JP2018518522A5 - - Google Patents

Info

Publication number

JP2018518522A5

JP2018518522A5 JP2017567214A JP2017567214A JP2018518522A5 JP 2018518522 A5 JP2018518522 A5 JP 2018518522A5 JP 2017567214 A JP2017567214 A JP 2017567214A JP 2017567214 A JP2017567214 A JP 2017567214A JP 2018518522 A5 JP2018518522 A5 JP 2018518522A5

Authority

JP

Japan

Prior art keywords

inhibitor

amino

methyl

group

chloro

Prior art date

2016-06-23

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.)

Pending

Links

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• 101000741929 Caenorhabditis elegans Serine/threonine-protein phosphatase 2A catalytic subunit Proteins 0.000 claims 7
• 239000012190 activator Substances 0.000 claims 7
• -1 varicitinib Chemical compound 0.000 claims 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims 5
• 150000001875 compounds Chemical class 0.000 claims 4
• 239000003909 protein kinase inhibitor Substances 0.000 claims 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims 3
• 229940043355 kinase inhibitor Drugs 0.000 claims 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
• 206010028980 Neoplasm Diseases 0.000 claims 2
• 201000011510 cancer Diseases 0.000 claims 2
• 125000004995 haloalkylthio group Chemical group 0.000 claims 2
• 229910052736 halogen Inorganic materials 0.000 claims 2
• 150000002367 halogens Chemical class 0.000 claims 2
• 125000001072 heteroaryl group Chemical group 0.000 claims 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
• KSOVGRCOLZZTPF-QMKUDKLTSA-N (1s,2s,3r,4r)-3-[[5-fluoro-2-[3-methyl-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound N([C@H]1[C@H]([C@@]2([H])C[C@@]1(C=C2)[H])C(N)=O)C(C(=CN=1)F)=NC=1NC(C=C1C)=CC=C1N1CCN(C)CC1 KSOVGRCOLZZTPF-QMKUDKLTSA-N 0.000 claims 1
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 1
• 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims 1
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims 1
• 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims 1
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 1
• FAYAUAZLLLJJGH-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[5-[2-(4-thieno[3,2-d]pyrimidinylamino)ethyl]-2-thiazolyl]urea Chemical compound ClC1=CC=CC(NC(=O)NC=2SC(CCNC=3C=4SC=CC=4N=CN=3)=CN=2)=C1 FAYAUAZLLLJJGH-UHFFFAOYSA-N 0.000 claims 1
• SYYBDNPGDKKJDU-ZDUSSCGKSA-N 1-[5-bromo-4-methyl-2-[[(2S)-2-morpholinyl]methoxy]phenyl]-3-(5-methyl-2-pyrazinyl)urea Chemical compound C1=NC(C)=CN=C1NC(=O)NC1=CC(Br)=C(C)C=C1OC[C@H]1OCCNC1 SYYBDNPGDKKJDU-ZDUSSCGKSA-N 0.000 claims 1
• IEDGRSYITLMBAN-UHFFFAOYSA-N 1-quinolin-4-yl-3-[6-(trifluoromethyl)pyridin-2-yl]urea Chemical compound FC(F)(F)C1=CC=CC(NC(=O)NC=2C3=CC=CC=C3N=CC=2)=N1 IEDGRSYITLMBAN-UHFFFAOYSA-N 0.000 claims 1
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims 1
• IAYGCINLNONXHY-LBPRGKRZSA-N 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-3-piperidinyl]-2-thiophenecarboxamide Chemical compound NC(=O)NC=1C=C(C=2C=C(F)C=CC=2)SC=1C(=O)N[C@H]1CCCNC1 IAYGCINLNONXHY-LBPRGKRZSA-N 0.000 claims 1
• NHFDRBXTEDBWCZ-ZROIWOOFSA-N 3-[2,4-dimethyl-5-[(z)-(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=C(C)NC(\C=C/2C3=CC=CC=C3NC\2=O)=C1C NHFDRBXTEDBWCZ-ZROIWOOFSA-N 0.000 claims 1
• MOVBBVMDHIRCTG-LJQANCHMSA-N 4-[(3s)-1-azabicyclo[2.2.2]oct-3-ylamino]-3-(1h-benzimidazol-2-yl)-6-chloroquinolin-2(1h)-one Chemical compound C([N@](CC1)C2)C[C@@H]1[C@@H]2NC1=C(C=2NC3=CC=CC=C3N=2)C(=O)NC2=CC=C(Cl)C=C21 MOVBBVMDHIRCTG-LJQANCHMSA-N 0.000 claims 1
