CA2666130A1

CA2666130A1 - Inhibiteurs de kinases

Inhibiteurs de kinases Download PDF

Info

Publication number: CA2666130A1
Authority: CA; Canada
Prior art keywords: alkyl; pyrido; phenyl; hetero; indole
Prior art date: 2006-10-09
Legal status : Abandoned

Application number

CA002666130A

Other languages

English (en)

Inventor

Jason W. Brown

Qing Dong

Bheema R. Paraselli

Jeffrey Alan Stafford

Michael B. Wallace

Current Assignee

Takeda Pharmaceutical Co Ltd

Original Assignee

Individual

Priority date

2006-10-09

Filing date

2007-10-08

Publication date

2008-04-17

2006-10-09 Priority claimed from US11/539,857 external-priority patent/US8119655B2/en

2007-10-08 Application filed by Individual filed Critical Individual

2008-04-17 Publication of CA2666130A1 publication Critical patent/CA2666130A1/fr

Status Abandoned legal-status Critical Current

Links

229940043355 kinase inhibitor Drugs 0.000 title description 52
239000003757 phosphotransferase inhibitor Substances 0.000 title description 52
150000001875 compounds Chemical class 0.000 claims abstract description 162
238000000034 method Methods 0.000 claims abstract description 66
102000001253 Protein Kinase Human genes 0.000 claims abstract description 21
108060006633 protein kinase Proteins 0.000 claims abstract description 21
238000004519 manufacturing process Methods 0.000 claims abstract description 13
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
125000000217 alkyl group Chemical group 0.000 claims description 1717
125000005842 heteroatom Chemical group 0.000 claims description 684
125000000753 cycloalkyl group Chemical group 0.000 claims description 514
125000003118 aryl group Chemical group 0.000 claims description 321
-1 cyano, thio, oxy, hydroxy, carbonyloxy Chemical group 0.000 claims description 264
125000005843 halogen group Chemical group 0.000 claims description 249
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 248
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 246
125000001072 heteroaryl group Chemical group 0.000 claims description 217
150000001602 bicycloalkyls Chemical group 0.000 claims description 215
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 214
229910052739 hydrogen Inorganic materials 0.000 claims description 160
239000001257 hydrogen Substances 0.000 claims description 160
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 159
125000003545 alkoxy group Chemical group 0.000 claims description 131
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 127
125000004429 atom Chemical group 0.000 claims description 123
125000004104 aryloxy group Chemical group 0.000 claims description 118
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 117
125000003282 alkyl amino group Chemical group 0.000 claims description 116
125000001841 imino group Chemical group [H]N=* 0.000 claims description 107
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 100
125000005553 heteroaryloxy group Chemical group 0.000 claims description 78
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 76
238000000926 separation method Methods 0.000 claims description 70
