AU2004279809B2 - Substituted isoquinolinones - Google Patents

Info

Publication number

AU2004279809B2

AU2004279809B2 AU2004279809A AU2004279809A AU2004279809B2 AU 2004279809 B2 AU2004279809 B2 AU 2004279809B2 AU 2004279809 A AU2004279809 A AU 2004279809A AU 2004279809 A AU2004279809 A AU 2004279809A AU 2004279809 B2 AU2004279809 B2 AU 2004279809B2

Authority

AU

Australia

Prior art keywords

fluoro

amino

give

phenyl

mmol

Prior art date

2003-10-03

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.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 title description 5
• 238000000034 method Methods 0.000 claims description 198
• 150000001875 compounds Chemical class 0.000 claims description 113
• 125000000217 alkyl group Chemical group 0.000 claims description 69
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 22
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
• 229910052739 hydrogen Inorganic materials 0.000 claims description 21
• 125000003342 alkenyl group Chemical group 0.000 claims description 16
• 125000001589 carboacyl group Chemical group 0.000 claims description 8
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
• 125000001544 thienyl group Chemical group 0.000 claims description 5
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 115
• 229940100389 Sulfonylurea Drugs 0.000 description 87
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 86
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 85
• -1 cyano, hydroxy Chemical group 0.000 description 67
• 239000000460 chlorine Substances 0.000 description 65
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 65
• 239000000203 mixture Substances 0.000 description 59
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
• 230000015572 biosynthetic process Effects 0.000 description 54
• 235000019439 ethyl acetate Nutrition 0.000 description 52
• 238000010511 deprotection reaction Methods 0.000 description 50
• 239000000243 solution Substances 0.000 description 49
• 238000005859 coupling reaction Methods 0.000 description 45
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 43
• 230000008878 coupling Effects 0.000 description 43
• 238000010168 coupling process Methods 0.000 description 43
• 210000001772 blood platelet Anatomy 0.000 description 41
• 238000006243 chemical reaction Methods 0.000 description 29
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 29
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 27
• 239000011541 reaction mixture Substances 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• 239000012267 brine Substances 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• FHLMXKNSZSQTMZ-UHFFFAOYSA-N tert-butyl n-[2-(4-aminophenyl)-7-fluoro-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C1=CC=C(N)C=C1 FHLMXKNSZSQTMZ-UHFFFAOYSA-N 0.000 description 26
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
• 229940093499 ethyl acetate Drugs 0.000 description 25
• PAFCHZQEOGJBRT-UHFFFAOYSA-N tert-butyl n-(7-fluoro-1-oxo-2h-isoquinolin-6-yl)-n-methylcarbamate Chemical compound C1=CNC(=O)C2=C1C=C(N(C(=O)OC(C)(C)C)C)C(F)=C2 PAFCHZQEOGJBRT-UHFFFAOYSA-N 0.000 description 25
• 238000005160 1H NMR spectroscopy Methods 0.000 description 23
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 23
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 23
• KTFDYVNEGTXQCV-UHFFFAOYSA-N 2-Thiophenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CS1 KTFDYVNEGTXQCV-UHFFFAOYSA-N 0.000 description 21
• 229910052799 carbon Inorganic materials 0.000 description 21
• 239000012044 organic layer Substances 0.000 description 21
• 239000008194 pharmaceutical composition Substances 0.000 description 21
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
• 125000003545 alkoxy group Chemical group 0.000 description 20
• 230000009467 reduction Effects 0.000 description 20
• 125000001188 haloalkyl group Chemical group 0.000 description 19
• 239000000543 intermediate Substances 0.000 description 19
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
• 239000000725 suspension Substances 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 17
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
• 125000003282 alkyl amino group Chemical group 0.000 description 17
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 17
• 238000004007 reversed phase HPLC Methods 0.000 description 17
• 150000003839 salts Chemical class 0.000 description 17
• 229910052736 halogen Inorganic materials 0.000 description 16
• 150000002367 halogens Chemical class 0.000 description 16
• 239000000047 product Substances 0.000 description 16
• 239000000377 silicon dioxide Substances 0.000 description 16
• 125000000304 alkynyl group Chemical group 0.000 description 15
• 238000004440 column chromatography Methods 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• FGUCQPJANCCELZ-UHFFFAOYSA-N [7-fluoro-2-(4-nitrophenyl)-1-oxoisoquinolin-6-yl] trifluoromethanesulfonate Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1C(=O)C2=CC(F)=C(OS(=O)(=O)C(F)(F)F)C=C2C=C1 FGUCQPJANCCELZ-UHFFFAOYSA-N 0.000 description 14
• 125000004093 cyano group Chemical group *C#N 0.000 description 14
• 230000000694 effects Effects 0.000 description 13
• 229910052757 nitrogen Inorganic materials 0.000 description 13
• 239000007787 solid Substances 0.000 description 13
• HJZIDJBZPYZBCZ-UHFFFAOYSA-N tert-butyl n-[7-fluoro-2-(4-nitrophenyl)-1-oxoisoquinolin-6-yl]carbamate Chemical compound O=C1C=2C=C(F)C(NC(=O)OC(C)(C)C)=CC=2C=CN1C1=CC=C([N+]([O-])=O)C=C1 HJZIDJBZPYZBCZ-UHFFFAOYSA-N 0.000 description 13
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
• 102100037600 P2Y purinoceptor 1 Human genes 0.000 description 12
• 108010085249 Purinergic P2 Receptors Proteins 0.000 description 12
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
• 229910000024 caesium carbonate Inorganic materials 0.000 description 12
• 238000001914 filtration Methods 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• 125000001424 substituent group Chemical group 0.000 description 12
• 238000011282 treatment Methods 0.000 description 12
• 229910052740 iodine Inorganic materials 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 208000007536 Thrombosis Diseases 0.000 description 10
• 150000001448 anilines Chemical class 0.000 description 10
• 229910052786 argon Inorganic materials 0.000 description 10
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 10
• 229940124530 sulfonamide Drugs 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• 125000003118 aryl group Chemical group 0.000 description 9
• 230000027455 binding Effects 0.000 description 9
• 230000005764 inhibitory process Effects 0.000 description 9
• 239000002253 acid Substances 0.000 description 8
• 230000029936 alkylation Effects 0.000 description 8
• 238000005804 alkylation reaction Methods 0.000 description 8
• 239000003146 anticoagulant agent Substances 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 230000001419 dependent effect Effects 0.000 description 8
• XALLJMFDLUYTTF-UHFFFAOYSA-N ethyl n-(5-chlorothiophen-2-yl)sulfonylcarbamate Chemical compound CCOC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 XALLJMFDLUYTTF-UHFFFAOYSA-N 0.000 description 8
• 210000004623 platelet-rich plasma Anatomy 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 8
• HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 7
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
• 230000002776 aggregation Effects 0.000 description 7
• 238000004220 aggregation Methods 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 238000001816 cooling Methods 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 7
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 7
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 6
• RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• WLMZTKAZJUWXCB-KQYNXXCUSA-N [(2r,3s,4r,5r)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound C12=NC(SC)=NC(N)=C2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O WLMZTKAZJUWXCB-KQYNXXCUSA-N 0.000 description 6
• 230000002785 anti-thrombosis Effects 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
• 239000000872 buffer Substances 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 239000012038 nucleophile Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 230000001732 thrombotic effect Effects 0.000 description 6
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• 241000124008 Mammalia Species 0.000 description 5
• 239000002168 alkylating agent Substances 0.000 description 5
• 229940100198 alkylating agent Drugs 0.000 description 5
• 150000003927 aminopyridines Chemical class 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 125000001072 heteroaryl group Chemical group 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 229910052715 tantalum Inorganic materials 0.000 description 5
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 5
• JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
• 238000010626 work up procedure Methods 0.000 description 5
• VGYVBEJDXIPSDL-UHFFFAOYSA-N 2-bromo-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1Br VGYVBEJDXIPSDL-UHFFFAOYSA-N 0.000 description 4
• SLRNETDLLJMLMR-UHFFFAOYSA-N 4-fluoro-1-nitro-2-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC(F)=CC=C1[N+]([O-])=O SLRNETDLLJMLMR-UHFFFAOYSA-N 0.000 description 4
• UZBBCHJGKXDFOR-UHFFFAOYSA-N 5-bromo-7-fluoro-6-(methylamino)-2-(4-nitrophenyl)isoquinolin-1-one Chemical compound BrC=1C(NC)=C(F)C=C(C2=O)C=1C=CN2C1=CC=C([N+]([O-])=O)C=C1 UZBBCHJGKXDFOR-UHFFFAOYSA-N 0.000 description 4
• RKLQLYBJAZBSEU-UHFFFAOYSA-N 5-chlorothiophene-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Cl)S1 RKLQLYBJAZBSEU-UHFFFAOYSA-N 0.000 description 4
• QQURWFRNETXFTN-UHFFFAOYSA-N 5-fluoro-2-nitrophenol Chemical compound OC1=CC(F)=CC=C1[N+]([O-])=O QQURWFRNETXFTN-UHFFFAOYSA-N 0.000 description 4
• MNYLLSMVYDGHNO-UHFFFAOYSA-N 7-fluoro-6-methoxy-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C2=C1C=C(OC)C(F)=C2 MNYLLSMVYDGHNO-UHFFFAOYSA-N 0.000 description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• 229910052771 Terbium Inorganic materials 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 229960000583 acetic acid Drugs 0.000 description 4
• 230000004913 activation Effects 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 239000012442 inert solvent Substances 0.000 description 4
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 4
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
• 238000001356 surgical procedure Methods 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• 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 4
• NVEDFCULNXTLOA-HWKANZROSA-N (e)-3-(4-fluoro-3-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1F NVEDFCULNXTLOA-HWKANZROSA-N 0.000 description 3
• KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• KQAKOKGCKNKARC-UHFFFAOYSA-N 2-(bromomethyl)-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(CBr)=C1 KQAKOKGCKNKARC-UHFFFAOYSA-N 0.000 description 3
• BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 3
• MUUOIQZAFWYPBG-UHFFFAOYSA-N 2-ethynyl-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(C#C)=C1 MUUOIQZAFWYPBG-UHFFFAOYSA-N 0.000 description 3
• FWBLGHHMIMJHNK-UHFFFAOYSA-N 7-fluoro-6-hydroxy-2-(4-nitrophenyl)isoquinolin-1-one Chemical compound O=C1C=2C=C(F)C(O)=CC=2C=CN1C1=CC=C([N+]([O-])=O)C=C1 FWBLGHHMIMJHNK-UHFFFAOYSA-N 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 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 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• 238000005481 NMR spectroscopy Methods 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• 208000007718 Stable Angina Diseases 0.000 description 3
• 208000032109 Transient ischaemic attack Diseases 0.000 description 3
• 229960001456 adenosine triphosphate Drugs 0.000 description 3
• 238000002399 angioplasty Methods 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
• 238000005119 centrifugation Methods 0.000 description 3
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
• 239000007819 coupling partner Substances 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 239000003814 drug Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 230000000302 ischemic effect Effects 0.000 description 3
• 239000002502 liposome Substances 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 230000009870 specific binding Effects 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 238000003756 stirring Methods 0.000 description 3
• 150000003456 sulfonamides Chemical class 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• BZNAUIQINJRLGK-UHFFFAOYSA-N tert-butyl n-[7-fluoro-2-(3-methylsulfonyl-4-nitrophenyl)-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C1=CC=C([N+]([O-])=O)C(S(C)(=O)=O)=C1 BZNAUIQINJRLGK-UHFFFAOYSA-N 0.000 description 3
• 201000010875 transient cerebral ischemia Diseases 0.000 description 3
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
• 125000004417 unsaturated alkyl group Chemical group 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 3
• IFIOUOYJVOSTFH-UHFFFAOYSA-N (2-fluoro-5-nitrophenyl)methanol Chemical compound OCC1=CC([N+]([O-])=O)=CC=C1F IFIOUOYJVOSTFH-UHFFFAOYSA-N 0.000 description 2
• FHKBOUCIPJARGI-UHFFFAOYSA-N (2-fluoro-5-nitrophenyl)methyl acetate Chemical compound CC(=O)OCC1=CC([N+]([O-])=O)=CC=C1F FHKBOUCIPJARGI-UHFFFAOYSA-N 0.000 description 2
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 2
• HXHKCSJIOCQROG-UHFFFAOYSA-N 1-(2-fluoro-5-nitrophenyl)-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC([N+]([O-])=O)=CC=C1F HXHKCSJIOCQROG-UHFFFAOYSA-N 0.000 description 2
• BCXOSCQTHVTUET-UHFFFAOYSA-N 1-(2-fluoro-5-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC([N+]([O-])=O)=CC=C1F BCXOSCQTHVTUET-UHFFFAOYSA-N 0.000 description 2
• VPAGKEZJDCSVOW-UHFFFAOYSA-N 1-(5-fluoro-2-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC=C1[N+]([O-])=O VPAGKEZJDCSVOW-UHFFFAOYSA-N 0.000 description 2
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
• WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 2
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
• VZPODWSIENREDT-UHFFFAOYSA-N 2-(4-aminophenyl)-7-fluoro-6-(methylamino)-3,4-dihydroisoquinolin-1-one Chemical compound O=C1C=2C=C(F)C(NC)=CC=2CCN1C1=CC=C(N)C=C1 VZPODWSIENREDT-UHFFFAOYSA-N 0.000 description 2
• REJKRTLCPQUTOG-UHFFFAOYSA-N 2-(5-fluoro-2-nitrophenoxy)-n,n-dimethylethanamine Chemical compound CN(C)CCOC1=CC(F)=CC=C1[N+]([O-])=O REJKRTLCPQUTOG-UHFFFAOYSA-N 0.000 description 2
