NO326475B1 - Cinnolinforbindelser, anvendelse og fremstilling derav samt farmasoytisk preparat - Google Patents

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Publication number

NO326475B1

NO326475B1 NO20030624A NO20030624A NO326475B1 NO 326475 B1 NO326475 B1 NO 326475B1 NO 20030624 A NO20030624 A NO 20030624A NO 20030624 A NO20030624 A NO 20030624A NO 326475 B1 NO326475 B1 NO 326475B1

Authority

NO

Norway

Prior art keywords

sub

sup

formula

compound

fluoro

Prior art date

2000-08-09

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• 238000002360 preparation method Methods 0.000 title claims abstract description 20
• 125000000259 cinnolinyl group Chemical class N1=NC(=CC2=CC=CC=C12)* 0.000 title claims description 7
• 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 177
• 150000003839 salts Chemical class 0.000 claims abstract description 75
• 238000000034 method Methods 0.000 claims abstract description 55
• -1 N-methylpiperazinly Chemical group 0.000 claims abstract description 41
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 40
• 239000001257 hydrogen Substances 0.000 claims abstract description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
• 230000000694 effects Effects 0.000 claims abstract description 23
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 19
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
• 230000008569 process Effects 0.000 claims abstract description 11
• 230000008728 vascular permeability Effects 0.000 claims abstract description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
• 201000011510 cancer Diseases 0.000 claims abstract description 9
• 201000010099 disease Diseases 0.000 claims abstract description 9
• 239000003814 drug Substances 0.000 claims abstract description 8
• 241001465754 Metazoa Species 0.000 claims abstract description 7
• 230000001772 anti-angiogenic effect Effects 0.000 claims abstract description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims abstract description 6
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims abstract description 3
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims abstract description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 3
• 238000006243 chemical reaction Methods 0.000 claims description 32
• 230000009467 reduction Effects 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 13
• 229910052736 halogen Inorganic materials 0.000 claims description 13
• 150000002367 halogens Chemical class 0.000 claims description 13
• 125000001424 substituent group Chemical group 0.000 claims description 12
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 230000035755 proliferation Effects 0.000 claims description 7
• 230000015572 biosynthetic process Effects 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 5
• 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 5
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 5
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 5
• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 201000011066 hemangioma Diseases 0.000 claims description 5
• 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 4
• 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 4
• 206010051113 Arterial restenosis Diseases 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 4
• 206010013908 Dysfunctional uterine bleeding Diseases 0.000 claims description 4
• 201000009273 Endometriosis Diseases 0.000 claims description 4
• 206010025282 Lymphoedema Diseases 0.000 claims description 4
• 206010027514 Metrorrhagia Diseases 0.000 claims description 4
• 208000022873 Ocular disease Diseases 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 208000038016 acute inflammation Diseases 0.000 claims description 4
• 230000006022 acute inflammation Effects 0.000 claims description 4
• 239000000654 additive Substances 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 208000002502 lymphedema Diseases 0.000 claims description 4
• 210000001210 retinal vessel Anatomy 0.000 claims description 4
• 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 3
• 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 3
• QBWWTOMIRYQQKX-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]cinnoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)C=NN=C2C=C1OCCCN1CCN(C)CC1 QBWWTOMIRYQQKX-UHFFFAOYSA-N 0.000 claims description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
• 230000000996 additive effect Effects 0.000 claims description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
• 229910052794 bromium Inorganic materials 0.000 claims description 3
• 239000000460 chlorine Substances 0.000 claims description 3
• 229910052801 chlorine Inorganic materials 0.000 claims description 3
• 235000019256 formaldehyde Nutrition 0.000 claims description 3
• 230000037390 scarring Effects 0.000 claims description 3
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 229910052731 fluorine Inorganic materials 0.000 claims description 2
• 239000011737 fluorine Substances 0.000 claims description 2
• 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 2
• 125000001041 indolyl group Chemical group 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 201000001119 neuropathy Diseases 0.000 claims description 2
• 230000007823 neuropathy Effects 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 16
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 15
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 15
• 238000011282 treatment Methods 0.000 abstract description 13
• 150000002431 hydrogen Chemical class 0.000 abstract description 11
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 9
• 125000003545 alkoxy group Chemical group 0.000 abstract description 8
• 229910052757 nitrogen Inorganic materials 0.000 abstract description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 7
• 238000004519 manufacturing process Methods 0.000 abstract description 5
• 239000004480 active ingredient Substances 0.000 abstract description 3
• 125000004093 cyano group Chemical group *C#N 0.000 abstract description 3
• 125000005843 halogen group Chemical group 0.000 abstract description 3
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 abstract description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract description 2
• 125000004043 oxo group Chemical group O=* 0.000 abstract description 2
• 230000001603 reducing effect Effects 0.000 abstract description 2
• 125000005505 thiomorpholino group Chemical group 0.000 abstract description 2
• 125000002393 azetidinyl group Chemical group 0.000 abstract 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 abstract 1
• 239000008194 pharmaceutical composition Substances 0.000 abstract 1
• 125000004193 piperazinyl group Chemical group 0.000 abstract 1
• 125000003386 piperidinyl group Chemical group 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 246
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 147
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 92
• 239000000203 mixture Substances 0.000 description 78
• 239000000243 solution Substances 0.000 description 64
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 55
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
• 238000004440 column chromatography Methods 0.000 description 32
• 239000012044 organic layer Substances 0.000 description 31
• 239000012267 brine Substances 0.000 description 30
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
• 239000007858 starting material Substances 0.000 description 27
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 26
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
• 239000003039 volatile agent Substances 0.000 description 25
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
• 239000000047 product Substances 0.000 description 24
• 239000007787 solid Substances 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
• 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 18
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
• 239000000725 suspension Substances 0.000 description 17
• 239000000706 filtrate Substances 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 239000002585 base Substances 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
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 14
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 14
• 239000002904 solvent Substances 0.000 description 14
• 239000003208 petroleum Substances 0.000 description 13
• 229910000027 potassium carbonate Inorganic materials 0.000 description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 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
• 238000001816 cooling Methods 0.000 description 11
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 11
• 238000012360 testing method Methods 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
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
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• 108090000790 Enzymes 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
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 8
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• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 229910021529 ammonia Inorganic materials 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• 239000003701 inert diluent Substances 0.000 description 8
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• 108091008598 receptor tyrosine kinases Proteins 0.000 description 8
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• DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 8
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 7
• 239000003102 growth factor Substances 0.000 description 7
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-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
• 108091003079 Bovine Serum Albumin Proteins 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
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-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
• 238000002474 experimental method Methods 0.000 description 6
• 238000006396 nitration reaction Methods 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
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• 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
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
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• 229910052783 alkali metal Inorganic materials 0.000 description 5
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• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 239000003085 diluting agent Substances 0.000 description 5
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
• 239000003480 eluent Substances 0.000 description 5
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• 241000701447 unidentified baculovirus Species 0.000 description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 4
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
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• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
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• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 229960001456 adenosine triphosphate Drugs 0.000 description 4
• 125000003342 alkenyl group Chemical group 0.000 description 4
• 125000000304 alkynyl group Chemical group 0.000 description 4
• 230000033115 angiogenesis Effects 0.000 description 4
• 125000003118 aryl group Chemical group 0.000 description 4
• 230000001086 cytosolic effect Effects 0.000 description 4
• 238000010511 deprotection reaction Methods 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
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