KR20030036686A - Ｖｅｇｆ 억제 활성이 있는 퀴놀린 유도체 - Google Patents

Info

Publication number

KR20030036686A

KR20030036686A KR10-2003-7001934A KR20037001934A KR20030036686A KR 20030036686 A KR20030036686 A KR 20030036686A KR 20037001934 A KR20037001934 A KR 20037001934A KR 20030036686 A KR20030036686 A KR 20030036686A

Authority

KR

South Korea

Prior art keywords

alkyl

cyano

ethyl

quinoline

propoxy

Prior art date

2000-08-09

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

• Espacenet
• Global Dossier
• Discuss

• 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims description 23
• 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
• 230000002401 inhibitory effect Effects 0.000 title description 2
• 101100372758 Danio rerio vegfaa gene Proteins 0.000 title 1
• 101150030763 Vegfa gene Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 192
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 147
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 127
• 239000001257 hydrogen Substances 0.000 claims abstract description 127
• 150000003839 salts Chemical class 0.000 claims abstract description 90
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 34
• 230000000694 effects Effects 0.000 claims abstract description 28
• 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 22
• 241001465754 Metazoa Species 0.000 claims abstract description 18
• 239000003814 drug Substances 0.000 claims abstract description 17
• 230000008728 vascular permeability Effects 0.000 claims abstract description 16
• 238000004519 manufacturing process Methods 0.000 claims abstract description 12
• 230000002137 anti-vascular effect Effects 0.000 claims abstract description 8
• 230000001603 reducing effect Effects 0.000 claims abstract description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• -1 N -methylpiperazinyl Chemical group 0.000 claims description 1255
• 125000000217 alkyl group Chemical group 0.000 claims description 655
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 174
• 125000003545 alkoxy group Chemical group 0.000 claims description 140
• 125000001424 substituent group Chemical group 0.000 claims description 116
• 125000005843 halogen group Chemical group 0.000 claims description 93
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 78
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 75
• 125000000623 heterocyclic group Chemical group 0.000 claims description 62
• 238000000034 method Methods 0.000 claims description 60
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 59
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 56
• 125000003282 alkyl amino group Chemical group 0.000 claims description 54
• 125000003386 piperidinyl group Chemical group 0.000 claims description 54
• 125000004043 oxo group Chemical group O=* 0.000 claims description 53
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 53
• 125000002393 azetidinyl group Chemical group 0.000 claims description 46
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 43
• 125000004122 cyclic group Chemical group 0.000 claims description 40
• 125000005842 heteroatom Chemical group 0.000 claims description 40
• 229910052717 sulfur Inorganic materials 0.000 claims description 40
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 37
• 125000004193 piperazinyl group Chemical group 0.000 claims description 37
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 35
• 238000006243 chemical reaction Methods 0.000 claims description 33
• 125000005505 thiomorpholino group Chemical group 0.000 claims description 33
• 229910052760 oxygen Inorganic materials 0.000 claims description 32
• 125000003342 alkenyl group Chemical group 0.000 claims description 31
• 229910052799 carbon Inorganic materials 0.000 claims description 28