229910052799 carbon Inorganic materials 0.000 claims description 61
229910052757 nitrogen Inorganic materials 0.000 claims description 51
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 50
201000010099 disease Diseases 0.000 claims description 48
229940002612 prodrug Drugs 0.000 claims description 45
239000000651 prodrug Substances 0.000 claims description 45
150000003839 salts Chemical class 0.000 claims description 45
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 44
150000002148 esters Chemical class 0.000 claims description 43
239000012453 solvate Substances 0.000 claims description 41
108091000080 Phosphotransferase Proteins 0.000 claims description 40
102000020233 phosphotransferase Human genes 0.000 claims description 40
229910052717 sulfur Inorganic materials 0.000 claims description 40
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 39
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 38
229910052760 oxygen Inorganic materials 0.000 claims description 38
239000001301 oxygen Substances 0.000 claims description 38
239000011593 sulfur Substances 0.000 claims description 38
238000001727 in vivo Methods 0.000 claims description 18
230000000694 effects Effects 0.000 claims description 17
230000002401 inhibitory effect Effects 0.000 claims description 15
230000007170 pathology Effects 0.000 claims description 14
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 13
206010028980 Neoplasm Diseases 0.000 claims description 9
201000011510 cancer Diseases 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 6
102000003989 Aurora kinases Human genes 0.000 claims description 5
108090000433 Aurora kinases Proteins 0.000 claims description 5
239000005022 packaging material Substances 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 4
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 3
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 3
238000003860 storage Methods 0.000 claims description 3
208000024827 Alzheimer disease Diseases 0.000 claims description 2
206010009944 Colon cancer Diseases 0.000 claims description 2
206010061218 Inflammation Diseases 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims description 2
230000004054 inflammatory process Effects 0.000 claims description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
150000003892 tartrate salts Chemical class 0.000 claims description 2
208000010877 cognitive disease Diseases 0.000 claims 5
206010012289 Dementia Diseases 0.000 claims 4
241000894007 species Species 0.000 claims 4
201000011240 Frontotemporal dementia Diseases 0.000 claims 3
206010027175 memory impairment Diseases 0.000 claims 3
CFPNWPQVXPCHAO-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-piperidin-3-yl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NC3CNCCC3)C=2)=C1 CFPNWPQVXPCHAO-UHFFFAOYSA-N 0.000 claims 2
IMBAZJVHDDPUKE-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-n-[2-[2-hydroxyethyl(methyl)amino]ethyl]-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCCN(C)CCO)C=2)=C1 IMBAZJVHDDPUKE-UHFFFAOYSA-N 0.000 claims 2
UUCHRJUIOWTNSS-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-n-[3-[2-hydroxyethyl(methyl)amino]propyl]-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCCCN(C)CCO)C=2)=C1 UUCHRJUIOWTNSS-UHFFFAOYSA-N 0.000 claims 2
