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
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- 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
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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
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- C—CHEMISTRY; METALLURGY
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- 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)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
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- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Tropical Medicine & Parasitology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Communicable Diseases (AREA)
- Orthopedic Medicine & Surgery (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)
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|---|---|
| AP9701080A0 AP9701080A0 (en) | 1997-10-31 |
| AP795A true AP795A (en) | 1999-12-28 |
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| 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) |
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| WO1997048697A1 (en) | 1996-06-19 | 1997-12-24 | Rhone-Poulenc Rorer Limited | Substituted azabicylic compounds and their use as inhibitors of the production of tnf and cyclic amp phosphodiesterase |
| US6716978B2 (en) * | 1997-11-04 | 2004-04-06 | Pfizer Inc | Therapeutically active compounds based on indazole bioisostere replacement of catechol in PDE4 inhibitors |
| US6391872B1 (en) * | 1997-11-04 | 2002-05-21 | Pfizer Inc | Indazole bioisostere replacement of catechol in therapeutically 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 |
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