1. A centrifugal compressor comprising a rotary shaft, a circular plate supported by the rotary shaft, and a plurality of blades substantially radially disposed and protruding from the circular plate, and having flow channels formed between the blades, in order to suck fluid from a front area in a shaft direction by rotating the circular plate with the rotary shaft and then discharge the fluid, which increases in pressure while passing through the flow channels, in a centrifugal direction,
wherein, assuming that a blade angle of a shroud side facing the circular plate of the blade is a first angle and a blade angle of a hub side disposed at the circular plate is a second angle,
the shroud side is formed in a curved shape having an angle distribution from the front area in the shaft direction toward the centrifugal direction in which the first angle is the local maximum point before a substantially middle portion and the local minimum point after the substantially middle point, and
the hub side is formed in a curved shape having an angle distribution from the front area in the shaft direction toward the centrifugal direction in which the second angle is the maximum local point before the substantially middle portion.
2. A centrifugal compressor comprising a rotary shaft, a circular plate supported by the rotary shaft, and a plurality of blades substantially radially disposed and protruding from the circular plate, and having flow channels formed between the blades, in order to suck fluid from a front area in a shaft direction by rotating the circular plate with the rotary shaft and then discharge the fluid, which increases in pressure while passing through the flow channels, in a centrifugal direction,
wherein, assuming that a blade angle of a shroud side facing the circular plate of the blade is a first angle and a blade angle of a hub side disposed at the circular plate is a second angle,
the shroud side is formed in a curved shape having a plurality of angle distributions from the front area in the shaft direction toward the centrifugal direction in which the first angle is alternately the local maximum point and the local minimum point, and
the hub side is formed in a curved shape having an angle distribution from the front area in the shaft direction toward the centrifugal direction in which the second angle is the local maximum point before a substantially middle portion.
3. A centrifugal compressor comprising a rotary shaft, a circular plate supported by the rotary shaft, and a plurality of blades substantially radially disposed and protruding from the circular plate, and having flow channels formed between the blades, in order to suck fluid from a front area in a shaft direction by rotating the circular plate with the rotary shaft and then discharge the fluid, which increases in pressure while passing through the flow channels, in a centrifugal direction,
a flow channel adjacent to a fluid intake of the shroud side of the blade facing the circular plate of the blade is enlarged and at least one of a flow channel adjacent to a fluid outlet of the shroud side and a fluid outlet of the hub side at the circular plate is reduced.
4. The centrifugal compressor according to claim 3, wherein the flow channel adjacent to the fluid intake is enlarged by tapering the shroud side at a predetermined angle in the shaft direction, and
the flow channel adjacent to the fluid outlet of the shroud side or the fluid outlet of the hub side at the circular plate is reduced by tapering the shroud side toward the centrifugal direction at a predetermined angle.
5. The centrifugal compressor according to claims 1, wherein an angle made by a straight line connecting the shroud side of the fluid outlet with the hub side and an edge of the circular plate that is perpendicular to the rotary shaft is in the range of 60\xb0 to 90\xb0 in a tangential direction of the circular plate.
6. The centrifugal compressor according to claims 2, wherein an angle made by a straight line connecting the shroud side of the fluid outlet with the hub side and an edge of the circular plate that is perpendicular to the rotary shaft is in the range of 60\xb0 to 90\xb0 in a tangential direction of the circular plate.
7. The centrifugal compressor according to claims 3, wherein an angle made by a straight line connecting the shroud side of the fluid outlet with the hub side and an edge of the circular plate that is perpendicular to the rotary shaft is in the range of 60\xb0 to 90\xb0 in a tangential direction of the circular plate.
8. The centrifugal compressor according to claims 1, wherein the shroud side is formed in an S-shape, and the hub side is formed in an S-shape.
9. The centrifugal compressor according to claims 2, wherein the shroud side is formed in an S-shape, and the hub side is formed in an S-shape.
10. The centrifugal compressor according to claims 3, wherein the shroud side is formed in an S-shape, and the hub side is formed in an S-shape.
11. The centrifugal compressor according to claim 1, wherein a width of the blade is gradually reduced from the end of the fluid discharging side of the flow channel to the downstream.
12. The centrifugal compressor according to claim 2, wherein a width of the blade is gradually reduced from the end of the fluid discharging side of the flow channel to the downstream.
13. The centrifugal compressor according to claim 1, wherein the end is formed in a cylindrical shape having elliptical surface such that a long axis is arranged in a direction of the flow channel and a short axis is arranged in a width direction of the blade.
