CA2692611A1 - Di(arylamino)aryl compounds - Google Patents
Di(arylamino)aryl compounds Download PDFInfo
- Publication number
- CA2692611A1 CA2692611A1 CA 2692611 CA2692611A CA2692611A1 CA 2692611 A1 CA2692611 A1 CA 2692611A1 CA 2692611 CA2692611 CA 2692611 CA 2692611 A CA2692611 A CA 2692611A CA 2692611 A1 CA2692611 A1 CA 2692611A1
- Authority
- CA
- Canada
- Prior art keywords
- ome
- substituted
- lower alkyl
- amino
- phenyl
- 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.)
- Abandoned
Links
- 125000001769 aryl amino group Chemical group 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 290
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 98
- 239000002157 polynucleotide Substances 0.000 claims abstract description 98
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 98
- -1 aryl compound Chemical class 0.000 claims abstract description 86
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims abstract description 74
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims abstract description 74
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 71
- 230000004927 fusion Effects 0.000 claims abstract description 69
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims abstract description 63
- 230000000694 effects Effects 0.000 claims abstract description 62
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 56
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 56
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 54
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 54
- 201000011510 cancer Diseases 0.000 claims abstract description 52
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 46
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 45
- 201000005202 lung cancer Diseases 0.000 claims abstract description 45
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims abstract description 43
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims abstract description 43
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
- 206010041067 Small cell lung cancer Diseases 0.000 claims abstract description 15
- 208000000587 small cell lung carcinoma Diseases 0.000 claims abstract description 15
- 239000003112 inhibitor Substances 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 240
- 229910052736 halogen Inorganic materials 0.000 claims description 137
- 150000002367 halogens Chemical class 0.000 claims description 100
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 93
- 150000003839 salts Chemical class 0.000 claims description 83
- 229910052757 nitrogen Inorganic materials 0.000 claims description 70
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 55
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 54
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 45
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 34
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 22
- 125000003386 piperidinyl group Chemical group 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 13
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 13
- MGGBYMDAPCCKCT-UHFFFAOYSA-N ASP-3026 Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C MGGBYMDAPCCKCT-UHFFFAOYSA-N 0.000 claims description 12
- 125000002393 azetidinyl group Chemical group 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 8
- QPTDTQDTFGFQRM-UHFFFAOYSA-N 2-[[4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-1,3,5-triazin-2-yl]amino]-n,n-dimethylbenzenesulfonamide Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)N(C)C QPTDTQDTFGFQRM-UHFFFAOYSA-N 0.000 claims description 7
- WYGMYTSFZVWSMF-UHFFFAOYSA-N n-ethyl-2-[[4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-1,3,5-triazin-2-yl]amino]benzenesulfonamide Chemical compound CCNS(=O)(=O)C1=CC=CC=C1NC1=NC=NC(NC=2C(=CC(=CC=2)N2CCC(CC2)N2CCN(C)CC2)OC)=N1 WYGMYTSFZVWSMF-UHFFFAOYSA-N 0.000 claims description 7
- OPUMDFYPVAENFG-UHFFFAOYSA-N 2-[[4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-1,3,5-triazin-2-yl]amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC=C1NC1=NC=NC(NC=2C(=CC(=CC=2)N2CCC(CC2)N2CCN(C)CC2)OC)=N1 OPUMDFYPVAENFG-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 5
