US20050222198A1 - Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment - Google Patents
Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment Download PDFInfo
- Publication number
- US20050222198A1 US20050222198A1 US11/019,830 US1983004A US2005222198A1 US 20050222198 A1 US20050222198 A1 US 20050222198A1 US 1983004 A US1983004 A US 1983004A US 2005222198 A1 US2005222198 A1 US 2005222198A1
- Authority
- US
- United States
- Prior art keywords
- alkyl
- aryl
- cycloalkyl
- compound
- cycloalkenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 79
- 238000011282 treatment Methods 0.000 title claims abstract description 13
- 230000000840 anti-viral effect Effects 0.000 title claims description 17
- UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical class C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 319
- 208000036142 Viral infection Diseases 0.000 claims abstract description 8
- 230000009385 viral infection Effects 0.000 claims abstract description 7
- 238000011321 prophylaxis Methods 0.000 claims abstract description 3
- 238000012216 screening Methods 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims description 226
- -1 —OH Chemical group 0.000 claims description 173
- 125000000217 alkyl group Chemical group 0.000 claims description 172
- 125000000623 heterocyclic group Chemical group 0.000 claims description 152
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 130
- 229910052739 hydrogen Inorganic materials 0.000 claims description 129
- 239000001257 hydrogen Substances 0.000 claims description 126
- 125000003342 alkenyl group Chemical group 0.000 claims description 97
- 239000000203 mixture Substances 0.000 claims description 96
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 82
- 125000003545 alkoxy group Chemical group 0.000 claims description 81
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 68
- 229910052736 halogen Inorganic materials 0.000 claims description 61
- 125000001188 haloalkyl group Chemical group 0.000 claims description 58
- 150000002367 halogens Chemical class 0.000 claims description 58
- 125000000304 alkynyl group Chemical group 0.000 claims description 57
- 125000000539 amino acid group Chemical group 0.000 claims description 49
- 125000004414 alkyl thio group Chemical group 0.000 claims description 47
- 125000004104 aryloxy group Chemical group 0.000 claims description 47
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 46
- 125000005110 aryl thio group Chemical group 0.000 claims description 45
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 37
- 229910052717 sulfur Inorganic materials 0.000 claims description 36
- 125000005842 heteroatom Chemical group 0.000 claims description 33
- 229910052760 oxygen Inorganic materials 0.000 claims description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 31
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 31
- 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 150000001413 amino acids Chemical class 0.000 claims description 28
- 241000711549 Hepacivirus C Species 0.000 claims description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000004450 alkenylene group Chemical group 0.000 claims description 24
- 125000004419 alkynylene group Chemical group 0.000 claims description 24
- 125000005361 aryl sulfoxide group Chemical group 0.000 claims description 24
- 125000004421 aryl sulphonamide group Chemical group 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 125000004122 cyclic group Chemical group 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 18
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000005362 aryl sulfone group Chemical group 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 14
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 13
- 208000015181 infectious disease Diseases 0.000 claims description 13
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 12
- 241000700605 Viruses Species 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 10
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 10
- 125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 10
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 10
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 9
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 239000004305 biphenyl Substances 0.000 claims description 9
- 235000010290 biphenyl Nutrition 0.000 claims description 9
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000004001 thioalkyl group Chemical group 0.000 claims description 9
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 8
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 8
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 8
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 8
- 125000000232 haloalkynyl group Chemical group 0.000 claims description 8
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 8
- 229930195733 hydrocarbon Natural products 0.000 claims description 8
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- 125000005647 linker group Chemical group 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 241000710781 Flaviviridae Species 0.000 claims description 5
- 241000709664 Picornaviridae Species 0.000 claims description 5
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 5
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 4
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims description 4
- 150000002430 hydrocarbons Chemical class 0.000 claims description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 229960000329 ribavirin Drugs 0.000 claims description 3
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 108010047761 Interferon-alpha Proteins 0.000 claims description 2
- 102000006992 Interferon-alpha Human genes 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 238000011374 additional therapy Methods 0.000 claims 1
- 125000004970 halomethyl group Chemical group 0.000 claims 1
- 125000004951 trihalomethoxy group Chemical group 0.000 claims 1
- 239000000651 prodrug Substances 0.000 abstract description 14
- 229940002612 prodrug Drugs 0.000 abstract description 14
- 238000002360 preparation method Methods 0.000 abstract description 13
- 230000008569 process Effects 0.000 abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 7
- 230000002265 prevention Effects 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 71
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 59
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 229910001868 water Inorganic materials 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 43
- 150000002431 hydrogen Chemical group 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 238000005160 1H NMR spectroscopy Methods 0.000 description 34
- 239000004480 active ingredient Substances 0.000 description 34
- 238000009472 formulation Methods 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
- 239000000047 product Substances 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 23
- 235000001014 amino acid Nutrition 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- 0 [1*][Y]c1n([26*])c2-c([2*])N(C[3*])c([4*])c([5*])c-2n1[25*] Chemical compound [1*][Y]c1n([26*])c2-c([2*])N(C[3*])c([4*])c([5*])c-2n1[25*] 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 239000000463 material Substances 0.000 description 19
- 239000003153 chemical reaction reagent Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- PTEXAXKWNFMOMW-UHFFFAOYSA-N 4-[4-[[2-(2,3-difluorophenyl)imidazo[4,5-c]pyridin-5-yl]methyl]phenyl]phenol Chemical class C1=CC(O)=CC=C1C(C=C1)=CC=C1CN1C=C2N=C(C=3C(=C(F)C=CC=3)F)N=C2C=C1 PTEXAXKWNFMOMW-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 15
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 235000019441 ethanol Nutrition 0.000 description 14
- 230000002163 immunogen Effects 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000000926 separation method Methods 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- YHWRNLFLGWSRMG-UHFFFAOYSA-N 2-(2,3-difluorophenyl)-3h-imidazo[4,5-c]pyridine Chemical compound FC1=CC=CC(C=2NC3=CN=CC=C3N=2)=C1F YHWRNLFLGWSRMG-UHFFFAOYSA-N 0.000 description 10
- 241000710780 Bovine viral diarrhea virus 1 Species 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 125000002015 acyclic group Chemical group 0.000 description 10
- 125000001183 hydrocarbyl group Chemical group 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 241000710778 Pestivirus Species 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000002585 base Chemical class 0.000 description 8
- 239000000969 carrier Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000003995 emulsifying agent Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- 230000002503 metabolic effect Effects 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 150000002500 ions Chemical class 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 239000002207 metabolite Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 230000010076 replication Effects 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- 239000004094 surface-active agent Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- SWKWSYUHDTYKCF-UHFFFAOYSA-N 2-(2,3-difluorophenyl)-5-[(4-iodophenyl)methyl]imidazo[4,5-c]pyridine Chemical compound FC1=CC=CC(C2=NC3=CN(CC=4C=CC(I)=CC=4)C=CC3=N2)=C1F SWKWSYUHDTYKCF-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- 108060001084 Luciferase Proteins 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 150000004676 glycans Chemical class 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 150000002923 oximes Chemical class 0.000 description 6
- 229920001282 polysaccharide Polymers 0.000 description 6
- 239000005017 polysaccharide Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- NSPBTJFAUPZOHK-UHFFFAOYSA-N 5-(chloromethyl)-3-(4-chlorophenyl)-1,2-oxazole Chemical compound O1C(CCl)=CC(C=2C=CC(Cl)=CC=2)=N1 NSPBTJFAUPZOHK-UHFFFAOYSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 230000005526 G1 to G0 transition Effects 0.000 description 5
- 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 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000013270 controlled release Methods 0.000 description 5
- 230000001085 cytostatic effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000003925 fat Substances 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 229960002743 glutamine Drugs 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 150000002545 isoxazoles Chemical group 0.000 description 5
- LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical compound ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 5
- 239000011343 solid material Substances 0.000 description 5
- IWKXBHQELWQLHF-CAPFRKAQSA-N (ne)-n-[(2-amino-3-propan-2-ylsulfonylbenzimidazol-5-yl)-phenylmethylidene]hydroxylamine Chemical compound C1=C2N(S(=O)(=O)C(C)C)C(N)=NC2=CC=C1C(=N\O)\C1=CC=CC=C1 IWKXBHQELWQLHF-CAPFRKAQSA-N 0.000 description 4
- JLZVIWSFUPLSOR-UHFFFAOYSA-N 2,3-difluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1F JLZVIWSFUPLSOR-UHFFFAOYSA-N 0.000 description 4
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VDYNKLQDXBZGGP-UHFFFAOYSA-N COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=N2)C=C1 Chemical compound COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=N2)C=C1 VDYNKLQDXBZGGP-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 241000531123 GB virus C Species 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 229910019093 NaOCl Inorganic materials 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 125000001041 indolyl group Chemical group 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000002736 nonionic surfactant Substances 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 150000003222 pyridines Chemical class 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- HBZBAMXERPYTFS-SECBINFHSA-N (4S)-2-(6,7-dihydro-5H-pyrrolo[3,2-f][1,3]benzothiazol-2-yl)-4,5-dihydro-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)[C@H]1CSC(=N1)c1nc2cc3CCNc3cc2s1 HBZBAMXERPYTFS-SECBINFHSA-N 0.000 description 3
- QTYBVTHJXSKUBV-UHFFFAOYSA-N 2-(2,3-difluorophenyl)-5-[[4-(trifluoromethoxy)phenyl]methyl]imidazo[4,5-c]pyridine Chemical compound FC1=CC=CC(C2=NC3=CN(CC=4C=CC(OC(F)(F)F)=CC=4)C=CC3=N2)=C1F QTYBVTHJXSKUBV-UHFFFAOYSA-N 0.000 description 3
- DFXVIZQVJLSYOJ-UHFFFAOYSA-N 2-(2-fluorophenyl)-3h-imidazo[4,5-c]pyridine Chemical compound FC1=CC=CC=C1C1=NC2=CC=NC=C2N1 DFXVIZQVJLSYOJ-UHFFFAOYSA-N 0.000 description 3
- NHBDOFACNWSCQU-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[[2-(2,3-difluorophenyl)imidazo[4,5-c]pyridin-5-yl]methyl]-1,2-oxazole Chemical compound FC1=CC=CC(C2=NC3=CN(CC=4ON=C(C=4)C=4C=CC(Cl)=CC=4)C=CC3=N2)=C1F NHBDOFACNWSCQU-UHFFFAOYSA-N 0.000 description 3
