AP795A - Indazole derivatives. - Google Patents
Indazole derivatives. Download PDFInfo
- Publication number
- AP795A AP795A APAP/P/1997/001080A AP9701080A AP795A AP 795 A AP795 A AP 795A AP 9701080 A AP9701080 A AP 9701080A AP 795 A AP795 A AP 795A
- Authority
- AP
- ARIPO
- Prior art keywords
- alkyl
- compound
- indazole
- phenyl
- mmol
- Prior art date
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- 125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 231
- 125000000217 alkyl group Chemical group 0.000 claims description 87
- 238000000034 method Methods 0.000 claims description 69
- -1 cyano, hydroxy Chemical group 0.000 claims description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 229910052799 carbon Inorganic materials 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000005843 halogen group Chemical group 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 18
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 18
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 17
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 206010040070 Septic Shock Diseases 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- ISIQAMHROGZHOV-UHFFFAOYSA-N 3,5-dichloropyridin-4-amine Chemical compound NC1=C(Cl)C=NC=C1Cl ISIQAMHROGZHOV-UHFFFAOYSA-N 0.000 claims description 10
- 208000030507 AIDS Diseases 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 150000001408 amides Chemical class 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 229910052684 Cerium Inorganic materials 0.000 claims description 7
- 206010040047 Sepsis Diseases 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
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- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
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- 125000004104 aryloxy group Chemical group 0.000 claims description 4
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- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 206010006451 bronchitis Diseases 0.000 claims description 4
- 201000010064 diabetes insipidus Diseases 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 3
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- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 230000002917 arthritic effect Effects 0.000 claims description 3
- 208000019664 bone resorption disease Diseases 0.000 claims description 3
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
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- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 230000009772 tissue formation Effects 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 claims description 2
- JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 claims description 2
- 201000010001 Silicosis Diseases 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- VDBCTDQYMZSQFQ-UHFFFAOYSA-N glycine hydroxamate Chemical compound NCC(=O)NO VDBCTDQYMZSQFQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 206010022000 influenza Diseases 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
- 229910014585 C2-Ce Inorganic materials 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- JMOMIZNLLRYUDW-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-6-thiophen-2-ylindazole Chemical compound C12=CC(C=3SC=CC=3)=CC=C2C(CC)=NN1C1CCCC1 JMOMIZNLLRYUDW-UHFFFAOYSA-N 0.000 claims 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims 1
- BAAQJFBTHFOHLY-UHFFFAOYSA-N 2-amino-n-hydroxypropanamide Chemical compound CC(N)C(=O)NO BAAQJFBTHFOHLY-UHFFFAOYSA-N 0.000 claims 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- 206010061216 Infarction Diseases 0.000 claims 1
- 125000005530 alkylenedioxy group Chemical group 0.000 claims 1