• 125000000304 alkynyl group Chemical group 0.000 claims description 27
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 26
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 25
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 22
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 22
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 20
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 20
• 238000002360 preparation method Methods 0.000 claims description 20
• 150000001721 carbon Chemical group 0.000 claims description 19
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 18
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 18
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 18
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 17
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 17
• 125000001041 indolyl group Chemical group 0.000 claims description 17
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
• 230000001772 anti-angiogenic effect Effects 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 14
• 125000001246 bromo group Chemical group Br* 0.000 claims description 13
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 13
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 12
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 11
• 239000002253 acid Substances 0.000 claims description 10
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 10
• 125000001589 carboacyl group Chemical group 0.000 claims description 10
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 10
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
• 241000282412 Homo Species 0.000 claims description 9
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
• 230000033115 angiogenesis Effects 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
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 5
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims description 5
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
• VUHHYGYHZFFHGJ-UHFFFAOYSA-N 4-(1,2-dimethylindol-5-yl)oxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C=1C=C2N(C)C(C)=CC2=CC=1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 VUHHYGYHZFFHGJ-UHFFFAOYSA-N 0.000 claims description 4
• PTRWPNOBURUKPH-UHFFFAOYSA-N 4-(1,2-dimethylindol-5-yl)oxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC2=NC=CC(OC=3C=C4C=C(C)N(C)C4=CC=3)=C2C=C1C#N PTRWPNOBURUKPH-UHFFFAOYSA-N 0.000 claims description 4
• DHPBSLWHZGVFFC-UHFFFAOYSA-N 4-(1h-indol-5-ylamino)-7-[2-(triazol-1-yl)ethoxy]quinoline-6-carbonitrile Chemical compound N#CC1=CC2=C(NC=3C=C4C=CNC4=CC=3)C=CN=C2C=C1OCCN1C=CN=N1 DHPBSLWHZGVFFC-UHFFFAOYSA-N 0.000 claims description 4
• FEZXBXSADXPMKQ-UHFFFAOYSA-N 4-(1h-indol-5-yloxy)-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound N#CC1=CC2=C(OC=3C=C4C=CNC4=CC=3)C=CN=C2C=C1OCCCN1CCCC1 FEZXBXSADXPMKQ-UHFFFAOYSA-N 0.000 claims description 4
• CJFLDEMFXGDSHD-UHFFFAOYSA-N 4-(1h-indol-5-yloxy)-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC2=NC=CC(OC=3C=C4C=CNC4=CC=3)=C2C=C1C#N CJFLDEMFXGDSHD-UHFFFAOYSA-N 0.000 claims description 4
• NULBUROORZYHIA-UHFFFAOYSA-N 4-[(2,3-dimethyl-1h-indol-5-yl)oxy]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C1=C2C(C)=C(C)NC2=CC=C1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 NULBUROORZYHIA-UHFFFAOYSA-N 0.000 claims description 4
• LIRLFOQNBSXMRM-UHFFFAOYSA-N 4-[(2,3-dimethyl-1h-indol-5-yl)oxy]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC2=NC=CC(OC=3C=C4C(C)=C(C)NC4=CC=3)=C2C=C1C#N LIRLFOQNBSXMRM-UHFFFAOYSA-N 0.000 claims description 4
• SJWWHEGQXCCLDO-UHFFFAOYSA-N 4-[(2-methyl-1h-indol-5-yl)oxy]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=CC=1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 SJWWHEGQXCCLDO-UHFFFAOYSA-N 0.000 claims description 4