• KSDOJCYMONFOCR-UHFFFAOYSA-N 2-(cyclopropylmethoxy)-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OCC1CC1 KSDOJCYMONFOCR-UHFFFAOYSA-N 0.000 description 2
• ADBUIWGABVQONJ-UHFFFAOYSA-N 2-(difluoromethyl)-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1C(F)F ADBUIWGABVQONJ-UHFFFAOYSA-N 0.000 description 2
• FAWMTDSAMOCUAR-UHFFFAOYSA-N 2-bromo-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(Br)=C1 FAWMTDSAMOCUAR-UHFFFAOYSA-N 0.000 description 2
• DPHCXXYPSYMICK-UHFFFAOYSA-N 2-chloro-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(Cl)=C1 DPHCXXYPSYMICK-UHFFFAOYSA-N 0.000 description 2
• SISIKMWLDURIDU-UHFFFAOYSA-N 2-ethenyl-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=C)=C1 SISIKMWLDURIDU-UHFFFAOYSA-N 0.000 description 2
• RKFMDUVMPSAXRJ-UHFFFAOYSA-N 2-ethenyl-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1C=C RKFMDUVMPSAXRJ-UHFFFAOYSA-N 0.000 description 2
• LEMJFSSYFHTFFP-UHFFFAOYSA-N 2-ethoxy-4-fluoro-1-nitrobenzene Chemical compound CCOC1=CC(F)=CC=C1[N+]([O-])=O LEMJFSSYFHTFFP-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• FOYQTDKPDAJMPF-UHFFFAOYSA-N 4-fluoro-1-nitro-2-phenylmethoxybenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OCC1=CC=CC=C1 FOYQTDKPDAJMPF-UHFFFAOYSA-N 0.000 description 2
• QSWFKHFKRPAQLI-UHFFFAOYSA-N 4-fluoro-2-(2-methoxyethoxy)-1-nitrobenzene Chemical compound COCCOC1=CC(F)=CC=C1[N+]([O-])=O QSWFKHFKRPAQLI-UHFFFAOYSA-N 0.000 description 2
• UWIZRXPPCYEUOZ-UHFFFAOYSA-N 4-fluoro-2-(methoxymethoxy)-1-nitrobenzene Chemical compound COCOC1=CC(F)=CC=C1[N+]([O-])=O UWIZRXPPCYEUOZ-UHFFFAOYSA-N 0.000 description 2
• WLKUSVNHZXUEFO-UHFFFAOYSA-N 4-fluoro-2-methoxy-1-nitrobenzene Chemical compound COC1=CC(F)=CC=C1[N+]([O-])=O WLKUSVNHZXUEFO-UHFFFAOYSA-N 0.000 description 2
• VLVCDUSVTXIWGW-UHFFFAOYSA-N 4-iodoaniline Chemical compound NC1=CC=C(I)C=C1 VLVCDUSVTXIWGW-UHFFFAOYSA-N 0.000 description 2
• GDRKWBTVOILQCX-UHFFFAOYSA-N 7-fluoro-6-(methylamino)-2-(4-nitrophenyl)isoquinolin-1-one Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C1=CC=C([N+]([O-])=O)C=C1 GDRKWBTVOILQCX-UHFFFAOYSA-N 0.000 description 2
• JCRRMZTXYTYQGT-UHFFFAOYSA-N 7-fluoro-6-(methylamino)-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1CNC(=O)C2=C1C=C(NC)C(F)=C2 JCRRMZTXYTYQGT-UHFFFAOYSA-N 0.000 description 2
• AWTBDSZQGDQAFM-UHFFFAOYSA-N 7-fluoro-6-methoxy-2-(4-nitrophenyl)isoquinolin-1-one Chemical compound O=C1C=2C=C(F)C(OC)=CC=2C=CN1C1=CC=C([N+]([O-])=O)C=C1 AWTBDSZQGDQAFM-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• 239000005725 8-Hydroxyquinoline Substances 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• 206010002388 Angina unstable Diseases 0.000 description 2
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• 108010035532 Collagen Proteins 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 206010051055 Deep vein thrombosis Diseases 0.000 description 2
• 208000005189 Embolism Diseases 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
• ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
• 208000018262 Peripheral vascular disease Diseases 0.000 description 2
• 206010037549 Purpura Diseases 0.000 description 2
• 241001672981 Purpura Species 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• 206010038563 Reocclusion Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 description 2
• 108090000190 Thrombin Proteins 0.000 description 2
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
• 208000007814 Unstable Angina Diseases 0.000 description 2
• 206010047249 Venous thrombosis Diseases 0.000 description 2
• PNDPGZBMCMUPRI-XXSWNUTMSA-N [125I][125I] Chemical compound [125I][125I] PNDPGZBMCMUPRI-XXSWNUTMSA-N 0.000 description 2
• 229940022663 acetate Drugs 0.000 description 2
• 229960001138 acetylsalicylic acid Drugs 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 206010000891 acute myocardial infarction Diseases 0.000 description 2
• 108060000200 adenylate cyclase Proteins 0.000 description 2
• 102000030621 adenylate cyclase Human genes 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• 230000000702 anti-platelet effect Effects 0.000 description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
• TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 239000004202 carbamide Substances 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• 229940126142 compound 16 Drugs 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 210000004351 coronary vessel Anatomy 0.000 description 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
• 230000017858 demethylation Effects 0.000 description 2
• 238000010520 demethylation reaction Methods 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 208000009190 disseminated intravascular coagulation Diseases 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000006196 drop Substances 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• UJIPWFPJAVYMHV-UHFFFAOYSA-N ethyl 2-fluoro-5-nitrobenzoate Chemical compound CCOC(=O)C1=CC([N+]([O-])=O)=CC=C1F UJIPWFPJAVYMHV-UHFFFAOYSA-N 0.000 description 2
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
• 239000003527 fibrinolytic agent Substances 0.000 description 2
• 239000012467 final product Substances 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 230000026030 halogenation Effects 0.000 description 2
• 238000005658 halogenation reaction Methods 0.000 description 2
• 229960002897 heparin Drugs 0.000 description 2
• 229920000669 heparin Polymers 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• NVJKMGDNYCDLGR-UHFFFAOYSA-N methyl 2-amino-5-bromo-3-methylbenzoate Chemical compound COC(=O)C1=CC(Br)=CC(C)=C1N NVJKMGDNYCDLGR-UHFFFAOYSA-N 0.000 description 2
• LCAUVFVOLNRVKG-UHFFFAOYSA-N methyl 5-fluoro-2-nitrobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1[N+]([O-])=O LCAUVFVOLNRVKG-UHFFFAOYSA-N 0.000 description 2
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 2
• 239000011259 mixed solution Substances 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
• 230000009871 nonspecific binding Effects 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 229960003540 oxyquinoline Drugs 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 210000002381 plasma Anatomy 0.000 description 2
• 230000010118 platelet activation Effects 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 201000011461 pre-eclampsia Diseases 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• WLMSZVULHUTVRG-UHFFFAOYSA-N prop-2-enoyl azide Chemical compound C=CC(=O)N=[N+]=[N-] WLMSZVULHUTVRG-UHFFFAOYSA-N 0.000 description 2
• 150000003230 pyrimidines Chemical class 0.000 description 2
• MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 2
• 235000011150 stannous chloride Nutrition 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• SJMPKYWDTOGJQU-UHFFFAOYSA-N tert-butyl n-[2-(3-bromo-4-nitrophenyl)-7-fluoro-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C1=CC=C([N+]([O-])=O)C(Br)=C1 SJMPKYWDTOGJQU-UHFFFAOYSA-N 0.000 description 2
• ULQKQRBKVIOXCO-UHFFFAOYSA-N tert-butyl n-[7-fluoro-2-(4-nitrophenyl)-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C1=CC=C([N+]([O-])=O)C=C1 ULQKQRBKVIOXCO-UHFFFAOYSA-N 0.000 description 2
• XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• 229960004072 thrombin Drugs 0.000 description 2
• 229960000103 thrombolytic agent Drugs 0.000 description 2
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
