Pyrazolo pyridine derivatives as NADPH oxidase inhibitors
First Claim
1. A method for the inhibiting, arresting the development of, relieving the symptoms of and/or causing regression of the symptoms of a patient suffering from a disease or condition selected from cardiovascular disorders, respiratory disorders, metabolism disorders, skin disorders, bone disorders, neuroinflammatory and/or neurodegenerative disorders, kidney diseases, reproduction disorders, diseases affecting the eye and/or the lens and/or conditions affecting the inner ear, inflammatory disorders, liver diseases, pain, cancers, allergic disorders, traumatisms, septic, hemorrhagic and anaphylactic shock, disorders of the gastrointestinal system, angiogenesis and angiogenesis-dependent conditions, the method comprising administering a pyrazolo pyridine derivative according to Formula (I):
1 Assignment
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Accused Products
Abstract
The present invention is related to pyrazolo pyridine derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).
33 Citations
31 Claims
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1. A method for the inhibiting, arresting the development of, relieving the symptoms of and/or causing regression of the symptoms of a patient suffering from a disease or condition selected from cardiovascular disorders, respiratory disorders, metabolism disorders, skin disorders, bone disorders, neuroinflammatory and/or neurodegenerative disorders, kidney diseases, reproduction disorders, diseases affecting the eye and/or the lens and/or conditions affecting the inner ear, inflammatory disorders, liver diseases, pain, cancers, allergic disorders, traumatisms, septic, hemorrhagic and anaphylactic shock, disorders of the gastrointestinal system, angiogenesis and angiogenesis-dependent conditions, the method comprising administering a pyrazolo pyridine derivative according to Formula (I):
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 30, 31)
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2. The method according to claim 1, wherein said disease or condition is selected from atherosclerosis, endothelial dysfunction, hypertension, cardiovascular complications of Type I or Type II diabetes, intimal hyperplasia, coronary heart disease, cerebral, coronary or arterial vasospasm, heart failure, congestive heart failure, peripheral artery disease, restenosis, trauma caused by a stent, stroke, ischemic attack, vascular complications after organ transplantation, myocardial infarction, hypertension, formation of atherosclerotic plaques, platelet aggregation, angina pectoris, aneurysm, aortic dissection, ischemic heart disease, cardiac hypertrophy, pulmonary embolus, thrombotic events, deep vein thrombosis, injury caused after ischemia by restoration of blood flow or oxygen delivery as in organ transplantation, open heart surgery, angioplasty, hemorrhagic shock, angioplasty of ischemic heart, brain, liver, kidney, retina and bowel, bronchial asthma, bronchitis, allergic rhinitis, adult respiratory syndrome, cystic fibrosis, lung viral infection (influenza), pulmonary hypertension, idiopathic pulmonary fibrosis, chronic obstructive pulmonary diseases (COPD), hay fever, asthma, obesity, metabolic syndrome, Type II diabetes, psoriasis, eczema, dermatitis, wound healing, scar formation, osteoporosis, osteoporasis, osteosclerosis, periodontitis, hyperparathyroidism, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, epilepsy, muscular dystrophy, leukoencephalopathies, leukodystrophies, multiple sclerosis, progressive multifocal leukoencephalopathy (PML), myelopathies, diabetic nephropathy, renal failure, glomerulonephritis, nephrotoxicity of aminoglycosides and platinum compounds, hyperactive bladder, chronic kidney diseases or disorders, erectile dysfunction, fertility disorders, prostatic hypertrophy, benign prostatic hypertrophy, cataract, diabetic cataract, re-opacification of the lens post cataract surgery, diabetic, retinopathy, presbyacusis, tinnitus, Meniere'"'"'s disease, utriculolithiasis, vestibular migraine, noise induced hearing loss, drug induced hearing loss (ototoxicity), 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, heart failure, myocardial infarction, psoriasis, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, myelitis, ankylosing spondylitis, Reuter syndrome, psoriatic arthritis, spondylarthritis, juvenile arthritis or juvenile ankylosing spondylitis, reactive arthritis, infectious arthritis or arthritis after infection, gonococcal arthritis, syphilitic arthritis, Lyme disease, arthritis induced by “
