Derivatives of thieno[2,3-d]pyrimidine-2,4(1h,3h)-dione, pharmaceutical composition, method of its receipt, the method of immunosuppression and a method of treating or reducing the risk of airway obstruction

 

The invention relates to new derivatives of thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione of General formula (I) or their pharmaceutically-acceptable salts, having immunosuppressive activity. The invention also relates to a pharmaceutical composition, its preparation, method of immunosuppression and to a method of treating or reducing the risk of airway obstruction. In the compounds of General formula (I), R represents-C(O)Ar1, -C(R4) (R5)Ar1or Ar2; Ar1represents naphthyl, hinely, ethanolic or benzofuranyl, or AG1represents phenyl, optionally substituted by one or more substituents selected from C1-4-alkyl, C1-4-alkoxy, halogen, trifloromethyl, amino, nitro, cyano, triptoreline, phenoxy, -CH2N(R6)2, -NHSO2CF3C1-4-alkylsulfonyl, -NHC(O)R6a, CO2R7or-C(O)NR8R8a; R4represents H; R5represents H or HE; each R6and R7represents N or C1-4-alkyl; R6arepresents H, C1-6is alkyl, aryl or aryl-C1-4-alkyl, where the aryl group or the aryl portion in arylalkyl group is phenyl or pyridyl, each of which can Brawley N, C1-4-alkyl, phenyl or pyridyl; AG2is acenaphtene, indanyl, iminodiacetonitrile or fluorenyl, each of which may be optionally substituted by one or more substituents, R1and R2independently represent C1-6-alkyl, C3-6alkenyl, CH2With3-5-cycloalkyl or3-6-cycloalkyl; R3is N, X-R9or X-AG3; X represents S(O)nC(O)NR10With(O)O, NH(CO)NR10, NH(CO)O or SO2NR10; n is 0, 1 or 2; X, R9and R10specified in the claims, and AG3represents phenyl, pyridyl or N-oxide of pyridine, each of which may be optionally substituted by one or more substituents selected from HE, NO2, NH2, -NS2CF3C1-4-alkoxy, bis-C1-4-alkanesulfonyl, C1-4-alkylcarboxylic or C1-4-alkoxycarbonyl. 6 C. and 11 C.p. f-crystals.

Description text in facsimile form (see graphic part)e

Claims

1. The compound of formula (I)

where R is-C(O)Ar1, -C(R4)(R5)Ardstanley phenyl, optionally substituted by one or more substituents selected from C1-4-alkyl, C1-4-alkoxy, halogen, trifloromethyl, amino, nitro, cyano, triptoreline, phenoxy, -CH2N(R6)2, -NHSO2CF3With1-4-alkylsulfonyl, -NHC(O)R6a, CO2R7or-C(O)NR8R8a;

R4is N;

R5represents H or HE;

each R6represents N or C1-4-alkyl;

R6arepresents H, C1-6is alkyl, aryl or aryl-C1-4-alkyl, where the aryl group or the aryl portion in arylalkyl group is phenyl or pyridyl, each of which may be optionally substituted by one or more substituents selected from C1-4-alkyl, C1-4-alkoxy, C1-4-alkylcarboxylic, halogen or trifloromethyl;

R7represents N or C1-4-alkyl;

R8and R8a, each independently, represent H, C1-4-alkyl, phenyl or pyridyl;

AG2is acenaphtene, indanyl, mindigit-benzofuranyl or fluorenyl, each of which may be optionally substituted by one or more substituents selected from HE, C1-4-alkyl, C1-4-alkoxy, halogen 2With3-5-cycloalkyl or3-6-cycloalkyl;

R3is N, X-R9or X-AG3;

X represents S(O)nC(O)NR10C(O)O, NH(CO)NR10, NHC(O)O or SO2NR10;

n is 0, 1 or 2;

R9represents a methyl group, optionally substituted by one or more substituents selected from CN, CO2H, C1-5-alkoxycarbonyl, 5-tetrazolyl, SO2NH2or C(O)NR11R12or R9is2-6-alkyl or C3-6alkenyl, each of which may be optionally substituted by one or more substituents selected from HE, CN, CO2H, C1-5-alkoxy, C1-5-alkoxycarbonyl, 5-tetrazolyl, azide, phthalimido, SO2NH2C(O)NR11R12, NR13R14, NHC(O)R15or NHSO2R16where R11, R12, R13and R14each independently represents N or C1-4-alkylamino or alkoxyalkyl containing up to 6 carbon atoms, and R16represents C1-4-alkyl or trifluoromethyl;

or, optionally, in the case where X is C(O)NR10, NH(CO)NR10or SO2NR10, R9and R10together with the nitrogen atom to which they are attached, can obrazovym the groups;

R10represents H, C1-6-alkyl or associated with R9as defined above, and

Ar3represents phenyl, pyridyl or N-oxide of pyridine, each of which may be optionally substituted by one or more substituents selected from HE, NO2, NH2, -NHSO2CF3With1-4-alkoxy, bis-C1-4-alkanesulfonyl, C1-4-alkylcarboxylic or1-4-alkoxycarbonyl;

or its pharmaceutically acceptable salt.