• QHGNHLZPVBIIPX-UHFFFAOYSA-N tin(ii) oxide Chemical compound [Sn]=O QHGNHLZPVBIIPX-UHFFFAOYSA-N 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 238000011269 treatment regimen Methods 0.000 description 2
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 210000005166 vasculature Anatomy 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 229960005080 warfarin Drugs 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• DOTAAODFKPTVCK-UHFFFAOYSA-N (1-diphenylphosphanyl-9h-xanthen-2-yl)-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C1=C2CC3=CC=CC=C3OC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 DOTAAODFKPTVCK-UHFFFAOYSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• JTVUWLQMIPZMQF-UHFFFAOYSA-N (7-fluoro-1-oxo-2h-isoquinolin-6-yl) trifluoromethanesulfonate Chemical compound C1=C(OS(=O)(=O)C(F)(F)F)C(F)=CC2=C1C=CNC2=O JTVUWLQMIPZMQF-UHFFFAOYSA-N 0.000 description 1
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
• RUBQQRMAWLSCCJ-UHFFFAOYSA-N 1,2-difluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1 RUBQQRMAWLSCCJ-UHFFFAOYSA-N 0.000 description 1
• 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
• YUMVVTMDQHKICR-UHFFFAOYSA-N 1-(5-bromothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Br)S1 YUMVVTMDQHKICR-UHFFFAOYSA-N 0.000 description 1
• RQIXVLGSIRQJFG-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[2-(cyclopropylmethoxy)-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1OCC2CC2)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 RQIXVLGSIRQJFG-UHFFFAOYSA-N 0.000 description 1
• AISLAGZALQUZNW-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[2-cyclopropyl-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1C2CC2)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 AISLAGZALQUZNW-UHFFFAOYSA-N 0.000 description 1
• LKDSMBAFZMEQAS-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[2-ethenyl-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1C=C)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 LKDSMBAFZMEQAS-UHFFFAOYSA-N 0.000 description 1
• CNTHSECNYMVVJC-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[2-ethyl-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound CCC1=CC(N2C(C3=CC(F)=C(NC)C=C3C=C2)=O)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 CNTHSECNYMVVJC-UHFFFAOYSA-N 0.000 description 1
• FODDWMIWEDUBPG-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[2-fluoro-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1F)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 FODDWMIWEDUBPG-UHFFFAOYSA-N 0.000 description 1
• DOIONSOKKZKYPM-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[3-[(dimethylamino)methyl]-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)CN(C)C)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 DOIONSOKKZKYPM-UHFFFAOYSA-N 0.000 description 1
• HBRNXBIYEALFTF-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[3-ethenyl-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)C=C)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 HBRNXBIYEALFTF-UHFFFAOYSA-N 0.000 description 1
• OJLMWJIRTKPPIY-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[3-ethynyl-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)C#C)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 OJLMWJIRTKPPIY-UHFFFAOYSA-N 0.000 description 1
• PEZJAQVDAPQPEZ-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[3-fluoro-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)F)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 PEZJAQVDAPQPEZ-UHFFFAOYSA-N 0.000 description 1
• JERCRQLLSUWHGP-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[4,5-dichloro-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound ClC=1C(NC)=C(F)C=C(C2=O)C=1C(Cl)=CN2C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 JERCRQLLSUWHGP-UHFFFAOYSA-N 0.000 description 1
• TVTRRGQXFWISJQ-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[5,7-difluoro-6-(methylamino)-1-oxo-3,4-dihydroisoquinolin-2-yl]phenyl]urea Chemical compound C1CC2=C(F)C(NC)=C(F)C=C2C(=O)N1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 TVTRRGQXFWISJQ-UHFFFAOYSA-N 0.000 description 1
• HDDSWQKDWHCMLB-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[5-cyano-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound N#CC=1C(NC)=C(F)C=C(C2=O)C=1C=CN2C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 HDDSWQKDWHCMLB-UHFFFAOYSA-N 0.000 description 1
• QJNIQXCTPWZWOG-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[5-cyclopropyl-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound C1CC1C=1C(NC)=C(F)C=C(C2=O)C=1C=CN2C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 QJNIQXCTPWZWOG-UHFFFAOYSA-N 0.000 description 1
• GCHUTTURNGSQCH-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[5-ethenyl-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound C=CC=1C(NC)=C(F)C=C(C2=O)C=1C=CN2C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 GCHUTTURNGSQCH-UHFFFAOYSA-N 0.000 description 1
• WCRWGMXEVWZVKN-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[6-(dimethylamino)-7-fluoro-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(N(C)C)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 WCRWGMXEVWZVKN-UHFFFAOYSA-N 0.000 description 1
• DKOSOZSHTAFCKA-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[6-(ethylamino)-7-fluoro-1-oxoisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NCC)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 DKOSOZSHTAFCKA-UHFFFAOYSA-N 0.000 description 1
• XDBUONORUSRMMQ-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-1-oxo-6-(prop-2-ynylamino)isoquinolin-2-yl]phenyl]urea Chemical compound C1=C(NCC#C)C(F)=CC(C2=O)=C1C=CN2C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 XDBUONORUSRMMQ-UHFFFAOYSA-N 0.000 description 1
• MBYPCBKFQBJMFX-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxo-3,4-dihydroisoquinolin-2-yl]phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2CCN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 MBYPCBKFQBJMFX-UHFFFAOYSA-N 0.000 description 1
• WXCRIVYHUVFZFS-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2,6-dimethylphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1C)=CC(C)=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 WXCRIVYHUVFZFS-UHFFFAOYSA-N 0.000 description 1
• MIUYVSXNWLBBHR-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-(2-hydroxyethoxy)phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1OCCO)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 MIUYVSXNWLBBHR-UHFFFAOYSA-N 0.000 description 1
• OYKTXPQIMRIQQL-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-(2-methoxyethoxy)phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1OCCOC)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 OYKTXPQIMRIQQL-UHFFFAOYSA-N 0.000 description 1
• PQTDBQREPSEGQC-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-(trifluoromethyl)phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1C(F)(F)F)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 PQTDBQREPSEGQC-UHFFFAOYSA-N 0.000 description 1
• YETKJYXJFMXFRE-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-methoxyphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1OC)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 YETKJYXJFMXFRE-UHFFFAOYSA-N 0.000 description 1