- BIICMGFVVMXKNY-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[[2-(2-fluorophenyl)imidazo[4,5-c]pyridin-5-yl]methyl]-1,2-oxazole Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC=3ON=C(C=3)C=3C=CC(Cl)=CC=3)C=CC2=N1 BIICMGFVVMXKNY-UHFFFAOYSA-N 0.000 description 3
- MKFCBJOVMMLPRT-UHFFFAOYSA-N 3-(chloromethyl)-1,2-oxazole Chemical compound ClCC=1C=CON=1 MKFCBJOVMMLPRT-UHFFFAOYSA-N 0.000 description 3
- 241001118702 Border disease virus Species 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- FPIVHKVPTBOGGR-UHFFFAOYSA-N CC(C)OC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CC(C)OC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 FPIVHKVPTBOGGR-UHFFFAOYSA-N 0.000 description 3
- MXZKIIFMEJQHCG-UHFFFAOYSA-N CCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 MXZKIIFMEJQHCG-UHFFFAOYSA-N 0.000 description 3
- VQVLGQKXQFGMSH-UHFFFAOYSA-N CN1C=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 Chemical compound CN1C=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 VQVLGQKXQFGMSH-UHFFFAOYSA-N 0.000 description 3
- IOOPQUXBLFXGSA-UHFFFAOYSA-N COC1=CC(C(F)(F)F)=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound COC1=CC(C(F)(F)F)=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 IOOPQUXBLFXGSA-UHFFFAOYSA-N 0.000 description 3
- UVXQHIVVSDCRLV-UHFFFAOYSA-N CSC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CSC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 UVXQHIVVSDCRLV-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 241000710777 Classical swine fever virus Species 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- ASYGLWKKYSEDGR-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Br)C=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Br)C=C5)=NO4)C=CC3=N2)=CC=C1 ASYGLWKKYSEDGR-UHFFFAOYSA-N 0.000 description 3
- QCBOBZWEXBIHFT-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Br)S5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Br)S5)=NO4)C=CC3=N2)=CC=C1 QCBOBZWEXBIHFT-UHFFFAOYSA-N 0.000 description 3
- ORVJNZUEMUKFGW-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(C(F)(F)F)C=C4C(F)(F)F)=NO3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(C(F)(F)F)C=C4C(F)(F)F)=NO3)C=CC2=N1 ORVJNZUEMUKFGW-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 3
- 241001144416 Picornavirales Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 102000006943 Uracil-DNA Glycosidase Human genes 0.000 description 3
- 108010072685 Uracil-DNA Glycosidase Proteins 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229950008161 enviroxime Drugs 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- KQOXLKOJHVFTRN-UHFFFAOYSA-N pleconaril Chemical compound O1N=C(C)C=C1CCCOC1=C(C)C=C(C=2N=C(ON=2)C(F)(F)F)C=C1C KQOXLKOJHVFTRN-UHFFFAOYSA-N 0.000 description 3
- 229960000471 pleconaril Drugs 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000005588 protonation Effects 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 229930195734 saturated hydrocarbon Natural products 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 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
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical class OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 2
- VTWKXBJHBHYJBI-SOFGYWHQSA-N (ne)-n-benzylidenehydroxylamine Chemical compound O\N=C\C1=CC=CC=C1 VTWKXBJHBHYJBI-SOFGYWHQSA-N 0.000 description 2
- MCHDHQVROPEJJT-UHFFFAOYSA-N 1-(chloromethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CCl)C=C1 MCHDHQVROPEJJT-UHFFFAOYSA-N 0.000 description 2
- OUKQTRFCDKSEPL-UHFFFAOYSA-N 1-Methyl-2-pyrrolecarboxaldehyde Chemical compound CN1C=CC=C1C=O OUKQTRFCDKSEPL-UHFFFAOYSA-N 0.000 description 2
- BFOWXBARPYDGQE-UHFFFAOYSA-N 3-methyl-5-nitropyridin-4-amine Chemical compound CC1=CN=CC([N+]([O-])=O)=C1N BFOWXBARPYDGQE-UHFFFAOYSA-N 0.000 description 2
- VGJLGPCXUGIXRQ-UHFFFAOYSA-N 3-methylpyridin-4-amine Chemical compound CC1=CN=CC=C1N VGJLGPCXUGIXRQ-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- FGXZWMCBNMMYPL-UHFFFAOYSA-N 4-propoxybenzaldehyde Chemical compound CCCOC1=CC=C(C=O)C=C1 FGXZWMCBNMMYPL-UHFFFAOYSA-N 0.000 description 2
- BGFLUWRHUKPQGE-UHFFFAOYSA-N 5-(chloromethyl)-3-(4-ethoxyphenyl)-1,2-oxazole Chemical compound C1=CC(OCC)=CC=C1C1=NOC(CCl)=C1 BGFLUWRHUKPQGE-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- GWSHQLNZKYWYGT-UHFFFAOYSA-N C#CCOC1=C(C(=O)O)C=CC=C1 Chemical compound C#CCOC1=C(C(=O)O)C=CC=C1 GWSHQLNZKYWYGT-UHFFFAOYSA-N 0.000 description 2
- FQCVFOURVBBGLF-UHFFFAOYSA-N C=CCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound C=CCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 FQCVFOURVBBGLF-UHFFFAOYSA-N 0.000 description 2
- MUXRRHJVBUNTJH-UHFFFAOYSA-N CC#CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC#CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 MUXRRHJVBUNTJH-UHFFFAOYSA-N 0.000 description 2
- QDAWXRKTSATEOP-UHFFFAOYSA-N CC(=O)C1=C(C(=O)O)C=CC=C1 Chemical compound CC(=O)C1=C(C(=O)O)C=CC=C1 QDAWXRKTSATEOP-UHFFFAOYSA-N 0.000 description 2
- MQDHVCSOMRGULO-UHFFFAOYSA-N CC(=O)OCCCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(=O)OCCCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 MQDHVCSOMRGULO-UHFFFAOYSA-N 0.000 description 2
- ZLQQUIHBQATFOP-UHFFFAOYSA-N CC(C)(C)C1=CC=C(C2=NOC(CCl)=N2)C=C1 Chemical compound CC(C)(C)C1=CC=C(C2=NOC(CCl)=N2)C=C1 ZLQQUIHBQATFOP-UHFFFAOYSA-N 0.000 description 2
- AIVSLDAXUIRICJ-UHFFFAOYSA-N CC(C)(C)C1=NC(CCl)=NO1 Chemical compound CC(C)(C)C1=NC(CCl)=NO1 AIVSLDAXUIRICJ-UHFFFAOYSA-N 0.000 description 2
- YOKSMJJQLRFLIP-UHFFFAOYSA-N CC(C)=CCCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CC(C)=CCCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 YOKSMJJQLRFLIP-UHFFFAOYSA-N 0.000 description 2
- AGSJGZSIRMVOOZ-UHFFFAOYSA-N CC(C)C1=CC=C(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)C=C1 Chemical compound CC(C)C1=CC=C(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)C=C1 AGSJGZSIRMVOOZ-UHFFFAOYSA-N 0.000 description 2
- PPUGTWAPVDDBEW-UHFFFAOYSA-N CC1=C(CCl)C(C2=C(Cl)C=CC=C2Cl)=NO1 Chemical compound CC1=C(CCl)C(C2=C(Cl)C=CC=C2Cl)=NO1 PPUGTWAPVDDBEW-UHFFFAOYSA-N 0.000 description 2
- ZZXPPJVCWYZKOI-UHFFFAOYSA-N CC1=C(Cl)C=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1 Chemical compound CC1=C(Cl)C=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1 ZZXPPJVCWYZKOI-UHFFFAOYSA-N 0.000 description 2
- ZZGGOSDHWXCOCA-UHFFFAOYSA-N CC1=C(F)C=CC(CBr)=C1 Chemical compound CC1=C(F)C=CC(CBr)=C1 ZZGGOSDHWXCOCA-UHFFFAOYSA-N 0.000 description 2
- AENYCMZUDXQARW-UHFFFAOYSA-N CC1=C(OCC(F)(F)F)C=CN=C1CCl Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CCl AENYCMZUDXQARW-UHFFFAOYSA-N 0.000 description 2
- OLEPXJOWXUPXRP-UHFFFAOYSA-N CC1=CC(C(=O)O)=C(C)N1C1=CC=CS1 Chemical compound CC1=CC(C(=O)O)=C(C)N1C1=CC=CS1 OLEPXJOWXUPXRP-UHFFFAOYSA-N 0.000 description 2
- UNRGEIXQCZHICP-UHFFFAOYSA-N CC1=CC(C)=C(CCl)C(C)=C1 Chemical compound CC1=CC(C)=C(CCl)C(C)=C1 UNRGEIXQCZHICP-UHFFFAOYSA-N 0.000 description 2
- RUTWRJDDOUUPKV-UHFFFAOYSA-N CC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 Chemical compound CC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 RUTWRJDDOUUPKV-UHFFFAOYSA-N 0.000 description 2
- ICQOWIXIHDDXDI-UHFFFAOYSA-N CC1=CC=C(C(=O)C2=C(C(=O)O)C=CC=C2)C=C1 Chemical compound CC1=CC=C(C(=O)C2=C(C(=O)O)C=CC=C2)C=C1 ICQOWIXIHDDXDI-UHFFFAOYSA-N 0.000 description 2
- KOXSRWSRJJAETI-UHFFFAOYSA-N CC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 KOXSRWSRJJAETI-UHFFFAOYSA-N 0.000 description 2
- SUMRDSZTAQHVFK-UHFFFAOYSA-N CC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=N2)C=C1 Chemical compound CC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=N2)C=C1 SUMRDSZTAQHVFK-UHFFFAOYSA-N 0.000 description 2
- QWQVTYYKMSFGGP-UHFFFAOYSA-N CC1=CC=C(Cl)C(CBr)=C1F Chemical compound CC1=CC=C(Cl)C(CBr)=C1F QWQVTYYKMSFGGP-UHFFFAOYSA-N 0.000 description 2
- MGOAXFPMFQUXGF-UHFFFAOYSA-N CC1=CC=C(NC(=O)C2=CC=C(CCl)C=C2)C(O)=C1 Chemical compound CC1=CC=C(NC(=O)C2=CC=C(CCl)C=C2)C(O)=C1 MGOAXFPMFQUXGF-UHFFFAOYSA-N 0.000 description 2
- BUYDDZAETOJPGQ-UHFFFAOYSA-N CCC(C)COC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound CCC(C)COC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 BUYDDZAETOJPGQ-UHFFFAOYSA-N 0.000 description 2
- ZVBNGIDVTPTFCL-UHFFFAOYSA-N CCC1=CC=C(C(=O)O)S1 Chemical compound CCC1=CC=C(C(=O)O)S1 ZVBNGIDVTPTFCL-UHFFFAOYSA-N 0.000 description 2
- PLKGTIAHVAXTDM-UHFFFAOYSA-N CCCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CCCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 PLKGTIAHVAXTDM-UHFFFAOYSA-N 0.000 description 2
- QOHJWGXVMZSTAZ-UHFFFAOYSA-N CCN(CC)CC(C)Cl Chemical compound CCN(CC)CC(C)Cl QOHJWGXVMZSTAZ-UHFFFAOYSA-N 0.000 description 2
- WZEKYBQHOINKGX-UHFFFAOYSA-N CCN(CC)CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCN(CC)CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 WZEKYBQHOINKGX-UHFFFAOYSA-N 0.000 description 2
- GSOOZINPSWIOAM-UHFFFAOYSA-N CCOC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCOC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 GSOOZINPSWIOAM-UHFFFAOYSA-N 0.000 description 2
- MQRFXFNAYCBZEW-UHFFFAOYSA-N CN(C)C1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CN(C)C1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 MQRFXFNAYCBZEW-UHFFFAOYSA-N 0.000 description 2
- WVYSDWZCQKLVQO-UHFFFAOYSA-N CN1C=C(C2=CC=CC=C2)C(CCl)=C1Cl Chemical compound CN1C=C(C2=CC=CC=C2)C(CCl)=C1Cl WVYSDWZCQKLVQO-UHFFFAOYSA-N 0.000 description 2
- ILAOVOOZLVGAJF-UHFFFAOYSA-N CN1C=CC=C1C(=O)O Chemical compound CN1C=CC=C1C(=O)O ILAOVOOZLVGAJF-UHFFFAOYSA-N 0.000 description 2
- LHQDLWDXCGLJAB-UHFFFAOYSA-N COC1=CC=C(C2=NC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=NO2)C=C1 Chemical compound COC1=CC=C(C2=NC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=NO2)C=C1 LHQDLWDXCGLJAB-UHFFFAOYSA-N 0.000 description 2
- LPRZPEXSIPYEAF-UHFFFAOYSA-N COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(C)=C1 Chemical compound COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(C)=C1 LPRZPEXSIPYEAF-UHFFFAOYSA-N 0.000 description 2
- OYWOFPYCWKBMEQ-UHFFFAOYSA-N COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(F)=C1 Chemical compound COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(F)=C1 OYWOFPYCWKBMEQ-UHFFFAOYSA-N 0.000 description 2
- JPPQTDNLUGNGDE-UHFFFAOYSA-N COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 JPPQTDNLUGNGDE-UHFFFAOYSA-N 0.000 description 2
- XFPFDOJPCKKGHT-UHFFFAOYSA-N COCCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 XFPFDOJPCKKGHT-UHFFFAOYSA-N 0.000 description 2
- HGKPAXHJTMHWAH-UHFFFAOYSA-N CS(=O)(=O)C1=CC=C(CBr)C=C1 Chemical compound CS(=O)(=O)C1=CC=C(CBr)C=C1 HGKPAXHJTMHWAH-UHFFFAOYSA-N 0.000 description 2
- WQRYDDUXWFSPQG-UHFFFAOYSA-N Cl.ClCCN1C=CN=C1 Chemical compound Cl.ClCCN1C=CN=C1 WQRYDDUXWFSPQG-UHFFFAOYSA-N 0.000 description 2
- CLOQXZUODIZVTN-UHFFFAOYSA-N ClCC1=C2OCOCC2=CC(Cl)=C1Cl Chemical compound ClCC1=C2OCOCC2=CC(Cl)=C1Cl CLOQXZUODIZVTN-UHFFFAOYSA-N 0.000 description 2
- IWJQBYQAGGHNAB-VOTSOKGWSA-N ClCC1=CC=C(/C=C/C2=CC=CC=C2)C=C1 Chemical compound ClCC1=CC=C(/C=C/C2=CC=CC=C2)C=C1 IWJQBYQAGGHNAB-VOTSOKGWSA-N 0.000 description 2
- SVEGSFSFMLCNFF-UHFFFAOYSA-N ClCC1=CSC(C2=CC=CC=C2)=N1 Chemical compound ClCC1=CSC(C2=CC=CC=C2)=N1 SVEGSFSFMLCNFF-UHFFFAOYSA-N 0.000 description 2
- 241000709687 Coxsackievirus Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000709661 Enterovirus Species 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- MSPOYOJPUQITPI-UHFFFAOYSA-N FC(F)(F)C1=CC(C#CCBr)=CC(C(F)(F)F)=C1 Chemical compound FC(F)(F)C1=CC(C#CCBr)=CC(C(F)(F)F)=C1 MSPOYOJPUQITPI-UHFFFAOYSA-N 0.000 description 2
- OINTXXMBRBLMHH-UHFFFAOYSA-N FC(F)(F)C1=CC(CCl)=CC(C(F)(F)F)=C1 Chemical compound FC(F)(F)C1=CC(CCl)=CC(C(F)(F)F)=C1 OINTXXMBRBLMHH-UHFFFAOYSA-N 0.000 description 2
- IOVWIIJODVBCRC-UHFFFAOYSA-N FC(F)(F)C1=CC=C(C2=NC(CCl)=NO2)C=C1 Chemical compound FC(F)(F)C1=CC=C(C2=NC(CCl)=NO2)C=C1 IOVWIIJODVBCRC-UHFFFAOYSA-N 0.000 description 2
- PRPAYPBERKUDKO-UHFFFAOYSA-N FC(F)(F)C1=NC=C(CCl)C=C1 Chemical compound FC(F)(F)C1=NC=C(CCl)C=C1 PRPAYPBERKUDKO-UHFFFAOYSA-N 0.000 description 2
- FUFNNZQWXRPQCW-UHFFFAOYSA-N FC(F)=CCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound FC(F)=CCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 FUFNNZQWXRPQCW-UHFFFAOYSA-N 0.000 description 2
- ZFMYYHUUPPWSDG-UHFFFAOYSA-N FC(F)SC1=CC=CC(CBr)=C1 Chemical compound FC(F)SC1=CC=CC(CBr)=C1 ZFMYYHUUPPWSDG-UHFFFAOYSA-N 0.000 description 2
- MOVSRIIBGRAUAF-UHFFFAOYSA-N FC1=C(C(F)(F)F)C=CC(CBr)=C1 Chemical compound FC1=C(C(F)(F)F)C=CC(CBr)=C1 MOVSRIIBGRAUAF-UHFFFAOYSA-N 0.000 description 2
- OTDSWTVCGLGBIH-UHFFFAOYSA-N FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(C(F)(F)F)C=C4C(F)(F)F)=NO3)C=CC2=N1 Chemical compound FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(C(F)(F)F)C=C4C(F)(F)F)=NO3)C=CC2=N1 OTDSWTVCGLGBIH-UHFFFAOYSA-N 0.000 description 2