- angiitis syndrome,”
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, disorders by repetitive use (typing), mixed form of arthritis, neuropathic arthropathy, hemorrhagic arthritis, vascular peliosis, hypertrophic osteoarthropathy, multicentric reticulohistiocytosis, arthritis, blood pigmentation, sickle cell disease , hemoglobin abnormality, hyperlipoproteinemia, dysgammaglobulinemia, hyperparathyroidism, acromegaly, familial Mediterranean fever, Bechet'"'"'s disease, systemic autoimmune disease erythematosus, multiple sclerosis and Crohn'"'"'s disease, relapsing polychondritis, chronic inflammatory bowel diseases (IBD), liver fibrosis, alcohol induced fibrosis, steatosis, non-alcoholic steatohepatitis, rheumatic arthritis, chronic rheumatoid arthritis, chlamydial arthritis, chronic absorptive arthritis, chylous arthritis, arthritis based on bowel disease, filarial arthritis, gonorrheal arthritis, gouty arthritis, hemophilic arthritis, hypertrophic arthritis, juvenile chronic arthritis, Lyme arthritis, neonatal foal arthritis, nodular arthritis, ochronotic arthritis, psoriatic arthritis, suppurative arthritis, hyperalgesia, inflammatory pain, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endothelium sarcoma, lymphangiosarcoma, lymphangioendothelioma, periosteoma, mesothelioma, Ewing'"'"'s tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, renal cancer, prostatic carcinoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms'"'"' tumor, cervical cancer, orchioncus, lung cancer, small-cell lung cancer, lung adenocarcinoma, bladder cancer, epithelial cancer, gastric mucosa disorders, ischemic bowel disease management, enteritis/colitis, cancer chemotherapy, neutropenia, sprouting angiogenesis, intussusceptive angiogenesis, vasculogenesis, arteriogenesis and lymphangiogenesis.
- angiitis syndrome,”
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3. The method according to claim 1, wherein said disease or condition is selected from atherosclerosis, hypertension, cardiovascular complications of Type I or Type II diabetes, intimal hyperplasia, coronary heart disease, cerebral, coronary or arterial vasospasm, endothelial dysfunction, heart failure, congestive heart failure, peripheral artery disease, restenosis, trauma caused by a stent, stroke, ischemic attack, vascular complications after organ transplantation, myocardial infarction, hypertension, formation of atherosclerotic plaques, platelet aggregation, angina pectoris, aneurysm, aortic dissection, ischemic heart disease, cardiac hypertrophy, pulmonary embolus, thrombotic events, deep vein thrombosis, injury caused after ischemia by restoration of blood flow or oxygen delivery as in organ transplantation, open heart surgery, angioplasty, hemorrhagic shock, angioplasty of ischemic heart, brain, liver, kidney, retina and bowel.
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4. The method according to claim 1, wherein said disease or condition is selected from bronchial asthma, bronchitis, allergic rhinitis, adult respiratory syndrome, cystic fibrosis, lung viral infection (influenza), pulmonary hypertension, idiopathic pulmonary fibrosis and chronic obstructive pulmonary diseases (COPD).
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5. The method according to claim 1, wherein said disease or condition is obesity, metabolic syndrome or Type II diabetes.
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6. The method according to claim 1, wherein said disease or condition is osteoporosis, osteoporasis, osteosclerosis, periodontitis, or hyperparathyroidism.
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7. The method according to claim 1, wherein said disease or condition is diabetic nephropathy, renal failure, glomerulonephritis, nephrotoxicity of aminoglycosides and platinum compounds or hyperactive bladder.
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8. The method according to claim 1, wherein said disease or condition is erectile dysfunction, fertility disorders, prostatic hypertrophy or benign prostatic hypertrophy.
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9. The method according to claim 1, wherein said disease or condition is cataracts, re-opacification of the lens post cataract surgery, or diabetic retinopathy.