- 208000024908 graft versus host disease Diseases 0.000 claims 1
- 125000001984 thiazolidinyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 57
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- 150000003432 sterols Chemical class 0.000 abstract 1
- 235000003702 sterols Nutrition 0.000 abstract 1
- 229960005486 vaccine Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 194
- 239000011541 reaction mixture Substances 0.000 description 74
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 71
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 70
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
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- 239000012267 brine Substances 0.000 description 36
- 239000000706 filtrate Substances 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
- 239000002585 base Substances 0.000 description 35
- 238000003756 stirring Methods 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
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- 238000005481 NMR spectroscopy Methods 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
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- 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Virology (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Neurology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- AIDS & HIV (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2544696P | 1996-09-04 | 1996-09-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9701080A0 AP9701080A0 (en) | 1997-10-31 |
| AP795A true AP795A (en) | 1999-12-28 |
Family
ID=21826124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1997/001080A AP795A (en) | 1996-09-04 | 1997-09-04 | Indazole derivatives. |
Country Status (35)
| Country | Link |
|---|---|
| US (1) | US6262040B1 (is) |
| EP (1) | EP0931075A1 (is) |
| JP (2) | JP3554337B2 (is) |
| KR (1) | KR100338610B1 (is) |
| CN (1) | CN1234031A (is) |
| AP (1) | AP795A (is) |
| AR (1) | AR008162A1 (is) |
| AU (1) | AU724549B2 (is) |
| BG (1) | BG64447B1 (is) |
| BR (1) | BR9712005A (is) |
| CA (1) | CA2264798A1 (is) |
| CO (1) | CO4600636A1 (is) |
| DZ (1) | DZ2303A1 (is) |
| EA (1) | EA002113B1 (is) |
| GT (1) | GT199700102A (is) |
| HN (1) | HN1997000126A (is) |
| HR (1) | HRP970478B1 (is) |
| HU (1) | HUP9903248A3 (is) |
| ID (1) | ID18157A (is) |
| IL (1) | IL128642A0 (is) |
| IS (1) | IS4979A (is) |
| MA (1) | MA26439A1 (is) |
| NO (1) | NO991048L (is) |
| NZ (1) | NZ334213A (is) |
| OA (1) | OA10985A (is) |
| PA (1) | PA8437301A1 (is) |
| PE (1) | PE107998A1 (is) |
| PL (1) | PL332187A1 (is) |
| SK (1) | SK27299A3 (is) |
| TN (1) | TNSN97148A1 (is) |
| TR (1) | TR199900481T2 (is) |
| TW (1) | TW402595B (is) |
| WO (1) | WO1998009961A1 (is) |
| YU (1) | YU11299A (is) |
| ZA (1) | ZA977903B (is) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4373497B2 (ja) | 1996-06-19 | 2009-11-25 | ローン−プーラン・ロレ・リミテツド | 置換されたアザビシクロ化合物、ならびにｔｎｆおよびサイクリックａｍｐホスホジエステラーゼ産生の阻害剤としてのそれらの使用 |
| IL135714A0 (en) * | 1997-11-04 | 2001-05-20 | Pfizer Prod Inc | Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors |
| IL135900A0 (en) * | 1997-11-04 | 2001-05-20 | Pfizer Prod Inc | Indazole bioisostere replacement of catechol in therapeuticaly active compounds |
| JP2000198734A (ja) * | 1998-12-30 | 2000-07-18 | Pfizer Inc | 胃運動性減弱および関連疾患の治療のための運動性増強薬 |
| US6191300B1 (en) | 1999-04-16 | 2001-02-20 | Eastman Chemical Company | Process for the preparation of cyclopropylacetonitrile |
| UA71971C2 (en) | 1999-06-04 | 2005-01-17 | Agoron Pharmaceuticals Inc | Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases |
| US7141581B2 (en) | 1999-07-02 | 2006-11-28 | Agouron Pharmaceuticals, Inc. | Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use |
| TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| PE20010306A1 (es) * | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
| CA2715683A1 (en) | 1999-08-21 | 2001-03-01 | Nycomed Gmbh | Synergistic combination |
| PT1244649E (pt) * | 1999-12-23 | 2005-06-30 | Icos Corp | Inibidores de fosfodiesterase especificos de mfa ciclica |
| US6362213B1 (en) | 1999-12-23 | 2002-03-26 | Icos Corporation | Cyclic AMP-specific phosphodiesterase inhibitors |
| US7217722B2 (en) * | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| MXPA02010222A (es) | 2000-04-18 | 2003-05-23 | Agouron Pharma | Pirazoles para inhibir proteina cinasa. |
| US7205320B2 (en) | 2001-01-22 | 2007-04-17 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| US7153871B2 (en) | 2001-01-22 | 2006-12-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs |
| CN1537018A (zh) * | 2001-05-23 | 2004-10-13 | 田边制药株式会社 | 一种用于软骨疾病再生治疗的组合物 |
| EP1389468A4 (en) * | 2001-05-23 | 2007-01-10 | Tanabe Seiyaku Co | COMPOSITIONS FOR PROMOTING BONE FRACTURE HEALING |
| TWI221838B (en) | 2001-08-09 | 2004-10-11 | Tanabe Seiyaku Co | Pyrazinoisoquinoline compound or naphthalene compound |
| PE20030701A1 (es) | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| MY140561A (en) | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
| JP2005522215A (ja) * | 2002-04-12 | 2005-07-28 | セルジーン・コーポレーション | 幹細胞及び前駆細胞の分化のモジュレーション、アッセイ、並びにそれらの使用 |
| CN1668733A (zh) * | 2002-05-30 | 2005-09-14 | 细胞基因公司 | 利用jnk或mkk抑制剂调节细胞分化并治疗骨髓增生异常和脊髓发育不良综合症的方法 |
| AU2003256616B2 (en) | 2002-07-19 | 2009-08-27 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including N-substituted aniline and diphenylamine analogs |
| DE60325984D1 (de) * | 2002-07-19 | 2009-03-12 | Memory Pharmaceutical Corp | 4-aminobenzofuranverbindungen als phosphodiesterase-4-inhibitoren |
| CA2506297A1 (en) | 2002-11-19 | 2004-06-03 | Memory Pharmaceuticals Corporation | Pyridine n-oxide compounds as phosphodiesterase 4 inhibitors |
| CA2529611C (en) | 2002-12-20 | 2009-12-15 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
| US7109337B2 (en) | 2002-12-20 | 2006-09-19 | Pfizer Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| US7135575B2 (en) | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
| US7153824B2 (en) | 2003-04-01 | 2006-12-26 | Applied Research Systems Ars Holding N.V. | Inhibitors of phosphodiesterases in infertility |
| US7297709B2 (en) * | 2003-05-22 | 2007-11-20 | Abbott Laboratories | Indazole, benzisoxazole, and benzisothiazole kinase inhibitors |
| US20090048255A1 (en) * | 2003-07-21 | 2009-02-19 | Schumacher Richard A | Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs |
| JP2005089457A (ja) | 2003-09-03 | 2005-04-07 | Yung Shin Pharmaceutical Industry Co Ltd | 骨成長を促進するまたは骨吸収を阻害するための薬剤組成物 |
| MY141255A (en) * | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
| RU2006134022A (ru) | 2004-02-27 | 2008-04-10 | Ф.Хоффманн-Ля Рош Аг (Ch) | Производные индазола и содержащие их фармацевтические композиции |
| WO2005085249A1 (en) | 2004-02-27 | 2005-09-15 | F. Hoffmann-La Roche Ag | Fused derivatives of pyrazole |
| CN1934111A (zh) | 2004-02-27 | 2007-03-21 | 霍夫曼-拉罗奇有限公司 | 杂芳基稠合的吡唑并衍生物 |
| MXPA06011658A (es) | 2004-05-14 | 2006-12-14 | Pfizer Prod Inc | Derivados de pirimidina para el tratamiento del crecimiento celular anormal. |
| JP2007537238A (ja) | 2004-05-14 | 2007-12-20 | ファイザー・プロダクツ・インク | 異常細胞増殖の治療のためのピリミジン誘導体 |
| JP2007537230A (ja) | 2004-05-14 | 2007-12-20 | ファイザー・プロダクツ・インク | 異常細胞増殖の処置用のピリミジン誘導体 |
| CA2573369A1 (en) * | 2004-07-12 | 2006-02-16 | Merck & Co., Inc. | Inhibitors of histone deacetylase |
