OA11733A - Combination chemotherapy. - Google Patents

Combination chemotherapy. Download PDF

Info

Publication number: OA11733A
Authority: OA; OAPI
Prior art keywords: iodo; benzamide; methyl; phenylamino; bromo
Prior art date: 1998-12-22

Application number

OA1200100161A

Other languages

English (en)

Inventor

Richard Carleton Gowan

Judith Sebolt-Leopold

Original Assignee

Warner Lambert Co

Priority date (The priority date 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 date listed.)

1998-12-22

Filing date

1999-12-21

Publication date

2005-05-12

1999-12-21 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2005-05-12 Publication of OA11733A publication Critical patent/OA11733A/en

Links

238000009096 combination chemotherapy Methods 0.000 title description 2
-1 phenyl amine compound Chemical class 0.000 claims abstract description 91
239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims abstract description 57
229940124647 MEK inhibitor Drugs 0.000 claims abstract description 48
229930012538 Paclitaxel Natural products 0.000 claims abstract description 34
229960001592 paclitaxel Drugs 0.000 claims abstract description 34
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims abstract description 34
239000003112 inhibitor Substances 0.000 claims abstract description 23
KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 131
150000001875 compounds Chemical class 0.000 claims description 84
125000000217 alkyl group Chemical group 0.000 claims description 47
239000005711 Benzoic acid Substances 0.000 claims description 38
229960004365 benzoic acid Drugs 0.000 claims description 38
229910052739 hydrogen Inorganic materials 0.000 claims description 32
229940121849 Mitotic inhibitor Drugs 0.000 claims description 31
239000001257 hydrogen Substances 0.000 claims description 31
229910052760 oxygen Inorganic materials 0.000 claims description 21
125000003118 aryl group Chemical group 0.000 claims description 19
125000005843 halogen group Chemical group 0.000 claims description 19
150000002431 hydrogen Chemical group 0.000 claims description 18
206010028980 Neoplasm Diseases 0.000 claims description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 15
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 14
150000002148 esters Chemical class 0.000 claims description 13
125000001153 fluoro group Chemical group F* 0.000 claims description 13
GFMMXOIFOQCCGU-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 GFMMXOIFOQCCGU-UHFFFAOYSA-N 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 12
150000001408 amides Chemical class 0.000 claims description 12
201000011510 cancer Diseases 0.000 claims description 12
125000001072 heteroaryl group Chemical group 0.000 claims description 12
108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims description 11
102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000003282 alkyl amino group Chemical group 0.000 claims description 10
125000000304 alkynyl group Chemical group 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000004122 cyclic group Chemical group 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 claims description 8
101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 claims description 8
102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 claims description 8
101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 claims description 8
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 8
229960004528 vincristine Drugs 0.000 claims description 8
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
229960003668 docetaxel Drugs 0.000 claims description 7
125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
229940002612 prodrug Drugs 0.000 claims description 7