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10. The method according to claim 1, 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, heart failure, myocardial infarction, psoriasis, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, myelitis, ankylosing spondylitis, Reuter syndrome, psoriatic arthritis, spondylarthritis, juvenile arthritis or juvenile ankylosing spondylitis, reactive arthritis, infectious arthritis or arthritis after infection, gonococcal arthritis, syphilitic arthritis, Lyme disease, arthritis induced by “
- angiitis syndrome,”
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, disorders by repetitive use (typing), mixed form of arthritis, neuropathic arthropathy, hemorrhagic arthritis, vascular peliosis, hypertrophic osteoarthropathy, multicentric reticulohistiocytosis, arthritis, blood pigmentation, sickle cell disease, hemoglobin abnormality, hyperlipoproteinemia, dysgammaglobulinemia, hyperparathyroidism, acromegaly, familial Mediterranean fever, Bechet'"'"' s disease, systemic autoimmune disease erythematosus, multiple sclerosis and Crohn'"'"'s disease, relapsing polychondritis or chronic inflammatory bowel diseases (IBD).
- angiitis syndrome,”
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11. The method according to claim 1, wherein said disease or condition is liver fibrosis, alcohol induced fibrosis, steatosis or non-alcoholic steatohepatitis.
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12. The method according to claim 1, wherein said disease or condition is pulmonary fibrosis.
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13. The method according to claim 1, wherein said disease or condition is inflammatory pain.
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14. The method according to claim 1, wherein said disease or condition is fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endothelium sarcoma, lymphangiosarcoma, lymphangioendothelioma, periosteoma, mesothelioma, Ewing'"'"'s tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, renal cancer, prostatic carcinoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms'"'"' tumor, cervical cancer, orchioncus, lung cancer, small-cell lung cancer, lung adenocarcinoma, bladder cancer or epithelial cancer.
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15. The method according to claim 14, wherein the pyrazolo pyridine derivative is administered in combination with a co-agent useful in the treatment of cancer.
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17. The method according to claim 1, wherein G1 is H.
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18. The method according to claim 1, wherein G3 is —
- (CH2)n—
R1;
R1 and n are as described in claim 1.
- (CH2)n—
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19. The method according to claim 1, wherein G3 is —
- (CH2)p—
R5;
R5 and p are as described in claim 1.
- (CH2)p—
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20. The method according to claim 1, wherein G5 is H.
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21. The method according to claim 1, wherein the pyrazolo pyridine derivative is selected from the following compounds:
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5-benzyl-2-(2-chlorophenyl)-4-(morpholin-4-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-butyl-2-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-[4-(benzyloxy)phenyl]-4-butyl-5-(4-chlorobenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-[4-(benzyloxy)phenyl]-4-butyl-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H) -dione; 2-[4-(benzyloxy)phenyl]-4-butyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-butyl-2-(2-chloro-4-fluorophenyl)-5-(furan-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6 (2H,5H)-dione; 4-butyl-2-(2-chloro-4-fluorophenyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 4-butyl-2-(2-chloro-4-fluorophenyl)-5-(2-methoxyethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-butyl-2-(2-chloro-4-fluorophenyl)-5-(2-pyridin-2-ylethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 4-butyl-2-(2-chloro-4-fluorophenyl)-5-(3,5-dimethoxybenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[benzyl(methyl)amino]methyl}-2-(2-chloro-4-fluorophenyl)-5-(3-methoxy propyl) -1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-[4-(benzyloxy)phenyl]-4-butyl-5-(2-methoxyethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-butyl-2-(2-chloro-4-fluorophenyl)-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(3-chlorophenyl)-4-(methoxymethyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(3-chlorophenyl)-4-(methoxymethyl)-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-benzyl-5-(3-ethoxypropyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(3-chlorophenyl)-5-methyl-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 5-(4-chlorobenzyl)-2-(3-chlorophenyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(3-chlorophenyl)-4-(methoxymethyl)-5-(2-pyridin-2-ylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 