2. Connection on p. 1, where Ar1represents naphthyl, chinolin or benzofuranyl or phenyl group, optionally substituted by one or two substituents selected from C1-4of alkyl, C1-4-alkoxy, halogen, trifloromethyl, nitro, amino, cyano, phenoxy or-NHC(O)R6a.

3. Connection under item 1 or 2, where R4represents H, methyl or ethyl.

4. The compound according to any one of paragraphs.1-3, where Ar2represents indanyl, iminodiacetonitrile or gidroksilimonna of indanyl.

5. The compound according to any one of paragraphs.1-4, where R1and R2represent, independently, C1-4-alkyl, C3-4alkenyl or3-6-cycloalkyl.

6. The compound according to any one of the preceding paragraphs, where R9represents a methyl group, not the optionally substituted by one or two substituents, selected from HE, CO2H, C1-5-alkoxycarbonyl, azide, phthalimido, NR13R14, NHC(O)R15or NHSO2R16or R9and R10together with the nitrogen atom to which they are attached, form a 5 - or 6-membered heterocyclic ring which may be optionally substituted HE group.

7. The compound according to any one of the preceding paragraphs, where R10represents H, methyl, or linked to R9as defined in paragraph 1.

8. The compound according to any one of the preceding paragraphs, where each of R11, R12, R13and R14represent hydrogen.

10. The compound according to any one of the preceding paragraphs, where R16represents methyl or trifluoromethyl.

11. The compound according to any one of the preceding paragraphs, where AG3represents phenyl, pyridyl or N-oxide of pyridine, each of which may be optionally substituted by one or two substituents selected from HE, NO2, NH2, methoxy, bistanbulholiday, methylcobalamin or methoxycarbonylamino.

12. Connection on p. 1, selected from the group including:

6-(4-Methoxyphenethyl)-3-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(4-Methoxyphenethyl)-3-methyl-1-(2-methyl-2-propenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

1-(2-Methylprop[2,3-d]-pyrimidine-2,4(1H,3H)-dione,

3-Methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-5-[(2-pyridinyl)thio]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

5-[(3-Hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl-6-(1-naphthaleneacetic)thieno [2,3-d] pyrimidine-2,4(1H,3H)-dione,

Methyl-4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)thio]butanoate,

4-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1 naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)thio]butane acid,

Methyl-4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)sulfinil] butanoate,

Methyl 4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)sulfonyl] butanoic,

4-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)sulfonyl]butane acid,

6-Benzyl-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

3-Methyl-1-(1-methylethyl)-6-(phenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-phenyl)methyl]-3-methyl-1-(2-methylpropyl " thieno[2,3-d] pyrimidine-2,4(1H,3H)-dione,

()-5-[(2-Hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

1,2,3,4-Tetrahydro-N-(2-hydroxyethyl)-3-methyl-1-(2-methylpropyl the l)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]carbonyl}pyrrolidin-3-ol,

1-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]carbonyl}piperidine-4-ol,

(3R)-1-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]carbonyl}piperidine-3-ol,

1,2,3,4-Tetrahydro-M-(2-hydroxyethyl)-3,N-dimethyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-carboxamide,

2-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]carboxamido} acetic acid,

3-([1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]carboxamido}propanoic acid,

2-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]carboxamido}ndimethylacetamide,

1-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]carbonyl}pyrrolidin,

1,2,3,4-Tetrahydro-N-(2-hydroxyethyl)-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-sulfonamide,

5-[(3-Methoxyphenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

5-[(3-Hydroxyphenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

3-Methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-5-[(3-nitrophenyl)thio]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

5-[(3-AMINOPHENYL)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

5-{[3-{(Biomethanation)amino}phenyl]thio}-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4 (1H,3H)-dione,

5-[(3-Methoxycarbonylaminophenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4-(1H,3H)-dione,

5-[(3-Acetamidophenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

3-Methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-5-[(4-nitrophenyl)thio]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