239000000651 prodrug Substances 0.000 claims description 7
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 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 claims description 6
229960000922 vinflunine Drugs 0.000 claims description 6
229960002066 vinorelbine Drugs 0.000 claims description 6
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
SRMDAFUJVQJZFI-UHFFFAOYSA-N 5-bromo-2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl SRMDAFUJVQJZFI-UHFFFAOYSA-N 0.000 claims description 4
VJNZMSLGVUSPCF-UHFFFAOYSA-N 5-bromo-2-(2-chloro-4-iodoanilino)-n-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C1CC1CONC(=O)C=1C=C(Br)C(F)=C(F)C=1NC1=CC=C(I)C=C1Cl VJNZMSLGVUSPCF-UHFFFAOYSA-N 0.000 claims description 4
CLOSFYSFDCNULT-UHFFFAOYSA-N 5-iodo-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NOCC1=CC=CC=C1 CLOSFYSFDCNULT-UHFFFAOYSA-N 0.000 claims description 4
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
229960003048 vinblastine Drugs 0.000 claims description 4
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 claims description 4
XKRVQEHFHLIYHN-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-n-methyl-5-nitro-n-phenylbenzamide Chemical compound C=1C=CC=CC=1N(C)C(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(I)C=C1C XKRVQEHFHLIYHN-UHFFFAOYSA-N 0.000 claims description 3
ILYBIGUHBUIMMX-UHFFFAOYSA-N 3,4-difluoro-n-hydroxy-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NO ILYBIGUHBUIMMX-UHFFFAOYSA-N 0.000 claims description 3
COEXMYRMIABFRK-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(N)=O COEXMYRMIABFRK-UHFFFAOYSA-N 0.000 claims description 3
IIJDQEBBOFOXKL-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(O)=O IIJDQEBBOFOXKL-UHFFFAOYSA-N 0.000 claims description 3
IPJAGDMRFVGHCN-UHFFFAOYSA-N 5-bromo-3,4-difluoro-n-hydroxy-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NO IPJAGDMRFVGHCN-UHFFFAOYSA-N 0.000 claims description 3
NRQYGGWYEHEXEJ-UHFFFAOYSA-N 5-chloro-n-cyclopropyl-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NC1CC1 NRQYGGWYEHEXEJ-UHFFFAOYSA-N 0.000 claims description 3
CCGNHTHRIVEZPG-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NOCC1=CC=CC=C1 CCGNHTHRIVEZPG-UHFFFAOYSA-N 0.000 claims description 3
NDLMMYHLEMKNIS-UHFFFAOYSA-N 5-fluoro-n-(3-hydroxypropyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCCO NDLMMYHLEMKNIS-UHFFFAOYSA-N 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
229940050390 benzoate Drugs 0.000 claims description 3
JDQKKPHXLMZTFM-UHFFFAOYSA-N n-(2-hydroxyethyl)-5-iodo-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NCCO JDQKKPHXLMZTFM-UHFFFAOYSA-N 0.000 claims description 3
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
LFKXETJHTXTXSA-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-5-nitrobenzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(O)=O LFKXETJHTXTXSA-UHFFFAOYSA-N 0.000 claims description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
XRNCNLRJMNWXRG-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(O)=O XRNCNLRJMNWXRG-UHFFFAOYSA-N 0.000 claims description 2
OEDQBUOUDGINPB-UHFFFAOYSA-N 4-fluoro-2-(2-fluoro-4-iodoanilino)-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1F OEDQBUOUDGINPB-UHFFFAOYSA-N 0.000 claims description 2
XYPDOWBXGOOEOA-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(2-phenoxyethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCCOC1=CC=CC=C1 XYPDOWBXGOOEOA-UHFFFAOYSA-N 0.000 claims description 2
FXKGVPODJZKPSN-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(2-thiophen-2-ylethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCCC1=CC=CS1 FXKGVPODJZKPSN-UHFFFAOYSA-N 0.000 claims description 2
