PYRAZOLO PYRIDINE DERIVATIVES AS NADPH OXIDASE INHIBITORS

• US 20130143879A1
• Filed: 01/31/2013
• Published: 06/06/2013
• Est. Priority Date: 09/23/2008
• Status: Active Grant

• Current Assignee: GenKyoTex Suisse SA (Calliditas Therapeutics AB)
• Original Assignee: Genkyotex SA (Calliditas Therapeutics AB)
• Inventors: PAGE, PATRICK, ORCHARD, MIKE, LALEU, BENOIT, GAGGINI, FRANCESCA
• Granted Patent: US 9,012,449 B2
• Time in Patent Office: Days
• US Class Current: 514/234.2
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 : for peripheral neuropathies
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/16 : Otologicals
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 231/22 : with aryl radicals attached to ring nitrogen atoms
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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).

Claims

1. A method for the treatment or prophylaxis of a patient suffering 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, angiogenesis-dependent conditions and other diseases and disorders associated with Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase), the method comprising administering a pyrazolo pyridine derivative according to Formula (I):

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 including congestive heart failure, peripheral artery disease, restenosis, trauma caused by a stent, stroke, ischemic attack, vascular complications such as 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 including 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 organs including 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 and other balance problems, 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 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 and Crohn'"'"'s disease or diseases like 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.

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 including congestive heart failure, peripheral artery disease, restenosis, trauma caused by a stent, stroke, ischemic attack, vascular complications such as 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 including 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 organs including heart, brain, liver, kidney, retina and bowel.

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).

5. The method according to claim 1, wherein said disease or condition is obesity, metabolic syndrome or Type II diabetes.

6. The method according to claim 1, wherein said disease or condition is osteoporosis, osteoporasis, osteosclerosis, periodontitis, or hyperparathyroidism.

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.

8. The method according to claim 1, wherein said disease or condition is erectile dysfunction, fertility disorders, prostatic hypertrophy or benign prostatic hypertrophy.

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.

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 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 and Crohn'"'"'s disease or diseases like relapsing polychondritis, chronic inflammatory bowel diseases (IBD).

11. The method according to claim 1, wherein said disease or condition is liver fibrosis, alcohol induced fibrosis, steatosis or non-alcoholic steatohepatitis.

12. The method according to claim 1, wherein said disease or condition is pulmonary fibrosis.

13. The method according to claim 1, wherein said disease or condition is inflammatory pain.

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.

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.

17. The method according to claim 1, wherein G₁ is H.

18. The method according to claim 1, wherein G₃ is —

(CH₂)_n—

R¹;

R¹ and n are as described in claim 1.

19. The method according to claim 1, wherein G₃ is —

(CH₂)_p—

R⁵;

R⁵ and p are as described in claim 1.

20. The method according to claim 1, wherein G₅ is H.

21. The method according to claim 1, wherein the pyrazolo pyridine derivative is selected from the following compounds:

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-tetrahydro-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-tetrahydro-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;

or

2-(2-chlorophenyl)-5-(pyrazin-2-ylmethyl)-4-[(pyridin-3-ylmethoxy)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione.

22. An intermediate of Formula (VIII):

23. An intermediate of Formula (X):

24. An intermediate of Formula (XII):

25. An intermediate of Formula (XIII):

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):

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):

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):

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):

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) or a tautomer, geometrical isomer, optically active form as enantiomer, diastereomer and racemate forms or a pharmaceutically acceptable salt thereof, in a patient in need thereof.