ZA200300221B - Cinnoline compounds. - Google Patents

Info

Publication number

ZA200300221B

ZA200300221B ZA200300221A ZA200300221A ZA200300221B ZA 200300221 B ZA200300221 B ZA 200300221B ZA 200300221 A ZA200300221 A ZA 200300221A ZA 200300221 A ZA200300221 A ZA 200300221A ZA 200300221 B ZA200300221 B ZA 200300221B

Authority

ZA

South Africa

Prior art keywords

salkyl

sub

ethyl

group

alkyl

Prior art date

2000-08-09

Links

• Espacenet
• Global Dossier
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• 125000000259 cinnolinyl group Chemical class N1=NC(=CC2=CC=CC=C12)* 0.000 title claims description 17
• -1 N-methylpiperazinly Chemical group 0.000 claims abstract description 1197
• 150000001875 compounds Chemical class 0.000 claims abstract description 193
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 143
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 123
• 239000001257 hydrogen Substances 0.000 claims abstract description 123
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 95
• 125000005843 halogen group Chemical group 0.000 claims abstract description 93
• 150000003839 salts Chemical class 0.000 claims abstract description 87
• 150000002431 hydrogen Chemical class 0.000 claims abstract description 85
• 238000000034 method Methods 0.000 claims abstract description 63
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 63
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 59
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 57
• 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 53
• 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 53
• 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 53
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 47
• 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 41
• 125000005505 thiomorpholino group Chemical group 0.000 claims abstract description 41
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 39
• 230000008569 process Effects 0.000 claims abstract description 36
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 34
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 32
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 26
• 238000004519 manufacturing process Methods 0.000 claims abstract description 24
• 230000008728 vascular permeability Effects 0.000 claims abstract description 21
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 20
• 238000011282 treatment Methods 0.000 claims abstract description 20
• 241001465754 Metazoa Species 0.000 claims abstract description 19
• 230000001772 anti-angiogenic effect Effects 0.000 claims abstract description 16
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims abstract description 15
• 239000003814 drug Substances 0.000 claims abstract description 15
• 230000001603 reducing effect Effects 0.000 claims abstract description 15
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims abstract description 13
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims abstract description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims abstract description 10
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims abstract description 10
• 238000002360 preparation method Methods 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• 125000001424 substituent group Chemical group 0.000 claims description 129
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 100
• 239000000203 mixture Substances 0.000 claims description 77
• 125000000623 heterocyclic group Chemical group 0.000 claims description 69
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 58
• 125000005842 heteroatom Chemical group 0.000 claims description 40
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
• 229910052717 sulfur Inorganic materials 0.000 claims description 38
• 125000004122 cyclic group Chemical group 0.000 claims description 36
• 229910052760 oxygen Inorganic materials 0.000 claims description 34
• 238000006243 chemical reaction Methods 0.000 claims description 32
• 125000001153 fluoro group Chemical group F* 0.000 claims description 24
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 23
• 150000001721 carbon Chemical group 0.000 claims description 21
• 125000001041 indolyl group Chemical group 0.000 claims description 21
• 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
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 13
• 125000001246 bromo group Chemical group Br* 0.000 claims description 13
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 11
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• 125000001589 carboacyl group Chemical group 0.000 claims description 9
• 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
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 7
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 7
• 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 7
• 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 7
• 239000000126 substance Substances 0.000 claims description 7
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
• 230000003647 oxidation Effects 0.000 claims description 5
• 238000007254 oxidation reaction Methods 0.000 claims description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 229940100198 alkylating agent Drugs 0.000 claims description 4
• 239000002168 alkylating agent Substances 0.000 claims description 4
• IEOZDJSISVPRJJ-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-(piperidin-4-ylmethoxy)cinnoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)C=NN=C2C=C1OCC1CCNCC1 IEOZDJSISVPRJJ-UHFFFAOYSA-N 0.000 claims description 3
• VTTNPVIKWRVRPS-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-phenylmethoxycinnoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)C=NN=C2C=C1OCC1=CC=CC=C1 VTTNPVIKWRVRPS-UHFFFAOYSA-N 0.000 claims description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
• 125000003277 amino group Chemical group 0.000 claims description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
• 239000012467 final product Substances 0.000 claims description 3
• 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 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• YMWVRUZZXFUWJP-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-(3-piperidin-1-ylpropoxy)cinnoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)C=NN=C2C=C1OCCCN1CCCCC1 YMWVRUZZXFUWJP-UHFFFAOYSA-N 0.000 claims description 2
• XWGHJVLDCIGIPD-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)cinnoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)C=NN=C2C=C1OCCCN1CCCC1 XWGHJVLDCIGIPD-UHFFFAOYSA-N 0.000 claims description 2