• FYFHRWXNXWAGMO-UHFFFAOYSA-N 4-[(2-methyl-1h-indol-5-yl)oxy]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC2=NC=CC(OC=3C=C4C=C(C)NC4=CC=3)=C2C=C1C#N FYFHRWXNXWAGMO-UHFFFAOYSA-N 0.000 claims description 4
• UERRCPKERQUKEX-UHFFFAOYSA-N 4-[(2-methyl-1h-indol-6-yl)oxy]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C1=C2NC(C)=CC2=CC=C1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 UERRCPKERQUKEX-UHFFFAOYSA-N 0.000 claims description 4
• WLOQJVDEBJMPKD-UHFFFAOYSA-N 4-[(4-fluoro-1h-indol-5-yl)oxy]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C1=CC=2NC=CC=2C(F)=C1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 WLOQJVDEBJMPKD-UHFFFAOYSA-N 0.000 claims description 4
• VMFGXMHNIPXDEN-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=C(F)C=1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 VMFGXMHNIPXDEN-UHFFFAOYSA-N 0.000 claims description 4
• VDGNZJPACKFZPX-UHFFFAOYSA-N 4-[(6-fluoro-1h-indol-5-yl)oxy]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC2=NC=CC(OC=3C(=CC=4NC=CC=4C=3)F)=C2C=C1C#N VDGNZJPACKFZPX-UHFFFAOYSA-N 0.000 claims description 4
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 4
• 229940100198 alkylating agent Drugs 0.000 claims description 4
• 239000002168 alkylating agent Substances 0.000 claims description 4
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 4
• 239000012467 final product Substances 0.000 claims description 4
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 4
• 230000003647 oxidation Effects 0.000 claims description 4
• 238000007254 oxidation reaction Methods 0.000 claims description 4
• DSPIJCMHZXUBNS-UHFFFAOYSA-N 4-(1h-indol-5-ylamino)-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC2=NC=CC(NC=3C=C4C=CNC4=CC=3)=C2C=C1C#N DSPIJCMHZXUBNS-UHFFFAOYSA-N 0.000 claims description 3
• QXVDMMKRUGBQDB-UHFFFAOYSA-N 4-[(2,3-dimethyl-1h-indol-5-yl)amino]-7-[2-(triazol-1-yl)ethoxy]quinoline-6-carbonitrile Chemical compound C1=C2C(C)=C(C)NC2=CC=C1NC(C1=CC=2C#N)=CC=NC1=CC=2OCCN1C=CN=N1 QXVDMMKRUGBQDB-UHFFFAOYSA-N 0.000 claims description 3
• FOZIMXIAYHRQLS-UHFFFAOYSA-N 4-[(2-methyl-1h-indol-5-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=CC=1NC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 FOZIMXIAYHRQLS-UHFFFAOYSA-N 0.000 claims description 3
• RCENIQLSAIMJLK-UHFFFAOYSA-N 4-[(2-methyl-1h-indol-5-yl)amino]-7-[2-(triazol-1-yl)ethoxy]quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=CC=1NC(C1=CC=2C#N)=CC=NC1=CC=2OCCN1C=CN=N1 RCENIQLSAIMJLK-UHFFFAOYSA-N 0.000 claims description 3
• GIERJSMFWYGRBE-UHFFFAOYSA-N 4-[(2-methyl-1h-indol-6-yl)oxy]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC2=NC=CC(OC=3C=C4NC(C)=CC4=CC=3)=C2C=C1C#N GIERJSMFWYGRBE-UHFFFAOYSA-N 0.000 claims description 3
• BILXLSMSUVWOOQ-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=C(F)C=1NC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 BILXLSMSUVWOOQ-UHFFFAOYSA-N 0.000 claims description 3
• ISKZMHUSPPQDMM-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC2=NC=CC(OC=3C(=C4C=C(C)NC4=CC=3)F)=C2C=C1C#N ISKZMHUSPPQDMM-UHFFFAOYSA-N 0.000 claims description 3
• VEZIJKGKKUAEHB-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7-[3-(triazol-1-yl)propoxy]quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=C(F)C=1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1C=CN=N1 VEZIJKGKKUAEHB-UHFFFAOYSA-N 0.000 claims description 3
• PPMXVQVFDKPOOU-UHFFFAOYSA-N 4-[(6-fluoro-1h-indol-5-yl)oxy]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound FC1=CC=2NC=CC=2C=C1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 PPMXVQVFDKPOOU-UHFFFAOYSA-N 0.000 claims description 3