- SSRMDSFCUCPRCW-UHFFFAOYSA-N FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC=C(Br)C=C3)C=CC2=N1 Chemical compound FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC=C(Br)C=C3)C=CC2=N1 SSRMDSFCUCPRCW-UHFFFAOYSA-N 0.000 description 2
- KHQUGOVKDZDXGD-UHFFFAOYSA-N FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC=C(C(F)(F)F)C=C3)C=CC2=N1 Chemical compound FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC=C(C(F)(F)F)C=C3)C=CC2=N1 KHQUGOVKDZDXGD-UHFFFAOYSA-N 0.000 description 2
- BAFGYLPMFBZPCD-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(C6=CC=CC=C6)C=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(C6=CC=CC=C6)C=C5)=NO4)C=CC3=N2)=CC=C1 BAFGYLPMFBZPCD-UHFFFAOYSA-N 0.000 description 2
- XZAIHEVMKNNJTM-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5Cl)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5Cl)=NO4)C=CC3=N2)=CC=C1 XZAIHEVMKNNJTM-UHFFFAOYSA-N 0.000 description 2
- RXQFEEAKJNDQMD-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)S5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)S5)=NO4)C=CC3=N2)=CC=C1 RXQFEEAKJNDQMD-UHFFFAOYSA-N 0.000 description 2
- AUYSBBWJOJGLQY-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OC6=CC=CC=C6)C=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OC6=CC=CC=C6)C=C5)=NO4)C=CC3=N2)=CC=C1 AUYSBBWJOJGLQY-UHFFFAOYSA-N 0.000 description 2
- CKZATIXPQCBSJG-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OCC6=CC=CC=C6)C=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OCC6=CC=CC=C6)C=C5)=NO4)C=CC3=N2)=CC=C1 CKZATIXPQCBSJG-UHFFFAOYSA-N 0.000 description 2
- GEHPOVRWMNZPLK-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=CO5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=CO5)=NO4)C=CC3=N2)=CC=C1 GEHPOVRWMNZPLK-UHFFFAOYSA-N 0.000 description 2
- FRDZPCUNKFZZNG-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=CS5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=CS5)=NO4)C=CC3=N2)=CC=C1 FRDZPCUNKFZZNG-UHFFFAOYSA-N 0.000 description 2
- AKFBDXMOJCOMOS-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=NC(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=NC(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)=CC=C1 AKFBDXMOJCOMOS-UHFFFAOYSA-N 0.000 description 2
- VSKMLLGUWKLTQV-UHFFFAOYSA-N FC1=CC(Br)=CC(F)=C1CBr Chemical compound FC1=CC(Br)=CC(F)=C1CBr VSKMLLGUWKLTQV-UHFFFAOYSA-N 0.000 description 2
- ABFZQPOPAPTHLD-UHFFFAOYSA-N FC1=CC(C2=CC=CC=C2OC(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC(F)=C3F)=NC2=C1 Chemical compound FC1=CC(C2=CC=CC=C2OC(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC(F)=C3F)=NC2=C1 ABFZQPOPAPTHLD-UHFFFAOYSA-N 0.000 description 2
- OZYILDHPUXSPLR-UHFFFAOYSA-N FC1=CC(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)=CC=C1Cl Chemical compound FC1=CC(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)=CC=C1Cl OZYILDHPUXSPLR-UHFFFAOYSA-N 0.000 description 2
- QYIIHORUKKNIAS-UHFFFAOYSA-N FC1=CC(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1 Chemical compound FC1=CC(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1 QYIIHORUKKNIAS-UHFFFAOYSA-N 0.000 description 2
- PCXKGYZPQAOKTH-UHFFFAOYSA-N FC1=CC(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1C(F)(F)F Chemical compound FC1=CC(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1C(F)(F)F PCXKGYZPQAOKTH-UHFFFAOYSA-N 0.000 description 2
- HMIAXVWVTBIGON-UHFFFAOYSA-N FC1=CC(Cl)=C(CCl)C=C1 Chemical compound FC1=CC(Cl)=C(CCl)C=C1 HMIAXVWVTBIGON-UHFFFAOYSA-N 0.000 description 2
- XVSJPGQIIKNEMG-UHFFFAOYSA-N FC1=CC(Cl)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 Chemical compound FC1=CC(Cl)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 XVSJPGQIIKNEMG-UHFFFAOYSA-N 0.000 description 2
- DYWUXMJTFWCBFC-UHFFFAOYSA-N FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(F)=C1 Chemical compound FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(F)=C1 DYWUXMJTFWCBFC-UHFFFAOYSA-N 0.000 description 2
- BNQFGMXBYMXLSF-UHFFFAOYSA-N FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C(C(F)(F)F)=C1 Chemical compound FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C(C(F)(F)F)=C1 BNQFGMXBYMXLSF-UHFFFAOYSA-N 0.000 description 2
- UXBAAXCVJHQPPT-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6CCCCC6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6CCCCC6)C=C5)C=C4)C=CC3=N2)=C1F UXBAAXCVJHQPPT-UHFFFAOYSA-N 0.000 description 2
- FOTQXEAMRZKSPM-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCCCCC(F)=C(F)F)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCCCCC(F)=C(F)F)C=C5)C=C4)C=CC3=N2)=C1F FOTQXEAMRZKSPM-UHFFFAOYSA-N 0.000 description 2
- QZUXKOMJMVHDDB-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCCCN6C=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCCCN6C=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F QZUXKOMJMVHDDB-UHFFFAOYSA-N 0.000 description 2
- KUMGAVBEUOPWJV-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(Cl)C=C5Cl)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(Cl)C=C5Cl)C=C4)C=CC3=N2)=C1F KUMGAVBEUOPWJV-UHFFFAOYSA-N 0.000 description 2
- UCCFHPKKUZUGEI-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OC(F)(F)F)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OC(F)(F)F)C=C5)C=C4)C=CC3=N2)=C1F UCCFHPKKUZUGEI-UHFFFAOYSA-N 0.000 description 2
- PTGQKYIJVDMBAC-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCC6=CC=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCC6=CC=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F PTGQKYIJVDMBAC-UHFFFAOYSA-N 0.000 description 2
- HACASPUISDPNHN-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCC6CCC6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCC6CCC6)C=C5)C=C4)C=CC3=N2)=C1F HACASPUISDPNHN-UHFFFAOYSA-N 0.000 description 2
- DACDRBPSRISRQJ-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCCC(F)=C(F)F)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCCC(F)=C(F)F)C=C5)C=C4)C=CC3=N2)=C1F DACDRBPSRISRQJ-UHFFFAOYSA-N 0.000 description 2
- QUHVUMGDOCHNFL-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CSC(C5=CC=CS5)=N4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CSC(C5=CC=CS5)=N4)C=CC3=N2)=C1F QUHVUMGDOCHNFL-UHFFFAOYSA-N 0.000 description 2
- GJHNDHAVUGPVDN-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(Cl)C=C4Cl)=NO3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(Cl)C=C4Cl)=NO3)C=CC2=N1 GJHNDHAVUGPVDN-UHFFFAOYSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108010093096 Immobilized Enzymes Proteins 0.000 description 2
- 108010078049 Interferon alpha-2 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- SRJYJXSRETZVRF-UHFFFAOYSA-N N#CC1(C2=CC=C(C3=CC=C(CN4C=CC5=NC(C6=CC=CC(F)=C6F)=NC5=C4)C=C3)C=C2)CC1 Chemical compound N#CC1(C2=CC=C(C3=CC=C(CN4C=CC5=NC(C6=CC=CC(F)=C6F)=NC5=C4)C=C3)C=C2)CC1 SRJYJXSRETZVRF-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- JKIPCFHOIXCVCK-UHFFFAOYSA-N O=C(C1=CC=CC=C1)C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound O=C(C1=CC=CC=C1)C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 JKIPCFHOIXCVCK-UHFFFAOYSA-N 0.000 description 2
- LPCHVFXOYSINGG-UHFFFAOYSA-N O=C(C1=CC=CC=C1)C1=CC=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1 Chemical compound O=C(C1=CC=CC=C1)C1=CC=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1 LPCHVFXOYSINGG-UHFFFAOYSA-N 0.000 description 2
- FJAZVXUPZQSZKI-UHFFFAOYSA-N O=C(O)C1=C(C(=O)C2=CC=C(F)C=C2)C=CC=C1 Chemical compound O=C(O)C1=C(C(=O)C2=CC=C(F)C=C2)C=CC=C1 FJAZVXUPZQSZKI-UHFFFAOYSA-N 0.000 description 2
- GNWTWXOZRSBCOZ-UHFFFAOYSA-N O=C(O)C1=C(N2C=CC=C2)C=CC=C1 Chemical compound O=C(O)C1=C(N2C=CC=C2)C=CC=C1 GNWTWXOZRSBCOZ-UHFFFAOYSA-N 0.000 description 2
- VKVLLEXFHZRIFS-UHFFFAOYSA-N O=C(O)C1=CC(C2=C(Cl)C=CC=C2)=NO1 Chemical compound O=C(O)C1=CC(C2=C(Cl)C=CC=C2)=NO1 VKVLLEXFHZRIFS-UHFFFAOYSA-N 0.000 description 2
- ONNFNEFYXIPHCA-UHFFFAOYSA-N O=C(O)C1=CC2=C(C=CC(Br)=C2)S1 Chemical compound O=C(O)C1=CC2=C(C=CC(Br)=C2)S1 ONNFNEFYXIPHCA-UHFFFAOYSA-N 0.000 description 2
- OZZMWXQJCJUCEJ-UHFFFAOYSA-N O=C(O)C1=CC=C2C=NC=CC2=N1 Chemical compound O=C(O)C1=CC=C2C=NC=CC2=N1 OZZMWXQJCJUCEJ-UHFFFAOYSA-N 0.000 description 2
- XIKZTCXYFVSBJT-UHFFFAOYSA-N O=C(O)C1=NNC(N2C=CC=C2)=N1 Chemical compound O=C(O)C1=NNC(N2C=CC=C2)=N1 XIKZTCXYFVSBJT-UHFFFAOYSA-N 0.000 description 2
- UJQIDMWXPJOIFS-UHFFFAOYSA-N O=S(=O)(C1=CC=C(CBr)C=C1)N1CCOCC1 Chemical compound O=S(=O)(C1=CC=C(CBr)C=C1)N1CCOCC1 UJQIDMWXPJOIFS-UHFFFAOYSA-N 0.000 description 2
- SYYPBRKVYRCLJS-UHFFFAOYSA-N O=S(=O)(C1=CC=CC=C1)N1C2=CC=CC=C2/C=C\1CBr Chemical compound O=S(=O)(C1=CC=CC=C1)N1C2=CC=CC=C2/C=C\1CBr SYYPBRKVYRCLJS-UHFFFAOYSA-N 0.000 description 2
- SYNKYJKCQBVGSL-UHFFFAOYSA-N O=S(=O)(CC1=C(CBr)C=CC=C1)C1=CC=CC=C1 Chemical compound O=S(=O)(CC1=C(CBr)C=CC=C1)C1=CC=CC=C1 SYNKYJKCQBVGSL-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- TZZCVTAPFGPKQK-UHFFFAOYSA-N [H]C1=C(F)C(C2=NC3=CN(CC4=CC(C5=C(F)C=C(F)C=C5)=CN=C4)C=CC3=N2)=CC=C1 Chemical compound [H]C1=C(F)C(C2=NC3=CN(CC4=CC(C5=C(F)C=C(F)C=C5)=CN=C4)C=CC3=N2)=CC=C1 TZZCVTAPFGPKQK-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- OYTKINVCDFNREN-UHFFFAOYSA-N amifampridine Chemical compound NC1=CC=NC=C1N OYTKINVCDFNREN-UHFFFAOYSA-N 0.000 description 2
- 229960004012 amifampridine Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 229960003121 arginine Drugs 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 150000001556 benzimidazoles Chemical class 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- VZSXFJPZOCRDPW-UHFFFAOYSA-N carbanide;trioxorhenium Chemical compound [CH3-].O=[Re](=O)=O VZSXFJPZOCRDPW-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 2
- 150000005829 chemical entities Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 125000004803 chlorobenzyl group Chemical group 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229910052681 coesite Inorganic materials 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000012084 conversion product Substances 0.000 description 2
- 229910052906 cristobalite Inorganic materials 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 150000002191 fatty alcohols Chemical class 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 125000004175 fluorobenzyl group Chemical group 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 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
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000003883 ointment base Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 2
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
- 125000002755 pyrazolinyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 239000000344 soap Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229940054269 sodium pyruvate Drugs 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 229910052682 stishovite Inorganic materials 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 229910052905 tridymite Inorganic materials 0.000 description 2
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 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
- SOCAXRLFGRNEPK-IFZYUDKTSA-N (1r,3s,5r)-2-n-[1-carbamoyl-5-(cyanomethoxy)indol-3-yl]-3-n-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide Chemical compound O=C([C@@H]1C[C@H]2C[C@H]2N1C(=O)NC1=CN(C2=CC=C(OCC#N)C=C21)C(=O)N)NCC1=CC=CC(Cl)=C1F SOCAXRLFGRNEPK-IFZYUDKTSA-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
- QQLRSCZSKQTFGY-UHFFFAOYSA-N (2,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C=C1F QQLRSCZSKQTFGY-UHFFFAOYSA-N 0.000 description 1
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 1
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- KOFNQIAWWVBBJZ-UHFFFAOYSA-N (4-fluoro-2-hydroxyphenyl)boronic acid Chemical class OB(O)C1=CC=C(F)C=C1O KOFNQIAWWVBBJZ-UHFFFAOYSA-N 0.000 description 1
- OYIYNIONWDBJIF-UHFFFAOYSA-N (4-hydroxy-2-methylphenyl)boronic acid Chemical compound CC1=CC(O)=CC=C1B(O)O OYIYNIONWDBJIF-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
- 150000005071 1,2,4-oxadiazoles Chemical class 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- MJUVRTYWUMPBTR-MRXNPFEDSA-N 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-n-[1-[(2r)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide Chemical compound FC=1C=C2N(C[C@@H](O)CO)C(C(C)(CO)C)=CC2=CC=1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 MJUVRTYWUMPBTR-MRXNPFEDSA-N 0.000 description 1
- BQTRMYJYYNQQGK-UHFFFAOYSA-N 1-(bromomethyl)-4-iodobenzene Chemical compound BrCC1=CC=C(I)C=C1 BQTRMYJYYNQQGK-UHFFFAOYSA-N 0.000 description 1
- XPGHWBDZNQUUQD-UHFFFAOYSA-N 1-(chloromethyl)-2,4-difluorobenzene Chemical group FC1=CC=C(CCl)C(F)=C1 XPGHWBDZNQUUQD-UHFFFAOYSA-N 0.000 description 1
- LBMKFQMJURUPKC-UHFFFAOYSA-N 1-(chloromethyl)-4-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(CCl)C=C1 LBMKFQMJURUPKC-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- LGEZTMRIZWCDLW-UHFFFAOYSA-N 14-methylpentadecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC(C)C LGEZTMRIZWCDLW-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- ARUHZHIPYAOZDW-UHFFFAOYSA-N 1h-indol-3-yl-[3-(2-methylimidazo[4,5-c]pyridine-5-carbonyl)phenyl]methanone Chemical compound C1=CC=C2C(C(=O)C=3C=CC=C(C=3)C(=O)N3C=CC4=NC(=NC4=C3)C)=CNC2=C1 ARUHZHIPYAOZDW-UHFFFAOYSA-N 0.000 description 1