• AFBNWJFYIAFJCE-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-methyl-6-propan-2-ylphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1C(C)C)=CC(C)=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 AFBNWJFYIAFJCE-UHFFFAOYSA-N 0.000 description 1
• TYXBOUYDAOMZOI-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-methylphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1C)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 TYXBOUYDAOMZOI-UHFFFAOYSA-N 0.000 description 1
• KFJHBPVGOLACOM-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-methylsulfonylphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1S(C)(=O)=O)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 KFJHBPVGOLACOM-UHFFFAOYSA-N 0.000 description 1
• BGRCEHWZVIJYPD-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-phenylmethoxyphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1OCC=2C=CC=CC=2)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 BGRCEHWZVIJYPD-UHFFFAOYSA-N 0.000 description 1
• HSXHRAGJDUNTLX-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-propan-2-yloxyphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1OC(C)C)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 HSXHRAGJDUNTLX-UHFFFAOYSA-N 0.000 description 1
• XPMQPSKKQCEDGG-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-2-propan-2-ylphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1C(C)C)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 XPMQPSKKQCEDGG-UHFFFAOYSA-N 0.000 description 1
• ICQCZUJNMWBKIF-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-3-(1-hydroxyethyl)phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)C(C)O)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 ICQCZUJNMWBKIF-UHFFFAOYSA-N 0.000 description 1
• HYZCYMPRJIILDF-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-3-(piperidin-1-ylmethyl)phenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)CN2CCCCC2)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 HYZCYMPRJIILDF-UHFFFAOYSA-N 0.000 description 1
• BBNBBCAQQMQMKH-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-3-methylphenyl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)C)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 BBNBBCAQQMQMKH-UHFFFAOYSA-N 0.000 description 1
• IDFMGUJJDVQPPD-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[5-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]pyridin-2-yl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=N1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 IDFMGUJJDVQPPD-UHFFFAOYSA-N 0.000 description 1
• ZSZZYTFVRQGUDG-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[6-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-4-methylpyridin-3-yl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(N=C1)=CC(C)=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 ZSZZYTFVRQGUDG-UHFFFAOYSA-N 0.000 description 1
• NTZSMSYZPWWZTI-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[6-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]-5-methylpyridin-3-yl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)C)=NC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 NTZSMSYZPWWZTI-UHFFFAOYSA-N 0.000 description 1
• BVLOJIUWCDULRZ-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)sulfonyl-3-[6-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]pyridin-3-yl]urea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(N=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 BVLOJIUWCDULRZ-UHFFFAOYSA-N 0.000 description 1
• KQNBRMUBPRGXSL-UHFFFAOYSA-N 1-(bromomethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1 KQNBRMUBPRGXSL-UHFFFAOYSA-N 0.000 description 1
• JCOWKNTYOGFPDK-UHFFFAOYSA-N 1-[2-(butylamino)-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]-3-(5-chlorothiophen-2-yl)sulfonylurea Chemical compound CCCCNC1=CC(N2C(C3=CC(F)=C(NC)C=C3C=C2)=O)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 JCOWKNTYOGFPDK-UHFFFAOYSA-N 0.000 description 1
• JILYXYDMMVWJOD-UHFFFAOYSA-N 1-[3-acetyl-4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]-3-(5-chlorothiophen-2-yl)sulfonylurea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)C(C)=O)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 JILYXYDMMVWJOD-UHFFFAOYSA-N 0.000 description 1
• JBZFWUHLXQPFBO-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-(3-chlorothiophen-2-yl)sulfonylurea Chemical compound O=C1C=2C=C(F)C(N)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C=1SC=CC=1Cl JBZFWUHLXQPFBO-UHFFFAOYSA-N 0.000 description 1
• DMXXJLDPEQTAKG-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-(4-chlorothiophen-2-yl)sulfonylurea Chemical compound O=C1C=2C=C(F)C(N)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC(Cl)=CS1 DMXXJLDPEQTAKG-UHFFFAOYSA-N 0.000 description 1
• YDALTXMVZZYYBT-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-(4-methylthiophen-2-yl)sulfonylurea Chemical compound CC1=CSC(S(=O)(=O)NC(=O)NC=2C=CC(=CC=2)N2C(C3=CC(F)=C(N)C=C3C=C2)=O)=C1 YDALTXMVZZYYBT-UHFFFAOYSA-N 0.000 description 1
• WTLYWPORZUBGCN-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-(5-chlorothiophen-2-yl)sulfonylurea Chemical compound O=C1C=2C=C(F)C(N)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 WTLYWPORZUBGCN-UHFFFAOYSA-N 0.000 description 1
• BCPUYQBPXXNGOS-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-(5-cyanothiophen-2-yl)sulfonylurea Chemical compound O=C1C=2C=C(F)C(N)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(C#N)S1 BCPUYQBPXXNGOS-UHFFFAOYSA-N 0.000 description 1
• CVFWMNKPKYAQPD-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-(5-ethynylthiophen-2-yl)sulfonylurea Chemical compound O=C1C=2C=C(F)C(N)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(C#C)S1 CVFWMNKPKYAQPD-UHFFFAOYSA-N 0.000 description 1
• QLOXVNNOIOYLKI-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-(5-propylthiophen-2-yl)sulfonylurea Chemical compound S1C(CCC)=CC=C1S(=O)(=O)NC(=O)NC1=CC=C(N2C(C3=CC(F)=C(N)C=C3C=C2)=O)C=C1 QLOXVNNOIOYLKI-UHFFFAOYSA-N 0.000 description 1
• YJRYIBYUJLPWIL-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-(benzenesulfonyl)urea Chemical compound O=C1C=2C=C(F)C(N)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=CC=C1 YJRYIBYUJLPWIL-UHFFFAOYSA-N 0.000 description 1
• QONXAGMKPALKBB-UHFFFAOYSA-N 1-[4-(6-amino-7-fluoro-1-oxoisoquinolin-2-yl)phenyl]-3-[4-(difluoromethyl)thiophen-2-yl]sulfonylurea Chemical compound O=C1C=2C=C(F)C(N)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC(C(F)F)=CS1 QONXAGMKPALKBB-UHFFFAOYSA-N 0.000 description 1
• KZWSSFACVJOICN-UHFFFAOYSA-N 1-[4-[5-acetyl-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]-3-(5-chlorothiophen-2-yl)sulfonylurea Chemical compound CC(=O)C=1C(NC)=C(F)C=C(C2=O)C=1C=CN2C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 KZWSSFACVJOICN-UHFFFAOYSA-N 0.000 description 1
• XGKCPQRXQPECHC-UHFFFAOYSA-N 1-[4-[5-chloro-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]-3-(5-chlorothiophen-2-yl)sulfonylurea Chemical compound ClC=1C(NC)=C(F)C=C(C2=O)C=1C=CN2C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 XGKCPQRXQPECHC-UHFFFAOYSA-N 0.000 description 1
• CVBMUQUTNDNGLD-UHFFFAOYSA-N 1-[4-[6-[(4-chlorophenyl)methyl-methylamino]-7-fluoro-1-oxoisoquinolin-2-yl]phenyl]-3-(5-chlorothiophen-2-yl)sulfonylurea Chemical compound C=1C=2C=CN(C=3C=CC(NC(=O)NS(=O)(=O)C=4SC(Cl)=CC=4)=CC=3)C(=O)C=2C=C(F)C=1N(C)CC1=CC=C(Cl)C=C1 CVBMUQUTNDNGLD-UHFFFAOYSA-N 0.000 description 1
