Source: https://russianpatents.com/patent/237/2379292.html
Timestamp: 2019-12-10 15:37:12
Document Index: 796910727

Matched Legal Cases: ['§ 38', '§ 38', '§ 38', '§ 42', '§ 42', '§ 38', '§ 45', '§ 51', '§ 42']

Pyrazole derivatives as phosphodiesterase 4 inhibitors
1. The compound of formula II, III, V Il is VI
L represents a simple bond; -(CH2)nCONH-; -(CH2)nCON(CH2CH3)-; (CH2)nSO2, (CH2)nCO2or C1-C6linear or branched alkylen,
which is unsubstituted or substituted by oxo or hydroxy;
n has a value from 0 to 3;
R1represents a C1-4alkyl, which is unsubstituted or
R3represents H, C1-8alkyl, C3-8cycloalkyl, pyridylmethyl,3-6cycloalkyl1-6alkyl,
phenyl, which is unsubstituted or substituted by one or two substituents selected from halogen, alkyl, alkoxy, halogenated C1-6of alkyl, halogenated C1-6alkoxy, nitro, amino, carboxy, cyano, alkylsulfonyl or morpholinyl,
heterocyclic group which is saturated, partially saturated or fully unsaturated, and which is monocyclic and has 5-6 atoms in the ring, or bicyclic and has 9-10 atoms in the ring, where 1-2 atom in the ring are N, O or S and which is unsubstituted or substituted by one or two substituents selected from halogen, alkyl and alkoxycarbonyl, or
phenylalkyl having 7 to 9 carbon atoms, which is unsubstituted or substituted by one or two substituents selected from halogen, alkyl, alkoxy, halogenated C1-6of alkyl, amino, carboxy, nitro, alkoxycarbonyl, alkylsulfonyl and arylsulfonyl;
heterocyclisation group, which is saturated, partially saturated or fully unsaturated, and which is monocyclic and has 5-6 atoms in the ring, or bicyclic and has 9-10 atoms in the ring, where 1-2 atom in the ring are N, O or S and which is unsubstituted or substituted by one or two substituents in the heterocyclic ring, selected from halogen, phenyl, alkyl, alkoxy, cyano, halogenated alkyl, nitro, oxo, amino, alkylamino, dialkylamino or carboxy, and/or is substituted in the alkyl group, halogen, oxo or cyano,
cycloalkenyl having from 4 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, oxo, alkyl, or
alkoxyalkyl having from 3 to 8 carbon atoms;
R4and R5each represents a C1-6alkyl;
R6represents a C3-8cycloalkyl,
R7represents H; and
R8represents H, carboxy, C2-6alkoxycarbonyl, -CO-C1-6alkyl or C1-6Ala is l, which is unsubstituted or substituted with one to three substituents selected from halogen and hydroxyl,
where the specified connection may be in the form of mixtures of enantiomers such as the racemate, or mixture of diastereomers, or can be in the form of a single enantiomer or a single diastereoisomer.
2. The compound according to claim 1, where the specified compound selected from compounds of formulas II, III, V and VI:
L represents a simple bond; -(CH2)nCONH-; (CH2)nSO2-, (CH2)nCO2
or C1-C6linear or branched alkylene, which is unsubstituted or substituted by oxo or hydroxy;
phenyl, which is unsubstituted or substituted by one or two substituents selected from halogen, alkyl, alkoxy, nitro, amino, carboxy or cyano,
heterocyclic group which is saturated, casticin is saturated or fully unsaturated, and which is monocyclic and has 5-6 atoms in the ring, or bicyclic and has 9-10 atoms in the ring, where 1-2 atom in the ring are N, O or S and which is unsubstituted or substituted by one or two substituents selected from halogen and alkyl,
phenylalkyl having 7 to 9 carbon atoms, which is unsubstituted or substituted by one or two substituents selected from halogen, alkyl, alkoxy, CF3, amino, carboxy, alkoxycarbonyl and alkylsulfonyl;
heterocyclyl-alkyl group, which is saturated, partially saturated or fully unsaturated, and which is monocyclic and has 5-6 atoms in the ring, or bicyclic and has 9-10 atoms in the ring, where 1-2 atom in the ring are N, O or S and which is unsubstituted or substituted by one or two substituents in the heterocyclic ring, selected from halogen, phenyl, alkyl, alkoxy, cyano, halogenated alkyl, nitro, oxo, amino, alkylamino, dialkylamino or carboxy, and/or is substituted in the alkyl group, halogen, oxo or cyano,
R4and R5each is own the th C 1-6alkyl;
R8represents H, carboxy, C2-6alkoxycarbonyl, -CO-C1-6alkyl or C1-6alkyl, which is unsubstituted or substituted one to three times by halogen,