- WDBAXYQUOZDFOJ-UHFFFAOYSA-N 2,3-difluorobenzaldehyde Chemical compound FC1=CC=CC(C=O)=C1F WDBAXYQUOZDFOJ-UHFFFAOYSA-N 0.000 description 1
- KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical compound C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 description 1
- JCRNSBKSAQHNIN-UHFFFAOYSA-N 2,4-dibutylnaphthalene-1-sulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(CCCC)=CC(CCCC)=C21 JCRNSBKSAQHNIN-UHFFFAOYSA-N 0.000 description 1
- FFMBYMANYCDCMK-UHFFFAOYSA-N 2,5-dihydro-1h-imidazole Chemical compound C1NCN=C1 FFMBYMANYCDCMK-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- JDSQBDGCMUXRBM-UHFFFAOYSA-N 2-[2-(2-butoxypropoxy)propoxy]propan-1-ol Chemical group CCCCOC(C)COC(C)COC(C)CO JDSQBDGCMUXRBM-UHFFFAOYSA-N 0.000 description 1
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 1
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
- WBIQQQGBSDOWNP-UHFFFAOYSA-N 2-dodecylbenzenesulfonic acid Chemical class CCCCCCCCCCCCC1=CC=CC=C1S(O)(=O)=O WBIQQQGBSDOWNP-UHFFFAOYSA-N 0.000 description 1
- SFAAOBGYWOUHLU-UHFFFAOYSA-N 2-ethylhexyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(CC)CCCC SFAAOBGYWOUHLU-UHFFFAOYSA-N 0.000 description 1
- UNWQNFJBBWXFBG-UHFFFAOYSA-N 2-fluoro-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(F)=C1 UNWQNFJBBWXFBG-UHFFFAOYSA-N 0.000 description 1
- NSTREUWFTAOOKS-UHFFFAOYSA-N 2-fluorobenzoic acid Chemical group OC(=O)C1=CC=CC=C1F NSTREUWFTAOOKS-UHFFFAOYSA-N 0.000 description 1
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 description 1
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 description 1
- 125000004922 2-methyl-3-pentyl group Chemical group CC(C)C(CC)* 0.000 description 1
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- KRTGJZMJJVEKRX-UHFFFAOYSA-N 2-phenylethan-1-yl Chemical group [CH2]CC1=CC=CC=C1 KRTGJZMJJVEKRX-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([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
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- AJRGDQWFWJDYDP-UHFFFAOYSA-N 3-chloro-1,2-oxazole Chemical class ClC=1C=CON=1 AJRGDQWFWJDYDP-UHFFFAOYSA-N 0.000 description 1
- RJXLUGSJEMSDPK-UHFFFAOYSA-N 3-methyl-1-phenylpyrazole Chemical compound N1=C(C)C=CN1C1=CC=CC=C1 RJXLUGSJEMSDPK-UHFFFAOYSA-N 0.000 description 1
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 1
- 125000004919 3-methyl-2-pentyl group Chemical group CC(C(C)*)CC 0.000 description 1
- 125000004921 3-methyl-3-pentyl group Chemical group CC(CC)(CC)* 0.000 description 1
- SSOURMYKACOBIV-UHFFFAOYSA-N 3-methyl-4-nitro-1-oxidopyridin-1-ium Chemical compound CC1=C[N+]([O-])=CC=C1[N+]([O-])=O SSOURMYKACOBIV-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
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 1
- MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical compound C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 description 1
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
- VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- APKUBUFFJNTCQM-UHFFFAOYSA-N 4-[5-(2-piperidin-1-ylethyl)-1,3-dihydroimidazo[4,5-c]pyridin-5-ium-2-ylidene]cyclohexa-2,5-dien-1-one;bromide Chemical compound [Br-].C1=CC(O)=CC=C1C1=NC2=C[N+](CCN3CCCCC3)=CC=C2N1 APKUBUFFJNTCQM-UHFFFAOYSA-N 0.000 description 1
- DFMWQHPDQOIQOF-UHFFFAOYSA-N 4-[5-[2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]ethyl]imidazo[4,5-c]pyridin-2-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=NC2=CN(CCN3CCN(CC3)C(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)C=CC2=N1 DFMWQHPDQOIQOF-UHFFFAOYSA-N 0.000 description 1
- OZWGZXRBGACUJX-UHFFFAOYSA-N 4-[5-[3-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]propyl]imidazo[4,5-c]pyridin-2-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=NC2=CN(CCCN3CCN(CC3)C(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)C=CC2=N1 OZWGZXRBGACUJX-UHFFFAOYSA-N 0.000 description 1
- XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
- CKTSBUTUHBMZGZ-CHKWXVPMSA-N 4-amino-1-[(2s,4r,5s)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 CKTSBUTUHBMZGZ-CHKWXVPMSA-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
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- XHWMNHADTZZHGI-UHFFFAOYSA-N 4-butoxybenzaldehyde Chemical compound CCCCOC1=CC=C(C=O)C=C1 XHWMNHADTZZHGI-UHFFFAOYSA-N 0.000 description 1
- UVGYSEIWAOOIJR-UHFFFAOYSA-N 4-chloro-2-fluorobenzaldehyde Chemical compound FC1=CC(Cl)=CC=C1C=O UVGYSEIWAOOIJR-UHFFFAOYSA-N 0.000 description 1
- UKIZCTHOMJXNIX-UHFFFAOYSA-N 4-chloro-3-nitro-1h-pyridin-2-one Chemical compound [O-][N+](=O)C1=C(Cl)C=CNC1=O UKIZCTHOMJXNIX-UHFFFAOYSA-N 0.000 description 1
- GJNGXPDXRVXSEH-UHFFFAOYSA-N 4-chlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1 GJNGXPDXRVXSEH-UHFFFAOYSA-N 0.000 description 1
- JRHHJNMASOIRDS-UHFFFAOYSA-N 4-ethoxybenzaldehyde Chemical compound CCOC1=CC=C(C=O)C=C1 JRHHJNMASOIRDS-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- XDJAAZYHCCRJOK-UHFFFAOYSA-N 4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C=C1 XDJAAZYHCCRJOK-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 1
- VCZNNAKNUVJVGX-UHFFFAOYSA-N 4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C=C1 VCZNNAKNUVJVGX-UHFFFAOYSA-N 0.000 description 1
- QRVYABWJVXXOTN-UHFFFAOYSA-N 4-methylsulfanylbenzaldehyde Chemical compound CSC1=CC=C(C=O)C=C1 QRVYABWJVXXOTN-UHFFFAOYSA-N 0.000 description 1
- IGFHQQFPSIBGKE-UHFFFAOYSA-N 4-nonylphenol Chemical compound CCCCCCCCCC1=CC=C(O)C=C1 IGFHQQFPSIBGKE-UHFFFAOYSA-N 0.000 description 1
- QWLHJVDRPZNVBS-UHFFFAOYSA-N 4-phenoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OC1=CC=CC=C1 QWLHJVDRPZNVBS-UHFFFAOYSA-N 0.000 description 1
- ISDBWOPVZKNQDW-UHFFFAOYSA-N 4-phenylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=C1 ISDBWOPVZKNQDW-UHFFFAOYSA-N 0.000 description 1
- ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 1
- TYNJQOJWNMZQFZ-UHFFFAOYSA-N 4-prop-2-enoxybenzaldehyde Chemical compound C=CCOC1=CC=C(C=O)C=C1 TYNJQOJWNMZQFZ-UHFFFAOYSA-N 0.000 description 1
- WDANSDASCKBVKH-UHFFFAOYSA-N 4-propan-2-yloxybenzaldehyde Chemical compound CC(C)OC1=CC=C(C=O)C=C1 WDANSDASCKBVKH-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
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
- YNYBXNJENJAYMC-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-(piperidin-1-ylmethyl)imidazo[4,5-c]pyridine Chemical compound C1=CC(Cl)=CC=C1CN1C=C2N=C(CN3CCCCC3)N=C2C=C1 YNYBXNJENJAYMC-UHFFFAOYSA-N 0.000 description 1
- WPEXHEMCFFLDLL-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-[(4-methylpiperazin-1-yl)methyl]imidazo[4,5-c]pyridine Chemical compound C1CN(C)CCN1CC1=NC2=CN(CC=3C=CC(Cl)=CC=3)C=CC2=N1 WPEXHEMCFFLDLL-UHFFFAOYSA-N 0.000 description 1
- FXAHKNLGANQPFC-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-n-methylimidazo[4,5-c]pyridin-2-amine Chemical compound C1=C2N=C(NC)N=C2C=CN1CC1=CC=C(F)C=C1 FXAHKNLGANQPFC-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- ORFVUAUAWHSESX-UHFFFAOYSA-N 5-[2-(4-phenoxyphenoxy)ethyl]imidazo[4,5-c]pyridine Chemical compound C1=CC2=NC=NC2=CN1CCOC(C=C1)=CC=C1OC1=CC=CC=C1 ORFVUAUAWHSESX-UHFFFAOYSA-N 0.000 description 1
- DDIPXECLLKIFRS-UHFFFAOYSA-N 5-[2-(4-phenylmethoxyphenoxy)ethyl]imidazo[4,5-c]pyridine Chemical compound C1=CC2=NC=NC2=CN1CCOC(C=C1)=CC=C1OCC1=CC=CC=C1 DDIPXECLLKIFRS-UHFFFAOYSA-N 0.000 description 1
- DWQLZPQNFNDXLZ-UHFFFAOYSA-N 5-[2-(4-phenylphenoxy)ethyl]imidazo[4,5-c]pyridine Chemical compound C1=CC2=NC=NC2=CN1CCOC(C=C1)=CC=C1C1=CC=CC=C1 DWQLZPQNFNDXLZ-UHFFFAOYSA-N 0.000 description 1
- MWYPGWRULWUANO-UHFFFAOYSA-N 5-[2-[4-(4-fluorophenoxy)phenoxy]ethyl]imidazo[4,5-c]pyridine Chemical compound C1=CC(F)=CC=C1OC(C=C1)=CC=C1OCCN1C=C2N=CN=C2C=C1 MWYPGWRULWUANO-UHFFFAOYSA-N 0.000 description 1
- UOLHABQKLSNTLW-UHFFFAOYSA-N 5-[3-(4-benzylphenoxy)propyl]imidazo[4,5-c]pyridine Chemical compound C1=CC2=NC=NC2=CN1CCCOC(C=C1)=CC=C1CC1=CC=CC=C1 UOLHABQKLSNTLW-UHFFFAOYSA-N 0.000 description 1
- ATUUQNUBTFHLSZ-UHFFFAOYSA-N 5-[3-(4-phenoxyphenoxy)propyl]imidazo[4,5-c]pyridine Chemical compound C1=CC2=NC=NC2=CN1CCCOC(C=C1)=CC=C1OC1=CC=CC=C1 ATUUQNUBTFHLSZ-UHFFFAOYSA-N 0.000 description 1
- JCRXLECODBLBHU-UHFFFAOYSA-N 5-benzyl-2-phenylimidazo[4,5-c]pyridine Chemical compound C1=CC2=NC(C=3C=CC=CC=3)=NC2=CN1CC1=CC=CC=C1 JCRXLECODBLBHU-UHFFFAOYSA-N 0.000 description 1
- ATXLHMZMMKUPNH-UHFFFAOYSA-N 5-benzylimidazo[4,5-c]pyridine Chemical compound C1=CC2=NC=NC2=CN1CC1=CC=CC=C1 ATXLHMZMMKUPNH-UHFFFAOYSA-N 0.000 description 1
- GFBVUFQNHLUCPX-UHFFFAOYSA-N 5-bromothiophene-2-carbaldehyde Chemical compound BrC1=CC=C(C=O)S1 GFBVUFQNHLUCPX-UHFFFAOYSA-N 0.000 description 1
- VWYFITBWBRVBSW-UHFFFAOYSA-N 5-chlorothiophene-2-carbaldehyde Chemical compound ClC1=CC=C(C=O)S1 VWYFITBWBRVBSW-UHFFFAOYSA-N 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- OYGKFYFRSKLQJM-UHFFFAOYSA-N 5-methylpyridine-3,4-diamine Chemical compound CC1=CN=CC(N)=C1N OYGKFYFRSKLQJM-UHFFFAOYSA-N 0.000 description 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
- FZEVMBJWXHDLDB-UHFFFAOYSA-N 5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical compound S1CC=CN2C(=O)CC21 FZEVMBJWXHDLDB-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- AELUJNUEAZSWSX-UHFFFAOYSA-N 6-(imidazo[4,5-c]pyridin-5-ylmethyl)-n-phenyl-n-propan-2-ylpyridine-3-carboxamide Chemical compound C=1C=C(CN2C=C3N=CN=C3C=C2)N=CC=1C(=O)N(C(C)C)C1=CC=CC=C1 AELUJNUEAZSWSX-UHFFFAOYSA-N 0.000 description 1
- WQZIDRAQTRIQDX-UHFFFAOYSA-N 6-carboxy-x-rhodamine Chemical compound OC(=O)C1=CC=C(C([O-])=O)C=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 WQZIDRAQTRIQDX-UHFFFAOYSA-N 0.000 description 1
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 1
- UNQYAAAWKOOBFQ-UHFFFAOYSA-N 7-[(4-chlorophenyl)methyl]-8-[4-chloro-3-(trifluoromethoxy)phenoxy]-1-(3-hydroxypropyl)-3-methylpurine-2,6-dione Chemical compound C=1C=C(Cl)C=CC=1CN1C=2C(=O)N(CCCO)C(=O)N(C)C=2N=C1OC1=CC=C(Cl)C(OC(F)(F)F)=C1 UNQYAAAWKOOBFQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 208000006740 Aseptic Meningitis Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- ZPWPMAAPQZXPDD-UHFFFAOYSA-N BrCC1=C(Br)SC=C1 Chemical compound BrCC1=C(Br)SC=C1 ZPWPMAAPQZXPDD-UHFFFAOYSA-N 0.000 description 1
- YQRIQBOWLXRKKG-UHFFFAOYSA-N BrCC1=C(OC2=CC=CC=C2)C=CC=C1 Chemical compound BrCC1=C(OC2=CC=CC=C2)C=CC=C1 YQRIQBOWLXRKKG-UHFFFAOYSA-N 0.000 description 1
- PWTFRUXTAFBWBW-UHFFFAOYSA-N BrCC1=CC(Br)=CC(Br)=C1 Chemical compound BrCC1=CC(Br)=CC(Br)=C1 PWTFRUXTAFBWBW-UHFFFAOYSA-N 0.000 description 1
- YMWNCAQFJODGRZ-UHFFFAOYSA-N BrCC1=CC(N2C=CC=C2)=CC=C1 Chemical compound BrCC1=CC(N2C=CC=C2)=CC=C1 YMWNCAQFJODGRZ-UHFFFAOYSA-N 0.000 description 1
- DGHQOPZIGDRUIT-UHFFFAOYSA-N BrCC1=CC=C(C2=CSN=N2)C=C1 Chemical compound BrCC1=CC=C(C2=CSN=N2)C=C1 DGHQOPZIGDRUIT-UHFFFAOYSA-N 0.000 description 1
- PHNRBSHOFSWNII-UHFFFAOYSA-N BrCC1=CC=C(N2C=CC=N2)C=C1 Chemical compound BrCC1=CC=C(N2C=CC=N2)C=C1 PHNRBSHOFSWNII-UHFFFAOYSA-N 0.000 description 1
- NOUAEJFAVOHNSY-UHFFFAOYSA-N BrCC1=CC=C(N2C=NC=N2)C=C1 Chemical compound BrCC1=CC=C(N2C=NC=N2)C=C1 NOUAEJFAVOHNSY-UHFFFAOYSA-N 0.000 description 1
- ITJWNXBZSFIJTP-UHFFFAOYSA-N BrCC1=CC=CC(OCC2=CC=CC=C2)=C1 Chemical compound BrCC1=CC=CC(OCC2=CC=CC=C2)=C1 ITJWNXBZSFIJTP-UHFFFAOYSA-N 0.000 description 1
- IAAUGSYGHOFWEW-UHFFFAOYSA-N BrCC1=CC=CC2=CC=CN=C21 Chemical compound BrCC1=CC=CC2=CC=CN=C21 IAAUGSYGHOFWEW-UHFFFAOYSA-N 0.000 description 1
- SEXZHJJUKFXNDY-UHFFFAOYSA-N BrCC1=CC=CC=C1C1=CC=CC=C1 Chemical compound BrCC1=CC=CC=C1C1=CC=CC=C1 SEXZHJJUKFXNDY-UHFFFAOYSA-N 0.000 description 1
- KBWHYRUAHXHHFO-UHFFFAOYSA-N BrCC1=CSC=C1 Chemical compound BrCC1=CSC=C1 KBWHYRUAHXHHFO-UHFFFAOYSA-N 0.000 description 1
- MJEXGQXHCPLOGP-UHFFFAOYSA-N BrCC1=NN(C2=CC=CC=C2)C=C1.CC1=NN(C2=CC=CC=C2)C=C1.FC1=CC=CC(C2=NC3=CN(CC4=NN(C5=CC=CC=C5)C=C4)C=CC3=N2)=C1F Chemical compound BrCC1=NN(C2=CC=CC=C2)C=C1.CC1=NN(C2=CC=CC=C2)C=C1.FC1=CC=CC(C2=NC3=CN(CC4=NN(C5=CC=CC=C5)C=C4)C=CC3=N2)=C1F MJEXGQXHCPLOGP-UHFFFAOYSA-N 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
- 239000004358 Butane-1, 3-diol Substances 0.000 description 1
- PZFBULOUMNPBFA-UHFFFAOYSA-N C#CC(C)Cl Chemical compound C#CC(C)Cl PZFBULOUMNPBFA-UHFFFAOYSA-N 0.000 description 1
- SJXHLZCPDZPBPW-UHFFFAOYSA-N C#CC1=CC=C(C(=O)O)C=C1 Chemical compound C#CC1=CC=C(C(=O)O)C=C1 SJXHLZCPDZPBPW-UHFFFAOYSA-N 0.000 description 1