QKKGHZYOULYFLH-UHFFFAOYSA-N 5-[3-(cyclopropylcarbamoyl)phenyl]-3,8-dimethyl-n-(1-methylpiperidin-4-yl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C1CN(C)CCC1NC(=O)C1=CC(C=2C=C(C=CC=2)C(=O)NC2CC2)=C(C=2C(=NC=C(C)C=2)N2)C2=C1C QKKGHZYOULYFLH-UHFFFAOYSA-N 0.000 claims 2
201000004384 Alopecia Diseases 0.000 claims 2
208000028698 Cognitive impairment Diseases 0.000 claims 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
KINUBLRFDKGIIY-UHFFFAOYSA-N n-[3-[ethyl(2-hydroxyethyl)amino]propyl]-5-(3-ethylsulfonylphenyl)-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C=12C3=CC(C)=CN=C3NC2=C(C)C(C(=O)NCCCN(CCO)CC)=CC=1C1=CC=CC(S(=O)(=O)CC)=C1 KINUBLRFDKGIIY-UHFFFAOYSA-N 0.000 claims 2
230000002265 prevention Effects 0.000 claims 2
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical class CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims 1
BOWWRKKKTUGCEQ-UHFFFAOYSA-N 2-[2-[[3-chloro-5-(3-cyclopropylsulfonylphenyl)-8-methyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]ethyl-methylamino]ethyl dihydrogen phosphate Chemical compound C=12C3=CC(Cl)=CN=C3NC2=C(C)C(C(=O)NCCN(C)CCOP(O)(O)=O)=CC=1C(C=1)=CC=CC=1S(=O)(=O)C1CC1 BOWWRKKKTUGCEQ-UHFFFAOYSA-N 0.000 claims 1
FQQVSIRNQVDVSK-UHFFFAOYSA-N 2-[2-[[3-chloro-5-(3-ethylsulfonylphenyl)-8-methyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]ethyl-methylamino]ethyl dihydrogen phosphate Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(Cl)=CN=C4NC=3C(C)=C(C(=O)NCCN(C)CCOP(O)(O)=O)C=2)=C1 FQQVSIRNQVDVSK-UHFFFAOYSA-N 0.000 claims 1
CCKJTULAKFXGSC-UHFFFAOYSA-N 2-[2-[[5-(3-cyclopropylsulfonylphenyl)-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]ethyl-methylamino]ethyl dihydrogen phosphate Chemical compound C=12C3=CC(C)=CN=C3NC2=C(C)C(C(=O)NCCN(C)CCOP(O)(O)=O)=CC=1C(C=1)=CC=CC=1S(=O)(=O)C1CC1 CCKJTULAKFXGSC-UHFFFAOYSA-N 0.000 claims 1
BCDJEUISIJXWNL-UHFFFAOYSA-N 2-[2-[[5-(3-ethylsulfonylphenyl)-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]ethyl-methylamino]ethyl dihydrogen phosphate Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCCN(C)CCOP(O)(O)=O)C=2)=C1 BCDJEUISIJXWNL-UHFFFAOYSA-N 0.000 claims 1
OAKCBRXGTSNKCO-UHFFFAOYSA-N 2-[3-[[5-(3-ethylsulfonylphenyl)-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]propyl-methylamino]ethyl dihydrogen phosphate Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCCCN(C)CCOP(O)(O)=O)C=2)=C1 OAKCBRXGTSNKCO-UHFFFAOYSA-N 0.000 claims 1
GPNIFWQXUCRIJA-UHFFFAOYSA-N 2-[4-[[3-chloro-5-(3-cyclopropylsulfonylphenyl)-8-methyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]piperidin-1-yl]ethyl dihydrogen phosphate Chemical compound C1=2C3=CC(Cl)=CN=C3NC=2C(C)=C(C(=O)NC2CCN(CCOP(O)(O)=O)CC2)C=C1C(C=1)=CC=CC=1S(=O)(=O)C1CC1 GPNIFWQXUCRIJA-UHFFFAOYSA-N 0.000 claims 1
SVOQQPBRIKSTOG-UHFFFAOYSA-N 2-[4-[[3-chloro-5-(3-ethylsulfonylphenyl)-8-methyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]piperidin-1-yl]ethyl dihydrogen phosphate Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(Cl)=CN=C4NC=3C(C)=C(C(=O)NC3CCN(CCOP(O)(O)=O)CC3)C=2)=C1 SVOQQPBRIKSTOG-UHFFFAOYSA-N 0.000 claims 1