5-[(4-AMINOPHENYL)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

3-Methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-5-[(5-nitropyridine-2-yl)thio]thieno [2,3-d] pyrimidine-2,4(1H,3H)-dione,

N-Oxide 2-{[1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]thio} pyridine,

5-[(3-Azithromy)thio)]-3-methyl-1-(2-methylpropyl)-6-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

5-[(3-Aminopropyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-3,4{1H,3H)-dione,

N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-who propyl)-6-(1-naphthaleneacetic]-2,4-dioxolane[2,3-d]pyrimidine-5-yl)thio]propyl)-N, N'-dimethyloxetane,

N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)thio]propyl]methoxyacetate,

Methyl-N-{3-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)thio]propyl}carbamate,

N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)thio]propyl)methanesulfonamide,

N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl)thio]propyl)triftormetilfullerenov,

5-([3-(1,3-Dihydro-1,3-dioxo-2H-isoindole-2-yl)propyl]thio}-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

N-(2-Hydroxyethyl)-N'-[1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d] pyrimidine-5-yl)]urea,

2-Hydroxyethyl-[1,2,3,4-tetrahydro-3-methyl-1-(2-methyl-propyl)-6-(1-naphthaleneacetic)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]carbamate,

N-(2-Hydroxyethyl)-N-methyl-N'-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-neftaliclothes)-2,4-dioxolane[2,3-d]pyrimidine-5-yl]urea,

6-[(1-Hydroxy-1-(3-forfinal))methyl]-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(3-Forfinal)methyl]-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

terphenyl))methyl]-3-methyl-1-(2-methylpropyl " thieno [2,3-d] pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-(3-cyanophenyl))methyl]-3-methyl-1-(2-methylpropyl " thieno [2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-(3-triptoreline))methyl]-3-methyl-1-(2-methylpropyl " thieno [2,3-d] pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-(3-phenoxyphenyl))methyl]-3-methyl-1-(2-methylpropyl " thieno [2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-(1-naphthalenyl))methyl]-3-methyl-1-(2-IU-ylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-(6-chinoline))methyl]-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-(4-chinoline))methyl]-3-methyl-1-(2-IU-ylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

()-6-[1-(Benzo[b]furan-2-yl)-1-hydroxymethyl]-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)dione,

6-[(1-Hydroxy-1-(2-chloro-6-forfinal))methyl]-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-phenyl)ethyl]-3-methyl-1-(2-methylpropyl)-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-(4-triptoreline))methyl]-3-methyl-1-(2-methylpropyl " thieno [2,3-d]pyrimidine-2,4(1H,3H)-dione,

()-6-(2,3-Dihydro-1-hydroxy-1H-indenyl)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-(2-chinoline))methyl]-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-[(1-Hydroxy-1-[3-chinoline]methyl]-3-methyl-1-(2-methylpropyl)Tien is 6-(2-Methylphenylethyl)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(3-Cyanovinylene)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione,

6-(3-Triftormetilfullerenov)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(3-Phenylenevinylene)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

3-Methyl-1-(2-methylpropyl)-6-(4-hyalinella)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

3-Methyl-1-(2-methylpropyl)-6-(6-hyalinella)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

3-Methyl-1-(2-methylpropyl)-6-(2-hyalinella)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, salt triperoxonane acid,

6-(2-Benzo[b]furylmethyl)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(2-Chloro-5-performer)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(1-Phenylethyl)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(4-Triftormetilfullerenov)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

()-6-(2,3-Dihydro-1H-inden-1-yl)-3-methyl-1-(2-methylpropyl " thieno [2,3-d] pyrimidine-2,4(1H,3H)-dione,

6-(3-Imino-1,3-dihydrobenzo[C]furan-1-yl)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

2-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxolane[2,3-d] pyrimidine-6-yl)methyl]benzamide,

()-6-(1-Hydroxy-1-[1-naphthalenyl]methyl)-5-([3-hydroxypropyl]thio)-3-methyl-1-(2-methylpropyl)-dione,

()-5-[(3-Hydroxybutyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(3-Forfinal)methyl-5-[(3-hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

5-[(5-Amino-2-pyridinyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthaleneacetic)thieno [2,3-d] pyrimidine-2,4(1H,3H)-dione,

Ethyl 1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-phenylmethyl-2,4-dioxolane[2,3-d]pyrimidine-5-carboxylate,

1,2,3,4-Tetrahydro-3,N,N-trimethyl-1-(2-methylpropyl)-6-phenylmethyl-2,4-dioxolane[2,3-d]pyrimidine-5-carboxamide,

6-[1-Hydroxy-(4-nitrophenyl)methyl]-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(4-Nitrophenylamino)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

6-(4-Aminophenylamino)-3-methyl-1-(2-methylpropyl " thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,

4-(3,4-Acid)-N - {4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxolane[2,3-d]pyrimidine-6-yl)-methyl]phenyl}butanamide and

3-Acetamido-N-(4-[1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxolane [2,3-d]pyrimidine-6-yl)methyl]phenyl)benzamide.