- ZXHHWYVTDCBPCX-UNSORALTSA-N C#CCCl.ClCCl.FC(F)(F)C1=CC(C(F)(F)F)=C(C2=NOC(CCl)=C2)C=C1.FC1=CC=CC=C1C1=NC2=CC=N(CC3=CC(C4=C(C(F)(F)F)C=C(C(F)(F)F)C=C4)=NO3)C=C2N1.FC1=CC=CC=C1C1=NC2=CC=NC=C2N1.O/N=C/C1=C(C(F)(F)F)C=C(C(F)(F)F)C=C1.O=CC1=C(C(F)(F)F)C=C(C(F)(F)F)C=C1.[Na]OCl Chemical compound C#CCCl.ClCCl.FC(F)(F)C1=CC(C(F)(F)F)=C(C2=NOC(CCl)=C2)C=C1.FC1=CC=CC=C1C1=NC2=CC=N(CC3=CC(C4=C(C(F)(F)F)C=C(C(F)(F)F)C=C4)=NO3)C=C2N1.FC1=CC=CC=C1C1=NC2=CC=NC=C2N1.O/N=C/C1=C(C(F)(F)F)C=C(C(F)(F)F)C=C1.O=CC1=C(C(F)(F)F)C=C(C(F)(F)F)C=C1.[Na]OCl ZXHHWYVTDCBPCX-UNSORALTSA-N 0.000 description 1
- CFOGJRDJRSWSRX-NZYHXYHESA-N C#CCCl.ClCCl.O/N=C/C1=CC=C(C(F)(F)F)C=C1F.[Na]OCl Chemical compound C#CCCl.ClCCl.O/N=C/C1=CC=C(C(F)(F)F)C=C1F.[Na]OCl CFOGJRDJRSWSRX-NZYHXYHESA-N 0.000 description 1
- MMGFPARBVIZOQF-NSCUHMNNSA-N C/C=C/COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound C/C=C/COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 MMGFPARBVIZOQF-NSCUHMNNSA-N 0.000 description 1
- GUIWDZOWGZKKAX-ONEGZZNKSA-N C/C=C/COC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound C/C=C/COC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 GUIWDZOWGZKKAX-ONEGZZNKSA-N 0.000 description 1
- JIMGGVCCBAJLIE-NSCUHMNNSA-N C/C=C/COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound C/C=C/COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 JIMGGVCCBAJLIE-NSCUHMNNSA-N 0.000 description 1
- GGJNWANUEZOJBN-UHFFFAOYSA-N C1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CSC=C5)=NC4=C3)=C2)C=C1 Chemical compound C1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CSC=C5)=NC4=C3)=C2)C=C1 GGJNWANUEZOJBN-UHFFFAOYSA-N 0.000 description 1
- AKZUOHAAAIKTPZ-UHFFFAOYSA-N C=CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound C=CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 AKZUOHAAAIKTPZ-UHFFFAOYSA-N 0.000 description 1
- ZRZHXNCATOYMJH-UHFFFAOYSA-N C=CC1=CC=C(CCl)C=C1 Chemical compound C=CC1=CC=C(CCl)C=C1 ZRZHXNCATOYMJH-UHFFFAOYSA-N 0.000 description 1
- ZPURSILASUFSKK-UHFFFAOYSA-N C=CCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound C=CCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 ZPURSILASUFSKK-UHFFFAOYSA-N 0.000 description 1
- HYGUMNHBCJPEKX-UHFFFAOYSA-N C=CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound C=CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 HYGUMNHBCJPEKX-UHFFFAOYSA-N 0.000 description 1
- ZBHLQWDYSNNEJX-UHFFFAOYSA-N C=CCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound C=CCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 ZBHLQWDYSNNEJX-UHFFFAOYSA-N 0.000 description 1
- QTWJSZQXTBDHJQ-UHFFFAOYSA-N C=CCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound C=CCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 QTWJSZQXTBDHJQ-UHFFFAOYSA-N 0.000 description 1
- LNNXOEHOXSYWLD-UHFFFAOYSA-N CC#CCBr Chemical compound CC#CCBr LNNXOEHOXSYWLD-UHFFFAOYSA-N 0.000 description 1
- WCYYQAIRDORVQU-UHFFFAOYSA-N CC#CCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound CC#CCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 WCYYQAIRDORVQU-UHFFFAOYSA-N 0.000 description 1
- YDOXGIMOIUYGJN-UHFFFAOYSA-N CC#CCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC#CCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 YDOXGIMOIUYGJN-UHFFFAOYSA-N 0.000 description 1
- CRIFYUMKBZEGDM-UHFFFAOYSA-N CC#CCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC#CCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 CRIFYUMKBZEGDM-UHFFFAOYSA-N 0.000 description 1
- QBHDSQZASIBAAI-UHFFFAOYSA-N CC(=O)C1=CC=C(C(=O)O)C=C1 Chemical compound CC(=O)C1=CC=C(C(=O)O)C=C1 QBHDSQZASIBAAI-UHFFFAOYSA-N 0.000 description 1
- FHWJHNTUHRNWGM-UHFFFAOYSA-N CC(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 FHWJHNTUHRNWGM-UHFFFAOYSA-N 0.000 description 1
- MZJZFHURQBUTTC-UHFFFAOYSA-N CC(=O)C1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound CC(=O)C1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 MZJZFHURQBUTTC-UHFFFAOYSA-N 0.000 description 1
- YLBVDIZZHXKFOR-UHFFFAOYSA-N CC(=O)CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(=O)CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 YLBVDIZZHXKFOR-UHFFFAOYSA-N 0.000 description 1
- YCCYANYOQAKHKF-UHFFFAOYSA-N CC(=O)OCCCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(=O)OCCCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 YCCYANYOQAKHKF-UHFFFAOYSA-N 0.000 description 1
- SHPWHVKVJCGWOG-UHFFFAOYSA-N CC(=O)OCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(=O)OCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 SHPWHVKVJCGWOG-UHFFFAOYSA-N 0.000 description 1
- JTIUBRXMILRHJE-UHFFFAOYSA-N CC(=O)OCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(=O)OCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 JTIUBRXMILRHJE-UHFFFAOYSA-N 0.000 description 1
- AJBWDFPJLDDEPQ-UHFFFAOYSA-N CC(Br)C1=CC=CC(C(F)(F)F)=C1 Chemical compound CC(Br)C1=CC=CC(C(F)(F)F)=C1 AJBWDFPJLDDEPQ-UHFFFAOYSA-N 0.000 description 1
- PEPKDJZVABBZDR-UHFFFAOYSA-N CC(C)(C)C(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)(C)C(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 PEPKDJZVABBZDR-UHFFFAOYSA-N 0.000 description 1
- SNRYBGHMHAJTTM-UHFFFAOYSA-N CC(C)(C)C1=CC(CBr)=CC(C(C)(C)C)=C1 Chemical compound CC(C)(C)C1=CC(CBr)=CC(C(C)(C)C)=C1 SNRYBGHMHAJTTM-UHFFFAOYSA-N 0.000 description 1
- KDVYCTOWXSLNNI-UHFFFAOYSA-N CC(C)(C)C1=CC=C(C(=O)O)C=C1 Chemical compound CC(C)(C)C1=CC=C(C(=O)O)C=C1 KDVYCTOWXSLNNI-UHFFFAOYSA-N 0.000 description 1
- FIESWYONJRGQDX-UHFFFAOYSA-N CC(C)(C)C1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=N2)C=C1 Chemical compound CC(C)(C)C1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=N2)C=C1 FIESWYONJRGQDX-UHFFFAOYSA-N 0.000 description 1
- XPWNBLMOSGGKJD-UHFFFAOYSA-N CC(C)(C)C1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)=N2)C=C1 Chemical compound CC(C)(C)C1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)=N2)C=C1 XPWNBLMOSGGKJD-UHFFFAOYSA-N 0.000 description 1
- YLVNKNGVHYIBFD-UHFFFAOYSA-N CC(C)(C)C1=CC=C(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)C=C1 Chemical compound CC(C)(C)C1=CC=C(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)C=C1 YLVNKNGVHYIBFD-UHFFFAOYSA-N 0.000 description 1
- CLBWDPLOQALFTP-UHFFFAOYSA-N CC(C)(C)OC(=O)COC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound CC(C)(C)OC(=O)COC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 CLBWDPLOQALFTP-UHFFFAOYSA-N 0.000 description 1
- QIOBYZLLBDXGAF-UHFFFAOYSA-N CC(C)(C)OC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)(C)OC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 QIOBYZLLBDXGAF-UHFFFAOYSA-N 0.000 description 1
- RYWJRIPAHRYYHA-UHFFFAOYSA-N CC(C)(C)OC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1F Chemical compound CC(C)(C)OC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1F RYWJRIPAHRYYHA-UHFFFAOYSA-N 0.000 description 1
- QWDDDGWIYOGITJ-UHFFFAOYSA-N CC(C)=CCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)=CCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 QWDDDGWIYOGITJ-UHFFFAOYSA-N 0.000 description 1
- ISWIRIDNAUABAR-UHFFFAOYSA-N CC(C)=CCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)=CCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 ISWIRIDNAUABAR-UHFFFAOYSA-N 0.000 description 1
- RGIDYKAVMYLDMF-UHFFFAOYSA-N CC(C)=CCCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)=CCCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 RGIDYKAVMYLDMF-UHFFFAOYSA-N 0.000 description 1
- MYLMEPOMMJENSB-UHFFFAOYSA-N CC(C)=CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)=CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 MYLMEPOMMJENSB-UHFFFAOYSA-N 0.000 description 1
- XIVNRYXNKFDSQC-UHFFFAOYSA-N CC(C)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 XIVNRYXNKFDSQC-UHFFFAOYSA-N 0.000 description 1
- GJVNZNVVLVNVLN-UHFFFAOYSA-N CC(C)C1=CC=C(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)C=C1 Chemical compound CC(C)C1=CC=C(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)C=C1 GJVNZNVVLVNVLN-UHFFFAOYSA-N 0.000 description 1
- NSKLNRWWULBAJO-UHFFFAOYSA-N CC(C)C1=CC=C(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)C=C1 Chemical compound CC(C)C1=CC=C(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)C=C1 NSKLNRWWULBAJO-UHFFFAOYSA-N 0.000 description 1
- UHUUSOAQVMKRTE-UHFFFAOYSA-N CC(C)CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 UHUUSOAQVMKRTE-UHFFFAOYSA-N 0.000 description 1
- GDMAURWEYVAKDF-UHFFFAOYSA-N CC(C)CCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound CC(C)CCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 GDMAURWEYVAKDF-UHFFFAOYSA-N 0.000 description 1
- XOCUTBLJCXQGNX-UHFFFAOYSA-N CC(C)CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)CCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 XOCUTBLJCXQGNX-UHFFFAOYSA-N 0.000 description 1
- XXMBSGLJJKGSQG-UHFFFAOYSA-N CC(C)COC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound CC(C)COC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 XXMBSGLJJKGSQG-UHFFFAOYSA-N 0.000 description 1
- UXMKJFWEXOTULL-UHFFFAOYSA-N CC(C)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 UXMKJFWEXOTULL-UHFFFAOYSA-N 0.000 description 1
- LSWFMLPXMVJFMF-UHFFFAOYSA-N CC(C)COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 LSWFMLPXMVJFMF-UHFFFAOYSA-N 0.000 description 1
- VJJSFKFZACRBKS-UHFFFAOYSA-N CC(C)OC(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(C)OC(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 VJJSFKFZACRBKS-UHFFFAOYSA-N 0.000 description 1
- GYXWNSDLDXGMGU-UHFFFAOYSA-N CC(Cl)CN(C)C.Cl Chemical compound CC(Cl)CN(C)C.Cl GYXWNSDLDXGMGU-UHFFFAOYSA-N 0.000 description 1
- JTANKYNILVCLDI-UHFFFAOYSA-N CC(O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC(O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 JTANKYNILVCLDI-UHFFFAOYSA-N 0.000 description 1
- YRSSLQXZDTXEBD-UHFFFAOYSA-N CC1(C)CCC(C)(C)C2=C1C=CC(CBr)=C2 Chemical compound CC1(C)CCC(C)(C)C2=C1C=CC(CBr)=C2 YRSSLQXZDTXEBD-UHFFFAOYSA-N 0.000 description 1
- VQBXUKGMJCPBMF-UHFFFAOYSA-N CC1=C(C(=O)O)C=NO1 Chemical compound CC1=C(C(=O)O)C=NO1 VQBXUKGMJCPBMF-UHFFFAOYSA-N 0.000 description 1
- LMHIBYREWJHKNZ-UHFFFAOYSA-N CC1=C(C(=O)O)N=CC=C1 Chemical compound CC1=C(C(=O)O)N=CC=C1 LMHIBYREWJHKNZ-UHFFFAOYSA-N 0.000 description 1
- ZGWGSEUMABQEMD-UHFFFAOYSA-N CC1=C(C(=O)O)SC=N1 Chemical compound CC1=C(C(=O)O)SC=N1 ZGWGSEUMABQEMD-UHFFFAOYSA-N 0.000 description 1
- DEGVSFJBDJUTBP-UHFFFAOYSA-N CC1=C(C(F)(F)F)C=C(CBr)C=C1 Chemical compound CC1=C(C(F)(F)F)C=C(CBr)C=C1 DEGVSFJBDJUTBP-UHFFFAOYSA-N 0.000 description 1
- CXKYWJUJRQLAQQ-UHFFFAOYSA-N CC1=C(C)C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 Chemical compound CC1=C(C)C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 CXKYWJUJRQLAQQ-UHFFFAOYSA-N 0.000 description 1
- UFYRPPWFKLXRQV-UHFFFAOYSA-N CC1=C(C)C(CBr)=CC=C1 Chemical compound CC1=C(C)C(CBr)=CC=C1 UFYRPPWFKLXRQV-UHFFFAOYSA-N 0.000 description 1
- UBQRAAXAHIKWRI-UHFFFAOYSA-N CC1=C(C)C=C(CCl)C=C1 Chemical compound CC1=C(C)C=C(CCl)C=C1 UBQRAAXAHIKWRI-UHFFFAOYSA-N 0.000 description 1
- XVJDNYYWYZRITH-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC(=O)OC(C)(C)C)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC(=O)OC(C)(C)C)=C1 XVJDNYYWYZRITH-UHFFFAOYSA-N 0.000 description 1
- RSXQGBUEGHRDLK-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC(C)C)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC(C)C)=C1 RSXQGBUEGHRDLK-UHFFFAOYSA-N 0.000 description 1
- YGZGSUWNUQPOMQ-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC2=CC=C(C(F)(F)F)O2)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC2=CC=C(C(F)(F)F)O2)=C1 YGZGSUWNUQPOMQ-UHFFFAOYSA-N 0.000 description 1
- GLBIOJYJNPKCFN-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC2CC2)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC2CC2)=C1 GLBIOJYJNPKCFN-UHFFFAOYSA-N 0.000 description 1
- YESIRRUXHCVRPO-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC2CCC2)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC2CCC2)=C1 YESIRRUXHCVRPO-UHFFFAOYSA-N 0.000 description 1
- PVJDBGMEXZXOBC-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC2CCCO2)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCC2CCCO2)=C1 PVJDBGMEXZXOBC-UHFFFAOYSA-N 0.000 description 1
- AECLIPZETPVPDP-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCCC2OCCCO2)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCCC2OCCCO2)=C1 AECLIPZETPVPDP-UHFFFAOYSA-N 0.000 description 1
- XHTCNLSPFUEMIQ-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCCCCC(F)=C(F)F)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCCCCC(F)=C(F)F)=C1 XHTCNLSPFUEMIQ-UHFFFAOYSA-N 0.000 description 1
- AWXALQJTKOAHPI-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCCCN2C=CC=C2)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCCCN2C=CC=C2)=C1 AWXALQJTKOAHPI-UHFFFAOYSA-N 0.000 description 1
- NWQBECAJRHNIDX-UHFFFAOYSA-N CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCCN2C=CC=C2)=C1 Chemical compound CC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(OCCN2C=CC=C2)=C1 NWQBECAJRHNIDX-UHFFFAOYSA-N 0.000 description 1