• LXKQJCGVMGEIIJ-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]cinnoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)C=NN=C2C=C1OCC1CCN(C)CC1 LXKQJCGVMGEIIJ-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• 150000002475 indoles Chemical group 0.000 claims description 2
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 21
• 206010028980 Neoplasm Diseases 0.000 abstract description 18
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 15
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 15
• 201000011510 cancer Diseases 0.000 abstract description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
• 201000010099 disease Diseases 0.000 abstract description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
• 239000004480 active ingredient Substances 0.000 abstract description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 223
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
• 239000000243 solution Substances 0.000 description 57
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
• 229940093499 ethyl acetate Drugs 0.000 description 42
• 235000019439 ethyl acetate Nutrition 0.000 description 42
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 32
• 239000012044 organic layer Substances 0.000 description 28
• 239000012267 brine Substances 0.000 description 27
• 238000004440 column chromatography Methods 0.000 description 27
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
• 239000007858 starting material Substances 0.000 description 27
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 26
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 26
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 25
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
• 239000003039 volatile agent Substances 0.000 description 24
• 239000007787 solid Substances 0.000 description 23
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 19
• 239000000047 product Substances 0.000 description 19
• 238000001228 spectrum Methods 0.000 description 18
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
• 239000000725 suspension Substances 0.000 description 17
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 150000002148 esters Chemical class 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 238000003756 stirring Methods 0.000 description 15
• MPYLBEQUYBSTNA-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxycinnolin-7-ol Chemical compound C1=C2NC(C)=CC2=C(F)C(OC2=C3C=C(C(=CC3=NN=C2)O)OC)=C1 MPYLBEQUYBSTNA-UHFFFAOYSA-N 0.000 description 14
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 14
• 150000001408 amides Chemical class 0.000 description 14
• 239000002585 base Substances 0.000 description 14
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 14
• 239000002904 solvent Substances 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 13
• 229960005419 nitrogen Drugs 0.000 description 13
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• 229910000027 potassium carbonate Inorganic materials 0.000 description 12
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 11
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 11
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 11
• UMWRMOYYUHIPDT-UHFFFAOYSA-N 4-fluoro-2-methyl-1h-indol-5-ol Chemical compound OC1=CC=C2NC(C)=CC2=C1F UMWRMOYYUHIPDT-UHFFFAOYSA-N 0.000 description 10
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 238000003556 assay Methods 0.000 description 10
• 238000001816 cooling Methods 0.000 description 10
• 239000003208 petroleum Substances 0.000 description 10
• 230000009467 reduction Effects 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• 102000004190 Enzymes Human genes 0.000 description 9
• 108090000790 Enzymes Proteins 0.000 description 9
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• 229940088598 enzyme Drugs 0.000 description 9
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 9
• 229940002612 prodrug Drugs 0.000 description 9
• 239000000651 prodrug Substances 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 229910021529 ammonia Inorganic materials 0.000 description 8
• 239000003701 inert diluent Substances 0.000 description 8
• 239000012442 inert solvent Substances 0.000 description 8
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 8
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 239000011575 calcium Substances 0.000 description 7
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 7
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 6
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 6
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• BZQJRBWTDBHAHT-UHFFFAOYSA-N 4-chloro-6-methoxycinnolin-7-ol Chemical compound C1=NN=C2C=C(O)C(OC)=CC2=C1Cl BZQJRBWTDBHAHT-UHFFFAOYSA-N 0.000 description 6
• 101150021185 FGF gene Proteins 0.000 description 6
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 6
• 125000003342 alkenyl group Chemical group 0.000 description 6
• 125000004848 alkoxyethyl group Chemical group 0.000 description 6
• 125000000304 alkynyl group Chemical group 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
• UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 6
• 239000003102 growth factor Substances 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• 238000006396 nitration reaction Methods 0.000 description 6
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
• RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 5
• WRDOWKZJEOFRSZ-UHFFFAOYSA-N 4-fluoro-5-methoxy-2-methyl-1h-indole Chemical compound COC1=CC=C2NC(C)=CC2=C1F WRDOWKZJEOFRSZ-UHFFFAOYSA-N 0.000 description 5
• 241000282412 Homo Species 0.000 description 5
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 5
• 229910052783 alkali metal Inorganic materials 0.000 description 5
• RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical group [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 description 5
• 230000033115 angiogenesis Effects 0.000 description 5
• 125000003118 aryl group Chemical group 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
• 239000003085 diluting agent Substances 0.000 description 5
• 239000003480 eluent Substances 0.000 description 5
• 238000001704 evaporation Methods 0.000 description 5
• 230000008020 evaporation Effects 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 239000001117 sulphuric acid Substances 0.000 description 5
• 235000011149 sulphuric acid Nutrition 0.000 description 5
• 150000003568 thioethers Chemical class 0.000 description 5
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