• QRBBFVYXIOIEJV-UHFFFAOYSA-N 1-[4-[7-chloro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]-3-(5-chlorothiophen-2-yl)sulfonylurea Chemical compound O=C1C=2C=C(Cl)C(NC)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 QRBBFVYXIOIEJV-UHFFFAOYSA-N 0.000 description 1
• FNTMOOOLSNWCIP-UHFFFAOYSA-N 1-[4-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]-3-thiophen-2-ylsulfonylurea Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=CS1 FNTMOOOLSNWCIP-UHFFFAOYSA-N 0.000 description 1
• JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 1
• DNTHMWUMRGOJRY-UHFFFAOYSA-N 1-fluoro-4-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(C(F)(F)F)=C1 DNTHMWUMRGOJRY-UHFFFAOYSA-N 0.000 description 1
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
• IGKCQDUYZULGBM-UHFFFAOYSA-N 2,2,2-trifluoroethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCC(F)(F)F)C=C1 IGKCQDUYZULGBM-UHFFFAOYSA-N 0.000 description 1
• VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical class C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
• RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 1
• BNLDQBOMHYPWIN-UHFFFAOYSA-N 2-(4-aminophenyl)-5-bromo-7-fluoro-6-(methylamino)isoquinolin-1-one Chemical compound BrC=1C(NC)=C(F)C=C(C2=O)C=1C=CN2C1=CC=C(N)C=C1 BNLDQBOMHYPWIN-UHFFFAOYSA-N 0.000 description 1
• ZRYCVKJGIVVCJM-UHFFFAOYSA-N 2-(4-aminophenyl)-5-ethenyl-7-fluoro-6-(methylamino)isoquinolin-1-one Chemical compound C=CC=1C(NC)=C(F)C=C(C2=O)C=1C=CN2C1=CC=C(N)C=C1 ZRYCVKJGIVVCJM-UHFFFAOYSA-N 0.000 description 1
• RRQPBSBYXWFWRN-UHFFFAOYSA-N 2-(4-aminophenyl)-6-(cyclopropylamino)-7-fluoroisoquinolin-1-one Chemical compound C1=CC(N)=CC=C1N1C(=O)C2=CC(F)=C(NC3CC3)C=C2C=C1 RRQPBSBYXWFWRN-UHFFFAOYSA-N 0.000 description 1
• LFBXHYKJLYQODV-UHFFFAOYSA-N 2-(5-fluoro-2-nitrophenoxy)ethyl acetate Chemical compound CC(=O)OCCOC1=CC(F)=CC=C1[N+]([O-])=O LFBXHYKJLYQODV-UHFFFAOYSA-N 0.000 description 1
• YKOLZVXSPGIIBJ-UHFFFAOYSA-N 2-Isopropylaniline Chemical compound CC(C)C1=CC=CC=C1N YKOLZVXSPGIIBJ-UHFFFAOYSA-N 0.000 description 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• REVQVNYTIQLHFW-UHFFFAOYSA-N 2-[2-[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]-5-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenoxy]ethyl acetate Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1OCCOC(C)=O)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 REVQVNYTIQLHFW-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• HUUFTVUBFFESEN-UHFFFAOYSA-N 2-bromo-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)N=C1 HUUFTVUBFFESEN-UHFFFAOYSA-N 0.000 description 1
• RGHQKFQZGLKBCF-UHFFFAOYSA-N 2-bromoethyl acetate Chemical compound CC(=O)OCCBr RGHQKFQZGLKBCF-UHFFFAOYSA-N 0.000 description 1
• OSIOIGXJUZTWRI-UHFFFAOYSA-N 2-chloro-3-methyl-5-nitropyridine Chemical compound CC1=CC([N+]([O-])=O)=CN=C1Cl OSIOIGXJUZTWRI-UHFFFAOYSA-N 0.000 description 1
• MYDAOWXYGPEPJT-UHFFFAOYSA-N 2-chloro-4-iodoaniline Chemical compound NC1=CC=C(I)C=C1Cl MYDAOWXYGPEPJT-UHFFFAOYSA-N 0.000 description 1
• HWZUMEVIIGNXGM-UHFFFAOYSA-N 2-chloro-4-methyl-5-nitropyridine Chemical compound CC1=CC(Cl)=NC=C1[N+]([O-])=O HWZUMEVIIGNXGM-UHFFFAOYSA-N 0.000 description 1
• BKDGUUZBJLNTOO-UHFFFAOYSA-N 2-ethynyl-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1C#C BKDGUUZBJLNTOO-UHFFFAOYSA-N 0.000 description 1
• NBCNUIXYBLFJMI-UHFFFAOYSA-N 2-fluoro-1-methyl-3-nitrobenzene Chemical compound CC1=CC=CC([N+]([O-])=O)=C1F NBCNUIXYBLFJMI-UHFFFAOYSA-N 0.000 description 1
• ICXSHFWYCHJILC-UHFFFAOYSA-N 2-fluoro-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1F ICXSHFWYCHJILC-UHFFFAOYSA-N 0.000 description 1
• YLACBMHBZVYOAP-UHFFFAOYSA-N 2-fluoro-5-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C#N)=C1 YLACBMHBZVYOAP-UHFFFAOYSA-N 0.000 description 1
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• POJDZWIPNZWPAU-UHFFFAOYSA-N 2-methyl-1-nitro-3-nitrosoguanidine Chemical compound O=NNC(=NC)N[N+]([O-])=O POJDZWIPNZWPAU-UHFFFAOYSA-N 0.000 description 1
• DDTKYVBFPULMGN-UHFFFAOYSA-N 2-methyl-6-propan-2-ylaniline Chemical compound CC(C)C1=CC=CC(C)=C1N DDTKYVBFPULMGN-UHFFFAOYSA-N 0.000 description 1
• SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
• SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
• HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• GIIGHSIIKVOWKZ-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine Chemical compound N1=CN=CC2=NNN=C21 GIIGHSIIKVOWKZ-UHFFFAOYSA-N 0.000 description 1
• SDYWXFYBZPNOFX-UHFFFAOYSA-N 3,4-dichloroaniline Chemical class NC1=CC=C(Cl)C(Cl)=C1 SDYWXFYBZPNOFX-UHFFFAOYSA-N 0.000 description 1
• JAHCMTGHACNEQB-UHFFFAOYSA-N 3-(4-fluoro-3-methoxyphenyl)prop-2-enoyl azide Chemical compound COC1=CC(C=CC(=O)N=[N+]=[N-])=CC=C1F JAHCMTGHACNEQB-UHFFFAOYSA-N 0.000 description 1
• PUCVWZXFTAPJFW-UHFFFAOYSA-N 3-(difluoromethyl)thiophene-2-sulfonic acid Chemical compound FC(F)C1=C(SC=C1)S(=O)(=O)O PUCVWZXFTAPJFW-UHFFFAOYSA-N 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• MGTZGHNFFLOPFR-UHFFFAOYSA-N 3-chlorothiophene-2-sulfonamide Chemical compound NS(=O)(=O)C=1SC=CC=1Cl MGTZGHNFFLOPFR-UHFFFAOYSA-N 0.000 description 1
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• CCCDPFVJVPDYRU-UHFFFAOYSA-N 3-methylthiophene-2-sulfonamide Chemical compound CC=1C=CSC=1S(N)(=O)=O CCCDPFVJVPDYRU-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• LKZDATCKBQFADP-UHFFFAOYSA-N 4-(difluoromethyl)thiophene-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC(C(F)F)=CS1 LKZDATCKBQFADP-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• QVILSWLYJYMGRN-UHFFFAOYSA-N 4-bromo-2-(trifluoromethoxy)aniline Chemical compound NC1=CC=C(Br)C=C1OC(F)(F)F QVILSWLYJYMGRN-UHFFFAOYSA-N 0.000 description 1
• VNYMMFINWSHARA-UHFFFAOYSA-N 4-chlorothiophene-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC(Cl)=CS1 VNYMMFINWSHARA-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• USOVRXNIZFSGEU-UHFFFAOYSA-N 4-fluoro-1-nitro-2-(2,2,2-trifluoroethoxy)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OCC(F)(F)F USOVRXNIZFSGEU-UHFFFAOYSA-N 0.000 description 1
• WMQOSURXFLBTPC-UHFFFAOYSA-N 4-fluoro-1-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1C(F)(F)F WMQOSURXFLBTPC-UHFFFAOYSA-N 0.000 description 1
• JHFOWEGCZWLHNW-UHFFFAOYSA-N 4-fluoro-2-methyl-1-nitrobenzene Chemical compound CC1=CC(F)=CC=C1[N+]([O-])=O JHFOWEGCZWLHNW-UHFFFAOYSA-N 0.000 description 1
• NALVGTOMKSKFFV-UHFFFAOYSA-N 4-fluoro-3-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1F NALVGTOMKSKFFV-UHFFFAOYSA-N 0.000 description 1
• DWQGELZWNCZPIP-UHFFFAOYSA-N 4-iodo-2-propan-2-ylaniline Chemical compound CC(C)C1=CC(I)=CC=C1N DWQGELZWNCZPIP-UHFFFAOYSA-N 0.000 description 1
• ZZIZNALHVCSALM-UHFFFAOYSA-N 4-methylthiophene-2-sulfonamide Chemical compound CC1=CSC(S(N)(=O)=O)=C1 ZZIZNALHVCSALM-UHFFFAOYSA-N 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
• IKDMDPZWUNMEPZ-UHFFFAOYSA-N 5-[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]-2-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]benzamide Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)C(N)=O)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 IKDMDPZWUNMEPZ-UHFFFAOYSA-N 0.000 description 1