14. The centrifugal compressor according to claim 2, wherein the end is formed in a cylindrical shape having elliptical surface such that a long axis is arranged in a direction of the flow channel and a short axis is arranged in a width direction of the blade.
15. The centrifugal compressor according to claim 1, wherein the end is formed in a semi-circular cylinder shape.
16. The centrifugal compressor according to claim 2, wherein the end is formed in a semi-circular cylinder shape.
17. The centrifugal compressor according to claim 1, wherein the end is formed in an edge shape.
18. The centrifugal compressor according to claim 2, wherein the end is formed in an edge shape.
19. An impeller of a centrifugal compressor comprising a rotary shaft and an impeller having a plurality of blades substantially radially disposed and protruding from a circular plate supported by the rotary shaft, and having flow channels formed between the blades, in order to suck fluid from a front area in a shaft direction by rotating the circular plate with the rotary shaft and then discharge the fluid, which increases in pressure while passing through the flow channels, in a centrifugal direction,
wherein, assuming that a blade angle of a shroud side facing the circular plate of the blade is a first angle and a blade angle of a hub side disposed at the circular plate is a second angle,
the shroud side is formed in a curved shape having an angle distribution from the front area in the shaft direction toward the centrifugal direction in which the first angle is the local maximum point before a substantially middle portion and the local minimum point after the substantially middle point, and
the hub side is formed in a curved shape having an angle distribution from the front area in the shaft direction toward the centrifugal direction in which the second angle is the maximum local point before the substantially middle portion.
20. A method of operating a centrifugal compressor including a rotary shaft and an impeller having a plurality of blades substantially radially disposed and protruding from a circular plate supported by the rotary shaft, and having flow channels formed between the blades, in order to suck fluid from a front area in a shaft direction by rotating the circular plate with the rotary shaft and then discharge the fluid, which increases in pressure while passing through the flow channels, in a centrifugal direction,
wherein, assuming that a blade angle of a shroud side facing the circular plate of the blade is a first angle and a blade angle of a hub side disposed at the circular plate is a second angle,
deceleration flow is promoted at a front half region of the flow channel and acceleration flow is promoted at a rear half region of the flow channel by the impeller that has the shroud side formed in a curved shape having an angle distribution from the front area in the shaft direction toward the centrifugal direction in which the first angle is the local maximum point before a substantially middle portion and the local minimum point after the substantially middle point, and the hub side is formed in a curved shape having an angle distribution from the front area in the shaft direction toward the centrifugal direction in which the second angle is the maximum local point before the substantially middle portion.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, diluent or excipient and at least one pyrazolo pyridine derivative according to Formula (I):
wherein G1is selected from H, optionally substituted alkyl, optionally substituted C3-C8-cycloalkyl alkyl, optionally substituted heterocycloalkyl alkyl, optionally substituted aryl alkyl and optionally substituted heteroaryl alkyl;
G2is selected from H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted alkyl aryl, optionally substituted aryl alkyl, optionally substituted heteroaryl, optionally substituted alkyl heteroaryl, optionally substituted heteroaryl alkyl, optionally substituted alkenyl aryl, optionally substituted aryl alkenyl, optionally substituted alkenyl heteroaryl, optionally substituted heteroaryl alkenyl, optionally substituted C3-C8-cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkyl C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkyl alkyl, optionally substituted alkyl heterocycloalkyl and optionally substituted heterocycloalkyl alkyl;
G3is selected from H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted alkyl aryl, optionally substituted aryl alkyl, optionally substituted heteroaryl, optionally substituted alkyl heteroaryl, optionally substituted heteroaryl alkyl, optionally substituted alkenyl aryl, optionally substituted aryl alkenyl, optionally substituted alkenyl heteroaryl, optionally substituted heteroaryl alkenyl, optionally substituted C3-C8-cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkyl C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkyl alkyl, optionally substituted alkyl heterocycloalkyl and optionally substituted heterocycloalkyl alkyl;
G4is selected from H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted alkyl aryl, optionally substituted aryl alkyl, optionally substituted heteroaryl, optionally substituted alkyl heteroaryl, optionally substituted heteroaryl alkyl, optionally substituted alkenyl aryl, optionally substituted aryl alkenyl, optionally substituted alkenyl heteroaryl, optionally substituted heteroaryl alkenyl, optionally substituted C3-C8-cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkyl C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkyl alkyl, optionally substituted alkyl heterocycloalkyl and optionally substituted heterocycloalkyl alkyl;
G5is selected from H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted alkyl aryl, optionally substituted aryl alkyl, optionally substituted heteroaryl, optionally substituted alkyl heteroaryl, optionally substituted heteroaryl alkyl, optionally substituted alkenyl aryl, optionally substituted aryl alkenyl, optionally substituted alkenyl heteroaryl, optionally substituted heteroaryl alkenyl, optionally substituted C3-C8-cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkyl C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkyl alkyl, optionally substituted alkyl heterocycloalkyl and optionally substituted heterocycloalkyl alkyl; or pharmaceutically acceptable salts thereof.
