TW396149B - 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives - Google Patents
4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives Download PDFInfo
- Publication number
- TW396149B TW396149B TW087110252A TW87110252A TW396149B TW 396149 B TW396149 B TW 396149B TW 087110252 A TW087110252 A TW 087110252A TW 87110252 A TW87110252 A TW 87110252A TW 396149 B TW396149 B TW 396149B
- Authority
- TW
- Taiwan
- Prior art keywords
- methyl
- phenylamino
- difluoro
- iodo
- bromo
- Prior art date
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- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 title description 4
- QAMBBWKIAJFFRF-UHFFFAOYSA-N n-hydroxy-2-(4-iodoanilino)benzamide Chemical class ONC(=O)C1=CC=CC=C1NC1=CC=C(I)C=C1 QAMBBWKIAJFFRF-UHFFFAOYSA-N 0.000 title 1
- -1 alkyl Chemical compound 0.000 claims abstract description 180
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 201000010099 disease Diseases 0.000 claims abstract description 17
- 201000011510 cancer Diseases 0.000 claims abstract description 15
- 230000002062 proliferating effect Effects 0.000 claims abstract description 13
- 208000037803 restenosis Diseases 0.000 claims abstract description 10
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 112
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 78
- 238000011049 filling Methods 0.000 claims description 39
- 238000002844 melting Methods 0.000 claims description 32
- 230000008018 melting Effects 0.000 claims description 32
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- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims description 22
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims description 22
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 238000005481 NMR spectroscopy Methods 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 230000027455 binding Effects 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 239000007789 gas Substances 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 229940067157 phenylhydrazine Drugs 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- OKRDHHWCFHEDRY-UHFFFAOYSA-N 5-bromo-3,4-difluoro-n-(furan-3-ylmethoxy)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NOCC1=COC=C1 OKRDHHWCFHEDRY-UHFFFAOYSA-N 0.000 claims description 2
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- UHAXDAKQGVISBZ-UHFFFAOYSA-N N-(cyclopropylmethoxy)-3,4,5-trifluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(F)C=C1C(=O)NOCC1CC1 UHAXDAKQGVISBZ-UHFFFAOYSA-N 0.000 claims description 2
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- 150000001408 amides Chemical class 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 230000001028 anti-proliverative effect Effects 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
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- 238000005160 1H NMR spectroscopy Methods 0.000 claims 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 4
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- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 claims 2
- 229910021529 ammonia Inorganic materials 0.000 claims 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 claims 2
- 239000013589 supplement Substances 0.000 claims 2
- GOYDNIKZWGIXJT-UHFFFAOYSA-N 1,2-difluorobenzene Chemical compound FC1=CC=CC=C1F GOYDNIKZWGIXJT-UHFFFAOYSA-N 0.000 claims 1
- KTXFXDMDYZIXSJ-UHFFFAOYSA-N 2,4-difluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C=C1F KTXFXDMDYZIXSJ-UHFFFAOYSA-N 0.000 claims 1
- JOTHHUQGLBMOTN-UHFFFAOYSA-N 2-(3-methylpent-2-en-4-ynoxy)benzamide Chemical compound C#CC(C)=CCOC1=CC=CC=C1C(N)=O JOTHHUQGLBMOTN-UHFFFAOYSA-N 0.000 claims 1