- PUJGUYFOFLFGPV-UHFFFAOYSA-N 2-n-[2-methoxy-4-[3-(4-methylpiperazin-1-yl)azetidin-1-yl]phenyl]-4-n-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine Chemical compound COC1=CC(N2CC(C2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C PUJGUYFOFLFGPV-UHFFFAOYSA-N 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 5
- GRJNLHCQIXDMEI-UHFFFAOYSA-N 2-[[4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-1,3,5-triazin-2-yl]amino]-n-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)NC(C)C GRJNLHCQIXDMEI-UHFFFAOYSA-N 0.000 claims description 4
- VTQRBWCLTQCCHB-UHFFFAOYSA-N 2-n-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-n-(2-propan-2-ylsulfonylphenyl)quinazoline-2,4-diamine Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C VTQRBWCLTQCCHB-UHFFFAOYSA-N 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- MCTXCWGGVNWKLZ-UHFFFAOYSA-N 2-[[4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-1,3,5-triazin-2-yl]amino]-n-methyl-n-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)N(C)C(C)C MCTXCWGGVNWKLZ-UHFFFAOYSA-N 0.000 claims description 3
- HRQQHZTXABKUDD-UHFFFAOYSA-N 2-n-(2-methoxy-4-piperazin-1-ylphenyl)-4-n-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine Chemical compound COC1=CC(N2CCNCC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C HRQQHZTXABKUDD-UHFFFAOYSA-N 0.000 claims description 3
- JSEXADUFTOLMMT-UHFFFAOYSA-N 2-n-[2-methoxy-4-(1-methyl-1,8-diazaspiro[4.5]decan-8-yl)phenyl]-4-n-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine Chemical compound COC1=CC(N2CCC3(N(CCC3)C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C JSEXADUFTOLMMT-UHFFFAOYSA-N 0.000 claims description 3
- LEZLBRINDWQJCR-UHFFFAOYSA-N 2-n-[2-methoxy-4-(1-methyl-1,9-diazaspiro[5.5]undecan-9-yl)phenyl]-4-n-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine Chemical compound COC1=CC(N2CCC3(N(CCCC3)C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C LEZLBRINDWQJCR-UHFFFAOYSA-N 0.000 claims description 3
- JCINKTNWNAFWSX-UHFFFAOYSA-N 2-n-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-4-n-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine Chemical compound COC1=CC(N2CCN(C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C JCINKTNWNAFWSX-UHFFFAOYSA-N 0.000 claims description 3
- IKGHMBRDXGQUHW-UHFFFAOYSA-N 2-n-[2-methoxy-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]-4-n-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine Chemical compound COC1=CC(N2CCC(CC2)N2CCCC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C IKGHMBRDXGQUHW-UHFFFAOYSA-N 0.000 claims description 3
- UZWXLRFFPGPPCS-UHFFFAOYSA-N 2-n-[2-methoxy-4-[methyl-(1-methylpiperidin-4-yl)amino]phenyl]-4-n-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine Chemical compound COC1=CC(N(C)C2CCN(C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C UZWXLRFFPGPPCS-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- MYVFHHNKLJDHTR-UHFFFAOYSA-N n-cyclopropyl-2-[[4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-1,3,5-triazin-2-yl]amino]benzenesulfonamide Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)NC1CC1 MYVFHHNKLJDHTR-UHFFFAOYSA-N 0.000 claims description 3
- WTGCKVTYMKQKTM-UHFFFAOYSA-N 1-[1-[3-methoxy-4-[[4-(2-propan-2-ylsulfonylanilino)-1,3,5-triazin-2-yl]amino]phenyl]piperidin-4-yl]pyrrolidin-3-ol Chemical compound COC1=CC(N2CCC(CC2)N2CC(O)CC2)=CC=C1NC(N=1)=NC=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C WTGCKVTYMKQKTM-UHFFFAOYSA-N 0.000 claims description 2
- ONMAHCKNTBHSEI-UHFFFAOYSA-N 2-n-[2-methoxy-4-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]phenyl]-4-n-(2-propan-2-ylsulfonylphenyl)quinazoline-2,4-diamine Chemical compound COC1=CC(N2CCN(CC2)C2CCN(C)CC2)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1NC1=CC=CC=C1S(=O)(=O)C(C)C ONMAHCKNTBHSEI-UHFFFAOYSA-N 0.000 claims description 2
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- 230000002401 inhibitory effect Effects 0.000 abstract description 56
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 788