3. The compound according to claim 1, where the specified compound selected from the compounds of formula II.
4. The compound according to claim 1, where the specified compound selected from the compounds of formula III.
5. The compound according to claim 1, where the specified compound selected from compounds of formula V.
6. The compound according to claim 1, where the specified compound selected from the compounds of formula VI.
7. The compound according to claim 1, where the specified compound is a compound of formula II or V, and R1represents CH3or CF2H.
8. The compound according to claim 1, where R3represents phenyl, bromophenyl, nitrophenyl, forfinal, trifloromethyl, methoxyphenyl, carboxyphenyl, dimetilfenil or methylpyridyl.
9. The compound according to claim 1, where R3is a 4-carboxyphenyl, 2,3-differenl, 4-were, 4-tert-butylphenyl, 4-methoxyphenyl is, 3,4-differenl or 4-forfinal.
10. The compound according to claim 1, where R3represents a cyclohexyl or cyclopentyl.
11. The compound according to claim 1, where R3represents ethyl, CH(CH3)2, n-propyl, n-butyl or tert-butyl.
12. The compound according to claim 1, where R3represents thiazolyl or benzothiazolyl.
13. The compound according to claim 1, where R3represents benzyl or phenethyl, which in each case is substituted or unsubstituted.
14. The compound according to claim 1, where R3represents benzyl, methylbenzyl, tert-butylbenzyl, methoxybenzyl, dimethoxybenzyl, carboxybenzoyl, tormentil, diferential, cryptomelane, chlorbenzyl, nitrobenzyl, methoxycarbonylbenzyl or phenethyl.
15. The compound according to claim 1, where the specified compound is a compound of formula II or V, and R4represents CH3.
16. The compound according to claim 1, where the specified compound is a compound of formula III or VI, and R5represents CH3or CH2CH3.
17. The compound according to claim 1, where the specified compound is a compound of formula III or VI, and X represents CH.
18. The compound according to claim 1, where the specified compound is a compound of formula III or VI, and X represents N.
19. The compound according to claim 1, where L is a bond, CH CH2CH2CH2WITH,
CH2CO2or CH2CONH.
20. The compound according to claim 1, where n is 0 or 1.
21. The compound according to claim 1, where R8represents N, CH3C2H5, CF3, hydroxymethyl, 2-(2-hydroxy)propyl, carboxy, etoxycarbonyl or CH3WITH.
22. The compound according to claim 1, where the specified compound has the formula II or V, and R1represents CH3or CF2H.
23. The compound according to claim 1, where the specified compound has the formula II or V, R1represents CH3or CF2H a R3represents optionally substituted phenyl, optionally substituted heterocycle, With1-8alkyl or C3-8cycloalkyl.
24. The compound according to claim 1, where the specified compound has the formula II or V, R1represents CH3or CF2H and R3represents a 2-(6-methyl-pyridyl), 2-cyanophenyl, 2,3-differenl, 2-were, 4-nitrophenyl, 4-AMINOPHENYL, phenyl, pyridyl, cyclohexyl, cyclopentyl, ethyl, tert-butyl, tetrahydroisoquinoline, 7-isoindolyl or 4-methylsulfinylphenyl.