SQKWOEQAJIDRHG-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(pyridin-4-ylmethyl)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NCC1=CC=NC=C1 SQKWOEQAJIDRHG-UHFFFAOYSA-N 0.000 claims description 2
PBAMOEUDSFIDGM-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(thiophen-2-ylmethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCC1=CC=CS1 PBAMOEUDSFIDGM-UHFFFAOYSA-N 0.000 claims description 2
IVJXLCPTSRJPLQ-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCC1=CC=CC=C1 IVJXLCPTSRJPLQ-UHFFFAOYSA-N 0.000 claims description 2
PFWAYQMMRCDJJX-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-prop-2-enoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCC=C PFWAYQMMRCDJJX-UHFFFAOYSA-N 0.000 claims description 2
VFLRZRPXLGMONP-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-prop-2-ynoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCC#C VFLRZRPXLGMONP-UHFFFAOYSA-N 0.000 claims description 2
AANZSIPSXXHMRM-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NOCC1=CC=CC=C1 AANZSIPSXXHMRM-UHFFFAOYSA-N 0.000 claims description 2
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 description 2
GUAFZVVAOQFCPJ-UHFFFAOYSA-N 5-bromo-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCO GUAFZVVAOQFCPJ-UHFFFAOYSA-N 0.000 claims description 2
GNQPYQRZLIRIAD-UHFFFAOYSA-N 5-bromo-n-cyclohexyl-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NC1CCCCC1 GNQPYQRZLIRIAD-UHFFFAOYSA-N 0.000 claims description 2
HXACAYXLBFGWMG-UHFFFAOYSA-N 5-bromo-n-ethoxy-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CCONC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1C HXACAYXLBFGWMG-UHFFFAOYSA-N 0.000 claims description 2
RTCMPVBAZMDRHK-UHFFFAOYSA-N 5-chloro-2-(4-iodo-2-methylanilino)-n-[(3-methylphenyl)methyl]benzamide Chemical compound CC1=CC=CC(CNC(=O)C=2C(=CC=C(Cl)C=2)NC=2C(=CC(I)=CC=2)C)=C1 RTCMPVBAZMDRHK-UHFFFAOYSA-N 0.000 claims description 2
FVMKNRIUORTHMN-UHFFFAOYSA-N 5-chloro-3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1F FVMKNRIUORTHMN-UHFFFAOYSA-N 0.000 claims description 2
HHLZFIBFGYVDRZ-UHFFFAOYSA-N 5-chloro-n-hydroxy-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NO HHLZFIBFGYVDRZ-UHFFFAOYSA-N 0.000 claims description 2
YSXVOTVVUSIKNI-UHFFFAOYSA-N 5-fluoro-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCO YSXVOTVVUSIKNI-UHFFFAOYSA-N 0.000 claims description 2
KDWCTADZBWWBLF-UHFFFAOYSA-N 5-fluoro-n-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCCN1CCN(CCO)CC1 KDWCTADZBWWBLF-UHFFFAOYSA-N 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
DMGLLVWXKXWTIL-UHFFFAOYSA-N n-(3-hydroxypropyl)-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NCCCO DMGLLVWXKXWTIL-UHFFFAOYSA-N 0.000 claims description 2
DQHARHQBVRLSQS-UHFFFAOYSA-N n-(cyclopropylmethoxy)-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide Chemical compound C=1C=C(I)C=C(F)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 DQHARHQBVRLSQS-UHFFFAOYSA-N 0.000 claims description 2
ZHKTXUBWPSVDAP-UHFFFAOYSA-N n-cyclohexyl-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NC1CCCCC1 ZHKTXUBWPSVDAP-UHFFFAOYSA-N 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
239000012635 anticancer drug combination Substances 0.000 claims 4
229940046044 combinations of antineoplastic agent Drugs 0.000 claims 4
DVENTWJICBBDAJ-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-n-(cyclopropylmethoxy)-4-fluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=CC(F)=CC=C1C(=O)NOCC1CC1 DVENTWJICBBDAJ-UHFFFAOYSA-N 0.000 claims 2
GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims 2
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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
- 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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Seasonings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