• KDKUVYLMPJIGKA-UHFFFAOYSA-N 4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide Chemical compound N=1N(C(=O)C=2C(=CC=CC=2F)F)C(N)=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 KDKUVYLMPJIGKA-UHFFFAOYSA-N 0.000 claims 1
• HHFBDROWDBDFBR-UHFFFAOYSA-N 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=C(CN=C(C=2C3=CC=C(Cl)C=2)C=2C(=CC=CC=2F)F)C3=N1 HHFBDROWDBDFBR-UHFFFAOYSA-N 0.000 claims 1
• ZLHFILGSQDJULK-UHFFFAOYSA-N 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C3C4=CC=C(Cl)C=C4C(=NCC3=CN=2)C=2C(=CC=CC=2F)OC)=C1 ZLHFILGSQDJULK-UHFFFAOYSA-N 0.000 claims 1
• NDFXSHIIGXVOKT-UHFFFAOYSA-N 6-n-[2-[[4-(2,4-dichlorophenyl)-5-(1h-imidazol-2-yl)pyrimidin-2-yl]amino]ethyl]-3-nitropyridine-2,6-diamine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(NCCNC=2N=C(C(C=3NC=CN=3)=CN=2)C=2C(=CC(Cl)=CC=2)Cl)=C1 NDFXSHIIGXVOKT-UHFFFAOYSA-N 0.000 claims 1
• FHCSBLWRGCOVPT-UHFFFAOYSA-N AZD2858 Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1 FHCSBLWRGCOVPT-UHFFFAOYSA-N 0.000 claims 1
• GBJVVSCPOBPEIT-UHFFFAOYSA-N AZT-1152 Chemical compound N=1C=NC2=CC(OCCCN(CC)CCOP(O)(O)=O)=CC=C2C=1NC(=NN1)C=C1CC(=O)NC1=CC=CC(F)=C1 GBJVVSCPOBPEIT-UHFFFAOYSA-N 0.000 claims 1
• 229940123877 Aurora kinase inhibitor Drugs 0.000 claims 1
• AQGNHMOJWBZFQQ-UHFFFAOYSA-N CT 99021 Chemical compound CC1=CNC(C=2C(=NC(NCCNC=3N=CC(=CC=3)C#N)=NC=2)C=2C(=CC(Cl)=CC=2)Cl)=N1 AQGNHMOJWBZFQQ-UHFFFAOYSA-N 0.000 claims 1
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 claims 1
• 206010014733 Endometrial cancer Diseases 0.000 claims 1
• 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 claims 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 claims 1
• 229940125497 HER2 kinase inhibitor Drugs 0.000 claims 1
• 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 claims 1
• 239000003458 I kappa b kinase inhibitor Substances 0.000 claims 1
• 229940121730 Janus kinase 2 inhibitor Drugs 0.000 claims 1
• 239000005411 L01XE02 - Gefitinib Substances 0.000 claims 1
• 239000005551 L01XE03 - Erlotinib Substances 0.000 claims 1
• 239000002067 L01XE06 - Dasatinib Substances 0.000 claims 1
• 239000002136 L01XE07 - Lapatinib Substances 0.000 claims 1
• 239000002145 L01XE14 - Bosutinib Substances 0.000 claims 1
• 239000002144 L01XE18 - Ruxolitinib Substances 0.000 claims 1
• UIARLYUEJFELEN-LROUJFHJSA-N LSM-1231 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3C(=O)NCC3=C2C2=CC=CC=C2N1[C@]1(C)[C@](CO)(O)C[C@H]4O1 UIARLYUEJFELEN-LROUJFHJSA-N 0.000 claims 1
• 239000012820 MEK1 Inhibitor Substances 0.000 claims 1
• PSPFQEBFYXJZEV-UHFFFAOYSA-N N'-(1,8-dimethyl-4-imidazo[1,2-a]quinoxalinyl)ethane-1,2-diamine Chemical compound C1=C(C)C=C2N3C(C)=CN=C3C(NCCN)=NC2=C1 PSPFQEBFYXJZEV-UHFFFAOYSA-N 0.000 claims 1
• JZRMBDHPALEPDM-UHFFFAOYSA-N N-(6-Chloro-9H-pyrido[3,4-b]indol-8-yl)-3-pyridinecarboxamide Chemical compound C=12NC3=CN=CC=C3C2=CC(Cl)=CC=1NC(=O)C1=CC=CN=C1 JZRMBDHPALEPDM-UHFFFAOYSA-N 0.000 claims 1
• XKFTZKGMDDZMJI-HSZRJFAPSA-N N-[5-[(2R)-2-methoxy-1-oxo-2-phenylethyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methyl-1-piperazinyl)benzamide Chemical compound O=C([C@H](OC)C=1C=CC=CC=1)N(CC=12)CC=1NN=C2NC(=O)C(C=C1)=CC=C1N1CCN(C)CC1 XKFTZKGMDDZMJI-HSZRJFAPSA-N 0.000 claims 1