| US7601847B2 (en) | 2004-10-26 | 2009-10-13 | Wyeth | Preparation and purification of 4-(indazol-3-yl)phenols |
| TW200621237A (en) | 2004-11-01 | 2006-07-01 | Wyeth Corp | [(1-h-indazol-3-yl)methyl]phenols and (hydroxyphenyl)(1h-indazol-3-yl)methanones |
| EP1891060A2 (en) * | 2005-05-30 | 2008-02-27 | Ranbaxy Laboratories Limited | 3-indazolyl-isoxazoline derivatives as inhibitors of phosphodiesterase type-iv |
| KR101011956B1 (ko) | 2005-08-25 | 2011-01-31 | 에프. 호프만-라 로슈 아게 | Ｐ３８ ｍαｐ 키나아제 저해제 및 이의 사용 방법 |
| US7781460B2 (en) | 2005-09-05 | 2010-08-24 | Ranbaxy Laboratories Limited | Substituted indazoles as inhibitors of phosphodiesterase type-IV |
| WO2007031838A1 (en) | 2005-09-16 | 2007-03-22 | Ranbaxy Laboratories Limited | Substituted pyrazolo [3,4-b] pyridines as phosphodiesterase inhibitors |
| RS52298B (sr) | 2006-01-31 | 2012-12-31 | Array Biopharma Inc. | Inhibitori kinaze i postupak njihove upotrebe |
| CA2661850A1 (en) * | 2006-09-01 | 2008-03-06 | Kyorin Pharmaceutical Co., Ltd. | Pyrazolopyridine carboxamide derivative and phosphodiesterase (pde) inhibitor containing the same |
| US7825261B2 (en) * | 2006-12-05 | 2010-11-02 | National Taiwan University | Indazole compounds |
| NZ579645A (en) | 2007-03-14 | 2012-01-12 | Ranbaxy Lab Ltd | Pyrazolo (3, 4-b) pyridine derivatives as phosphodiesterase inhibitors |
| US20100029689A1 (en) * | 2008-07-02 | 2010-02-04 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| US8569512B2 (en) * | 2009-03-23 | 2013-10-29 | Merck Sharp & Dohme Corp. | P2X3 receptor antagonists for treatment of pain |
| US8822447B2 (en) | 2010-04-22 | 2014-09-02 | Janssen Pharmaceutica Nv | Indazole compounds useful as ketohexokinase inhibitors |
| WO2012118812A2 (en) | 2011-02-28 | 2012-09-07 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
| EP3137454A1 (en) | 2014-04-28 | 2017-03-08 | Pfizer Inc. | Heteroaromatic compounds and their use as dopamine d1 ligands |
| AU2017360939B2 (en) | 2016-11-18 | 2022-03-03 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2 |
| AU2020311940A1 (en) | 2019-07-11 | 2022-02-03 | ESCAPE Bio, Inc. | Indazoles and azaindazoles as LRRK2 inhibitors |
| GB201910608D0 (en) * | 2019-07-24 | 2019-09-04 | Enterprise Therapeutics Ltd | Compounds |
| CN112694474B (zh) * | 2019-10-23 | 2022-03-18 | 四川大学 | 吲唑类衍生物及其制备方法和用途 |
| EP4347110A4 (en) * | 2021-05-31 | 2025-04-09 | Genscript USA Inc. | Electrografted films for DNA synthesis |
| TWI907890B (zh) * | 2022-12-14 | 2025-12-11 | 國立成功大學 | 化合物及其合成方法與應用 |
| CN116003325B (zh) * | 2023-01-09 | 2025-04-25 | 南方医科大学 | 吲唑类化合物或其药学上可接受的盐及其制备方法和应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0381422A1 (en) * | 1989-02-02 | 1990-08-08 | Yamanouchi Pharmaceutical Co. Ltd. | Tetrahydrobenzimidazole derivatives |
| WO1991017748A1 (de) * | 1990-05-18 | 1991-11-28 | Hoechst Aktiengesellschaft | Isoxazol-4-carbonsäureamide und hydroxyalkyliden-cyanessigsäureamide, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US5444038A (en) * | 1992-03-09 | 1995-08-22 | Zeneca Limited | Arylindazoles and their use as herbicides |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE531433A (is) * | 1953-06-17 | |||
| US4665397A (en) | 1983-11-01 | 1987-05-12 | Universal Photonics, Inc. | Apparatus and method for a universal electronic locking system |
| GB8524157D0 (en) * | 1984-10-19 | 1985-11-06 | Ici America Inc | Heterocyclic amides |
| JPH061350B2 (ja) * | 1985-07-26 | 1994-01-05 | コニカ株式会社 | ハロゲン化銀写真感光材料 |
| JPS6250751A (ja) * | 1985-08-29 | 1987-03-05 | Konishiroku Photo Ind Co Ltd | ハロゲン化銀写真感光材料 |
| GB8609175D0 (en) * | 1986-04-15 | 1986-05-21 | Ici America Inc | Heterocyclic carboxamides |
| HUT74170A (en) * | 1993-07-06 | 1996-11-28 | Pfizer | Bicyclic tetrahydro pyrazolopyridines |