- VYMOPINAHSCMIG-UHFFFAOYSA-N 2-(furan-3-ylmethoxy)benzamide Chemical compound NC(=O)C1=CC=CC=C1OCC1=COC=C1 VYMOPINAHSCMIG-UHFFFAOYSA-N 0.000 claims 1
- MZVRISJEIOCFDW-UHFFFAOYSA-N 2-cyclopentyloxybenzamide Chemical compound NC(=O)C1=CC=CC=C1OC1CCCC1 MZVRISJEIOCFDW-UHFFFAOYSA-N 0.000 claims 1
- ODJFDWIECLJWSR-UHFFFAOYSA-N 3-bromobenzamide Chemical compound NC(=O)C1=CC=CC(Br)=C1 ODJFDWIECLJWSR-UHFFFAOYSA-N 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- FAFKBERCJNKWJO-UHFFFAOYSA-N 4-(4-aminophenyl)-3-propoxyaniline Chemical compound C(CC)OC1=C(C=CC(=C1)N)C1=CC=C(N)C=C1 FAFKBERCJNKWJO-UHFFFAOYSA-N 0.000 claims 1
- OFJHKJAWPYMKAO-UHFFFAOYSA-N 4-bromo-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(Br)=CC=C1C(=O)NOCC1=CC=CC=C1 OFJHKJAWPYMKAO-UHFFFAOYSA-N 0.000 claims 1
- PCHYYOCUCGCSBU-UHFFFAOYSA-N 4-bromo-2-methylaniline Chemical compound CC1=CC(Br)=CC=C1N PCHYYOCUCGCSBU-UHFFFAOYSA-N 0.000 claims 1
- GRGWLBCAWYUDDI-UHFFFAOYSA-N 4-fluoro-n-hydroxy-2-(4-iodo-2-methylanilino)-n-propan-2-ylbenzamide Chemical compound CC(C)N(O)C(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C GRGWLBCAWYUDDI-UHFFFAOYSA-N 0.000 claims 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims 1
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- JPTMITNHGROJHE-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-morpholin-4-ylethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NOCCN1CCOCC1 JPTMITNHGROJHE-UHFFFAOYSA-N 0.000 claims 1
- FUJHMFIVMFQFRQ-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-piperidin-1-ylethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NOCCN1CCCCC1 FUJHMFIVMFQFRQ-UHFFFAOYSA-N 0.000 claims 1
- CYHKFEHMDJDUCY-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(pyridin-3-ylmethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NOCC1=CC=CN=C1 CYHKFEHMDJDUCY-UHFFFAOYSA-N 0.000 claims 1
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- WBQVEORRHAMIPY-UHFFFAOYSA-N 5-bromo-n-(cyclobutylmethoxy)-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NOCC1CCC1 WBQVEORRHAMIPY-UHFFFAOYSA-N 0.000 claims 1
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- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
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- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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
- C07D309/10—Oxygen atoms
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- 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
- C07D333/06—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
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| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
| US11078540B2 (en) | 2010-03-09 | 2021-08-03 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
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| AP2001002225A0 (en) | 1999-01-13 | 2001-09-30 | Warner Lambert Co | 1-heterocycle substituted diarylamines. |
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| ATE311363T1 (de) | 1999-01-13 | 2005-12-15 | Warner Lambert Co | Sulfohydroxamsäure and sulfohydroxamate und ihre verwendung als mek-inhibitoren |
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| US6686499B1 (en) | 1999-04-21 | 2004-02-03 | Warner-Lambert Company | Method for making 2-(N-phenylamino)benzoic acids |
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| AU5610398A (en) * | 1997-02-28 | 1998-09-18 | Warner-Lambert Company | Method of treating or preventing septic shock by administering a mek inhibitor |
-
1998
- 1998-06-24 JP JP50722899A patent/JP2002511092A/ja not_active Abandoned
- 1998-06-24 CA CA002290506A patent/CA2290506C/en not_active Expired - Fee Related