2. The pharmaceutical composition according to claim 1, wherein G1is H.
3. The pharmaceutical composition according to claim 1, wherein G1is optionally substituted aryl alkyl and optionally substituted heteroaryl alkyl.
4. The pharmaceutical composition according to claim 1, wherein G1is optionally substituted alkyl.
5. The pharmaceutical composition according to claim 1, wherein G2is selected from optionally substituted aryl and optionally substituted heteroaryl.
6. The pharmaceutical composition according to claim 1, wherein G3is H.
7. The pharmaceutical composition according to claim 1, wherein G3is optionally substituted alkyl.
8. The pharmaceutical composition according to claim 1, wherein G3is optionally substituted aryl.
9. The pharmaceutical composition according to claim 1, wherein G4is selected from optionally substituted alkyl, optionally substituted alkenyl and optionally substituted alkynyl.
10. The pharmaceutical composition according to claim 1, wherein G4is selected from optionally substituted aryl alkyl and optionally substituted heteroaryl alkyl.
11. The pharmaceutical composition according to claim 1, wherein G4is selected from optionally substituted heterocycloalkyl alkyl and optionally substituted C3-C8-cycloalkyl alkyl.
12. The pharmaceutical composition according to claim 1, wherein G4is optionally substituted heterocycloalkyl.
13. The pharmaceutical composition according to claim 1, wherein G5is H.
14. The pharmaceutical composition according to claim 1, wherein the pyrazolo pyridine derivative is selected from the following group:
4-methyl-2-phenyl-5-(thiophen-2-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H.5H)-dione;
2-(1,3-benzothiazol-2-yl)-5-2-(1H-imidazol-4-yl)ethyl-4-methyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-5-2-(1H-indol-3-yl)ethyl-4-methyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-methyl-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
5-(furan-2-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-{2-(1,3-benzothiazol-2-yl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo 4,3-cpyridin-5-ylmethyl}benzoic acid;
4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-methyl-2-phenyl-5-(2-phenylethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
5-2-(4-acetylpiperazin-1-ypethyl-2-(1,3-benzothiazol-2-yl)-4-methyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-methyl-5-(2-methylbutyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-5-2-(4-methoxyphenyl)ethyl-4-methyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-5-2-(4-hexanoylpiperazin-1-yl)ethyl-4-methyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-1-benzyl-5-(furan-2-ylmethyl) -4-methyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
5-2-(1H-indo1-3-yl)ethyl-4-methyl-1-(3-methylbenzyl)-2-phenyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
1-(4-fluorobenzyl)-5-2-(1H-indol-3-yl)ethyl-4-methyl-2-phenyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
1-(2-chlorobenzyl)-4-methyl-5-3-(2-oxopyrrolidin-1-yl)propyl-2-phenyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-1-benzyl-4-methyl-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
1-(4-chlorobenzyl)-5-2-(1H-imidazol-4-yl)ethyl-4-methyl-2-phenyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
5-(1,3-benzodioxol-5-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
5-benzyl-4-methyl-2-phenyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
5-benzyl-2-(4-fluorophenyl)-4-methyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
5-benzyl-2-(4-methoxyphenyl)-4-methyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-methyl-5-morpholin-4-yl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
5-benzyl-4-methyl-2-(4-nitrophenyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H, 5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-methyl-1-(3-methylbenzyl)-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-1-(4-fluorobenzyl)-4-methyl-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-methyl-1-(4-methylbenzyl)-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-1-(2-chlorobenzyl)-4-methyl-5-morpholin-4-yl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-1-(4-bromobenzyl)-4-methyl-5-(2-morpholin-4-ylethyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-2-(1,3-benzothiazol-2-yl)-4-methyl-5-(3-morpholin-4-ylpropyl)-3,6-dioxo-2,3,5,6-tetrahydro-1H-pyrazolo 4,3-cpyridin-1-yl-N-phenylacetamide;
4-methyl-2-phenyl-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-methyl-5-(2-phenylethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
5-2-(1H-indo1-3-yl)ethyl-4-methyl-2-phenyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-methyl-5-morpholin-4-yl-2-phenyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-1-(2-chlorobenzyl)-4-methyl-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