| GB9401460D0 (en) | 1994-01-26 | 1994-03-23 | Rhone Poulenc Rorer Ltd | Compositions of matter |
| EP0745063B1 (en) * | 1994-02-17 | 1999-03-24 | American Home Products Corporation | Substituted biphenyl derivatives as phosphodiesterase inhibitors |
| WO1995027692A1 (en) * | 1994-04-08 | 1995-10-19 | Smithkline Beecham Corporation | Subtituted biphenyl tnf inhibitors |
| JPH08143525A (ja) * | 1994-11-21 | 1996-06-04 | Banyu Pharmaceut Co Ltd | ヒドロキシ安息香酸アミド誘導体を有効成分とする骨疾患の予防・治療剤 |
| SI0912558T1 (en) * | 1996-06-25 | 2003-10-31 | Pfizer Inc. | Substituted indazole derivatives and their use as phosphodiesterase (pde) type iv and tumor necrosis factor (tnf) inhibitors |
| EP0816357B1 (en) * | 1996-06-27 | 2002-01-09 | Pfizer Inc. | Substituted indazole derivatives |
-
1997
- 1997-08-25 EA EA199900183A patent/EA002113B1/ru not_active IP Right Cessation
- 1997-08-25 HU HU9903248A patent/HUP9903248A3/hu unknown
- 1997-08-25 EP EP97934678A patent/EP0931075A1/en not_active Withdrawn
- 1997-08-25 BR BR9712005A patent/BR9712005A/pt not_active Application Discontinuation
- 1997-08-25 YU YU11299A patent/YU11299A/sh unknown
- 1997-08-25 TR TR1999/00481T patent/TR199900481T2/xx unknown
- 1997-08-25 US US09/254,346 patent/US6262040B1/en not_active Expired - Fee Related
- 1997-08-25 NZ NZ334213A patent/NZ334213A/xx unknown
- 1997-08-25 KR KR1019997001779A patent/KR100338610B1/ko not_active Expired - Fee Related
- 1997-08-25 AU AU37813/97A patent/AU724549B2/en not_active Ceased
- 1997-08-25 SK SK272-99A patent/SK27299A3/sk unknown
- 1997-08-25 CN CN97199022A patent/CN1234031A/zh active Pending
- 1997-08-25 WO PCT/IB1997/001023 patent/WO1998009961A1/en not_active Ceased
- 1997-08-25 CA CA002264798A patent/CA2264798A1/en not_active Abandoned
- 1997-08-25 IL IL12864297A patent/IL128642A0/xx unknown
- 1997-08-25 PL PL97332187A patent/PL332187A1/xx unknown
- 1997-08-25 JP JP51240998A patent/JP3554337B2/ja not_active Expired - Fee Related
- 1997-08-29 HN HN1997000126A patent/HN1997000126A/es unknown
- 1997-09-01 TW TW086112518A patent/TW402595B/zh not_active IP Right Cessation
- 1997-09-02 AR ARP970104001A patent/AR008162A1/es unknown
- 1997-09-02 PE PE1997000777A patent/PE107998A1/es not_active Application Discontinuation
- 1997-09-03 ZA ZA977903A patent/ZA977903B/xx unknown
- 1997-09-03 ID IDP973065A patent/ID18157A/id unknown
- 1997-09-03 DZ DZ970153A patent/DZ2303A1/xx active
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- 1997-09-03 PA PA19978437301A patent/PA8437301A1/es unknown
- 1997-09-03 MA MA24783A patent/MA26439A1/fr unknown
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- 1997-09-04 AP APAP/P/1997/001080A patent/AP795A/en active
- 1997-09-04 CO CO97051473A patent/CO4600636A1/es unknown
- 1997-09-04 HR HR970478A patent/HRP970478B1/xx not_active IP Right Cessation
-
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- 1999-02-16 IS IS4979A patent/IS4979A/is unknown
- 1999-02-22 BG BG103195A patent/BG64447B1/bg unknown
- 1999-03-01 OA OA9900046A patent/OA10985A/en unknown
- 1999-03-03 NO NO991048A patent/NO991048L/no unknown
-
2004
- 2004-03-23 JP JP2004083812A patent/JP2004217668A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0381422A1 (en) * | 1989-02-02 | 1990-08-08 | Yamanouchi Pharmaceutical Co. Ltd. | Tetrahydrobenzimidazole derivatives |
| WO1991017748A1 (de) * | 1990-05-18 | 1991-11-28 | Hoechst Aktiengesellschaft | Isoxazol-4-carbonsäureamide und hydroxyalkyliden-cyanessigsäureamide, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US5444038A (en) * | 1992-03-09 | 1995-08-22 | Zeneca Limited | Arylindazoles and their use as herbicides |
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