13. Pharmaceutical composition having immunosuppressive activity, comprising a compound of formula (I) or its pharmaceutically acceptable salt according to any one of paragraphs.1-12 in conjunction with the pharmaceutical and under item 13, having immunosuppressive activity, which involves mixing the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of paragraphs.1-12 with a pharmaceutically acceptable adjuvant, diluent or carrier.

15. The compound of formula (I) or its pharmaceutically acceptable salt according to any one of paragraphs.1-12, having immunosuppressive activity.

16. The way immunosuppression, including introduction to the patient a therapeutically effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of paragraphs.1-12.

17. A method of treating or reducing the risk of reversible airway obstruction in a patient suffering from the said disease or having a risk of such a disease, comprising the administration to a patient a therapeutically effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of paragraphs.1-12.

 

Same patents:

The invention relates to novel condensed to thienopyrimidine formula I and their physiologically acceptable salts, having the effect of inhibitors of phosphodiesterase V(PDE V), and which can be used for the treatment of diseases of the cardiovascular system and for the treatment and/or therapy of disorders of potency

The invention relates to compounds of formula (1), where X and Y Is N or O; R1substituted alkyl, substituted arylalkyl or cycloalkyl; R2and R3Is h or alkyl; And a Is-C(O)-, -OC(O)-, -S(O)2-; R4- alkyl, cycloalkyl or (C5-C12)aryl; compounds of the formula (2), where X and Y are O, S or N; R1- alkyl, optionally substituted arylalkyl; R2and R3Is h or alkyl;- C(O)-; R6- Deputy, including the condensed heterocyclic rings; and compounds of the formula (3), where X and Y are O, S or N; R1- alkyl, alkylsilane, (C5-C12)arylalkyl, (C5-C12)aryl; R2and R3Is h or alkyl; R2' and R3' - N; R11, R12and E together form a mono - or bicyclic ring which may contain heteroatoms

The invention relates to new thienopyrimidine formula I, their pharmaceutically acceptable salts, having the effect of inhibitors of phosphodiesterase V, which can be used to combat diseases of the cardiovascular system and for the treatment and/or therapy of disorders, to pharmaceutical compositions in a form suitable for the treatment

-converting enzyme)" target="_blank">

The invention relates to novel ortho-sulfonamidophenylhydrazine heteroaryl hydroxamic acids of the formula

< / BR>
where W and X are both carbon, T is nitrogen, U represents CR1where R1represents hydrogen, or alkyl containing 1-8 carbon atoms, R represents-N(CH2R5)-SO2Z, Q represents -(C=O)-NHOH, with

< / BR>
is a benzene ring, or is a heteroaryl ring of 5 to 6 atoms in the cycle, which may contain 0-2 heteroatoms selected from nitrogen, oxygen and sulfur, in addition to the heteroatom of nitrogen, denoted as W, where benzene or heteroaryl ring may optionally contain one or two substituent R1where permissible; Z is phenyl, which is optionally substituted by phenyl, alkyl with 1-8 carbon atoms, or a group OR2; R1represents halogen, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl from 1 to 4 carbon atoms, phenyl, optionally substituted by 1-2 groups OR2group-NO2group -(CH2)nZ, where Z is a phenyl which allows an alkyl with 1-8 carbon atoms, phenyl, optionally substituted with halogen, or heteroaryl radical containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; R5represents hydrogen, alkyl with 1-8 carbon atoms, phenyl, or heteroaryl containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; or their pharmaceutically acceptable salts

The invention relates to new thienopyrimidine General formula I or their physiologically acceptable salts, having the properties of an inhibitor of phosphodiesterase V, which can be used in the pharmaceutical industry for the treatment of diseases of the cardiovascular system, in particular heart failure, and for treatment of violations of a potentiality