5-benzyl-4-ethyl-2-(4-fluorophenyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(2-phenylethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-morpholin-4-yl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-methyl-5-(2-morpholin-4-ylethyl)-2-phenyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-5-morpholin-4-yl-2-phenyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-methyl-2-(2-methylphenyl)-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-methyl-1-(pyridin-2-ylmethyl)-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(pyridin-2-ylmethyl) -1H-pyrazolo4,3-cpyridine-3,6 (2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(2-methoxyethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(4-methylpiperazin-1-yl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-1-(4-methylbenzyl)piperidin-4-yl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6 (2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(2-methoxyethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
5-(2-morpholin-4-ylethyl)-2-pyridin-2-yl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2,4-diphenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(2-chlorophenyl)-4-ethyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-methyl-2-(2-methylphenyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-5-(3-morpholin-4-ylpropyl)-2-4-(trifluoromethyl)phenyl-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-5-(3-morpholin-4-ylpropyl)-2-4-(trifluoromethoxy)phenyl-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(2,5-difluorophenyl)-4-ethyl-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6 (2H,5H)-dione; or
4-ethyl-2-(2-methoxyphenyl)-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6 (2H,5H)-dione.
15. A method of preparing a pharmaceutical composition comprising combining a pyrazolo pyridine derivative according to claim 1, or pharmaceutically acceptable salts thereof, with a pharmaceutically acceptable carrier, excipient or diluent.
16. A method for the treatment of a patient suffering from disease or condition selected from hypertension, atherosclerosis, pulmonary fibrosis, pulmonary hypertension, Alzheimer’s disease, diabetes, asthma, hearing loss and balance problems in response to ototoxic drugs, vascular injuries after balloon surgery, inflammation, cardiovascular complications of Type I or Type II diabetes, intimal hyperplasia, coronary heart disease, cerebral, coronary or arterial vasospasm, endothelial dysfunction, heart failure, peripheral artery disease, restenosis, trauma caused by a stent, stroke, ischemic attack, vascular complications after organ transplantation, viral or bacterial infections, myocardial infarction, platelet aggregation, angina pectoris, aneurysm, aortic dissection, ischemic heart disease, cardiac hypertrophy, pulmonary embolus, thrombotic events, injury caused after ischemia by restoration of blood flow or oxygen delivery in or an transplantation, open heart surgery angioplasty, hemorrhagic shock, angioplasty of ischemic organs, bronchial asthma, bronchitis, allergic rhinitis, adult respiratory syndrome, viral lung infection (influenza), pulmonary hypertension, chronic obstructive pulmonary diseases (COPD), hay fever, obesity, metabolic syndrome, Type II diabetes, soriasis eczema, dermatitis, wound healing, scar formation, osteoporosis, osteoporasis, osteosclerosis, periodontitis, hyperparathyroidism, Huntington’s disease, amyotrophic lateral sclerosis, epilepsy, muscular dystrophy, leukoencephalopathies, leukodystrophies, diabetic nephropathy, renal failure, glomerulonephritis, nephrotoxicity of aminoglycosides and platinum compounds, hyperactive bladder, erectile dysfunction, fertility disorders, prostatic hypertrophy, benign prostatic hypertrophy cataracts re-opacification of the lens post cataract surgery, diabetic retinopathy, presbyacusis, tinnitus, Meniere’s disease and other balance problems, utriculolithiasis, vestibular migraine, noise induced hearing loss, inflammatory bowel disease, sepsis, septic shock, adult respiratory distress syndrome, pancreatitis, shock induced by trauma, bronchial asthma, allergic rhinitis, rheumatoid arthritis, chronic rheumatoid arthritis, arteriosclerosis, intracerebral hemorrhage, cerebral infarction, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, myelitis, ankylosing spondylitis, Reuter syndrome psoriatic arthritis, spondylarthritis, juvenile arthritis, juvenile ankylosing spondylitis, reactive arthritis, gonococcal arthritis, tuberculous arthritis, viral arthritis, bacterial arthritis, syphilitic arthritis, Lyme disease, polyarteritis nodosa, anaphylactic angiitis, Luegenec granulomatosis, rheumatoid polymyalgia, articular cell rheumatism, calcium crystal deposition arthritis, pseudogout, non-arthritic rheumatism, bursitis, tendosynovitis, epicondyle inflammation (tennis elbow), carpal tunnel syndrome, mixed form of arthritis, neuropathic arthropathy, hemorrhagic arthritis, vascular peliosis, hypertrophic osteoarthropathy, multicentric reticulohistiocytosis, arthritis induced by specific diseases, blood pigmentation, sickle cell disease and other hemoglobin abnormality, hyperlipoproteinemia, dysgammaglobulinemia, hyperparathyroidism, acromegaly, familial Mediterranean fever, Bechet’s disease, systemic autoimmune disease erythematosus, multiple sclerosis, Crohn’s disease, chronic inflammatory bowel diseases (IBD), liver fibrosis, alcohol induced fibrosis, steatosis, non alcoholic steatohepatitis, pain, prostate cancer, breast cancer, pancreatic cancer or renal cancer comprising administering a composition according to claim 1, to a patient in need of treatment of said disease or condition.
