ZA200602588B - N3 alkylated benzimidazole derivatives as MEK inhibitors - Google Patents
N3 alkylated benzimidazole derivatives as MEK inhibitors Download PDFInfo
- Publication number
- ZA200602588B ZA200602588B ZA200602588A ZA200602588A ZA200602588B ZA 200602588 B ZA200602588 B ZA 200602588B ZA 200602588 A ZA200602588 A ZA 200602588A ZA 200602588 A ZA200602588 A ZA 200602588A ZA 200602588 B ZA200602588 B ZA 200602588B
- Authority
- ZA
- South Africa
- Prior art keywords
- fluoro
- aryl
- heteroaryl
- bromo
- heterocyclyl
- Prior art date
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- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title description 4
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 133
- -1 triflmoromethyl Chemical group 0.000 claims description 113
- 125000000217 alkyl group Chemical group 0.000 claims description 81
- 125000003118 aryl group Chemical group 0.000 claims description 70
- 125000000623 heterocyclic group Chemical group 0.000 claims description 70
- 125000001072 heteroaryl group Chemical group 0.000 claims description 65
- 239000000203 mixture Substances 0.000 claims description 50
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- 229910052736 halogen Inorganic materials 0.000 claims description 45
- 150000002367 halogens Chemical group 0.000 claims description 45
- 150000003839 salts Chemical class 0.000 claims description 43
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 38
- 229940002612 prodrug Drugs 0.000 claims description 38
- 239000000651 prodrug Substances 0.000 claims description 38
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 32
- 125000003342 alkenyl group Chemical group 0.000 claims description 31
- 125000000304 alkynyl group Chemical group 0.000 claims description 31
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 30
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 29
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- 229910052792 caesium Inorganic materials 0.000 claims description 3
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- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
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- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
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- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
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- 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
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- 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
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- 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
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
- C07D417/06—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 carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
- C07F9/65068—Five-membered rings having the nitrogen atoms in positions 1 and 3 condensed with carbocyclic rings or carbocyclic ring systems
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
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Applications Claiming Priority (1)
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US10/652,733 US7235537B2 (en) | 2002-03-13 | 2003-08-29 | N3 alkylated benzimidazole derivatives as MEK inhibitors |
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ZA200602588A ZA200602588B (en) | 2003-08-29 | 2004-08-20 | N3 alkylated benzimidazole derivatives as MEK inhibitors |
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US (2) | US7235537B2 (es) |
EP (1) | EP1663210B1 (es) |
JP (1) | JP5026076B2 (es) |
KR (1) | KR20060121853A (es) |
CN (1) | CN1874768A (es) |
AR (1) | AR045738A1 (es) |
AU (1) | AU2004270166A1 (es) |
BR (1) | BRPI0413152A (es) |
CA (1) | CA2537098A1 (es) |
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TW (1) | TW200524879A (es) |
WO (1) | WO2005023251A1 (es) |
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NZ535158A (en) * | 2002-03-13 | 2007-06-29 | Array Biopharma Inc | N3 alkylated benzimidazole derivatives as MEK inhibitors |
BRPI0412851A (pt) | 2003-07-24 | 2006-10-03 | Warner Lambert Co | benzamidazóis de n-metila-substituìdos |
US7144907B2 (en) * | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
US7538120B2 (en) * | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
US7732616B2 (en) * | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
WO2005051906A2 (en) * | 2003-11-19 | 2005-06-09 | Array Biopharma Inc. | Heterocyclic inhibitors of mek and methods of use thereof |
US7517994B2 (en) * | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
CN1882347A (zh) * | 2003-11-21 | 2006-12-20 | 阿雷生物药品公司 | Akt蛋白激酶抑制剂 |
US8299076B2 (en) | 2005-05-18 | 2012-10-30 | Array Biopharma Inc. | Crystalline forms of 2-(2-flouro-4-iodophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide |
JP5129143B2 (ja) * | 2005-10-07 | 2013-01-23 | エグゼリクシス, インコーポレイテッド | Mekインヒビターおよびその使用方法 |
CA2632194C (en) | 2005-11-15 | 2012-01-03 | Array Biopharma Inc. | N4-phenyl-quinazoline-4-amine derivatives and related compounds as erbb type i receptor tyrosine kinase inhibitors for the treatment of hyperproliferative diseases |
TWI405756B (zh) | 2005-12-21 | 2013-08-21 | Array Biopharma Inc | 新穎硫酸氫鹽 |
WO2007071951A1 (en) * | 2005-12-21 | 2007-06-28 | Astrazeneca Ab | Tosylate salt of 6- (4-br0m0-2-chl0r0phenylamin0) -7-fluoro-n- (2-hydroxyethoxy) -3-methyl-3h-benzimi dazole- 5 - carboxamide , mek inhibitor useful in the treatment of cancer |
GB0601962D0 (en) | 2006-01-31 | 2006-03-15 | Ucb Sa | Therapeutic agents |
CA2656618C (en) * | 2006-07-06 | 2014-08-26 | Array Biopharma Inc. | Cyclopenta [d] pyrimidines as akt protein kinase inhibitors |
CN101511842B (zh) | 2006-07-06 | 2012-10-31 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的二氢呋喃并嘧啶 |
EP2054418B1 (en) | 2006-07-06 | 2011-11-09 | Array Biopharma Inc. | Dihydrothieno pyrimidines as akt protein kinase inhibitors |
US8063050B2 (en) | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
WO2008016123A1 (fr) * | 2006-08-03 | 2008-02-07 | Takeda Pharmaceutical Company Limited | INHIBITEUR DE LA GSK-3β |
PL2099796T3 (pl) * | 2006-11-30 | 2011-10-31 | Genentech Inc | Związki azaindolilowe i sposoby ich zastosowania |
CN101605540A (zh) * | 2006-12-14 | 2009-12-16 | 埃克塞利希斯股份有限公司 | 使用mek抑制剂的方法 |
ES2551352T3 (es) | 2007-07-05 | 2015-11-18 | Array Biopharma, Inc. | Pirimido ciclopentanos útiles para el tratamiento de enfermedades inflamatorias o hiperproliferativas |
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WO2005023251A1 (en) | 2005-03-17 |
US7235537B2 (en) | 2007-06-26 |
US20070299063A1 (en) | 2007-12-27 |
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