBSTANCE: invention relates to novel substituted esters of 1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazin-5-carboxylic acids of the general formula (1): or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and/or hydrates possessing the antiviral effect. In compounds of the general formula (1) each R1 and R4 represents independently of one another a substitutes of amino group chosen from hydrogen atom, optionally substituted linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and possibly an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides; R2 represents alkyl substitute chosen from hydrogen atom, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl or cycloalkyl; R5 represents a substitute of cyclic system chosen from hydrogen atom, optionally substituted linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and optionally an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides; R6 represents a substitute of cyclic system chosen from hydrogen atom, halogen atom, cyano group, optionally substituted aryl or optionally substituted and optionally annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides. Also, invention relates to methods for treatment, drugs and pharmaceutical compositions using compounds of this invention. Proposed compounds can be used as active components of drugs used in treatment of such diseases as infectious hepatitis, human immunodeficiency, atypical pneumonia and avian influenza.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods of synthesis.

22 cl, 3 tbl, 6 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the method for preparation of hexachloroantimonates of 2,3-dihydro[1,3]thiazolium of general formula wherein R1 is alkyl or phenyl, R2 is alkyl, phenyl or hydrogen, R1+R2 is cycloalkyl by the interreaction of 4,6-dimethyl-2-pyrimidinsulfenyl chloride with corresponding olefine in presence of antimony pentachloride in equimolar ratio in the media of methylene chloride.

EFFECT: claimed compounds can be used in production of pharmaceutical preparations and biologically active substances.

2 ex

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