- UICMWXWMCOJBIQ-UHFFFAOYSA-N CC1=C(CBr)C(C2=CC=CC=C2)=NO1 Chemical compound CC1=C(CBr)C(C2=CC=CC=C2)=NO1 UICMWXWMCOJBIQ-UHFFFAOYSA-N 0.000 description 1
- DRIYGEORZARQGO-UHFFFAOYSA-N CC1=C(CBr)C=C(F)C=C1 Chemical compound CC1=C(CBr)C=C(F)C=C1 DRIYGEORZARQGO-UHFFFAOYSA-N 0.000 description 1
- DYXSRRSEVMRNPQ-UHFFFAOYSA-N CC1=C(CCl)C2=C(C=CC=C2)S1 Chemical compound CC1=C(CCl)C2=C(C=CC=C2)S1 DYXSRRSEVMRNPQ-UHFFFAOYSA-N 0.000 description 1
- VCTKYTBWZTZPHF-UHFFFAOYSA-N CC1=C(CCl)N=C(C2=CC=CC=C2)O1 Chemical compound CC1=C(CCl)N=C(C2=CC=CC=C2)O1 VCTKYTBWZTZPHF-UHFFFAOYSA-N 0.000 description 1
- ITWDHLJAFFVQSF-VFIHMSHVSA-N CC1=C(CCl)ON=C1[Ar].CC1=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)ON=C1[Ar].CCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C=C1.ClCC1=CC([Ar])=NO1.FC1=CC=CC(C2=NC3=CN(CC4=CC([Ar])=NO4)C=CC3=N2)=C1F.O=C[Ar].[H]/C([Ar])=N\O Chemical compound CC1=C(CCl)ON=C1[Ar].CC1=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)ON=C1[Ar].CCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C=C1.ClCC1=CC([Ar])=NO1.FC1=CC=CC(C2=NC3=CN(CC4=CC([Ar])=NO4)C=CC3=N2)=C1F.O=C[Ar].[H]/C([Ar])=N\O ITWDHLJAFFVQSF-VFIHMSHVSA-N 0.000 description 1
- JTMYLQKKQFLIGV-UHFFFAOYSA-N CC1=C(Cl)C=C(CCl)C=C1 Chemical compound CC1=C(Cl)C=C(CCl)C=C1 JTMYLQKKQFLIGV-UHFFFAOYSA-N 0.000 description 1
- YAPOYZMZHWXAOX-UHFFFAOYSA-N CC1=C(F)C(F)=C(CBr)C=C1 Chemical compound CC1=C(F)C(F)=C(CBr)C=C1 YAPOYZMZHWXAOX-UHFFFAOYSA-N 0.000 description 1
- YOACSNDETIDTAY-UHFFFAOYSA-N CC1=C(F)C=C(CBr)C=C1 Chemical compound CC1=C(F)C=C(CBr)C=C1 YOACSNDETIDTAY-UHFFFAOYSA-N 0.000 description 1
- IGKKIMBNJIAVLF-UHFFFAOYSA-N CC1=C(F)C=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound CC1=C(F)C=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 IGKKIMBNJIAVLF-UHFFFAOYSA-N 0.000 description 1
- XMKZAIHFVHJGPV-UHFFFAOYSA-N CC1=C(F)C=CC=C1C(=O)O Chemical compound CC1=C(F)C=CC=C1C(=O)O XMKZAIHFVHJGPV-UHFFFAOYSA-N 0.000 description 1
- NCPKUFTZNGXYNT-UHFFFAOYSA-N CC1=C2N=C(C3=C(F)C(F)=CC=C3)N=C2C=CN1CC1=CC(C2=CC=C(Cl)C=C2)=NO1.[H]N1C(C2=C(F)C(F)=CC=C2)=NC2=C1C(C)=NC=C2.[H]N1C(C2=C(F)C(F)=CC=C2)=NC2=C1C=N(=O)C=C2.[H]N1C(C2=C(F)C(F)=CC=C2)=NC2=C1C=NC=C2 Chemical compound CC1=C2N=C(C3=C(F)C(F)=CC=C3)N=C2C=CN1CC1=CC(C2=CC=C(Cl)C=C2)=NO1.[H]N1C(C2=C(F)C(F)=CC=C2)=NC2=C1C(C)=NC=C2.[H]N1C(C2=C(F)C(F)=CC=C2)=NC2=C1C=N(=O)C=C2.[H]N1C(C2=C(F)C(F)=CC=C2)=NC2=C1C=NC=C2 NCPKUFTZNGXYNT-UHFFFAOYSA-N 0.000 description 1
- IHQUENCAKSKBOG-UHFFFAOYSA-N CC1=CC(C(=O)O)=C(C)N1CC1=CC=NC=C1 Chemical compound CC1=CC(C(=O)O)=C(C)N1CC1=CC=NC=C1 IHQUENCAKSKBOG-UHFFFAOYSA-N 0.000 description 1
- NMSCRLBUJIWGBQ-UHFFFAOYSA-N CC1=CC(C(F)(F)F)=C(CBr)C=C1 Chemical compound CC1=CC(C(F)(F)F)=C(CBr)C=C1 NMSCRLBUJIWGBQ-UHFFFAOYSA-N 0.000 description 1
- WGLUZJWOTTXZIC-UHFFFAOYSA-N CC1=CC(C)=C(CBr)C=C1 Chemical compound CC1=CC(C)=C(CBr)C=C1 WGLUZJWOTTXZIC-UHFFFAOYSA-N 0.000 description 1
- QXDHXCVJGBTQMK-UHFFFAOYSA-N CC1=CC(C)=CC(CBr)=C1 Chemical compound CC1=CC(C)=CC(CBr)=C1 QXDHXCVJGBTQMK-UHFFFAOYSA-N 0.000 description 1
- ILMHSXQELRNACG-UHFFFAOYSA-N CC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1F Chemical compound CC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1F ILMHSXQELRNACG-UHFFFAOYSA-N 0.000 description 1
- DHJPEGRMZQBUMM-UHFFFAOYSA-N CC1=CC(CBr)=C(C)C=C1 Chemical compound CC1=CC(CBr)=C(C)C=C1 DHJPEGRMZQBUMM-UHFFFAOYSA-N 0.000 description 1
- GZJBZDJGNUXMNN-UHFFFAOYSA-N CC1=CC(CBr)=CC(C(F)(F)F)=C1 Chemical compound CC1=CC(CBr)=CC(C(F)(F)F)=C1 GZJBZDJGNUXMNN-UHFFFAOYSA-N 0.000 description 1
- ASGJFGPILHALRC-UHFFFAOYSA-N CC1=CC(CBr)=NO1 Chemical compound CC1=CC(CBr)=NO1 ASGJFGPILHALRC-UHFFFAOYSA-N 0.000 description 1
- PECXPZGFZFGDRD-UHFFFAOYSA-N CC1=CC(CCl)=C(C)C=C1 Chemical compound CC1=CC(CCl)=C(C)C=C1 PECXPZGFZFGDRD-UHFFFAOYSA-N 0.000 description 1
- FEXTXBAFBURKGS-UHFFFAOYSA-N CC1=CC(CCl)=NO1 Chemical compound CC1=CC(CCl)=NO1 FEXTXBAFBURKGS-UHFFFAOYSA-N 0.000 description 1
- OWNMIFIKFVXHGA-UHFFFAOYSA-N CC1=CC(COC2=CC(C)=C(C3=CC=C(CN4C=CC5=NC(C6=C(F)C(F)=CC=C6)=NC5=C4)C=C3)C=C2)=NO1 Chemical compound CC1=CC(COC2=CC(C)=C(C3=CC=C(CN4C=CC5=NC(C6=C(F)C(F)=CC=C6)=NC5=C4)C=C3)C=C2)=NO1 OWNMIFIKFVXHGA-UHFFFAOYSA-N 0.000 description 1
- CYUVWXNLTGMMCL-UHFFFAOYSA-N CC1=CC(Cl)=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=C1 Chemical compound CC1=CC(Cl)=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=C1 CYUVWXNLTGMMCL-UHFFFAOYSA-N 0.000 description 1
- PVDKNKUVHSULSN-UHFFFAOYSA-N CC1=CC(F)=CC(CBr)=C1 Chemical compound CC1=CC(F)=CC(CBr)=C1 PVDKNKUVHSULSN-UHFFFAOYSA-N 0.000 description 1
- YSSTUSPGSMZBGV-UHFFFAOYSA-N CC1=CC(F)=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound CC1=CC(F)=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 YSSTUSPGSMZBGV-UHFFFAOYSA-N 0.000 description 1
- IONLKNVIDYSRPP-UHFFFAOYSA-N CC1=CC(NC(=O)C2=CC=C(CCl)C=C2)=NO1 Chemical compound CC1=CC(NC(=O)C2=CC=C(CCl)C=C2)=NO1 IONLKNVIDYSRPP-UHFFFAOYSA-N 0.000 description 1
- DIVAXDGCLDCEEX-UHFFFAOYSA-N CC1=CC(OC(F)(F)F)=CC=C1CBr Chemical compound CC1=CC(OC(F)(F)F)=CC=C1CBr DIVAXDGCLDCEEX-UHFFFAOYSA-N 0.000 description 1
- VBKBGUGLHHTLQT-UHFFFAOYSA-N CC1=CC2=C(C=C1)N=C(C1=CC=CC(CCl)=C1)OC2=O Chemical compound CC1=CC2=C(C=C1)N=C(C1=CC=CC(CCl)=C1)OC2=O VBKBGUGLHHTLQT-UHFFFAOYSA-N 0.000 description 1
- RHWJGEHHXOYVBH-UHFFFAOYSA-N CC1=CC=C(C)C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=C1 Chemical compound CC1=CC=C(C)C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=C1 RHWJGEHHXOYVBH-UHFFFAOYSA-N 0.000 description 1
- NJPUZFUOUGTNOV-UHFFFAOYSA-N CC1=CC=C(C)N1C1=CC(C(=O)O)=CC=C1 Chemical compound CC1=CC=C(C)N1C1=CC(C(=O)O)=CC=C1 NJPUZFUOUGTNOV-UHFFFAOYSA-N 0.000 description 1
- WNZAIUIEXCYTCY-UHFFFAOYSA-N CC1=CC=C(C)N1C1=CC=C(C(=O)O)C=C1 Chemical compound CC1=CC=C(C)N1C1=CC=C(C(=O)O)C=C1 WNZAIUIEXCYTCY-UHFFFAOYSA-N 0.000 description 1
- CAIIPVGUMFTWKJ-UHFFFAOYSA-N CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 CAIIPVGUMFTWKJ-UHFFFAOYSA-N 0.000 description 1
- FWSPYRZJKDHUDO-UHFFFAOYSA-N CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1C Chemical compound CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1C FWSPYRZJKDHUDO-UHFFFAOYSA-N 0.000 description 1
- JDAULQMOFMANSL-UHFFFAOYSA-N CC1=CC=C(C2=NN=C(CCl)O2)C=C1 Chemical compound CC1=CC=C(C2=NN=C(CCl)O2)C=C1 JDAULQMOFMANSL-UHFFFAOYSA-N 0.000 description 1
- WJJOIKINHLUANK-UHFFFAOYSA-N CC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C(F)=C1 Chemical compound CC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C(F)=C1 WJJOIKINHLUANK-UHFFFAOYSA-N 0.000 description 1
- JRELITWZSIEWAE-UHFFFAOYSA-N CC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)=C2)C(F)=C1 Chemical compound CC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)=C2)C(F)=C1 JRELITWZSIEWAE-UHFFFAOYSA-N 0.000 description 1
- SSDOQXRIONFILC-UHFFFAOYSA-N CC1=CC=C(CBr)C(F)=C1 Chemical compound CC1=CC=C(CBr)C(F)=C1 SSDOQXRIONFILC-UHFFFAOYSA-N 0.000 description 1
- QHXSBKTZBDHBKF-UHFFFAOYSA-N CC1=CC=C(CCl)C2=C1C=CC=C2 Chemical compound CC1=CC=C(CCl)C2=C1C=CC=C2 QHXSBKTZBDHBKF-UHFFFAOYSA-N 0.000 description 1
- NUTRPKLAEPAMQD-UHFFFAOYSA-N CC1=CC=C(Cl)C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)=C1F Chemical compound CC1=CC=C(Cl)C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)=C1F NUTRPKLAEPAMQD-UHFFFAOYSA-N 0.000 description 1
- VVENASDXYZLBHC-UHFFFAOYSA-N CC1=CC=C(F)C(C2=NC3=CN(CC4=CC=C(C(C)C)C=C4)C=CC3=N2)=C1 Chemical compound CC1=CC=C(F)C(C2=NC3=CN(CC4=CC=C(C(C)C)C=C4)C=CC3=N2)=C1 VVENASDXYZLBHC-UHFFFAOYSA-N 0.000 description 1
- YQOMYXFWWLUPBB-UHFFFAOYSA-N CC1=CC=C(F)C(C2=NC3=CN(CC4=CC=C(C(F)(F)F)C=C4)C=CC3=N2)=C1 Chemical compound CC1=CC=C(F)C(C2=NC3=CN(CC4=CC=C(C(F)(F)F)C=C4)C=CC3=N2)=C1 YQOMYXFWWLUPBB-UHFFFAOYSA-N 0.000 description 1
- DKUVOSFSXNJCNG-UHFFFAOYSA-N CC1=CC=C(F)C(C2=NC3=CN(CC4=CC=C(OC(F)(F)F)C=C4)C=CC3=N2)=C1 Chemical compound CC1=CC=C(F)C(C2=NC3=CN(CC4=CC=C(OC(F)(F)F)C=C4)C=CC3=N2)=C1 DKUVOSFSXNJCNG-UHFFFAOYSA-N 0.000 description 1
- VAMCJPJZOSMZGT-UHFFFAOYSA-N CC1=CC=C(F)C(CBr)=C1Cl Chemical compound CC1=CC=C(F)C(CBr)=C1Cl VAMCJPJZOSMZGT-UHFFFAOYSA-N 0.000 description 1
- STBYRSZXHDPASK-UHFFFAOYSA-N CC1=CC=C2/C=C\C=C/C2=C1CCl Chemical compound CC1=CC=C2/C=C\C=C/C2=C1CCl STBYRSZXHDPASK-UHFFFAOYSA-N 0.000 description 1
- DGNAETGARNTCIL-UHFFFAOYSA-N CC1=CC=CC(C(=O)O)=C1F Chemical compound CC1=CC=CC(C(=O)O)=C1F DGNAETGARNTCIL-UHFFFAOYSA-N 0.000 description 1
- LTUUGSGSUZRPRV-UHFFFAOYSA-N CC1=CC=CC(C(=O)O)=N1 Chemical compound CC1=CC=CC(C(=O)O)=N1 LTUUGSGSUZRPRV-UHFFFAOYSA-N 0.000 description 1
- PDDDLYSFLMCVLZ-UHFFFAOYSA-N CC1=CC=CC(C)=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound CC1=CC=CC(C)=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 PDDDLYSFLMCVLZ-UHFFFAOYSA-N 0.000 description 1
- PSRARXVEBZQEML-UHFFFAOYSA-N CC1=CC=CC(C)=C1CBr Chemical compound CC1=CC=CC(C)=C1CBr PSRARXVEBZQEML-UHFFFAOYSA-N 0.000 description 1
- HPVRFWQMBYLJRL-UHFFFAOYSA-N CC1=CC=CC(C)=C1CCl Chemical compound CC1=CC=CC(C)=C1CCl HPVRFWQMBYLJRL-UHFFFAOYSA-N 0.000 description 1
- RVHNMTZIMVVQPJ-UHFFFAOYSA-N CC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound CC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 RVHNMTZIMVVQPJ-UHFFFAOYSA-N 0.000 description 1
- HLIJMHKQYSUDOJ-UHFFFAOYSA-N CC1=NC2=C(C=CC(C(=O)O)=C2)N1C1=CC=CC=C1 Chemical compound CC1=NC2=C(C=CC(C(=O)O)=C2)N1C1=CC=CC=C1 HLIJMHKQYSUDOJ-UHFFFAOYSA-N 0.000 description 1
- OQWAOAIUESMDOS-UHFFFAOYSA-N CC1=NOC(C)=C1CBr Chemical compound CC1=NOC(C)=C1CBr OQWAOAIUESMDOS-UHFFFAOYSA-N 0.000 description 1
- NIFAUKBQIAURIM-UHFFFAOYSA-N CC1=NOC(C)=C1CCl Chemical compound CC1=NOC(C)=C1CCl NIFAUKBQIAURIM-UHFFFAOYSA-N 0.000 description 1
- KCGVZUOBUPWFJC-UHFFFAOYSA-N CC1=NOC(C2=CC=CC=C2)=C1CBr Chemical compound CC1=NOC(C2=CC=CC=C2)=C1CBr KCGVZUOBUPWFJC-UHFFFAOYSA-N 0.000 description 1
- MNWWXFPCHXGIGF-UHFFFAOYSA-N CC1CCCC(C)N1C(=O)C1=CC=C(CCl)C=C1 Chemical compound CC1CCCC(C)N1C(=O)C1=CC=C(CCl)C=C1 MNWWXFPCHXGIGF-UHFFFAOYSA-N 0.000 description 1
- JBKXDMAPOZZDCE-UHFFFAOYSA-N CCC#CCCl Chemical compound CCC#CCCl JBKXDMAPOZZDCE-UHFFFAOYSA-N 0.000 description 1
- KGDAJCOORONRPN-UHFFFAOYSA-N CCC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 KGDAJCOORONRPN-UHFFFAOYSA-N 0.000 description 1
- ANTAHNHDOWVFKW-UHFFFAOYSA-N CCC(C)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCC(C)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 ANTAHNHDOWVFKW-UHFFFAOYSA-N 0.000 description 1
- JAMYVORBQOENRN-UHFFFAOYSA-N CCC(CC)COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CCC(CC)COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 JAMYVORBQOENRN-UHFFFAOYSA-N 0.000 description 1
- DUBCVXSYZVTCOC-UHFFFAOYSA-N CCC1=CC=C(CCl)C=C1 Chemical compound CCC1=CC=C(CCl)C=C1 DUBCVXSYZVTCOC-UHFFFAOYSA-N 0.000 description 1
- KKVJQVVJVBSSTH-UHFFFAOYSA-N CCCCC(CC)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCCCC(CC)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 KKVJQVVJVBSSTH-UHFFFAOYSA-N 0.000 description 1
- XJDWNYHDHXXLFZ-UHFFFAOYSA-N CCCCC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCCCC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 XJDWNYHDHXXLFZ-UHFFFAOYSA-N 0.000 description 1
- OUMUOQQKEAGFCJ-UHFFFAOYSA-N CCCCCC#CCCl Chemical compound CCCCCC#CCCl OUMUOQQKEAGFCJ-UHFFFAOYSA-N 0.000 description 1
- NBFGTJSZHGCJOO-UHFFFAOYSA-N CCCCCC#CCN1C=CC2=NC(C3=C(F)C(F)=CC=C3)=NC2=C1 Chemical compound CCCCCC#CCN1C=CC2=NC(C3=C(F)C(F)=CC=C3)=NC2=C1 NBFGTJSZHGCJOO-UHFFFAOYSA-N 0.000 description 1
- HXNZYJWGJDFBHG-UHFFFAOYSA-N CCCCCCCCCCCCC1=CC=C(CCl)C=C1 Chemical compound CCCCCCCCCCCCC1=CC=C(CCl)C=C1 HXNZYJWGJDFBHG-UHFFFAOYSA-N 0.000 description 1
- LTAYZYBHZDEDLN-UHFFFAOYSA-N CCCCCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CCCCCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 LTAYZYBHZDEDLN-UHFFFAOYSA-N 0.000 description 1
- QOCIDCALZGBZEC-UHFFFAOYSA-N CCCCCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound CCCCCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 QOCIDCALZGBZEC-UHFFFAOYSA-N 0.000 description 1
- ZOUXMQIILALARG-UHFFFAOYSA-N CCCCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCCCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 ZOUXMQIILALARG-UHFFFAOYSA-N 0.000 description 1
- LENNICPPAAOANK-UHFFFAOYSA-N CCCCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CCCCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 LENNICPPAAOANK-UHFFFAOYSA-N 0.000 description 1
- NWHPLVDGDPBTTP-UHFFFAOYSA-N CCCCN(C)CCCl.Cl Chemical compound CCCCN(C)CCCl.Cl NWHPLVDGDPBTTP-UHFFFAOYSA-N 0.000 description 1
- CPJPAUTYYDWZNP-UHFFFAOYSA-N CCCCOC1=CC(C(F)(F)F)=NC2=CC=C(CBr)C=C21 Chemical compound CCCCOC1=CC(C(F)(F)F)=NC2=CC=C(CBr)C=C21 CPJPAUTYYDWZNP-UHFFFAOYSA-N 0.000 description 1
- CIHMJHYUNVUATL-UHFFFAOYSA-N CCCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 CIHMJHYUNVUATL-UHFFFAOYSA-N 0.000 description 1
- LAUFPZPAKULAGB-UHFFFAOYSA-N CCCCOC1=CC=C(C(=O)O)C=C1 Chemical compound CCCCOC1=CC=C(C(=O)O)C=C1 LAUFPZPAKULAGB-UHFFFAOYSA-N 0.000 description 1