• 206010060862 Prostate cancer Diseases 0.000 claims 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
• 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 claims 1
• 229940122924 Src inhibitor Drugs 0.000 claims 1
• 101710164184 Synaptic vesicular amine transporter Proteins 0.000 claims 1
• 102100034333 Synaptic vesicular amine transporter Human genes 0.000 claims 1
• 125000004442 acylamino group Chemical group 0.000 claims 1
• 125000003545 alkoxy group Chemical group 0.000 claims 1
• 125000000217 alkyl group Chemical group 0.000 claims 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 claims 1
• 239000003719 aurora kinase inhibitor Substances 0.000 claims 1
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 1
• UBPYILGKFZZVDX-UHFFFAOYSA-N bosutinib Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CC=2C#N)=C1Cl UBPYILGKFZZVDX-UHFFFAOYSA-N 0.000 claims 1
• 229960003736 bosutinib Drugs 0.000 claims 1
• 239000003795 chemical substances by application Substances 0.000 claims 1
• 229960002448 dasatinib Drugs 0.000 claims 1
• 229940121647 egfr inhibitor Drugs 0.000 claims 1
• 229960001433 erlotinib Drugs 0.000 claims 1
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims 1
• 229960002584 gefitinib Drugs 0.000 claims 1
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims 1
• 125000004438 haloalkoxy group Chemical group 0.000 claims 1
• 125000001188 haloalkyl group Chemical group 0.000 claims 1
• 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 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 claims 1
• 229960004891 lapatinib Drugs 0.000 claims 1
• BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims 1
• 229950001845 lestaurtinib Drugs 0.000 claims 1
• 208000032839 leukemia Diseases 0.000 claims 1
• ZVHNDZWQTBEVRY-UHFFFAOYSA-N momelotinib Chemical compound C1=CC(C(NCC#N)=O)=CC=C1C1=CC=NC(NC=2C=CC(=CC=2)N2CCOCC2)=N1 ZVHNDZWQTBEVRY-UHFFFAOYSA-N 0.000 claims 1
• 229950008814 momelotinib Drugs 0.000 claims 1
• OBWNXGOQPLDDPS-UHFFFAOYSA-N n-(2,6-diethylphenyl)-3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-4,6-dihydro-1h-pyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)N1CC(C(NC(=O)C=2C=CC(=CC=2)N2CCN(C)CC2)=NN2)=C2C1 OBWNXGOQPLDDPS-UHFFFAOYSA-N 0.000 claims 1
• 239000003176 neuroleptic agent Substances 0.000 claims 1
• 230000000701 neuroleptic effect Effects 0.000 claims 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
• RYYNGWLOYLRZLK-RBUKOAKNSA-N pf03814735 Chemical compound C1([C@H]2CC[C@@H](C1=CC=1)N2C(=O)CNC(=O)C)=CC=1NC(N=1)=NC=C(C(F)(F)F)C=1NC1CCC1 RYYNGWLOYLRZLK-RBUKOAKNSA-N 0.000 claims 1
• 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims 1
• HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical compound C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 claims 1
• 229960000215 ruxolitinib Drugs 0.000 claims 1
• 125000001424 substituent group Chemical group 0.000 claims 1
• 230000001225 therapeutic effect Effects 0.000 claims 1
• 229960004066 trametinib Drugs 0.000 claims 1
• LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical compound CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 claims 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
• 0 *c(cc1)ccc1S Chemical compound *c(cc1)ccc1S 0.000 description 1
• WCMLRSZJUIKVCW-UHFFFAOYSA-N FC(c(cc1)ccc1S)(F)F Chemical compound FC(c(cc1)ccc1S)(F)F WCMLRSZJUIKVCW-UHFFFAOYSA-N 0.000 description 1