5-(4-chlorobenzyl)-4-(methoxymethyl)-2-methyl-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-methyl-4-(3-phenoxypropyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-benzyl-5-(2-methoxyethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-benzyl-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-5-(2-methoxyethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(3-chlorophenyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-5-(2-pyridin-2-yl ethyl) -1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chloro-4-fluorophenyl)-5-(3,5-dimethoxybenzyl)-4-(methoxymethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chloro-4-fluorophenyl)-5-(2-pyridin-2-ylethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(3-chlorophenyl)-5-(2-pyridin-2-ylethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chloro-4-fluorophenyl)-5-(furan-2-ylmethyl)-4-(methoxymethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chloro-4-fluorophenyl)-4-(methoxymethyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-benzyl-5-(3,5-dimethoxybenzyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(3-chlorophenyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-5-(2-methoxy ethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-[4-(benzyloxy)phenyl]-5-(pyridin-3-ylmethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-(methoxymethyl)-2-methyl-5-(2-pyridin-2-ylethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-(3-chlorophenyl)-5-(2-methoxyethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chloro-4-fluorophenyl)-5-(2-methoxyethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chloro-4-fluorophenyl)-5-(3-ethoxypropyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(3-chlorophenyl)-5-(3-ethoxypropyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-benzyl-5-(3-ethoxypropyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-[4-(benzyloxy)phenyl]-5-(4-chlorobenzyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-[4-(benzyloxy)phenyl]-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-[4-(benzyloxy)phenyl]-5-(4-chlorobenzyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-[4-(benzyloxy)phenyl]-5-methyl-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 5-(4-chlorobenzyl)-2-methyl-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; N-[3-({2-[4-(benzyloxy)phenyl]-3,6-dioxo-4-(pyrrolidin-1-ylmethyl)-1,2,3,6-tetrahydro -5H-pyrazolo[4,3-c]pyridin-5-yl}methyl)phenyl]acetamide; N-{3-[(2-[4-(benzyloxy)phenyl]-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-3,6-dioxo -1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl]phenyl}acetamide; 2-(3-chlorophenyl)-5-(3-ethoxypropyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-methyl-4-(phenoxymethyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(4-fluorophenoxy)methyl]-2-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-(2-methoxyethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-(2,5-dichlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2,5-dichlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-(2-methoxyethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 5-(4-chlorobenzyl)-4-[(4-fluorophenoxy)methyl]-2-methyl-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 5-(2-methoxybenzyl)-2-methyl-4-(3-phenoxypropyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 4-[(4-fluorophenoxy)methyl]-2-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)methyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(4-fluorophenoxy)methyl]-2-methyl-5-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(4-fluorophenoxy)methyl]-2-methyl-5-(2-pyridin-2-ylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 5-(3-methoxybenzyl)-2-methyl-4-(3-phenoxypropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-methyl-4-(3-phenoxypropyl)-5-(2-pyridin-2-ylethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 4-[(4-chlorophenoxy)methyl]-5-(3-methoxybenzyl)-2-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-5-(3-ethoxypropyl)-2-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-5-(3-methoxybenzyl)-2-methyl-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 4-[(4-chlorophenoxy)methyl]-5-(3-ethoxypropyl)-2-methyl-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 4-[(4-chlorophenoxy)methyl]-2-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-methyl-5-(2-pyridin-2-ylethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; N-[3-({4-[(benzyloxy)methyl]-2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl}methyl)phenyl]acetamide; N-[3-({4-[(4-chlorophenoxy)methyl]-2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H -pyrazolo [4,3-c]pyridin-5-yl}methyl)phenyl]acetamide; 4-[(4-fluorophenoxy)methyl]-2-methyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-(pyridin-2-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-(pyridin-3-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-methyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-[(5-methyl-1,2,4-oxadiazol-3-yl) methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-(4-benzylmorpholin-2-yl)-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-(3-ethoxypropyl)-4-[(4-fluorophenoxy)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-(2-pyridin-2-ylethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(4-chlorophenoxy)methyl]-2-(2-chlorophenyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-[(2-methyl-1,3-thiazol-4-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(2-pyridin-2-ylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(3-ethoxypropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; N-[3-({2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-3,6-dioxo-1,2,3,6-tetra