17. The composition according to claim 1, wherein said pyrazolo pyridine derivative has Formula (I):
wherein G1, G2, G3, G4and G5are as defined in claim 1, and said derivative is selected from the group consisting of:
5-benzyl-4-ethyl-2-(4-fluorophenyl)-1H-pyrazolo4,3cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(2-phenylethyl)-1Hpyrazolo 4,3-cpyridine-3,6(2,H5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-morpholin-4-yl-1Hpyrazolo4,3-cpyridine-3,6(2,H5H)-dione;
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1Hpyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-methyl-2-(2-methylphenyl)-5-(3-morpholin-4-ylpropyl)1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-{1,3-benzothiazol-2-yl)-4-methyl-1-(pyridin-2-ylmethyl)5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H}-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(pyridin-2-ylmethyl)1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(3-morpholin-4ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(2-methoxyethyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(4-methylpiperazin-1y1)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(2-methoxyethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
5-(2-morpholin-4-ylethyl)-2-pyridin-2-yl-1H-pyrazolo4,3cpyridine-3,6(2H,5H)-dione;
4-ethyl-5-(3-morpholin-4-ylpropyl)-2-4-(trifluoromethyl)phenyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-5-(3-morpholin-4-ylpropyl)-2-4-(trifluoromethoxy)phenyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione; or
2-(2,5-difluorophenyl)-4-ethyl-5-(3-morpholin-4-ylpropyl)1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione; and pharmaceutically acceptable salts thereof.
18. The method according to claim 16, wherein said disease or condition is selected from hypertension, atherosclerosis, pulmonary fibrosis, pulmonary hypertension, Alzheimer’s disease, diabetes, asthma, hearing loss and balance problems in response to ototoxic drugs, or vascular injuries after balloon surgery.
19. The method according to claim 16, wherein said disease or condition is inflammation.
20. A pyrazolo pyridine derivative selected from the group consisting of:
5-benzyl-4-ethyl-2-(4-fluorophenyl)-1H-pyrazolo4,3cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(2-phenylethyl)-1Hpyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-morpholin-4-yl-1Hpyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1Hpyrazolo 4,3-cpyridine-3,6(2,5H)-dione;
4-methyl-2-(2-methylphenyl)-5-(3-morpholin-4-ylpropyl)1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-{1,3-benzothiazol-2-yl)-4-methyl-1-(pyridin-2-ylmethyl)5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H}-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(pyridin-2-ylmethyl)1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(3-morpholin-4ylpropyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(2-methoxyethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(4-methylpiperazin-1yl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(3-morpholin-4-ylpropyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-2-(4-fluorophenyl)-5-(2-methoxyethyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,5H)-dione;
5-(2-morpholin-4-ylethyl)-2-pyridin-2-yl-1H-pyrazolo4,3cpyridine-3,6(2H,5H)-dione;
4-ethyl-5-(3-morpholin-4-ylpropyl)-2-4-(trifluoromethyl)phenyl)-1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione;
4-ethyl-5-(3-morpholin-4-ylpropyl)-2-4-(trifluoromethoxy)phenyl)-1H-pyrazolo4,3-cpyridine-3,6(2H,-5H)-dione;
2-(2,5-difluorophenyl)-4-ethyl-5-(3-morpholin-4-ylpropyl)1H-pyrazolo 4,3-cpyridine-3,6(2H,5H)-dione; and pharmaceutically acceptable salts thereof.