• NJEHWNDNCVKTEC-UHFFFAOYSA-N 7-[3-(1,1-dioxo-1,4-thiazinan-4-yl)propoxy]-4-(1h-indol-5-ylamino)quinoline-6-carbonitrile Chemical compound C1CS(=O)(=O)CCN1CCCOC1=CC2=NC=CC(NC=3C=C4C=CNC4=CC=3)=C2C=C1C#N NJEHWNDNCVKTEC-UHFFFAOYSA-N 0.000 claims description 3
• CHEBQPAAQRATQM-UHFFFAOYSA-N 7-[3-(1,1-dioxo-1,4-thiazinan-4-yl)propoxy]-4-(1h-indol-5-yloxy)quinoline-6-carbonitrile Chemical compound C1CS(=O)(=O)CCN1CCCOC1=CC2=NC=CC(OC=3C=C4C=CNC4=CC=3)=C2C=C1C#N CHEBQPAAQRATQM-UHFFFAOYSA-N 0.000 claims description 3
• PKIIAMQOTXMRTH-UHFFFAOYSA-N 7-[3-(1,1-dioxo-1,4-thiazinan-4-yl)propoxy]-4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=C(F)C=1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCS(=O)(=O)CC1 PKIIAMQOTXMRTH-UHFFFAOYSA-N 0.000 claims description 3
• 125000003277 amino group Chemical group 0.000 claims description 3
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 3
• 239000008280 blood Substances 0.000 claims description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
• 125000004310 dioxan-2-yl group Chemical group [H]C1([H])OC([H])([H])C([H])(*)OC1([H])[H] 0.000 claims description 3
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
• RUFWSKPZRFHCNX-UHFFFAOYSA-N 4-[(2,3-dimethyl-1h-indol-5-yl)amino]-7-[3-(1,1-dioxo-1,4-thiazinan-4-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1=C2C(C)=C(C)NC2=CC=C1NC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCS(=O)(=O)CC1 RUFWSKPZRFHCNX-UHFFFAOYSA-N 0.000 claims description 2
• SRPTWIZIVZDCDR-UHFFFAOYSA-N 4-[(2,3-dimethyl-1h-indol-5-yl)oxy]-7-[3-(1,1-dioxo-1,4-thiazinan-4-yl)propoxy]quinoline-6-carbonitrile Chemical compound C1=C2C(C)=C(C)NC2=CC=C1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCS(=O)(=O)CC1 SRPTWIZIVZDCDR-UHFFFAOYSA-N 0.000 claims description 2
• AAJHXZJODPGDFR-UHFFFAOYSA-N 4-[(3-methyl-1h-indol-5-yl)oxy]-7-(3-pyrrolidin-1-ylpropoxy)quinoline-6-carbonitrile Chemical compound C1=C2C(C)=CNC2=CC=C1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCCC1 AAJHXZJODPGDFR-UHFFFAOYSA-N 0.000 claims description 2
• YQGWGQXZPGIVFU-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7-(2-methoxyethoxy)quinoline-6-carbonitrile Chemical compound C1=C2NC(C)=CC2=C(F)C(OC=2C=CN=C3C=C(C(=CC3=2)C#N)OCCOC)=C1 YQGWGQXZPGIVFU-UHFFFAOYSA-N 0.000 claims description 2
• NIOWUECZTUUUFM-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7-[2-(triazol-1-yl)ethoxy]quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=C(F)C=1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCN1C=CN=N1 NIOWUECZTUUUFM-UHFFFAOYSA-N 0.000 claims description 2
• CDVPZGQINUKZLF-UHFFFAOYSA-N 7-[3-(1,1-dioxo-1,4-thiazinan-4-yl)propoxy]-4-[(2-methyl-1h-indol-5-yl)oxy]quinoline-6-carbonitrile Chemical compound C=1C=C2NC(C)=CC2=CC=1OC(C1=CC=2C#N)=CC=NC1=CC=2OCCCN1CCS(=O)(=O)CC1 CDVPZGQINUKZLF-UHFFFAOYSA-N 0.000 claims description 2
• NRYFZKZFAXHGEJ-UHFFFAOYSA-N C=1C=C2NC(C)=CC2=CC=1NC(C1=CC=CC=C1N=1)=CC=1OCCCN1CCS(=O)(=O)CC1 Chemical compound C=1C=C2NC(C)=CC2=CC=1NC(C1=CC=CC=C1N=1)=CC=1OCCCN1CCS(=O)(=O)CC1 NRYFZKZFAXHGEJ-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 150000002475 indoles Chemical class 0.000 claims description 2
• RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 18
• BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 claims 2
• YYFFEPUCAKVRJX-UHFFFAOYSA-N 6-fluoro-1h-indole Chemical group FC1=CC=C2C=CNC2=C1 YYFFEPUCAKVRJX-UHFFFAOYSA-N 0.000 claims 1
• 150000003018 phosphorus compounds Chemical class 0.000 claims 1
• 206010028980 Neoplasm Diseases 0.000 abstract description 18
• 230000015572 biosynthetic process Effects 0.000 abstract description 8
• 201000011510 cancer Diseases 0.000 abstract description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
• 201000010099 disease Diseases 0.000 abstract description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
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