hydro -5H-pyrazolo[4,3-c]pyridin-5-yl}methyl)phenyl]acetamide; 4-[(4-chlorophenoxy)methyl]-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[methyl(phenyl)amino]methyl}-5-(2-pyridin-2-ylethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-(3-ethoxypropyl)-4-{[methyl(phenyl)amino]methyl}-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[methyl(phenyl)amino]methyl}-5-(pyridin-4-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(4-chlorophenoxy)methyl]-2-(2-chlorophenyl)-5-(pyridin-3-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(pyridin-4-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(1,3-thiazol-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; tert-butyl 4-({4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-3,6-dioxo-1,2,3,6-tetra hydro -5H-pyrazolo[4,3-c]pyridin-5-yl}methyl)piperidine-1-carboxylate; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(piperidin-4-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-[3-(diethylamino)propyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(2-methoxyethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(4-chlorophenoxy)methyl]-2-(2-chlorophenyl)-5-(pyridin-4-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-[(1-methylpiperidin-4-yl)methyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(3-chlorophenoxy)methyl]-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-methyl-4-[(2,2,2-trifluoro-1-phenylethoxy)methyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-methyl-4-(3-phenoxypropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-[(2-methyl-1,3-thiazol-4-yl)methyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(pyrazin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-5-methyl-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-methyl-4-[(4-phenylpiperidin-1-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-{4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-3,6-dioxo-1,2,3,6-tetrahydro-5H -pyrazolo [4,3-c]pyridin-5-yl}-N,N-dimethylacetamide; 2-(2-chlorophenyl)-4-[(3-methoxyphenoxy)methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-(pyridin-4-ylmethyl)-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)oxy]methyl}-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-methyl-4-{3-[methyl(phenyl)amino]propyl}-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(4-methoxybenzyl)oxy]methyl}-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)oxy]methyl}-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[3-(2,3-dihydro-1H-indol-1-yl)propyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-methyl-4-[(naphthalen-1-yloxy)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(4-chlorobenzyl)oxy]methyl}-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[2-(4-chlorophenyl)ethoxy]methyl}-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[benzyl(methyl)amino]methyl}-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-[(4-methylmorpholin-2-yl)methyl]-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(piperidin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[3-(dimethylamino)phenoxy]methyl}-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-methyl-4-{[methyl(pyridin-2-ylmethyl)amino]methyl}-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)oxy]methyl}-2-(2-chlorophenyl)-5-(pyridin-4-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)oxy]methyl}-2-(2-chlorophenyl)-5-(pyridin-3-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)oxy]methyl}-2-(2-chlorophenyl)-5-(2-methoxyethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-(2-methoxyethyl)-4-[(3-methoxyphenoxy)methyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-5-(2-methoxy ethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(3-methoxyphenoxy)methyl]-5-(pyridin-4-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(3-chlorobenzyl)oxy]methyl}-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-({[3-(dimethylamino)benzyl]oxy}methyl)-5-methyl-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(diphenylmethoxy)methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine -3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(3-methoxyphenoxy)methyl]-5-(pyridin-3-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)(methyl)amino]methyl}-5-methyl-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-5-[(1-methyl-1H -pyrazol-3-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)(methyl)amino]methyl}-2-(2-chlorophenyl)-5-(2-methoxy ethyl) -1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)oxy]methyl}-2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl) methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-methyl-4-{[methyl(pyridin-3-ylmethyl)amino]methyl}-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)(methyl)amino]methyl}-2-(2-chlorophenyl)-5-[(1-methyl-1H -pyrazol-3-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)(methyl)amino]methyl}-5-[(1-methyl-1H -pyrazol-3-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)oxy]methyl}-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(3-methoxyphenoxy)methyl]-5-[(1-methyl-1H-pyrazol-3-yl) methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(3-methoxyphenoxy)methyl]-5-(pyrazin-2-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-(2-methoxyethyl)-4-{[(3-methoxyphenyl)(methyl)amino]methyl}-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxyphenyl)(methyl)amino]methyl}-5-[(1-methyl-1H -pyrazol-3-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)(methyl)amino]methyl}-2-(2-chlorophenyl)-5-(pyridin-3-yl methyl) -1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)oxy]methyl}-5-(pyrazin-2-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)oxy]methyl}-5-(pyridin-3-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)oxy]methyl}-5-(2-methoxyethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-fluorobenzyl)(methyl)amino]methyl}-5-(pyridin-3-yl methyl) -1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)(methyl)amino]methyl}-2-(2-chlorophenyl)-5-(pyrazin-2-yl methyl) -1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)(methyl)amino]methyl}-5-(pyridin-3-yl methyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-[(3-methoxyphenoxy)methyl]-5-[(4-methylmorpholin-2-yl) methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[4-(3-methoxyphenyl)piperazin-1-yl]methyl}-5-methyl-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxyphenyl)(methyl)amino]methyl}-5-(pyridin-3-yl methyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[4-(2-chlorophenyl)piperazin-1-yl]methyl}-5-methyl-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[4-(3-chlorophenyl)piperazin-1-yl]methyl}-5-methyl-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)oxy]methyl}-2-(2-methoxyphenyl)-5-(pyridin-3-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)oxy]methyl}-2-(2-chlorophenyl)-5-(pyrazin-2-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[methyl(pyridin-2-ylmethyl)amino]methyl}-5-(pyridin-3-yl methyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-4-{[methyl(pyridin-2-yl methyl)amino]methyl}-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(3-methoxybenzyl)oxy]methyl}-2-(2-methoxyphenyl)-5-(pyrazin-2-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(3-methoxybenzyl)oxy]methyl}-2-(2-methoxyphenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[(3-methoxybenzyl)(methyl)amino]methyl}-5-(pyrazin-2-yl methyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-methoxyphenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(3-methoxyphenoxy)methyl]-2-(2-methoxyphenyl)-5-[(1-methyl-1H-pyrazol-3-yl) methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-4-{[methyl(pyridin-3-yl methyl)amino]methyl}-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-4-{[methyl(pyridin-2-ylmethyl)amino]methyl}-5-(pyrazin-2-yl methyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-methoxyphenyl)-4-{[4-(3-methoxyphenyl)piperazin-1-yl]methyl}-5-methyl-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-methoxyphenyl)-5-methyl-4-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-methyl-4-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 4-{[(2-chlorobenzyl)oxy]methyl}-2-(2-methoxyphenyl)-5-(pyrazin-2-ylmethyl)-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione; 4-[(benzyloxy)methyl]-2-(2-methoxyphenyl)-5-(pyrazin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; 2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-4-[(pyridin-3-ylmethoxy) methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; and 2-(2-chlorophenyl)-5-(pyrazin-2-ylmethyl)-4-[(pyridin-3-ylmethoxy)methyl]-1H -pyrazolo [4,3-c]pyridine-3,6(2H,5H)-dione.
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30. The method according to claim 1, wherein said method comprises the administration of a pyrazolo pyridine derivative according to Formula (I) in an amount that causes regression of the disease and/or reduces the symptoms associated with said disease.
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31. The method according to claim 1, wherein said disease or condition is acute myeloid leukemia, lung cancer, prostate cancer, pulmonary hypertension, COPD, lung carcinoma or prostatic carcinoma.
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2. The method according to claim 1, wherein said disease or condition is selected from atherosclerosis, endothelial dysfunction, hypertension, cardiovascular complications of Type I or Type II diabetes, intimal hyperplasia, coronary heart disease, cerebral, coronary or arterial vasospasm, heart failure, congestive heart failure, peripheral artery disease, restenosis, trauma caused by a stent, stroke, ischemic attack, vascular complications after organ transplantation, myocardial infarction, hypertension, formation of atherosclerotic plaques, platelet aggregation, angina pectoris, aneurysm, aortic dissection, ischemic heart disease, cardiac hypertrophy, pulmonary embolus, thrombotic events, deep vein thrombosis, injury caused after ischemia by restoration of blood flow or oxygen delivery as in organ transplantation, open heart surgery, angioplasty, hemorrhagic shock, angioplasty of ischemic heart, brain, liver, kidney, retina and bowel, bronchial asthma, bronchitis, allergic rhinitis, adult