YBOHLXXHTBBAMJ-UHFFFAOYSA-N 2-[4-[[5-(3-cyclopropylsulfonylphenyl)-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]piperidin-1-yl]ethyl dihydrogen phosphate Chemical compound C=12C3=CC(C)=CN=C3NC2=C(C)C(C(=O)NC2CCN(CCOP(O)(O)=O)CC2)=CC=1C(C=1)=CC=CC=1S(=O)(=O)C1CC1 YBOHLXXHTBBAMJ-UHFFFAOYSA-N 0.000 claims 1
BMCLQYCZVDORPQ-UHFFFAOYSA-N 2-[4-[[5-(3-ethylsulfonylphenyl)-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]piperidin-1-yl]ethyl dihydrogen phosphate Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NC3CCN(CCOP(O)(O)=O)CC3)C=2)=C1 BMCLQYCZVDORPQ-UHFFFAOYSA-N 0.000 claims 1
VXROJXAYJNYVSF-UHFFFAOYSA-N 2-[ethyl-[3-[[5-(3-ethylsulfonylphenyl)-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carbonyl]amino]propyl]amino]ethyl dihydrogen phosphate Chemical compound C=12C3=CC(C)=CN=C3NC2=C(C)C(C(=O)NCCCN(CC)CCOP(O)(O)=O)=CC=1C1=CC=CC(S(=O)(=O)CC)=C1 VXROJXAYJNYVSF-UHFFFAOYSA-N 0.000 claims 1
NPOPXOBRQAOSDN-UHFFFAOYSA-N 3-chloro-5-(3-cyclopropylsulfonylphenyl)-8-methyl-n-(1-methylpiperidin-4-yl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C1CN(C)CCC1NC(=O)C1=CC(C=2C=C(C=CC=2)S(=O)(=O)C2CC2)=C(C=2C(=NC=C(Cl)C=2)N2)C2=C1C NPOPXOBRQAOSDN-UHFFFAOYSA-N 0.000 claims 1
VOGWPKHEICDHSX-UHFFFAOYSA-N 3-chloro-5-(3-cyclopropylsulfonylphenyl)-n-[1-(2-hydroxyethyl)piperidin-4-yl]-8-methyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C1=2C3=CC(Cl)=CN=C3NC=2C(C)=C(C(=O)NC2CCN(CCO)CC2)C=C1C(C=1)=CC=CC=1S(=O)(=O)C1CC1 VOGWPKHEICDHSX-UHFFFAOYSA-N 0.000 claims 1
UEAOBPNBGJIEEC-UHFFFAOYSA-N 3-chloro-5-(3-cyclopropylsulfonylphenyl)-n-[2-[2-hydroxyethyl(methyl)amino]ethyl]-8-methyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C=12C3=CC(Cl)=CN=C3NC2=C(C)C(C(=O)NCCN(CCO)C)=CC=1C(C=1)=CC=CC=1S(=O)(=O)C1CC1 UEAOBPNBGJIEEC-UHFFFAOYSA-N 0.000 claims 1
DTVMIDUSFPYSCA-UHFFFAOYSA-N 3-chloro-5-(3-ethylsulfonylphenyl)-n-[1-(2-hydroxyethyl)piperidin-4-yl]-8-methyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(Cl)=CN=C4NC=3C(C)=C(C(=O)NC3CCN(CCO)CC3)C=2)=C1 DTVMIDUSFPYSCA-UHFFFAOYSA-N 0.000 claims 1
LDVIEWNALTZGBL-UHFFFAOYSA-N 3-chloro-5-(3-ethylsulfonylphenyl)-n-[2-[2-hydroxyethyl(methyl)amino]ethyl]-8-methyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(Cl)=CN=C4NC=3C(C)=C(C(=O)NCCN(C)CCO)C=2)=C1 LDVIEWNALTZGBL-UHFFFAOYSA-N 0.000 claims 1
JQTMGOLZSBTZMS-UHFFFAOYSA-N 4-methylpiperazine-1-carbaldehyde Chemical compound CN1CCN(C=O)CC1 JQTMGOLZSBTZMS-UHFFFAOYSA-N 0.000 claims 1
BAHSOKHXJFGVMP-UHFFFAOYSA-N 5-(3-cyclopropylsulfonylphenyl)-3,8-dimethyl-n-(1-methylpiperidin-4-yl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C1CN(C)CCC1NC(=O)C1=CC(C=2C=C(C=CC=2)S(=O)(=O)C2CC2)=C(C=2C(=NC=C(C)C=2)N2)C2=C1C BAHSOKHXJFGVMP-UHFFFAOYSA-N 0.000 claims 1
UNWHHRWXCNJSLG-UHFFFAOYSA-N 5-(3-cyclopropylsulfonylphenyl)-3-fluoro-8-methyl-n-(1-methylpiperidin-4-yl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C1CN(C)CCC1NC(=O)C1=CC(C=2C=C(C=CC=2)S(=O)(=O)C2CC2)=C(C=2C(=NC=C(F)C=2)N2)C2=C1C UNWHHRWXCNJSLG-UHFFFAOYSA-N 0.000 claims 1
HRUSRAUYBJJJIB-UHFFFAOYSA-N 5-(3-cyclopropylsulfonylphenyl)-8-methyl-n-(1-methylpiperidin-4-yl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C1CN(C)CCC1NC(=O)C1=CC(C=2C=C(C=CC=2)S(=O)(=O)C2CC2)=C(C=2C(=NC=CC=2)N2)C2=C1C HRUSRAUYBJJJIB-UHFFFAOYSA-N 0.000 claims 1