25. The compound according to claim 1, where the specified compound has the formula II or V, R1represents CH3or CF2H and R4represents CH3.
26. The compound according to claim 1, where the specified compound has the formula II or V, R1is Soboh the CH 3or CF2H, R3represents phenyl, benzyl, phenethyl, cyclohexyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-trifloromethyl, 4-bromophenyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 3,5-dimethoxybenzyl, 3-tormentil, 2,6-diferensial, 4-tormentil, 3,4-diferensial or 4-carboxybenzoyl and L is a bond, CH2CH2CH2or CH2CONH.
27. The compound according to claim 1, where the specified compound has the formula II or V, R1represents CH3or CF2H, R3represents phenyl, benzyl, phenethyl, cyclohexyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-trifloromethyl, 4-bromophenyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 3,5-dimethoxybenzyl, 3-tormentil, 2,6-diferensial, 4-tormentil, 3,4-diferensial or 4-carboxybenzoyl, L is a bond, CH2CH2CH2or CH2CONH and R4represents CH3.
28. The compound according to claim 1, where the specified compound has the formula III or VI, and R3represents optionally substituted phenyl, optionally substituted heterocycle, With1-8alkyl or C3-8cycloalkyl.
29. The compound according to claim 1, where the specified compound has the formula III or VI and R5represents alkyl having from 1 to 3 carbon atoms.
30. The compound according to claim 1, where the specified compound has the formula III or VI and R6is cycloalkyl having from 4 to 7 carbon atoms.
31. The compound according to claim 1, where the specified compound has the formula III or VI, R3represents optionally substituted phenyl, optionally substituted heterocycle, With1-8alkyl or C3-8cycloalkyl, R5represents CH2CH3and R6is cyclopentyl.
32. The compound according to claim 1, where the specified compound has the formula III or VI, R3represents optionally substituted phenyl, optionally substituted heterocycle, With1-8alkyl or C3-8cycloalkyl, R5represents CH2CH3, R6is cyclopentyl, X represents CH and L is
a CH2CH2CH2CH2CH2CH2CH2CO, CH2CO2, SO2or CH2CONH.
33. The compound according to claim 1, where the specified connection is selected from the following compounds:
3-(2-acetyl-7-methoxybenzophenone-4-yl)-1H-pyrazole;
3-[(1-cyclopentyl-3-ethylindole)-6-yl]-1H-pyrazole;
3-(2-acetyl-7-methoxybenzophenone-4-yl)-1-(2-methylbenzyl)-1H-pyrazole;
3-[(1-cyclopentyl-3-ethylindole)-6-yl]-1-(2,3-diferensial)-1H-pyrazole;
3-[(1-cyclopentyl-3-ethylindole)-6-yl]-1-(4-carboxyphenyl)-1H-pyrazole;
3-[(1-cyclopentyl-3-this is indazol)-6-yl]-1-(4-methoxyphenyl)-1H-pyrazole;
3-[(1-cyclopentyl-3-ethylindole)-6-yl]-1-(2-methylbenzyl)-1H-pyrazole;
3-[(1-cyclopentyl-3-ethylindole)-6-yl]-1-(4-methylsulfonylbenzoyl)-1H-pyrazole;
3-[(1-cyclopentyl-3-ethylindole)-6-yl])-1-(2-pyridylmethyl)-1H-pyrazole;
5-[(1-cyclopentyl-3-ethylindole)-6-yl])-1-(2-pyridylmethyl)-1H-pyrazole;
and their pharmaceutically acceptable salts, where in each case the compound can be in the form of mixtures of enantiomers such as the racemate, or mixture of diastereomers, or can be in the form of a single enantiomer or a single diastereoisomer.