respiratory syndrome, cystic fibrosis, lung viral infection (influenza), pulmonary hypertension, idiopathic pulmonary fibrosis, chronic obstructive pulmonary diseases (COPD), hay fever, asthma, obesity, metabolic syndrome, Type II diabetes, psoriasis, eczema, dermatitis, wound healing, scar formation, osteoporosis, osteoporasis, osteosclerosis, periodontitis, hyperparathyroidism, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, epilepsy, muscular dystrophy, leukoencephalopathies, leukodystrophies, multiple sclerosis, progressive multifocal leukoencephalopathy (PML), myelopathies, diabetic nephropathy, renal failure, glomerulonephritis, nephrotoxicity of aminoglycosides and platinum compounds, hyperactive bladder, chronic kidney diseases or disorders, erectile dysfunction, fertility disorders, prostatic hypertrophy, benign prostatic hypertrophy, cataract, diabetic cataract, re-opacification of the lens post cataract surgery, diabetic, retinopathy, presbyacusis, tinnitus, Meniere'"'"'s disease, utriculolithiasis, vestibular migraine, noise induced hearing loss, drug induced hearing loss (ototoxicity), 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, heart failure, myocardial infarction, psoriasis, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, myelitis, ankylosing spondylitis, Reuter syndrome, psoriatic arthritis, spondylarthritis, juvenile arthritis or juvenile ankylosing spondylitis, reactive arthritis, infectious arthritis or arthritis after infection, gonococcal arthritis, syphilitic arthritis, Lyme disease, arthritis induced by “
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16. A method for inhibiting angiogenesis in a patient suffering from angiogenesis or angiogenesis dependent disorder, wherein the method comprises administering an angiogenesis inhibitory dose of a compound of Formula (I)
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22. An intermediate of Formula (VIII):
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23. An intermediate of Formula (X):
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24. An intermediate of Formula (XII):
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25. An intermediate of Formula (XIII):
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26. A process for the preparation of an intermediate according to Formula (VIII) comprising reacting a compound according to Formula (VII) with an amine of Formula (II):
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27. A process for the preparation of an intermediate according to Formula (X), comprising reacting a compound of Formula (IV) with an acyl chloride of Formula (IX):
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28. A process for the preparation of an intermediate according to Formula (XII), comprising reacting a compound of Formula (IV) with a trialkyl orthoester of Formula (XI):
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29. A process for the preparation of an intermediate according to Formula (XIII), comprising the step of reacting a compound of Formula (XII) with an amine of Formula (II):
Specification
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Current AssigneeGenKyoTex Suisse SA (Calliditas Therapeutics AB)
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Original AssigneeGenkyotex SA (Calliditas Therapeutics AB)
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InventorsPage, Patrick, Orchard, Mike, Laleu, Benoit, Gaggini, Francesca
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Primary Examiner(s)SHTERENGARTS, SAMANTHA L
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Application NumberUS13/755,387Publication NumberTime in Patent Office810 DaysField of Search514/234.2, 514/252.1, 514/255.05, 514/303US Class Current514/234.2CPC Class CodesA61K 31/437 the heterocyclic ring syste...A61K 31/444 containing a six-membered r...A61K 31/4545 containing a six-membered r...A61K 31/496 Non-condensed piperazines c...A61K 31/497 containing further heterocy...A61K 31/5377 not condensed and containin...A61K 45/06 Mixtures of active ingredie...A61P 1/00 Drugs for disorders of the ...A61P 1/04 for ulcers, gastritis or re...A61P 1/16 for liver or gallbladder di...A61P 11/00 Drugs for disorders of the ...A61P 13/12 of the kidneysA61P 15/00 Drugs for genital or sexual...A61P 17/00 Drugs for dermatological di...A61P 17/02 for treating wounds, ulcers...A61P 17/06 AntipsoriaticsA61P 19/00 Drugs for skeletal disordersA61P 19/02 for joint disorders, e.g. a...A61P 19/08 for bone diseases, e.g. rac...A61P 25/00 Drugs for disorders of the ...A61P 25/02 : for peripheral neuropathiesA61P 25/28 : for treating neurodegenerat...A61P 27/02 : Ophthalmic agentsA61P 27/16 : OtologicalsA61P 29/00 : Non-central analgesic, anti...A61P 3/00 : Drugs for disorders of the ...A61P 31/00 : Antiinfectives, i.e. antibi...A61P 35/00 : Antineoplastic agentsA61P 37/00 : Drugs for immunological or ...A61P 37/08 : Antiallergic agents antiast...A61P 43/00 : Drugs for specific purposes...A61P 7/04 : Antihaemorrhagics; Procoagu...A61P 9/00 : Drugs for disorders of the ...C07D 231/22 : with aryl radicals attached...C07D 471/04 : Ortho-condensed systemsY02A 50/30 : Against vector-borne diseas...