CA2291065C - Raf kinase inhibitors - Google Patents
Raf kinase inhibitors Download PDFInfo
- Publication number
- CA2291065C CA2291065C CA2291065A CA2291065A CA2291065C CA 2291065 C CA2291065 C CA 2291065C CA 2291065 A CA2291065 A CA 2291065A CA 2291065 A CA2291065 A CA 2291065A CA 2291065 C CA2291065 C CA 2291065C
- Authority
- CA
- Canada
- Prior art keywords
- thiophene
- carboxylic acid
- ureido
- butyl
- mmol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
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- 108010077182 raf Kinases Proteins 0.000 title claims abstract description 20
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
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- 238000000034 method Methods 0.000 abstract description 54
- 206010028980 Neoplasm Diseases 0.000 abstract description 17
- 150000003672 ureas Chemical class 0.000 abstract 1
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- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
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- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- XGUABPXHAFXZBI-UHFFFAOYSA-N methyl 3-amino-5-tert-butyl-1-methylpyrrole-2-carboxylate Chemical compound COC(=O)C1=C(N)C=C(C(C)(C)C)N1C XGUABPXHAFXZBI-UHFFFAOYSA-N 0.000 description 1
- PBFZVARLSANULU-UHFFFAOYSA-N methyl 5-tert-butyl-1-methyl-3-nitropyrrole-2-carboxylate Chemical compound COC(=O)C1=C([N+]([O-])=O)C=C(C(C)(C)C)N1C PBFZVARLSANULU-UHFFFAOYSA-N 0.000 description 1
- DVMWBXHQQKQEEE-UHFFFAOYSA-N methyl 5-tert-butyl-3-isocyanothiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C(C)(C)C)=CC=1[N+]#[C-] DVMWBXHQQKQEEE-UHFFFAOYSA-N 0.000 description 1
- UBRPDRSWIRZWQG-UHFFFAOYSA-N methyl 5-tert-butylfuran-2-carboxylate Chemical compound COC(=O)C1=CC=C(C(C)(C)C)O1 UBRPDRSWIRZWQG-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
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- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 231100000344 non-irritating Toxicity 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 1
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- 235000011149 sulphuric acid Nutrition 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- OQNKBMATPLZSST-UHFFFAOYSA-N thiophen-3-ylurea Chemical class NC(=O)NC=1C=CSC=1 OQNKBMATPLZSST-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
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Classifications
-
- 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
- C07D409/12—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 linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86302197A | 1997-05-23 | 1997-05-23 | |
| US12642097P | 1997-05-23 | 1997-05-23 | |
| US08/863,021 | 1997-05-23 | ||
| PCT/US1998/010376 WO1998052559A1 (en) | 1997-05-23 | 1998-05-21 | Raf kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2291065A1 CA2291065A1 (en) | 1998-11-26 |
| CA2291065C true CA2291065C (en) | 2010-02-09 |
Family
ID=26824631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2291065A Expired - Fee Related CA2291065C (en) | 1997-05-23 | 1998-05-21 | Raf kinase inhibitors |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0986382B1 (https=) |
| JP (1) | JP2002500650A (https=) |
| AT (1) | ATE399007T1 (https=) |
| AU (1) | AU7585598A (https=) |
| CA (1) | CA2291065C (https=) |
| DE (2) | DE69839639D1 (https=) |
| DK (1) | DK0986382T3 (https=) |
| ES (1) | ES2153337T3 (https=) |
| GR (1) | GR20010300033T1 (https=) |
| WO (1) | WO1998052559A1 (https=) |
Families Citing this family (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7329670B1 (en) | 1997-12-22 | 2008-02-12 | Bayer Pharmaceuticals Corporation | Inhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas |
| ID26328A (id) * | 1997-12-22 | 2000-12-14 | Bayer Ag | Penghambat raf kinase menggunakan urea heterosiklik tersubstitusi aril dan heteroaril |
| US7517880B2 (en) | 1997-12-22 | 2009-04-14 | Bayer Pharmaceuticals Corporation | Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas |
| AU2003204708B2 (en) * | 1997-12-22 | 2006-05-25 | Bayer Healthcare Llc | Inhibition of Raf Kinase using Substituted Heterocyclic Ureas |
| SK286213B6 (sk) * | 1997-12-22 | 2008-05-06 | Bayer Corporation | Substituované heterocyklické močoviny, farmaceutický prípravok ich obsahujúci a ich použitie |
| US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| WO2000042012A1 (en) * | 1999-01-13 | 2000-07-20 | Bayer Corporation | φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS |
| EP1690853B1 (en) * | 1999-01-13 | 2010-03-10 | Bayer HealthCare LLC | Use of omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61268678A (ja) * | 1985-05-17 | 1986-11-28 | バイエル・アクチエンゲゼルシヤフト | 生産増進剤 |
| US5597719A (en) * | 1994-07-14 | 1997-01-28 | Onyx Pharmaceuticals, Inc. | Interaction of RAF-1 and 14-3-3 proteins |
| US5773459A (en) * | 1995-06-07 | 1998-06-30 | Sugen, Inc. | Urea- and thiourea-type compounds |
| WO1998052558A1 (en) * | 1997-05-23 | 1998-11-26 | Bayer Corporation | INHIBITION OF p38 KINASE ACTIVITY BY ARYL UREAS |
-
1998
- 1998-05-21 AT AT98923601T patent/ATE399007T1/de not_active IP Right Cessation
- 1998-05-21 JP JP55061898A patent/JP2002500650A/ja active Pending
- 1998-05-21 DK DK98923601T patent/DK0986382T3/da active
- 1998-05-21 DE DE69839639T patent/DE69839639D1/de not_active Expired - Lifetime
- 1998-05-21 DE DE0986382T patent/DE986382T1/de active Pending
- 1998-05-21 CA CA2291065A patent/CA2291065C/en not_active Expired - Fee Related
- 1998-05-21 AU AU75855/98A patent/AU7585598A/en not_active Abandoned
- 1998-05-21 WO PCT/US1998/010376 patent/WO1998052559A1/en not_active Ceased
- 1998-05-21 EP EP98923601A patent/EP0986382B1/en not_active Expired - Lifetime
- 1998-05-21 ES ES98923601T patent/ES2153337T3/es not_active Expired - Lifetime
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2001
- 2001-06-29 GR GR20010300033T patent/GR20010300033T1/el unknown
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|---|---|
| EP0986382A4 (en) | 2001-04-11 |
| EP0986382B1 (en) | 2008-06-25 |
| AU7585598A (en) | 1998-12-11 |
| DE69839639D1 (en) | 2008-08-07 |
| ES2153337T3 (es) | 2008-11-01 |
| DE986382T1 (de) | 2001-01-25 |
| EP0986382A1 (en) | 2000-03-22 |
| DK0986382T3 (da) | 2008-10-20 |
| JP2002500650A (ja) | 2002-01-08 |
| ES2153337T1 (es) | 2001-03-01 |
| CA2291065A1 (en) | 1998-11-26 |
| GR20010300033T1 (en) | 2001-06-29 |
| WO1998052559A1 (en) | 1998-11-26 |
| ATE399007T1 (de) | 2008-07-15 |
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