OA1200100161A 1998-12-22 1999-12-21 Combination chemotherapy. OA11733A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US11329198P	1998-12-22	1998-12-22
US16478899P	1999-11-10	1999-11-10

Publications (1)

Publication Number	Publication Date
OA11733A true OA11733A (en)	2005-05-12

Family

ID=26810891

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200100161A OA11733A (en)	1998-12-22	1999-12-21	Combination chemotherapy.

Country Status (31)

Country	Link
EP (1)	EP1140291B1 (fr)
JP (1)	JP2002532570A (fr)
KR (1)	KR20010099877A (fr)
CN (1)	CN1333698A (fr)
AP (1)	AP2001002175A0 (fr)
AT (1)	ATE310567T1 (fr)
AU (1)	AU2203900A (fr)
BG (1)	BG105715A (fr)
BR (1)	BR9916839A (fr)
CA (1)	CA2352326A1 (fr)
CZ (1)	CZ20012139A3 (fr)
DE (1)	DE69928568T2 (fr)
EA (1)	EA200100687A1 (fr)
EE (1)	EE200100339A (fr)
ES (1)	ES2253928T3 (fr)
GE (1)	GEP20043172B (fr)
HK (1)	HK1042057A1 (fr)
HR (1)	HRP20010473A2 (fr)
HU (1)	HUP0104844A3 (fr)
ID (1)	ID30250A (fr)
IL (1)	IL143939A0 (fr)
IS (1)	IS5969A (fr)
MA (1)	MA26768A1 (fr)
NO (1)	NO20013099L (fr)
NZ (1)	NZ512859A (fr)
OA (1)	OA11733A (fr)
PL (1)	PL348326A1 (fr)
SK (1)	SK8712001A3 (fr)
TR (1)	TR200101871T2 (fr)
WO (1)	WO2000037141A1 (fr)
YU (1)	YU45401A (fr)

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AP2001002217A0 (fr) *	2000-07-19	2001-09-30	Warner Lambert Co	Esters oxygenes d'acides 4-iodophenylamino benzhydroxamiques
AU8856201A (en)	2000-09-01	2002-03-13	Andel Inst Van	Inhibition of mitogen-activated protein kinase (mapk) pathway: a selective therapeutic strategy against melanoma
WO2002076496A1 (fr) *	2001-03-22	2002-10-03	Van Andel Institute	Facteur letal de l'anthrax inhibant la croissance tumorale et l'angiogenese
IL149462A0 (en)	2001-05-09	2002-11-10	Warner Lambert Co	Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor
CZ20022216A3 (cs) *	2001-07-02	2003-05-14	Warner-Lambert Company	Kombinační chemoterapie
AU2004279721A1 (en) *	2003-10-08	2005-04-21	Teijin Pharma Limited	Process for producing aminopyrrolidine derivative and intermediate compound
NZ546011A (en)	2003-10-21	2009-09-25	Warner Lambert Co	Polymorphic form of N-[(R)-2,3-dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-benzamide
AR051248A1 (es)	2004-10-20	2007-01-03	Applied Research Systems	Derivados de 3-arilamino piridina
CN1807413B (zh) *	2005-09-28	2010-05-05	中国医学科学院医药生物技术研究所	咔唑磺酰胺衍生物及其制备方法
CA3052368A1 (fr)	2005-10-07	2007-04-19	Exelixis, Inc.	Azetidines comme inhibiteurs de mek
EP1790342A1 (fr)	2005-11-11	2007-05-30	Zentaris GmbH	Dérivés de pyridopyrazine et leur utilisation comme modulateurs de transduction de signal
US8217042B2 (en)	2005-11-11	2012-07-10	Zentaris Gmbh	Pyridopyrazines and their use as modulators of kinases
CA2628039A1 (fr)	2005-11-11	2007-05-18	Aeterna Zentaris Gmbh	Nouvelle pyridopyrazine et son utilisation pour la modulation de kinases
EP2101759B1 (fr)	2006-12-14	2018-10-10	Exelixis, Inc.	Procédés d'utilisation d'inhibiteurs de mek
JP5651125B2 (ja)	2008-12-10	2015-01-07	デイナファーバーキャンサーインスティチュート，インコーポレイテッド	Ｍｅｋ阻害剤に対する耐性を付与するｍｅｋ突然変異
RU2571930C2 (ru)	2010-02-25	2015-12-27	Дана-Фарбер Кэнсер Инститьют, Инк.	Мутации braf, обеспечивающие резистентность к ингибиторам braf
US20130059851A1 (en)	2010-03-09	2013-03-07	Dana-Farber Cancer Institute, Inc.	Methods of Diagnosing and Treating Cancer in Patients Having or Developing Resistance to a First Cancer Therapy
CN103301096B (zh) *	2012-03-14	2015-05-06	中国中化股份有限公司	取代二苯胺类化合物作为制备抗肿瘤药物的应用
US20150141470A1 (en)	2012-05-08	2015-05-21	The Broad Institute, Inc.	Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy
KR102204520B1 (ko)	2012-10-12	2021-01-20	엑셀리시스, 인코포레이티드	암의 치료에 사용하기 위한 화합물의 신규 제조 방법
ES2703208T3 (es) *	2013-02-27	2019-03-07	Daiichi Sankyo Co Ltd	Método de predicción de la sensibilidad a un compuesto que inhibe la vía de transducción de señales de MAPK
CN105384754B (zh) *	2014-09-02	2018-04-20	上海科州药物研发有限公司	作为蛋白激酶抑制剂的杂环类化合物及其制备方法和用途
CN111909053B (zh) *	2020-08-06	2022-12-06	湖北省生物农药工程研究中心	基于二芳胺单元的酰胺类衍生物及其制备方法和应用