The invention relates to sulfonamidnuyu to the compound of formula I, where R1- alkyl, alkenyl, quinil; a represents optionally substituted heterocyclic group, excluding benzimidazolyl, indolyl, 4,7-dehydrobenzperidol and 2,3-dihydrobenzofuranyl; X - alkylene, oxa, oxa(lower) alkylene; R2- optional substituted aryl, substituted biphenyl, its salts and pharmaceutical compositions comprising this compound

The invention relates to new thienopyrimidine, as well as their physiologically acceptable salts with inhibitory activity against phosphodiesterase V (PDE V), which can be used to combat diseases of the cardiovascular system and for the treatment and/or therapy of disorders of potency

The invention relates to thiophene derivative of the formula I, in which Ra and Rb may be the same or different and mean hydrogen, alkyl, acyl, alkenyl, phenyl, or Ra and Rb together may form a benzene ring or cyclohexanone ring, its pharmaceutically acceptable salts and hydrates

The invention relates to inhibitors tyrosinekinase type bis-indolylmaleimide compounds of the formula I

< / BR>
where Z denotes a group of General formula II

< / BR>
where A, B, X, Z, R1-R10have the meanings indicated in the claims, as well as the way they are received and drug based on these compounds

The invention relates to novel condensed to thienopyrimidine formula I and their physiologically acceptable salts, having the effect of inhibitors of phosphodiesterase V(PDE V), and which can be used for the treatment of diseases of the cardiovascular system and for the treatment and/or therapy of disorders of potency

The invention relates to new derivatives of N, S-substituted N'-1-[(hetero)aryl] -N'-[(hetero)aryl] methylisothiazoline General formula I or their salts with pharmacologically acceptable acids HX in the form of a racemic mixture or in the form of a mixture of stereoisomers, which can be used for the treatment and prevention of diseases associated with dysfunction glutamatergic nanoperiodic

The invention relates to new derivatives of N, S-substituted N'-1-[(hetero)aryl] -N'-[(hetero)aryl] methylisothiazoline General formula I or their salts with pharmacologically acceptable acids HX in the form of a racemic mixture or in the form of a mixture of stereoisomers, which can be used for the treatment and prevention of diseases associated with dysfunction glutamatergic nanoperiodic

The invention relates to new sulfadimethoxine bellrowan five-membered cyclic compounds of General formula I

< / BR>
where R(1), R(2) mean N; R(3) means R(10b)-CnH2nwhere n=0, 1; R(10b) means methyl; R(4) means R(13)-CrH2rwhere r=0, 1, 2, 3, 4, 5, 6; R(13) means methyl, nitrogen-containing aromatic 6-membered heterocycle; R(5), R(6) R(7) R(8) independently of one another denote H, F, Cl, Br, I, -NO2, -Y-CsH2s-R(18); Y represents-O-; s=1, 2, 3, 4, 5, 6; R(18)=H, methyl; X is-CR(22)R(23)-, -SO2- where R(22) R(23) means H or methyl, and their physiologically acceptable salts

The invention relates to new N-sulfonylpiperidinylmethylene derivative of the formula I

< / BR>
where n = 1; R1means1-C6alkyl, C3-C6cycloalkyl,2-C6alkenyl, C1-C6haloalkyl or a group NR11R12where R11and R12each independently from one another mean H, C1-C6alkyl; R2means N; R3means1-C6alkyl; R4, R5, R6and R7have the same or different values and each independently from one another mean H, C1-C4alkyl; R8means C1-C6alkyl; a represents C1-C6alkylen; means phenyl, optionally substituted by 1-3 substituents, which may be the same or different and selected from the group comprising C1-C8alkyl, C1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy, C2-C8alkanoyl, halogen, C1-C8alkoxycarbonyl, nitro; or naphthyl or thienyl

The invention relates to new derivatives of 2-aminopyridine F.-ly (1) where denotes unsubstituted or substituted phenyl, pyridyl, thienyl, thiazolyl, hinely, cinoxacin-2-yl or Antonelliana derivatives; D is unsubstituted or substituted phenyl, pyridyl, thienyl, pyrimidyl, indolyl, thiazolyl, imidazolyl, hinely, triazolyl, oxazolyl, isoxazolyl or Antonelliana derivatives, provided that C and D are not simultaneously have the following values: S - phenyl, and D is phenyl, S - phenyl, and D - pyridyl, With - pyridyl and D - phenyl, - pyridyl and D - pyridyl; R1- R4- hydrogen, NO2or NH2

The invention relates to new triazolo[4,5-d]pyrimidine compounds of General formula (I) or their pharmaceutically acceptable salts, which have the effect of P2T-antagonists, in particular, show inhibitory platelet aggregation activity
Up!