21. The method according to claim 16, wherein said disease or condition is cardiovascular complications of Type I or Type II diabetes, intimal hyperplasia, coronary heart disease, cerebral, coronary or arterial vasospasm, endothelial dysfunction, heart failure, peripheral artery disease, restenosis, trauma caused by a stent, stroke, ischemic attack, vascular complications after organ transplantation, viral or bacterial infections, myocardial infarction, platelet aggregation, angina pectoris, aneurysm, aortic dissection, ischemic heart disease, cardiac hypertrophy, pulmonary embolus, thrombotic events, injury caused after ischemia by restoration of blood flow or oxygen delivery in organ transplantation, open heart surgery, angioplasty, hemorrhagic shock, or angioplasty of ischemic organs.
22. The method according to claim 16, wherein said disease or condition is bronchial asthma, bronchitis, allergic rhinitis, adult respiratory syndrome, viral lung infection (influenza), pulmonary hypertension or chronic obstructive pulmonary diseases (COPD).
23. The method according to claim 16, wherein said disease or condition is hay fever.
24. The method according to claim 16, wherein said disease or condition is obesity, metabolic syndrome or Type II diabetes.
25. The method according to claim 16, wherein said disease or condition is psoriasis, eczema, dermatitis, wound healing or scar formation.
26. The method according to claim 16, wherein said disease or condition is osteoporosis, osteoporasis, osteosclerosis, periodontitis, or hyperparathyroidism.
27. The method according to claim 16, wherein said disease or condition is Huntington’s disease, amyotrophic lateral sclerosis, epilepsy, muscular dystrophy, leukoencephalopathies or leukodystrophies.
28. The method according to claim 16, wherein said disease or condition is diabetic nephropathy, renal failure, glomerulonephritis, nephrotoxicity of aminoglycosides and platinum compounds or hyperactive bladder.
29. The method according to claim 16, wherein said disease or condition is erectile dysfunction, fertility disorders, prostatic hypertrophy or benign prostatic hypertrophy.
30. The method according to claim 16, wherein said disease or condition is cataracts, re-opacification of the lens post cataract surgery, or diabetic retinopathy.
31. The method according to claim 16, wherein said disease or condition presbyacusis, tinnitus, Meniere’s disease and other balance problems, utriculolithiasis, vestibular migraine, or noise induced hearing loss.
32. The method according to claim 16, wherein said disease or condition is inflammatory bowel disease, sepsis, septic shock, adult respiratory distress syndrome, pancreatitis, shock induced by trauma, bronchial asthma, allergic rhinitis, rheumatoid arthritis, chronic rheumatoid arthritis, arteriosclerosis, intracerebral hemorrhage, cerebral infarction, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, myelitis, ankylosing spondylitis, Reuter syndrome, psoriatic arthritis, spondylarthritis, juvenile arthritis, juvenile ankylosing spondylitis, reactive arthritis, gonococcal arthritis, tuberculous arthritis, viral arthritis, bacterial arthritis, syphilitic arthritis, Lyme disease, polyarteritis nodosa, anaphylactic angiitis, Luegenec granulomatosis, rheumatoid polymyalgia, articular cell rheumatism, calcium crystal deposition arthritis, pseudogout, non-arthritic rheumatism, bursitis, tendosynovitis, epicondyle inflammation (tennis elbow), carpal tunnel syndrome, mixed form of arthritis, neuropathic arthropathy, hemorrhagic arthritis, vascular peliosis, hypertrophic osteoarthropathy, multicentric reticulohistiocytosis, arthritis induced by specific diseases, blood pigmentation, sickle cell disease and other hemoglobin abnormality, hyperlipoproteinemia, dysgammaglobulinemia, hyperparathyroidism, acromegaly, familial Mediterranean fever, Bechet’s disease, systemic autoimmune disease erythematosus, multiple sclerosis, Crohn’s disease, or chronic inflammatory bowel diseases (IBD).
33. The method according to claim 16, wherein said disease or condition is liver fibrosis, alcohol induced fibrosis, steatosis or non alcoholic steatohepatitis.
34. The method according to claim 16, wherein said disease or condition is pain.
35. The method according to claim 16, wherein said disease or condition is pancreatic cancer, breast cancer, prostatic carcinoma or renal cell carcinoma.