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IL112248A0 (en) *	1994-01-25	1995-03-30	Warner Lambert Co	Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them
WO1997032604A1 (fr) *	1996-03-07	1997-09-12	Novartis Ag	Combinaisons antiproliferatives contenant des oligonucleotides cibles sur raf et des composes chimiotherapeutiques
WO1998037881A1 (fr) *	1997-02-28	1998-09-03	Warner Lambert Company	Methode de traitement ou de prevention du choc septique par administration d'un inhibiteur mek
AU6580598A (en) *	1997-03-21	1998-10-20	Board Of Regents, The University Of Texas System	(noey2) gene compositions and methods of use
US6002008A (en) *	1997-04-03	1999-12-14	American Cyanamid Company	Substituted 3-cyano quinolines
US6040321A (en) *	1997-11-12	2000-03-21	Bristol-Myers Squibb Company	Aminothiazole inhibitors of cyclin dependent kinases
US5959097A (en) *	1998-11-20	1999-09-28	Isis Pharmaceuticals, Inc.	Antisense modulation of MEK2 expression

1999
- 1999-12-21 EA EA200100687A patent/EA200100687A1/ru unknown
- 1999-12-21 ID IDW00200101616A patent/ID30250A/id unknown
- 1999-12-21 BR BR9916839-1A patent/BR9916839A/pt not_active Application Discontinuation
- 1999-12-21 KR KR1020017007874A patent/KR20010099877A/ko not_active Withdrawn
- 1999-12-21 WO PCT/US1999/030485 patent/WO2000037141A1/fr not_active Ceased
- 1999-12-21 YU YU45401A patent/YU45401A/sh unknown
- 1999-12-21 AU AU22039/00A patent/AU2203900A/en not_active Abandoned
- 1999-12-21 JP JP2000589248A patent/JP2002532570A/ja active Pending
- 1999-12-21 ES ES99966523T patent/ES2253928T3/es not_active Expired - Lifetime
- 1999-12-21 AP APAP/P/2001/002175A patent/AP2001002175A0/en unknown
- 1999-12-21 AT AT99966523T patent/ATE310567T1/de not_active IP Right Cessation
- 1999-12-21 GE GEAP19996007A patent/GEP20043172B/en unknown
- 1999-12-21 NZ NZ512859A patent/NZ512859A/en unknown
- 1999-12-21 CN CN99815040A patent/CN1333698A/zh active Pending
- 1999-12-21 CA CA002352326A patent/CA2352326A1/fr not_active Abandoned
- 1999-12-21 CZ CZ20012139A patent/CZ20012139A3/cs unknown
- 1999-12-21 SK SK871-2001A patent/SK8712001A3/sk unknown
- 1999-12-21 PL PL99348326A patent/PL348326A1/xx not_active Application Discontinuation
- 1999-12-21 EE EEP200100339A patent/EE200100339A/xx unknown
- 1999-12-21 OA OA1200100161A patent/OA11733A/en unknown
- 1999-12-21 HK HK02103397.1A patent/HK1042057A1/zh unknown
- 1999-12-21 IL IL14393999A patent/IL143939A0/xx unknown
- 1999-12-21 DE DE69928568T patent/DE69928568T2/de not_active Expired - Fee Related
- 1999-12-21 HR HR20010473A patent/HRP20010473A2/hr not_active Application Discontinuation
- 1999-12-21 TR TR2001/01871T patent/TR200101871T2/xx unknown
- 1999-12-21 EP EP99966523A patent/EP1140291B1/fr not_active Expired - Lifetime
- 1999-12-21 HU HU0104844A patent/HUP0104844A3/hu unknown
2001
- 2001-06-14 IS IS5969A patent/IS5969A/is unknown
- 2001-06-21 NO NO20013099A patent/NO20013099L/no not_active Application Discontinuation
- 2001-07-18 BG BG105715A patent/BG105715A/xx unknown
- 2001-07-19 MA MA26275A patent/MA26768A1/fr unknown