• KWSLGOVYXMQPPX-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-2h-tetrazole Chemical compound FC(F)(F)C1=CC=CC(C2=NNN=N2)=C1 KWSLGOVYXMQPPX-UHFFFAOYSA-N 0.000 description 1
• KBLGGRWUEVCNPY-UHFFFAOYSA-N 5-bromo-3-methylpyridin-2-amine Chemical compound CC1=CC(Br)=CN=C1N KBLGGRWUEVCNPY-UHFFFAOYSA-N 0.000 description 1
• WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 1
• WXJQQLDICAOBJB-UHFFFAOYSA-N 5-bromothiophene-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Br)S1 WXJQQLDICAOBJB-UHFFFAOYSA-N 0.000 description 1
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
• BLKOSTJSUMJMSR-UHFFFAOYSA-N 5-chlorothiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)S1 BLKOSTJSUMJMSR-UHFFFAOYSA-N 0.000 description 1
• SOTJMJKWBXAHDP-UHFFFAOYSA-N 5-cyanothiophene-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=C(C#N)S1 SOTJMJKWBXAHDP-UHFFFAOYSA-N 0.000 description 1
• OSQLGPYKHWNEJD-UHFFFAOYSA-N 5-ethylthiophene-2-sulfonamide Chemical compound CCC1=CC=C(S(N)(=O)=O)S1 OSQLGPYKHWNEJD-UHFFFAOYSA-N 0.000 description 1
• HCEALRCEDNZDIJ-UHFFFAOYSA-N 5-ethynylthiophene-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=C(C#C)S1 HCEALRCEDNZDIJ-UHFFFAOYSA-N 0.000 description 1
• KKAFVHUJZPVWND-UHFFFAOYSA-N 5-fluoro-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1C=O KKAFVHUJZPVWND-UHFFFAOYSA-N 0.000 description 1
• GHYZIXDKAPMFCS-UHFFFAOYSA-N 5-fluoro-2-nitrobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1[N+]([O-])=O GHYZIXDKAPMFCS-UHFFFAOYSA-N 0.000 description 1
• IVILGUFRMDBUEQ-UHFFFAOYSA-N 5-iodopyridin-2-amine Chemical compound NC1=CC=C(I)C=N1 IVILGUFRMDBUEQ-UHFFFAOYSA-N 0.000 description 1
• HAFKCGZQRIIADX-UHFFFAOYSA-N 5-iodopyrimidin-2-amine Chemical compound NC1=NC=C(I)C=N1 HAFKCGZQRIIADX-UHFFFAOYSA-N 0.000 description 1
• CXLPLLMEAMSLTA-UHFFFAOYSA-N 5-methoxythiophene-2-sulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)S1 CXLPLLMEAMSLTA-UHFFFAOYSA-N 0.000 description 1
• QIFRWYJBGDRVKY-UHFFFAOYSA-N 5-methylthiophene-2-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)S1 QIFRWYJBGDRVKY-UHFFFAOYSA-N 0.000 description 1
• JBYBPABTMFORGK-UHFFFAOYSA-N 5-propylthiophene-2-sulfonamide Chemical compound CCCC1=CC=C(S(N)(=O)=O)S1 JBYBPABTMFORGK-UHFFFAOYSA-N 0.000 description 1
• CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
• GHSRMSJVYMITDX-UHFFFAOYSA-N 6-chloro-2-methyl-3-nitropyridine Chemical compound CC1=NC(Cl)=CC=C1[N+]([O-])=O GHSRMSJVYMITDX-UHFFFAOYSA-N 0.000 description 1
• 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 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 102000007347 Apyrase Human genes 0.000 description 1
• 108010007730 Apyrase Proteins 0.000 description 1
• 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
• 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 229910014265 BrCl Inorganic materials 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
• 206010022562 Intermittent claudication Diseases 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• KRWTYRJZIGBAQX-UHFFFAOYSA-N N-(chlorosulfonylcarbamoyl)sulfamoyl chloride Chemical compound ClS(=O)(=O)NC(NS(=O)(=O)Cl)=O KRWTYRJZIGBAQX-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• GNBRODFSORETDH-UHFFFAOYSA-N N-bromo-2-methyl-6-propan-2-ylaniline Chemical compound BrNC1=C(C=CC=C1C)C(C)C GNBRODFSORETDH-UHFFFAOYSA-N 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 108010001014 Plasminogen Activators Proteins 0.000 description 1
• 102000001938 Plasminogen Activators Human genes 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 206010050496 Reversible ischaemic neurological deficit Diseases 0.000 description 1
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
• 229910006404 SnO 2 Inorganic materials 0.000 description 1
• 238000006619 Stille reaction Methods 0.000 description 1
• 108010023197 Streptokinase Proteins 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 229940122388 Thrombin inhibitor Drugs 0.000 description 1
• 206010043647 Thrombotic Stroke Diseases 0.000 description 1
• 102100036704 Thromboxane A2 receptor Human genes 0.000 description 1
• 108090000300 Thromboxane Receptors Proteins 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 102000014384 Type C Phospholipases Human genes 0.000 description 1
• 108010079194 Type C Phospholipases Proteins 0.000 description 1
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
• 206010053648 Vascular occlusion Diseases 0.000 description 1
• ABSLITZGLWBCJS-UHFFFAOYSA-N [5-[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]-2-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]phenyl]methyl acetate Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C(=C1)COC(C)=O)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 ABSLITZGLWBCJS-UHFFFAOYSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical group 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 150000005005 aminopyrimidines Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• VWCXMBAXZIFWRS-UHFFFAOYSA-N aniline tert-butyl N-[2-(4-amino-2-chlorophenyl)-7-fluoro-1-oxoisoquinolin-6-yl]-N-methylcarbamate Chemical compound NC1=CC=CC=C1.O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C1=CC=C(N)C=C1Cl VWCXMBAXZIFWRS-UHFFFAOYSA-N 0.000 description 1
• 239000003529 anticholesteremic agent Substances 0.000 description 1
• 229940127226 anticholesterol agent Drugs 0.000 description 1
• 229940127090 anticoagulant agent Drugs 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 229940127218 antiplatelet drug Drugs 0.000 description 1
• 229960004676 antithrombotic agent Drugs 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 150000001491 aromatic compounds Chemical class 0.000 description 1
• 230000003143 atherosclerotic effect Effects 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
• HGXJOXHYPGNVNK-UHFFFAOYSA-N butane;ethenoxyethane;tin Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)OCC HGXJOXHYPGNVNK-UHFFFAOYSA-N 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 150000001722 carbon compounds Chemical class 0.000 description 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
• 238000013172 carotid endarterectomy Methods 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 229920005556 chlorobutyl Polymers 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 229960003009 clopidogrel Drugs 0.000 description 1
• GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
• 230000015271 coagulation Effects 0.000 description 1
• 238000005345 coagulation Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• 229940124301 concurrent medication Drugs 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 238000007887 coronary angioplasty Methods 0.000 description 1
• 229940072645 coumadin Drugs 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 108010011222 cyclo(Arg-Pro) Proteins 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 1
• 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
• GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 125000003963 dichloro group Chemical group Cl* 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 210000003038 endothelium Anatomy 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000010685 fatty oil Substances 0.000 description 1