RSNWLZDNQOINNY-UHFFFAOYSA-N 5-(3-cyclopropylsulfonylphenyl)-n-[1-(2-hydroxyethyl)piperidin-4-yl]-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C=12C3=CC(C)=CN=C3NC2=C(C)C(C(=O)NC2CCN(CCO)CC2)=CC=1C(C=1)=CC=CC=1S(=O)(=O)C1CC1 RSNWLZDNQOINNY-UHFFFAOYSA-N 0.000 claims 1
UOLVTQVDQGYRIM-UHFFFAOYSA-N 5-(3-cyclopropylsulfonylphenyl)-n-[2-[2-hydroxyethyl(methyl)amino]ethyl]-3,8-dimethyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound C=12C3=CC(C)=CN=C3NC2=C(C)C(C(=O)NCCN(CCO)C)=CC=1C(C=1)=CC=CC=1S(=O)(=O)C1CC1 UOLVTQVDQGYRIM-UHFFFAOYSA-N 0.000 claims 1
OPVLGALLXCRSQV-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-(1-propan-2-ylpiperidin-4-yl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NC3CCN(CC3)C(C)C)C=2)=C1 OPVLGALLXCRSQV-UHFFFAOYSA-N 0.000 claims 1
SRPNBIMCYCBPSJ-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-(2-pyrrolidin-1-ylethyl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCCN3CCCC3)C=2)=C1 SRPNBIMCYCBPSJ-UHFFFAOYSA-N 0.000 claims 1
PASFSCJSUBYROD-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-(3-morpholin-4-ylpropyl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCCCN3CCOCC3)C=2)=C1 PASFSCJSUBYROD-UHFFFAOYSA-N 0.000 claims 1
AWARSJUWIHDHFR-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-[(1-methylpiperidin-4-yl)methyl]-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCC3CCN(C)CC3)C=2)=C1 AWARSJUWIHDHFR-UHFFFAOYSA-N 0.000 claims 1
HGVWYUIMNDQLPT-HXUWFJFHSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-[(3r)-1-methylpiperidin-3-yl]-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)N[C@H]3CN(C)CCC3)C=2)=C1 HGVWYUIMNDQLPT-HXUWFJFHSA-N 0.000 claims 1
HGVWYUIMNDQLPT-FQEVSTJZSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-[(3s)-1-methylpiperidin-3-yl]-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)N[C@@H]3CN(C)CCC3)C=2)=C1 HGVWYUIMNDQLPT-FQEVSTJZSA-N 0.000 claims 1
JLIOCHSVVUNIQE-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-[2-(methylamino)ethyl]-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCCNC)C=2)=C1 JLIOCHSVVUNIQE-UHFFFAOYSA-N 0.000 claims 1
FYPYMNHYLXASMS-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-[3-(4-methylpiperazin-1-yl)propyl]-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NCCCN3CCN(C)CC3)C=2)=C1 FYPYMNHYLXASMS-UHFFFAOYSA-N 0.000 claims 1
LVVLBPZNPPPSEO-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-n-piperidin-4-yl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C(C)=C(C(=O)NC3CCNCC3)C=2)=C1 LVVLBPZNPPPSEO-UHFFFAOYSA-N 0.000 claims 1
HYQDFMCWJXSLJF-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-3-methyl-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC(C)=CN=C4NC=3C=C(C=2)C(N)=O)=C1 HYQDFMCWJXSLJF-UHFFFAOYSA-N 0.000 claims 1
FKVUUHNQEIBVAF-UHFFFAOYSA-N 5-(3-ethylsulfonylphenyl)-8-methyl-n-(1-methylpiperidin-4-yl)-9h-pyrido[2,3-b]indole-7-carboxamide Chemical compound CCS(=O)(=O)C1=CC=CC(C=2C=3C4=CC=CN=C4NC=3C(C)=C(C(=O)NC3CCN(C)CC3)C=2)=C1 FKVUUHNQEIBVAF-UHFFFAOYSA-N 0.000 claims 1
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