34. The compound according to claim 1, where the specified connection is selected from the following compounds:
3-(2-acetyl-7-methoxybenzophenone-4-yl)pyrazole;
3-[(1-cyclopentyl-3-ethylindole)-6-yl]pyrazole,
3-(2-acetyl-7-methoxybenzophenone-4-yl)-1-(2,3-diferensial)pyrazole,
3-(2-acetyl-7-methoxybenzophenone-4-yl)-1-(4-methylsulfonylbenzoyl)pyrazole,
3-[(1-cyclopentyl-3-ethylindole)-6-yl]-1-(2,3-differenl)pyrazole,
3-[(1-cyclopentyl-3-ethylindole)-6-yl])-1-(2-methylbenzyl)pyrazole,
3-[(1-cyclopentyl-3-ethylindole)-6-yl])-1-(4-methylsulfonylbenzoyl)pyrazole,
3-[(1-cyclopentyl-3-ethylindole)-6-yl])-1-(2-pyridylmethyl)pyrazole,
and their pharmaceutically acceptable salts, where in each case the compound can be in the form of mixtures of enantiomers such as the racemate, or mixture of diastereomers, or can be in the form of an individual enantiomer or otdelnov is the diastereoisomer.
35. The compound according to claim 1, where the specified connection is selected from the following compounds:
3-(2-acetyl-7-methoxybenzophenone-4-yl)pyrazole,
36. Pharmaceutical composition having inhibitory activity against PDE4 enzyme, comprising the compound according to any one of claims 1 to 35 and a pharmaceutically acceptable carrier.
37. The pharmaceutical composition according p where connection provides a dose of 0.1-50 mg
38. The use of compounds according to any one of claims 1 to 35 for the preparation of medicines intended to improve cognitive abilities and/or treatment of psychosis.
39. The application of § 38, where the specified compound is administered in a unit dosage form suitable for injection of the compounds in an amount of 0.01-100 mg/kg of body weight per day.
40. Application pop, where the specified compound is administered in a unit dosage form suitable for administration person.
41. The application of § 38, where the specified drug is intended for treatment of deterioration or weakening of cognitive abilities.
42. The application of § 38, where the specified drug is intended for treatment of memory loss.
43. The application of § 42, where the specified drug is intended for treatment of memory loss associated with Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, a disease of the Peak, disease, Jakob-Creutzfeldt, HIV, cardiovascular disease, head trauma or age-related weakening of cognitive abilities.
44. The application of § 42, where the specified drug is intended for treatment of memory loss associated with dementia.
45. The application of § 38, where the specified drug is intended for treatment of psychosis.
46. The application of § 45, where the specified drug is intended for the treatment of schizophrenia, bipolar or manic depression or severe depression.
47. A method of treating a patient suffering from a disease involving decreased camp levels, including the introduction of a specified patient an effective amount of a compound according to any one of claims 1 to 35.
48. The application is connected to the I according to any one of claims 1 to 35 for the preparation of a medicinal product, designed for treatment of a patient suffering from an allergic or inflammatory disease.
49. Use p, where the specified drug is intended for treatment of chronic obstructive pulmonary disease.
50. Use p, where the specified drug is intended to treat asthma.
51. The use of compounds according to any one of claims 1 to 35 for the preparation of medicinal products intended for treatment of a patient suffering from neurodegeneration, caused by disease or injury.
52. The application of § 51, where the illness or injury is a stroke, spinal cord injury, Alzheimer's disease, multiple sclerosis, aminosterols or multiple system atrophy.
53. The application of § 42, where the specified drug is intended for treatment of memory loss associated with Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, a disease of the Peak, disease, Jakob-Creutzfeldt, depression, aging, head trauma, stroke, CNS hypoxia, cerebral dementia, multi-infarct dementia, acute neural disease, HIV or heart disease.
54. The use of compounds according to any one of claims 1 to 35 for the preparation of medicines intended for the treatment of the patient is and, suffering from drug or morphine addiction.
55. A method of inhibiting PDE4 enzyme to improve cognitive abilities and/or treatment of psychosis in a patient, comprising the introduction of a specified patient an effective amount of a compound according to any one of claims 1 to 35.