- 1998-06-24 AU AU82627/98A patent/AU757046B2/en not_active Ceased
- 1998-06-24 PT PT98932830T patent/PT993439E/pt unknown
- 1998-06-24 KR KR1019997012519A patent/KR20010014362A/ko not_active Ceased
- 1998-06-24 AT AT98932830T patent/ATE277895T1/de not_active IP Right Cessation
- 1998-06-24 WO PCT/US1998/013106 patent/WO1999001426A1/en not_active Ceased
- 1998-06-24 BR BR9810366-0A patent/BR9810366A/pt not_active Application Discontinuation
- 1998-06-24 HU HU0003731A patent/HUP0003731A3/hu unknown
- 1998-06-24 NZ NZ501276A patent/NZ501276A/xx unknown
- 1998-06-24 ES ES98932830T patent/ES2229515T3/es not_active Expired - Lifetime
- 1998-06-24 PL PL98337698A patent/PL337698A1/xx unknown
- 1998-06-24 DE DE69826662T patent/DE69826662T2/de not_active Expired - Lifetime
- 1998-06-24 IL IL13284098A patent/IL132840A/en not_active IP Right Cessation
- 1998-06-24 EP EP98932830A patent/EP0993439B1/en not_active Expired - Lifetime
- 1998-06-24 CN CNB988067501A patent/CN1163475C/zh not_active Expired - Fee Related
- 1998-06-25 TW TW087110252A patent/TW396149B/zh not_active IP Right Cessation
- 1998-06-29 MY MYPI98002946A patent/MY120994A/en unknown
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- 1998-06-30 HR HR60/051,440A patent/HRP980368A2/hr not_active Application Discontinuation
- 1998-06-30 PE PE1998000579A patent/PE97999A1/es not_active Application Discontinuation
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- 1998-06-30 AR ARP980103165A patent/AR016762A1/es unknown
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1999
- 1999-11-19 IS IS5256A patent/IS5256A/is unknown
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| US9084781B2 (en) | 2008-12-10 | 2015-07-21 | Novartis Ag | MEK mutations conferring resistance to MEK inhibitors |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| US8637246B2 (en) | 2010-02-25 | 2014-01-28 | Dana-Farber Cancer Institute, Inc. | BRAF mutations conferring resistance to BRAF inhibitors |
| US9279144B2 (en) | 2010-02-25 | 2016-03-08 | Dana-Farber Cancer Institute, Inc. | Screening method for BRAF inhibitors |
| EP3028699A1 (en) | 2010-02-25 | 2016-06-08 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| US11078540B2 (en) | 2010-03-09 | 2021-08-03 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
| WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
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|---|---|
| AU757046B2 (en) | 2003-01-30 |
| CA2290506A1 (en) | 1999-01-14 |
| HUP0003731A3 (en) | 2002-11-28 |
| PT993439E (pt) | 2004-12-31 |
| WO1999001426A1 (en) | 1999-01-14 |
| DE69826662D1 (de) | 2004-11-04 |
| IL132840A (en) | 2004-12-15 |
| ATE277895T1 (de) | 2004-10-15 |
| PL337698A1 (en) | 2000-08-28 |
| BR9810366A (pt) | 2000-08-29 |
| NZ501276A (en) | 2000-10-27 |
| HUP0003731A2 (hu) | 2001-04-28 |
| CA2290506C (en) | 2005-12-27 |
| ES2229515T3 (es) | 2005-04-16 |
| KR20010014362A (ko) | 2001-02-26 |
| NO996491D0 (no) | 1999-12-27 |
| JP2002511092A (ja) | 2002-04-09 |
| NO996491L (no) | 1999-12-29 |
| CN1261877A (zh) | 2000-08-02 |
| HRP980368A2 (en) | 1999-04-30 |
| UY25076A1 (es) | 1998-12-01 |
| IL132840A0 (en) | 2001-03-19 |
| EP0993439B1 (en) | 2004-09-29 |
| IS5256A (is) | 1999-11-19 |
| DE69826662T2 (de) | 2005-02-17 |
| MY120994A (en) | 2005-12-30 |
| EP0993439A1 (en) | 2000-04-19 |
| ZA985728B (en) | 1999-01-27 |
| NO315271B1 (no) | 2003-08-11 |
| AR016762A1 (es) | 2001-08-01 |
| CO4940442A1 (es) | 2000-07-24 |
| CN1163475C (zh) | 2004-08-25 |
| PE97999A1 (es) | 1999-11-05 |
| AU8262798A (en) | 1999-01-25 |
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