• 230000003480 fibrinolytic effect Effects 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 230000002008 hemorrhagic effect Effects 0.000 description 1
• 230000023597 hemostasis Effects 0.000 description 1
• 150000002390 heteroarenes Chemical class 0.000 description 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 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• AJKLKFPOECCSOO-UHFFFAOYSA-N hydrochloride;hydroiodide Chemical compound Cl.I AJKLKFPOECCSOO-UHFFFAOYSA-N 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 230000036512 infertility Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 208000021156 intermittent vascular claudication Diseases 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 229940044173 iodine-125 Drugs 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000000155 isotopic effect Effects 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229910052746 lanthanum Inorganic materials 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
• 229940118179 lovenox Drugs 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• UQAODHIQPCPQDF-UHFFFAOYSA-N methyl 2-[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]-5-[7-fluoro-6-(methylamino)-1-oxoisoquinolin-2-yl]benzoate Chemical compound O=C1C=2C=C(F)C(NC)=CC=2C=CN1C(C=C1C(=O)OC)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 UQAODHIQPCPQDF-UHFFFAOYSA-N 0.000 description 1
• VSFYTPXXMLJNAU-UHFFFAOYSA-N methyl 2-amino-3-methylbenzoate Chemical compound COC(=O)C1=CC=CC(C)=C1N VSFYTPXXMLJNAU-UHFFFAOYSA-N 0.000 description 1
• NJHDBIXFFZVJGZ-UHFFFAOYSA-N methyl 3-methyl-2-nitrobenzoate Chemical compound COC(=O)C1=CC=CC(C)=C1[N+]([O-])=O NJHDBIXFFZVJGZ-UHFFFAOYSA-N 0.000 description 1
• 230000001035 methylating effect Effects 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 238000007392 microtiter assay Methods 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 125000006682 monohaloalkyl group Chemical group 0.000 description 1
• 230000002107 myocardial effect Effects 0.000 description 1
• JIRZAQDQJCRNSS-UHFFFAOYSA-N n-[2-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]phenyl]-7-fluoro-1-oxoisoquinolin-6-yl]-n-methylformamide Chemical compound O=C1C=2C=C(F)C(N(C=O)C)=CC=2C=CN1C(C=C1)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 JIRZAQDQJCRNSS-UHFFFAOYSA-N 0.000 description 1
• FAYVSPJQASODMO-UHFFFAOYSA-N n-bromo-2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1NBr FAYVSPJQASODMO-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• DBMRSXHNJMWYGQ-UHFFFAOYSA-N n-fluoro-4-iodoaniline Chemical compound FNC1=CC=C(I)C=C1 DBMRSXHNJMWYGQ-UHFFFAOYSA-N 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• FRCFWPVMFJMNDP-UHFFFAOYSA-N n-propan-2-ylaniline Chemical compound CC(C)NC1=CC=CC=C1 FRCFWPVMFJMNDP-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 101150009274 nhr-1 gene Proteins 0.000 description 1
• 125000004999 nitroaryl group Chemical group 0.000 description 1
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
• OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 229940127126 plasminogen activator Drugs 0.000 description 1
• 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 125000006684 polyhaloalkyl group Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 239000002213 purine nucleotide Substances 0.000 description 1
• 239000000719 purinergic P2Y receptor antagonist Substances 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• 239000002719 pyrimidine nucleotide Substances 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• 239000012066 reaction slurry Substances 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 238000001525 receptor binding assay Methods 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• 238000012827 research and development Methods 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000000284 resting effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 108010073863 saruplase Proteins 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 239000012363 selectfluor Substances 0.000 description 1
• 229940076279 serotonin Drugs 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 229920000260 silastic Polymers 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 239000010703 silicon Substances 0.000 description 1
• 229920002379 silicone rubber Polymers 0.000 description 1
• 239000004945 silicone rubber Substances 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 229910001379 sodium hypophosphite Inorganic materials 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 229960005202 streptokinase Drugs 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 230000000153 supplemental effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000012622 synthetic inhibitor Substances 0.000 description 1
• PZTGHCPATICQJM-UHFFFAOYSA-N tert-butyl n-[2-(2-ethenyl-4-nitrophenyl)-7-fluoro-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C1=CC=C([N+]([O-])=O)C=C1C=C PZTGHCPATICQJM-UHFFFAOYSA-N 0.000 description 1
• OSLUFWIXVKUCSC-UHFFFAOYSA-N tert-butyl n-[2-(3-cyclopropyl-4-nitrophenyl)-7-fluoro-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C(C=1)=CC=C([N+]([O-])=O)C=1C1CC1 OSLUFWIXVKUCSC-UHFFFAOYSA-N 0.000 description 1
• SSWGBGXVSYPQLD-UHFFFAOYSA-N tert-butyl n-[2-(5-aminopyridin-2-yl)-7-fluoro-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C1=CC=C(N)C=N1 SSWGBGXVSYPQLD-UHFFFAOYSA-N 0.000 description 1
• CDHVGJJSRPFDNP-UHFFFAOYSA-N tert-butyl n-[2-(6-aminopyridin-3-yl)-7-fluoro-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound O=C1C=2C=C(F)C(N(C(=O)OC(C)(C)C)C)=CC=2C=CN1C1=CC=C(N)N=C1 CDHVGJJSRPFDNP-UHFFFAOYSA-N 0.000 description 1
• MFYFOOOGDIXCGE-UHFFFAOYSA-N tert-butyl n-[2-[3-(butylamino)-4-nitrophenyl]-7-fluoro-1-oxoisoquinolin-6-yl]-n-methylcarbamate Chemical compound C1=C([N+]([O-])=O)C(NCCCC)=CC(N2C(C3=CC(F)=C(N(C)C(=O)OC(C)(C)C)C=C3C=C2)=O)=C1 MFYFOOOGDIXCGE-UHFFFAOYSA-N 0.000 description 1
• NBHNYJALMLQTEO-UHFFFAOYSA-N tert-butyl n-[7-fluoro-1-oxo-2-(2-trimethylsilylethoxymethyl)isoquinolin-6-yl]carbamate Chemical compound C1=CN(COCC[Si](C)(C)C)C(=O)C2=C1C=C(NC(=O)OC(C)(C)C)C(F)=C2 NBHNYJALMLQTEO-UHFFFAOYSA-N 0.000 description 1
• DXXUHRDGGXVULG-UHFFFAOYSA-N tert-butyl n-[7-fluoro-5-methyl-1-oxo-2-(2-trimethylsilylethoxymethyl)isoquinolin-6-yl]-n-methylcarbamate Chemical compound C1=CN(COCC[Si](C)(C)C)C(=O)C=2C1=C(C)C(N(C(=O)OC(C)(C)C)C)=C(F)C=2 DXXUHRDGGXVULG-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• ZGNPLWZYVAFUNZ-UHFFFAOYSA-N tert-butylphosphane Chemical compound CC(C)(C)P ZGNPLWZYVAFUNZ-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 229940125670 thienopyridine Drugs 0.000 description 1
• 239000002175 thienopyridine Substances 0.000 description 1
• 125000005309 thioalkoxy group Chemical group 0.000 description 1
• 239000003868 thrombin inhibitor Substances 0.000 description 1
• 230000002537 thrombolytic effect Effects 0.000 description 1
• 229960005001 ticlopidine Drugs 0.000 description 1
• PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• WARKYKQCOXTIAO-UHFFFAOYSA-N tributyl(2-ethoxyethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)\C=C/OCC WARKYKQCOXTIAO-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 229960005356 urokinase Drugs 0.000 description 1
• 208000021331 vascular occlusion disease Diseases 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1