Also Published As

Publication number	Publication date
YU45401A (sh)	2004-07-15
DE69928568T2 (de)	2006-07-27
TR200101871T2 (tr)	2001-10-22
HRP20010473A2 (en)	2002-08-31
JP2002532570A (ja)	2002-10-02
CZ20012139A3 (cs)	2002-01-16
DE69928568D1 (de)	2005-12-29
AP2001002175A0 (en)	2001-06-21
PL348326A1 (en)	2002-05-20
MA26768A1 (fr)	2004-12-20
EE200100339A (et)	2002-10-15
IL143939A0 (en)	2002-04-21
KR20010099877A (ko)	2001-11-09
ATE310567T1 (de)	2005-12-15
ES2253928T3 (es)	2006-06-01
EP1140291A1 (fr)	2001-10-10
EA200100687A1 (ru)	2001-12-24
NO20013099L (no)	2001-08-20
IS5969A (is)	2001-06-14
NO20013099D0 (no)	2001-06-21
AU2203900A (en)	2000-07-12
EP1140291B1 (fr)	2005-11-23
CN1333698A (zh)	2002-01-30
GEP20043172B (en)	2004-02-25
HUP0104844A2 (en)	2002-06-29
WO2000037141A1 (fr)	2000-06-29
BR9916839A (pt)	2001-10-09
HUP0104844A3 (en)	2003-05-28
NZ512859A (en)	2004-06-25
HK1042057A1 (zh)	2002-08-02
BG105715A (en)	2002-04-30
WO2000037141A9 (fr)	2000-12-07
CA2352326A1 (fr)	2000-06-29
ID30250A (id)	2001-11-15
SK8712001A3 (en)	2002-02-05

Publication	Publication Date	Title
OA11733A (en)	2005-05-12	Combination chemotherapy.
AU776788C (en)	2005-10-27	Treatment of arthritis with MEK inhibitors
US6251943B1 (en)	2001-06-26	Method of treating or preventing septic shock by administering a MEK inhibitor
EP0993437B1 (fr)	2006-11-08	Derives d'acide benzoique 2-(4-bromo ou 4-iodo phenylamino) et utilisation de ces derniers en tant qu'inhibiteurs de mek
EP1140062B1 (fr)	2005-04-06	Traitement de l'asthme a l'aide d'inhibiteurs de mek
US7019033B2 (en)	2006-03-28	2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives
ZA200104000B (en)	2002-08-16	Antiviral method using MEK inhibitors.
EP1140046A1 (fr)	2001-10-10	Technique de prevention du rejet de greffe par utilisation d'un inhibiteur du mek
US20040171632A1 (en)	2004-09-02	Combination chemotherapy
MXPA01005476A (en)	2002-03-26	Combination chemotherapy