JP4344607B2 - 蛋白キナーゼ阻害剤としてのピロロピリミジン - Google Patents
蛋白キナーゼ阻害剤としてのピロロピリミジン Download PDFInfo
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- JP4344607B2 JP4344607B2 JP2003507098A JP2003507098A JP4344607B2 JP 4344607 B2 JP4344607 B2 JP 4344607B2 JP 2003507098 A JP2003507098 A JP 2003507098A JP 2003507098 A JP2003507098 A JP 2003507098A JP 4344607 B2 JP4344607 B2 JP 4344607B2
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- Prior art keywords
- alkyl
- substituted
- group
- heteroaryl
- aryl
- Prior art date
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- 150000004944 pyrrolopyrimidines Chemical class 0.000 title description 2
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title 1
- 239000003909 protein kinase inhibitor Substances 0.000 title 1
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- -1 cyclic acetal Chemical class 0.000 claims description 83
- 125000000217 alkyl group Chemical group 0.000 claims description 80
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 229910005965 SO 2 Inorganic materials 0.000 claims description 40
- 125000001072 heteroaryl group Chemical group 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 125000001041 indolyl group Chemical group 0.000 claims description 24
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 19
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- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 13
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- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
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- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
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- 230000000694 effects Effects 0.000 description 11
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 10
- 102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 10
- 108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 10
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- 102000001253 Protein Kinase Human genes 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
- 108060006633 protein kinase Proteins 0.000 description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 8
- 229910052763 palladium Inorganic materials 0.000 description 8
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
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- 239000011630 iodine Substances 0.000 description 7
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- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 7
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
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- 125000004076 pyridyl group Chemical group 0.000 description 6
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- ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 6
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- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
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- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
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- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
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- 229940007718 zinc hydroxide Drugs 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Otolaryngology (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0115393.1A GB0115393D0 (en) | 2001-06-23 | 2001-06-23 | Chemical compounds |
| US30167801P | 2001-06-28 | 2001-06-28 | |
| PCT/GB2002/002835 WO2003000695A1 (en) | 2001-06-23 | 2002-06-21 | Pyrrolopyrimidines as protein kinase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005508300A JP2005508300A (ja) | 2005-03-31 |
| JP2005508300A5 JP2005508300A5 (https=) | 2006-01-05 |
| JP4344607B2 true JP4344607B2 (ja) | 2009-10-14 |
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| JP (1) | JP4344607B2 (https=) |
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| CA (1) | CA2451932C (https=) |
| CZ (1) | CZ20033443A3 (https=) |
| EA (1) | EA007415B1 (https=) |
| EC (1) | ECSP034922A (https=) |
| EE (1) | EE05432B1 (https=) |
| GB (1) | GB0115393D0 (https=) |
| HU (1) | HUP0400300A3 (https=) |
| ME (1) | MEP19308A (https=) |
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| OA (1) | OA12632A (https=) |
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| RS (1) | RS51698B (https=) |
| SK (1) | SK15882003A3 (https=) |
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| FR2876103B1 (fr) | 2004-10-01 | 2008-02-22 | Aventis Pharma Sa | Nouveaux derives bis-azaindoles, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
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| JP2008543855A (ja) | 2005-06-13 | 2008-12-04 | ライジェル ファーマシューティカルズ， インコーポレイテッド | 変形性骨疾患を処置するための方法および組成物 |
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| AU1441497A (en) * | 1996-01-23 | 1997-08-20 | Novartis Ag | Pyrrolopyrimidines and processes for their preparation |
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| DE60037345T2 (de) * | 1999-12-10 | 2008-11-13 | Pfizer Products Inc., Groton | Pyrrolo(2,3-d)pyrimidin-Verbindungen |
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Also Published As
| Publication number | Publication date |
|---|---|
| TR200302242T2 (tr) | 2004-12-21 |
| CA2451932C (en) | 2009-12-29 |
| AU2002314325B2 (en) | 2009-01-08 |
| BR0210652A (pt) | 2004-08-10 |
| OA12632A (en) | 2006-06-14 |
| NZ529766A (en) | 2008-11-28 |
| WO2003000695A1 (en) | 2003-01-03 |
| SK15882003A3 (sk) | 2004-07-07 |
| EA200400073A1 (ru) | 2004-08-26 |
| UA76760C2 (uk) | 2006-09-15 |
| HUP0400300A3 (en) | 2010-12-28 |
| CN1294135C (zh) | 2007-01-10 |
| EA007415B1 (ru) | 2006-10-27 |
| EP1404676A1 (en) | 2004-04-07 |
| CZ20033443A3 (en) | 2004-03-17 |
| GB0115393D0 (en) | 2001-08-15 |
| EE200400003A (et) | 2004-02-16 |
| PL374096A1 (en) | 2005-09-19 |
| RS99203A (sr) | 2006-12-15 |
| HUP0400300A2 (en) | 2007-08-28 |
| EE05432B1 (et) | 2011-06-15 |
| ECSP034922A (es) | 2004-04-28 |
| TNSN03144A1 (en) | 2005-12-23 |
| WO2003000695A8 (en) | 2004-03-11 |
| CA2451932A1 (en) | 2003-01-03 |
| CN1518552A (zh) | 2004-08-04 |
| MEP19308A (en) | 2010-06-10 |
| JP2005508300A (ja) | 2005-03-31 |
| RS51698B (sr) | 2011-10-31 |
| AU2002314325B8 (en) | 2009-01-29 |
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