- YBBNEPPZQMIZMY-UHFFFAOYSA-N CCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C=C1 Chemical compound CCCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C=C1 YBBNEPPZQMIZMY-UHFFFAOYSA-N 0.000 description 1
- LKFZXNUTEIHUEH-UHFFFAOYSA-N CCN(C)CCCl.Cl Chemical compound CCN(C)CCCl.Cl LKFZXNUTEIHUEH-UHFFFAOYSA-N 0.000 description 1
- YMDNODNLFSHHCV-UHFFFAOYSA-N CCN(CC)CCCl.Cl Chemical compound CCN(CC)CCCl.Cl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 1
- SDJLVPMBBFRBLL-UHFFFAOYSA-N CCN(CCCl)CC1=CC=CC=C1Br.Cl Chemical compound CCN(CCCl)CC1=CC=CC=C1Br.Cl SDJLVPMBBFRBLL-UHFFFAOYSA-N 0.000 description 1
- XHRCFGDFESIFRG-UHFFFAOYSA-N CCN(CCCl)CC1=CC=CC=C1C.Cl Chemical compound CCN(CCCl)CC1=CC=CC=C1C.Cl XHRCFGDFESIFRG-UHFFFAOYSA-N 0.000 description 1
- UNAXSEJHNLEOKE-UHFFFAOYSA-N CCN(CCCl)CCOC(C)=O.Cl Chemical compound CCN(CCCl)CCOC(C)=O.Cl UNAXSEJHNLEOKE-UHFFFAOYSA-N 0.000 description 1
- YRKRPSDCHZQNDF-UHFFFAOYSA-N CCN1C=CC(C(=O)O)=N1 Chemical compound CCN1C=CC(C(=O)O)=N1 YRKRPSDCHZQNDF-UHFFFAOYSA-N 0.000 description 1
- YJZGLOWGIXIHQG-QPJJXVBHSA-N CCOC(=O)/C=C/COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCOC(=O)/C=C/COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 YJZGLOWGIXIHQG-QPJJXVBHSA-N 0.000 description 1
- LLBMEYOCUIUIQZ-UHFFFAOYSA-N CCOC(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCOC(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 LLBMEYOCUIUIQZ-UHFFFAOYSA-N 0.000 description 1
- SXJJFZYSLGSBKP-UHFFFAOYSA-N CCOC(=O)CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCOC(=O)CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 SXJJFZYSLGSBKP-UHFFFAOYSA-N 0.000 description 1
- ISRRCCYZZBQFKY-UHFFFAOYSA-N CCOC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 Chemical compound CCOC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 ISRRCCYZZBQFKY-UHFFFAOYSA-N 0.000 description 1
- WZZUAFPQRMRDSZ-UHFFFAOYSA-N CCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 WZZUAFPQRMRDSZ-UHFFFAOYSA-N 0.000 description 1
- FLRLJRLQBBOCRH-UHFFFAOYSA-N CCOC1=CC=C(C2=NOC(CN3C=C(Cl)C4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C=C1 Chemical compound CCOC1=CC=C(C2=NOC(CN3C=C(Cl)C4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C=C1 FLRLJRLQBBOCRH-UHFFFAOYSA-N 0.000 description 1
- NTRRRJVKYQYWRC-UHFFFAOYSA-N CCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound CCOC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 NTRRRJVKYQYWRC-UHFFFAOYSA-N 0.000 description 1
- JQAPTBGZAVQNPT-UHFFFAOYSA-N CCOC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound CCOC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 JQAPTBGZAVQNPT-UHFFFAOYSA-N 0.000 description 1
- SKNSLUAUOKEWPV-UHFFFAOYSA-N CCOP(=O)(CCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1)OCC Chemical compound CCOP(=O)(CCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1)OCC SKNSLUAUOKEWPV-UHFFFAOYSA-N 0.000 description 1
- AEOBUNHZRCEGDT-UHFFFAOYSA-N CCOP(=O)(CCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1)OCC Chemical compound CCOP(=O)(CCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1)OCC AEOBUNHZRCEGDT-UHFFFAOYSA-N 0.000 description 1
- ASUOPZFXNPFJLR-UHFFFAOYSA-N CN(C)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CN(C)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 ASUOPZFXNPFJLR-UHFFFAOYSA-N 0.000 description 1
- NEGFNJRAUMCZMY-UHFFFAOYSA-N CN(C)C1=CC=CC(C(=O)O)=C1 Chemical compound CN(C)C1=CC=CC(C(=O)O)=C1 NEGFNJRAUMCZMY-UHFFFAOYSA-N 0.000 description 1
- WQMAANNAZKNUDL-UHFFFAOYSA-N CN(C)CCCl.Cl Chemical compound CN(C)CCCl.Cl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 1
- PBEDVTDUVXFSMW-UHFFFAOYSA-N CN1C=NC=C1C(=O)O Chemical compound CN1C=NC=C1C(=O)O PBEDVTDUVXFSMW-UHFFFAOYSA-N 0.000 description 1
- MFYGUNWIOIAUJB-UHFFFAOYSA-N CN1N=C(C(F)(F)F)C2=C1S/C(CBr)=C\2 Chemical compound CN1N=C(C(F)(F)F)C2=C1S/C(CBr)=C\2 MFYGUNWIOIAUJB-UHFFFAOYSA-N 0.000 description 1
- FWNDOEOTZSEKSP-UHFFFAOYSA-N CN1N=C(C(F)(F)F)C2=C1SC(CN1C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C1)=C2 Chemical compound CN1N=C(C(F)(F)F)C2=C1SC(CN1C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C1)=C2 FWNDOEOTZSEKSP-UHFFFAOYSA-N 0.000 description 1
- WKZYNELEMQLPMG-UHFFFAOYSA-N CN1N=C(C(F)(F)F)C2=C1SC(CN1C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C1)=C2 Chemical compound CN1N=C(C(F)(F)F)C2=C1SC(CN1C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C1)=C2 WKZYNELEMQLPMG-UHFFFAOYSA-N 0.000 description 1
- JREJQAWGQCMSIY-UHFFFAOYSA-N CN1N=CC=C1C(=O)O Chemical compound CN1N=CC=C1C(=O)O JREJQAWGQCMSIY-UHFFFAOYSA-N 0.000 description 1
- FGINNLOSASTMRE-UHFFFAOYSA-N CN1N=CC=C1NC(=O)C1=CC=CC(CCl)=C1 Chemical compound CN1N=CC=C1NC(=O)C1=CC=CC(CCl)=C1 FGINNLOSASTMRE-UHFFFAOYSA-N 0.000 description 1
- HDJARFAOADAJAR-ZZXKWVIFSA-N COC(=O)/C=C/COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COC(=O)/C=C/COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 HDJARFAOADAJAR-ZZXKWVIFSA-N 0.000 description 1
- XSFMEQYVNDBTFL-QPJJXVBHSA-N COC(=O)/C=C/COC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COC(=O)/C=C/COC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 XSFMEQYVNDBTFL-QPJJXVBHSA-N 0.000 description 1
- DFMGLKILOQZZDX-ZZXKWVIFSA-N COC(=O)/C=C/COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COC(=O)/C=C/COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 DFMGLKILOQZZDX-ZZXKWVIFSA-N 0.000 description 1
- YOVSCTKBQMYDQN-UHFFFAOYSA-N COC(=O)C1=C(NC(=O)C2=CC=CC(CCl)=C2)SC=C1 Chemical compound COC(=O)C1=C(NC(=O)C2=CC=CC(CCl)=C2)SC=C1 YOVSCTKBQMYDQN-UHFFFAOYSA-N 0.000 description 1
- XSSTWQUMDHEYOZ-UHFFFAOYSA-N COC(=O)C1=C(NC(=O)COC2=C(C3=CC=C(CN4C=CC5=NC(C6=C(F)C(F)=CC=C6)=NC5=C4)C=C3)C=CC(F)=C2)C=CS1 Chemical compound COC(=O)C1=C(NC(=O)COC2=C(C3=CC=C(CN4C=CC5=NC(C6=C(F)C(F)=CC=C6)=NC5=C4)C=C3)C=CC(F)=C2)C=CS1 XSSTWQUMDHEYOZ-UHFFFAOYSA-N 0.000 description 1
- PZLBTHYOJWXUGD-UHFFFAOYSA-N COC(=O)C1=C(NC(=O)COC2=CC(C(F)(F)F)=C(C3=CC=C(CN4C=CC5=NC(C6=C(F)C(F)=CC=C6)=NC5=C4)C=C3)C=C2)C=CS1 Chemical compound COC(=O)C1=C(NC(=O)COC2=CC(C(F)(F)F)=C(C3=CC=C(CN4C=CC5=NC(C6=C(F)C(F)=CC=C6)=NC5=C4)C=C3)C=C2)C=CS1 PZLBTHYOJWXUGD-UHFFFAOYSA-N 0.000 description 1
- PRWIVJBRUZPFRC-UHFFFAOYSA-N COC(=O)C1=C(NC(=O)COC2=CC=C(C3=CC=C(CN4C=CC5=NC(C6=C(F)C(F)=CC=C6)=NC5=C4)C=C3)C=C2)C=CS1 Chemical compound COC(=O)C1=C(NC(=O)COC2=CC=C(C3=CC=C(CN4C=CC5=NC(C6=C(F)C(F)=CC=C6)=NC5=C4)C=C3)C=C2)C=CS1 PRWIVJBRUZPFRC-UHFFFAOYSA-N 0.000 description 1
- UPTGCPWBNGJHMA-UHFFFAOYSA-N COC(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COC(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 UPTGCPWBNGJHMA-UHFFFAOYSA-N 0.000 description 1
- QVHRCBZPKCKTKE-UHFFFAOYSA-N COC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 QVHRCBZPKCKTKE-UHFFFAOYSA-N 0.000 description 1
- SOWDWUPMHVDZGL-UHFFFAOYSA-N COC1=C(C(=O)O)C=CC(C)=C1 Chemical compound COC1=C(C(=O)O)C=CC(C)=C1 SOWDWUPMHVDZGL-UHFFFAOYSA-N 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N COC1=C(C(=O)O)C=CC=C1 Chemical compound COC1=C(C(=O)O)C=CC=C1 ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- FZICFAROPYFJMF-UHFFFAOYSA-N COC1=C(C(F)(F)F)C=C(CBr)C=C1 Chemical compound COC1=C(C(F)(F)F)C=C(CBr)C=C1 FZICFAROPYFJMF-UHFFFAOYSA-N 0.000 description 1
- WNLMNECFTJPWCU-UHFFFAOYSA-N COC1=C(C(F)(F)F)C=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound COC1=C(C(F)(F)F)C=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 WNLMNECFTJPWCU-UHFFFAOYSA-N 0.000 description 1
- CQOYRKTWRNUDPN-UHFFFAOYSA-N COC1=C(C(F)(F)F)C=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1 Chemical compound COC1=C(C(F)(F)F)C=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1 CQOYRKTWRNUDPN-UHFFFAOYSA-N 0.000 description 1
- BWIOURVJVDKDOC-UHFFFAOYSA-N COC1=C(CCl)C2=CC=C(Br)C=C2C=C1 Chemical compound COC1=C(CCl)C2=CC=C(Br)C=C2C=C1 BWIOURVJVDKDOC-UHFFFAOYSA-N 0.000 description 1
- AVGWCJLTQZQLCN-UHFFFAOYSA-N COC1=C(F)C(C(=O)O)=CC=C1 Chemical compound COC1=C(F)C(C(=O)O)=CC=C1 AVGWCJLTQZQLCN-UHFFFAOYSA-N 0.000 description 1
- KWLIGHXPUYUTBH-UHFFFAOYSA-N COC1=C(F)C(C(=O)O)=CC=C1F Chemical compound COC1=C(F)C(C(=O)O)=CC=C1F KWLIGHXPUYUTBH-UHFFFAOYSA-N 0.000 description 1
- KJYAOISGZXNSPI-UHFFFAOYSA-N COC1=C(F)C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 Chemical compound COC1=C(F)C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 KJYAOISGZXNSPI-UHFFFAOYSA-N 0.000 description 1
- MJRVJLUCLPUZER-UHFFFAOYSA-N COC1=C(OC)C(CCl)=CC=C1 Chemical compound COC1=C(OC)C(CCl)=CC=C1 MJRVJLUCLPUZER-UHFFFAOYSA-N 0.000 description 1
- PORJYADIGOBLRM-UHFFFAOYSA-N COC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 Chemical compound COC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 PORJYADIGOBLRM-UHFFFAOYSA-N 0.000 description 1
- BTHIGJGJAPYFSJ-UHFFFAOYSA-N COC1=CC(CBr)=CC(OC)=C1 Chemical compound COC1=CC(CBr)=CC(OC)=C1 BTHIGJGJAPYFSJ-UHFFFAOYSA-N 0.000 description 1
- CCAWDIFJOBKBSE-UHFFFAOYSA-N COC1=CC(CCl)=CC(OC)=C1 Chemical compound COC1=CC(CCl)=CC(OC)=C1 CCAWDIFJOBKBSE-UHFFFAOYSA-N 0.000 description 1
- XXRUQNNAKXZSOS-UHFFFAOYSA-N COC1=CC(CCl)=CC(OC)=C1OC Chemical compound COC1=CC(CCl)=CC(OC)=C1OC XXRUQNNAKXZSOS-UHFFFAOYSA-N 0.000 description 1
- XZNBASKTBIQNRA-UHFFFAOYSA-N COC1=CC(OC)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C(F)=C1 Chemical compound COC1=CC(OC)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C(F)=C1 XZNBASKTBIQNRA-UHFFFAOYSA-N 0.000 description 1
- BWCCPOQIMGGGQX-UHFFFAOYSA-N COC1=CC(OC)=NC(CCl)=N1 Chemical compound COC1=CC(OC)=NC(CCl)=N1 BWCCPOQIMGGGQX-UHFFFAOYSA-N 0.000 description 1
- XZELWEMGWISCTP-UHFFFAOYSA-N COC1=CC2=C(C=C1)OC(C(=O)O)=C2 Chemical compound COC1=CC2=C(C=C1)OC(C(=O)O)=C2 XZELWEMGWISCTP-UHFFFAOYSA-N 0.000 description 1
- BNLRVFJSVGTTGG-UHFFFAOYSA-N COC1=CC=C(C(C)=O)C=C1CCl Chemical compound COC1=CC=C(C(C)=O)C=C1CCl BNLRVFJSVGTTGG-UHFFFAOYSA-N 0.000 description 1
- LYSIXLOBJJQDNS-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C(OC)=C1 Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C(OC)=C1 LYSIXLOBJJQDNS-UHFFFAOYSA-N 0.000 description 1
- LWPMLGVOKXFJMN-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 LWPMLGVOKXFJMN-UHFFFAOYSA-N 0.000 description 1
- JWLUWFUDBHQBDK-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1F Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1F JWLUWFUDBHQBDK-UHFFFAOYSA-N 0.000 description 1
- RHMQHQKDKDCJMZ-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1OC Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1OC RHMQHQKDKDCJMZ-UHFFFAOYSA-N 0.000 description 1
- GIZJWAPONLQQAK-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)C=C2F)C=C1 Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)C=C2F)C=C1 GIZJWAPONLQQAK-UHFFFAOYSA-N 0.000 description 1
- SVICODLLYVPBOI-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C(F)=C2)C=C1 Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C(F)=C2)C=C1 SVICODLLYVPBOI-UHFFFAOYSA-N 0.000 description 1
- BMJZEYDTTZMERX-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C=C2F)C=C1 Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C=C2F)C=C1 BMJZEYDTTZMERX-UHFFFAOYSA-N 0.000 description 1
- LXKRXCCLFFUMCG-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C(F)=C2)C=C1 Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C(F)=C2)C=C1 LXKRXCCLFFUMCG-UHFFFAOYSA-N 0.000 description 1
- DWKAFHCXYPPNQW-UHFFFAOYSA-N COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C=C2F)C=C1 Chemical compound COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C=C2F)C=C1 DWKAFHCXYPPNQW-UHFFFAOYSA-N 0.000 description 1
- LSYCZBSPYWGGHC-UHFFFAOYSA-N COC1=CC=C(C2=NC(CCl)=NO2)C=C1 Chemical compound COC1=CC=C(C2=NC(CCl)=NO2)C=C1 LSYCZBSPYWGGHC-UHFFFAOYSA-N 0.000 description 1
- IEMOMRMJXWHIIL-UHFFFAOYSA-N COC1=CC=C(C2=NC(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)=NO2)C=C1 Chemical compound COC1=CC=C(C2=NC(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)=NO2)C=C1 IEMOMRMJXWHIIL-UHFFFAOYSA-N 0.000 description 1
- GEHIXSKXGCIKJJ-UHFFFAOYSA-N COC1=CC=C(C2=NN=C(CCl)O2)C=C1 Chemical compound COC1=CC=C(C2=NN=C(CCl)O2)C=C1 GEHIXSKXGCIKJJ-UHFFFAOYSA-N 0.000 description 1
- WPYBLXMGRFTENB-UHFFFAOYSA-N COC1=CC=C(C2=NNC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound COC1=CC=C(C2=NNC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 WPYBLXMGRFTENB-UHFFFAOYSA-N 0.000 description 1
- CAKWMWORYTVBFV-UHFFFAOYSA-N COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(OC)=C1 Chemical compound COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(OC)=C1 CAKWMWORYTVBFV-UHFFFAOYSA-N 0.000 description 1
- QXPLPCRREOHVHN-UHFFFAOYSA-N COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C(OC)=C1 Chemical compound COC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C(OC)=C1 QXPLPCRREOHVHN-UHFFFAOYSA-N 0.000 description 1