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- QQWUGDVOUVUTOY-UHFFFAOYSA-N 5-chloro-N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1S(=O)(=O)C(C)C QQWUGDVOUVUTOY-UHFFFAOYSA-N 0.000 description 64
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DK2016089T3 (da) | 2006-04-14 | 2014-04-22 | Cell Signaling Technology Inc | Gendefekter og mutant-alk-kinase i humane faste tumorer |
EP1914240B1 (en) | 2006-10-11 | 2009-12-02 | Astellas Pharma Inc. | EML4-ALK fusion gene |
CA2598893C (en) | 2006-10-11 | 2012-04-10 | Astellas Pharma Inc. | Eml4-alk fusion gene |
WO2008051547A1 (en) | 2006-10-23 | 2008-05-02 | Cephalon, Inc. | Fused bicyclic derivatives of 2,4-diaminopyrimidine as alk and c-met inhibitors |
ME00811B (me) * | 2006-12-08 | 2012-03-20 | Novartis Ag | JEDINJENJA l KOMPOZICIJE KAO INHIBITORI PROTEIN KINAZE |
CL2008002319A1 (es) | 2007-08-08 | 2009-01-02 | Mithkline Beecham Corp | Compuestos derivados de pirrolopirimidina; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar cancer. |
AU2008296479A1 (en) | 2007-08-28 | 2009-03-12 | Dana Farber Cancer Institute | Amino substituted pyrimidine, pyrollopyridine and pyrazolopyrimidine derivatives useful as kinase inhibitors and in treating proliferative disorders and diseases associated with angiogenesis |
JP2011522212A (ja) | 2007-10-19 | 2011-07-28 | セル・シグナリング・テクノロジー・インコーポレイテツド | 癌の分類および使用法 |
CN102131788B (zh) | 2008-04-07 | 2014-03-19 | Irm责任有限公司 | 作为蛋白激酶抑制剂的化合物和组合物 |
JP5214799B2 (ja) | 2008-04-07 | 2013-06-19 | アイアールエム・リミテッド・ライアビリティ・カンパニー | キナーゼ阻害剤としての化合物および組成物 |
NO2300013T3 (ja) | 2008-05-21 | 2018-02-03 |
-
2008
- 2008-07-03 TW TW097125119A patent/TWI389893B/zh not_active IP Right Cessation
- 2008-07-04 AU AU2008273426A patent/AU2008273426B2/en not_active Ceased
- 2008-07-04 JP JP2009522627A patent/JP5233996B2/ja not_active Expired - Fee Related
- 2008-07-04 EP EP08777903A patent/EP2172461A4/en not_active Withdrawn
- 2008-07-04 WO PCT/JP2008/062188 patent/WO2009008371A1/ja active Application Filing
- 2008-07-04 US US12/448,759 patent/US8318702B2/en active Active
- 2008-07-04 BR BRPI0814809-0A2A patent/BRPI0814809A2/pt not_active IP Right Cessation
- 2008-07-04 MX MX2009013625A patent/MX2009013625A/es active IP Right Grant
- 2008-07-04 CN CN2008800236055A patent/CN101687822B/zh not_active Expired - Fee Related
- 2008-07-04 KR KR1020097026439A patent/KR101323566B1/ko not_active IP Right Cessation
- 2008-07-04 CA CA 2692611 patent/CA2692611A1/en not_active Abandoned
- 2008-07-04 RU RU2010103969/04A patent/RU2463299C2/ru not_active IP Right Cessation
-
2009
- 2009-11-24 ZA ZA2009/08305A patent/ZA200908305B/en unknown
-
2012
- 2012-09-14 US US13/618,732 patent/US20130096100A1/en not_active Abandoned
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2428508A1 (en) * | 2009-05-08 | 2012-03-14 | Astellas Pharma Inc. | Diamino heterocyclic carboxamide compound |
EP2428508A4 (en) * | 2009-05-08 | 2012-11-28 | Astellas Pharma Inc | HETEROCYCLIC DIAMINO CARBOXAMIDE COMPOUND |
US8969336B2 (en) | 2009-05-08 | 2015-03-03 | Astellas Pharma Inc. | Diamino heterocyclic carboxamide compound |
EP3009428A1 (en) * | 2009-05-08 | 2016-04-20 | Astellas Pharma Inc. | Diamino heterocyclic carboxamide compound |
US9487491B2 (en) | 2009-05-08 | 2016-11-08 | Astellas Pharma Inc. | Diamino heterocyclic carboxamide compound |
Also Published As
Publication number | Publication date |
---|---|
ZA200908305B (en) | 2011-02-23 |
BRPI0814809A2 (pt) | 2015-02-03 |
TWI389893B (zh) | 2013-03-21 |
US8318702B2 (en) | 2012-11-27 |
US20130096100A1 (en) | 2013-04-18 |
KR101323566B1 (ko) | 2013-10-29 |
KR20100028563A (ko) | 2010-03-12 |
MX2009013625A (es) | 2010-01-26 |
US20100099658A1 (en) | 2010-04-22 |
JP5233996B2 (ja) | 2013-07-10 |
CN101687822B (zh) | 2012-11-07 |
TW200918508A (en) | 2009-05-01 |
JPWO2009008371A1 (ja) | 2010-09-09 |
EP2172461A1 (en) | 2010-04-07 |
RU2010103969A (ru) | 2011-08-20 |
EP2172461A4 (en) | 2011-06-08 |
CN101687822A (zh) | 2010-03-31 |
RU2463299C2 (ru) | 2012-10-10 |
AU2008273426A1 (en) | 2009-01-15 |
WO2009008371A1 (ja) | 2009-01-15 |
AU2008273426B2 (en) | 2012-11-08 |
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