- KLWYYWVSFYRPLM-UHFFFAOYSA-N COC1=CC=C(CBr)C=C1F Chemical compound COC1=CC=C(CBr)C=C1F KLWYYWVSFYRPLM-UHFFFAOYSA-N 0.000 description 1
- BHEHNICAPZVKRH-UHFFFAOYSA-N COC1=CC=C(CCl)C=C1C Chemical compound COC1=CC=C(CCl)C=C1C BHEHNICAPZVKRH-UHFFFAOYSA-N 0.000 description 1
- PQJLHABRQMTVEJ-UHFFFAOYSA-N COC1=CC=C(F)C(C2=NC3=CN(CC4=CC=C(OC(F)(F)F)C=C4)C=CC3=N2)=C1 Chemical compound COC1=CC=C(F)C(C2=NC3=CN(CC4=CC=C(OC(F)(F)F)C=C4)C=CC3=N2)=C1 PQJLHABRQMTVEJ-UHFFFAOYSA-N 0.000 description 1
- NJBICLSFUUJIDH-UHFFFAOYSA-N COC1=CC=C(OC)C(CCl)=C1 Chemical compound COC1=CC=C(OC)C(CCl)=C1 NJBICLSFUUJIDH-UHFFFAOYSA-N 0.000 description 1
- WZCOSNHGAXPKIN-UHFFFAOYSA-N COCCCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound COCCCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 WZCOSNHGAXPKIN-UHFFFAOYSA-N 0.000 description 1
- VNPAYJNDWUBCNB-UHFFFAOYSA-N COCCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 VNPAYJNDWUBCNB-UHFFFAOYSA-N 0.000 description 1
- SEMDUVVJKWMSCZ-UHFFFAOYSA-N COCCCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 SEMDUVVJKWMSCZ-UHFFFAOYSA-N 0.000 description 1
- NWARAUVQDMZKLG-UHFFFAOYSA-N COCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 NWARAUVQDMZKLG-UHFFFAOYSA-N 0.000 description 1
- LNGUWNGFAXFWHV-UHFFFAOYSA-N COCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 LNGUWNGFAXFWHV-UHFFFAOYSA-N 0.000 description 1
- SUQQIZZOFLSPQA-UHFFFAOYSA-N COCCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 SUQQIZZOFLSPQA-UHFFFAOYSA-N 0.000 description 1
- OPOATXJJTMGZKR-UHFFFAOYSA-N COCCOCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCOCCOC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 OPOATXJJTMGZKR-UHFFFAOYSA-N 0.000 description 1
- BEKMUTLLDQGWBK-UHFFFAOYSA-N COCCOCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCOCCOC1=CC(C)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 BEKMUTLLDQGWBK-UHFFFAOYSA-N 0.000 description 1
- VPBZELRVROQHAB-UHFFFAOYSA-N COCCOCCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound COCCOCCOC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 VPBZELRVROQHAB-UHFFFAOYSA-N 0.000 description 1
- AJBWNNKDUMXZLM-UHFFFAOYSA-N CS(=O)(=O)C1=CC=C(C(=O)O)C=C1 Chemical compound CS(=O)(=O)C1=CC=C(C(=O)O)C=C1 AJBWNNKDUMXZLM-UHFFFAOYSA-N 0.000 description 1
- VVWFGSVCLUNXDO-UHFFFAOYSA-N CS(=O)(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CS(=O)(=O)C1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 VVWFGSVCLUNXDO-UHFFFAOYSA-N 0.000 description 1
- LXPRVXKHIXWBJZ-UHFFFAOYSA-N CS(=O)(=O)C1=CC=C(CCl)C=C1 Chemical compound CS(=O)(=O)C1=CC=C(CCl)C=C1 LXPRVXKHIXWBJZ-UHFFFAOYSA-N 0.000 description 1
- KUTBMATZUQWFSR-UHFFFAOYSA-N CS(=O)(=O)C1=CC=CC(C(=O)O)=C1 Chemical compound CS(=O)(=O)C1=CC=CC(C(=O)O)=C1 KUTBMATZUQWFSR-UHFFFAOYSA-N 0.000 description 1
- BZSXEZOLBIJVQK-UHFFFAOYSA-N CS(=O)(=O)C1=CC=CC=C1C(=O)O Chemical compound CS(=O)(=O)C1=CC=CC=C1C(=O)O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 description 1
- HQONTGVVLBRGMY-UHFFFAOYSA-N CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 HQONTGVVLBRGMY-UHFFFAOYSA-N 0.000 description 1
- MUBUJMXHUFEWAD-UHFFFAOYSA-N CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)C(F)=C2)C=C1 Chemical compound CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)C(F)=C2)C=C1 MUBUJMXHUFEWAD-UHFFFAOYSA-N 0.000 description 1
- NQZDQSKTOPRNON-UHFFFAOYSA-N CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)C=C2F)C=C1 Chemical compound CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)C=C2F)C=C1 NQZDQSKTOPRNON-UHFFFAOYSA-N 0.000 description 1
- OEJIOBBCQMFNNN-UHFFFAOYSA-N CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C(F)=C2)C=C1 Chemical compound CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C(F)=C2)C=C1 OEJIOBBCQMFNNN-UHFFFAOYSA-N 0.000 description 1
- OHYIAQXADQYCME-UHFFFAOYSA-N CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C=C2F)C=C1 Chemical compound CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C=C2F)C=C1 OHYIAQXADQYCME-UHFFFAOYSA-N 0.000 description 1
- PCURIHLSDXVIPC-UHFFFAOYSA-N CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C(F)=C2)C=C1 Chemical compound CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C(F)=C2)C=C1 PCURIHLSDXVIPC-UHFFFAOYSA-N 0.000 description 1
- PFTMETREMDJIOS-UHFFFAOYSA-N CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C=C2F)C=C1 Chemical compound CSC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C=C2F)C=C1 PFTMETREMDJIOS-UHFFFAOYSA-N 0.000 description 1
- VTCIGSMGYNKICT-UHFFFAOYSA-N CSC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound CSC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 VTCIGSMGYNKICT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- GSLWSSUWNCJILM-UHFFFAOYSA-N Cl.ClCCN(CC1=CC=CC=C1)CC1=CC=CC=C1 Chemical compound Cl.ClCCN(CC1=CC=CC=C1)CC1=CC=CC=C1 GSLWSSUWNCJILM-UHFFFAOYSA-N 0.000 description 1
- RMGFLMXDCGQKPS-UHFFFAOYSA-N Cl.ClCCN1CCCC1 Chemical compound Cl.ClCCN1CCCC1 RMGFLMXDCGQKPS-UHFFFAOYSA-N 0.000 description 1
- WNRWEBKEQARBKV-UHFFFAOYSA-N Cl.ClCCN1CCCCC1 Chemical compound Cl.ClCCN1CCCCC1 WNRWEBKEQARBKV-UHFFFAOYSA-N 0.000 description 1
- ZAPMTSHEXFEPSD-UHFFFAOYSA-N Cl.ClCCN1CCOCC1 Chemical compound Cl.ClCCN1CCOCC1 ZAPMTSHEXFEPSD-UHFFFAOYSA-N 0.000 description 1
- OWYVDLOGYIFMCM-UHFFFAOYSA-N ClC1=C(CBr)SC2=C1C=CC=C2 Chemical compound ClC1=C(CBr)SC2=C1C=CC=C2 OWYVDLOGYIFMCM-UHFFFAOYSA-N 0.000 description 1
- FKQSFVITUNJLCY-UHFFFAOYSA-N ClC1=CC2=C(C=C1)SC=C2CBr Chemical compound ClC1=CC2=C(C=C1)SC=C2CBr FKQSFVITUNJLCY-UHFFFAOYSA-N 0.000 description 1
- COIHXGCRGHUPHW-UHFFFAOYSA-N ClC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CSC=C5)=NC4=C3)=C2)C=C1 Chemical compound ClC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CSC=C5)=NC4=C3)=C2)C=C1 COIHXGCRGHUPHW-UHFFFAOYSA-N 0.000 description 1
- IRSVDHPYXFLLDS-UHFFFAOYSA-N ClCC1=C(Cl)C=C(Cl)C=C1 Chemical compound ClCC1=C(Cl)C=C(Cl)C=C1 IRSVDHPYXFLLDS-UHFFFAOYSA-N 0.000 description 1
- PCVRSXXPGXRVEZ-UHFFFAOYSA-N ClCC1=C2C=CC=CC2=CC2=CC=CC=C21 Chemical compound ClCC1=C2C=CC=CC2=CC2=CC=CC=C21 PCVRSXXPGXRVEZ-UHFFFAOYSA-N 0.000 description 1
- VTGZBAPPBYBUBD-UHFFFAOYSA-N ClCC1=CC(C2=CC=C(Cl)C=C2)=NO1.FC1=C(F)C(C2=NC3=CC=NC=C3N2)=CC=C1.FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound ClCC1=CC(C2=CC=C(Cl)C=C2)=NO1.FC1=C(F)C(C2=NC3=CC=NC=C3N2)=CC=C1.FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)=CC=C1 VTGZBAPPBYBUBD-UHFFFAOYSA-N 0.000 description 1
- ILPUQJWXEGFFNK-UHFFFAOYSA-N ClCC1=CC(C2=CC=C(Cl)C=C2)=NO1.FC1=CC=CC=C1C1=NC2=CC=NC=C2N1.FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(Cl)C=C4)=NO3)C=CC2=N1 Chemical compound ClCC1=CC(C2=CC=C(Cl)C=C2)=NO1.FC1=CC=CC=C1C1=NC2=CC=NC=C2N1.FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(Cl)C=C4)=NO3)C=CC2=N1 ILPUQJWXEGFFNK-UHFFFAOYSA-N 0.000 description 1
- WKLODVHSLLFKMY-UHFFFAOYSA-N ClCC1=CC(C2=CC=CC=C2)=NO1 Chemical compound ClCC1=CC(C2=CC=CC=C2)=NO1 WKLODVHSLLFKMY-UHFFFAOYSA-N 0.000 description 1
- QUYVTGFWFHQVRO-UHFFFAOYSA-N ClCC1=CC(OC2=CC=CC=C2)=CC=C1 Chemical compound ClCC1=CC(OC2=CC=CC=C2)=CC=C1 QUYVTGFWFHQVRO-UHFFFAOYSA-N 0.000 description 1
- PXZCFOABYOEFPQ-UHFFFAOYSA-N ClCC1=CC2=C(C=C1)OCCCO2 Chemical compound ClCC1=CC2=C(C=C1)OCCCO2 PXZCFOABYOEFPQ-UHFFFAOYSA-N 0.000 description 1
- APJKOQPCHGXQBI-UHFFFAOYSA-N ClCC1=CC2=C(C=C1Cl)OCO2 Chemical compound ClCC1=CC2=C(C=C1Cl)OCO2 APJKOQPCHGXQBI-UHFFFAOYSA-N 0.000 description 1
- WKZPQAHPSROHBX-UHFFFAOYSA-N ClCC1=CC=C(C2=NC3=CC=CC=C3N2)C=C1 Chemical compound ClCC1=CC=C(C2=NC3=CC=CC=C3N2)C=C1 WKZPQAHPSROHBX-UHFFFAOYSA-N 0.000 description 1
- DDAGFZBQVSGXJN-UHFFFAOYSA-N ClCC1=CC=C(OCC2=CC=CC=C2)C(OCC2=CC=CC=C2)=C1 Chemical compound ClCC1=CC=C(OCC2=CC=CC=C2)C(OCC2=CC=CC=C2)=C1 DDAGFZBQVSGXJN-UHFFFAOYSA-N 0.000 description 1
- XMWGTKZEDLCVIG-UHFFFAOYSA-N ClCC1=CC=CC2=CC=CC=C21 Chemical compound ClCC1=CC=CC2=CC=CC=C21 XMWGTKZEDLCVIG-UHFFFAOYSA-N 0.000 description 1
- FUOHKPSBGLXIRL-UHFFFAOYSA-N ClCC1=CC=CS1 Chemical compound ClCC1=CC=CS1 FUOHKPSBGLXIRL-UHFFFAOYSA-N 0.000 description 1
- LBCREEUWXFNSAC-UHFFFAOYSA-N ClCC1=CN2C=CC=CC2=N1 Chemical compound ClCC1=CN2C=CC=CC2=N1 LBCREEUWXFNSAC-UHFFFAOYSA-N 0.000 description 1
- VRMUIVKEHJSADG-UHFFFAOYSA-N ClCC1=CN=C(Cl)S1 Chemical compound ClCC1=CN=C(Cl)S1 VRMUIVKEHJSADG-UHFFFAOYSA-N 0.000 description 1
- UEJQTBKTWJQBRN-UHFFFAOYSA-N ClCC1=CSC(C2=CC=C(Cl)C=C2)=N1 Chemical compound ClCC1=CSC(C2=CC=C(Cl)C=C2)=N1 UEJQTBKTWJQBRN-UHFFFAOYSA-N 0.000 description 1
- CGJJBHKYGNSTDK-UHFFFAOYSA-N ClCC1=CSC(C2=CC=CS2)=N1 Chemical compound ClCC1=CSC(C2=CC=CS2)=N1 CGJJBHKYGNSTDK-UHFFFAOYSA-N 0.000 description 1
- QKWSLYINUYKIRF-UHFFFAOYSA-N ClCC1=CSC=N1 Chemical compound ClCC1=CSC=N1 QKWSLYINUYKIRF-UHFFFAOYSA-N 0.000 description 1
- BJVYSQGEJHKTBW-UHFFFAOYSA-N ClCC1=NC(C2=CC=C(Cl)C=C2)=NO1 Chemical compound ClCC1=NC(C2=CC=C(Cl)C=C2)=NO1 BJVYSQGEJHKTBW-UHFFFAOYSA-N 0.000 description 1
- VDRLGRBSQTUUOX-UHFFFAOYSA-N ClCC1=NC2=C(C=CC(Cl)=C2)C=C1 Chemical compound ClCC1=NC2=C(C=CC(Cl)=C2)C=C1 VDRLGRBSQTUUOX-UHFFFAOYSA-N 0.000 description 1
- AJKIAERFLWQLAM-UHFFFAOYSA-N ClCC1=NN=C(C2=CC=C(Cl)C=C2)O1 Chemical compound ClCC1=NN=C(C2=CC=C(Cl)C=C2)O1 AJKIAERFLWQLAM-UHFFFAOYSA-N 0.000 description 1
- VEIXFEJMHJPUBS-UHFFFAOYSA-N ClCC1=NOC(C2=CC=CC=C2)=N1 Chemical compound ClCC1=NOC(C2=CC=CC=C2)=N1 VEIXFEJMHJPUBS-UHFFFAOYSA-N 0.000 description 1
- YVYZVJRSESVBCM-UHFFFAOYSA-N ClCC1=NOC(C2=CC=CS2)=N1 Chemical compound ClCC1=NOC(C2=CC=CS2)=N1 YVYZVJRSESVBCM-UHFFFAOYSA-N 0.000 description 1
- YSNKGJCEHOJIDK-UHFFFAOYSA-N ClCC1=NOC=N1 Chemical compound ClCC1=NOC=N1 YSNKGJCEHOJIDK-UHFFFAOYSA-N 0.000 description 1
- FFFMIFUBJZBTCG-UHFFFAOYSA-N ClCC1=NSC(Cl)=N1 Chemical compound ClCC1=NSC(Cl)=N1 FFFMIFUBJZBTCG-UHFFFAOYSA-N 0.000 description 1
- CZYATLREQUGMIQ-UHFFFAOYSA-N ClCCN1C=CC=C1 Chemical compound ClCCN1C=CC=C1 CZYATLREQUGMIQ-UHFFFAOYSA-N 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 241000694440 Colpidium aqueous Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010014978 Epidemic pleurodynia Diseases 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical class C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- OUNFGTVHRCWPKY-UHFFFAOYSA-N FC(F)(F)C1=C(CBr)C=C(Cl)C=C1 Chemical compound FC(F)(F)C1=C(CBr)C=C(Cl)C=C1 OUNFGTVHRCWPKY-UHFFFAOYSA-N 0.000 description 1
- LZLIPLUATRVXSB-UHFFFAOYSA-N FC(F)(F)C1=C(Cl)C=CC(CBr)=C1 Chemical compound FC(F)(F)C1=C(Cl)C=CC(CBr)=C1 LZLIPLUATRVXSB-UHFFFAOYSA-N 0.000 description 1
- SWFFFUJOWAJJCH-UHFFFAOYSA-N FC(F)(F)C1=CC(C(F)(F)F)=C(CBr)C=C1 Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=C(CBr)C=C1 SWFFFUJOWAJJCH-UHFFFAOYSA-N 0.000 description 1
- DPKQSESRNWBUFZ-UHFFFAOYSA-N FC(F)(F)C1=CC(C(F)(F)F)=C(CCl)C=C1 Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=C(CCl)C=C1 DPKQSESRNWBUFZ-UHFFFAOYSA-N 0.000 description 1
- BWOOBQYXRVOJSZ-UHFFFAOYSA-N FC(F)(F)C1=CC(CBr)=C(Cl)C=C1 Chemical compound FC(F)(F)C1=CC(CBr)=C(Cl)C=C1 BWOOBQYXRVOJSZ-UHFFFAOYSA-N 0.000 description 1
- QOWNNZROJKFRSK-UHFFFAOYSA-N FC(F)(F)C1=CC=C(C2=NC(CCl)=CS2)C=C1 Chemical compound FC(F)(F)C1=CC=C(C2=NC(CCl)=CS2)C=C1 QOWNNZROJKFRSK-UHFFFAOYSA-N 0.000 description 1
- YNHVBNGRNNVEMD-UHFFFAOYSA-N FC(F)(F)C1=CC=C(CBr)O1 Chemical compound FC(F)(F)C1=CC=C(CBr)O1 YNHVBNGRNNVEMD-UHFFFAOYSA-N 0.000 description 1
- FFTAVZITFBFVEC-UHFFFAOYSA-N FC(F)(F)C1=CC=C(CCl)C(Br)=C1 Chemical compound FC(F)(F)C1=CC=C(CCl)C(Br)=C1 FFTAVZITFBFVEC-UHFFFAOYSA-N 0.000 description 1
- INANILNLXTUPHD-UHFFFAOYSA-N FC(F)(F)C1=CC=CC(C2=NC(CCl)=NO2)=C1 Chemical compound FC(F)(F)C1=CC=CC(C2=NC(CCl)=NO2)=C1 INANILNLXTUPHD-UHFFFAOYSA-N 0.000 description 1
- SJBKLFYWXYFAGT-UHFFFAOYSA-N FC(F)(F)C1=NC2=C(C=C(CBr)C=C2)C(Cl)=C1 Chemical compound FC(F)(F)C1=NC2=C(C=C(CBr)C=C2)C(Cl)=C1 SJBKLFYWXYFAGT-UHFFFAOYSA-N 0.000 description 1
- QSIVWRRHVXSDNE-UHFFFAOYSA-N FC(F)(F)OC1=CC(CBr)=CC=C1 Chemical compound FC(F)(F)OC1=CC(CBr)=CC=C1 QSIVWRRHVXSDNE-UHFFFAOYSA-N 0.000 description 1
- YTXRMMJPEBWDPE-UHFFFAOYSA-N FC(F)(F)OC1=CC=C(CBr)C=C1Cl Chemical compound FC(F)(F)OC1=CC=C(CBr)C=C1Cl YTXRMMJPEBWDPE-UHFFFAOYSA-N 0.000 description 1
- SBVPAYRDPWENAX-UHFFFAOYSA-N FC(F)(F)OC1=CC=C(CCl)C=C1.FC1=C(F)C(C2=NC3=CC=NC=C3N2)=CC=C1.FC1=C(F)C(C2=NC3=CN(CC4=CC=C(OC(F)(F)F)C=C4)C=CC3=N2)=CC=C1 Chemical compound FC(F)(F)OC1=CC=C(CCl)C=C1.FC1=C(F)C(C2=NC3=CC=NC=C3N2)=CC=C1.FC1=C(F)C(C2=NC3=CN(CC4=CC=C(OC(F)(F)F)C=C4)C=CC3=N2)=CC=C1 SBVPAYRDPWENAX-UHFFFAOYSA-N 0.000 description 1
- ZGXDTWNEZOBSBJ-UHFFFAOYSA-N FC(F)(F)OC1=CC=CC=C1CCl Chemical compound FC(F)(F)OC1=CC=CC=C1CCl ZGXDTWNEZOBSBJ-UHFFFAOYSA-N 0.000 description 1
- DMFKZZXVNAKILD-UHFFFAOYSA-N FC(F)(F)SC1=CC(CCl)=CC=C1 Chemical compound FC(F)(F)SC1=CC(CCl)=CC=C1 DMFKZZXVNAKILD-UHFFFAOYSA-N 0.000 description 1
- QMCUHVLWLOWATL-UHFFFAOYSA-N FC(F)=CCCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound FC(F)=CCCOC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 QMCUHVLWLOWATL-UHFFFAOYSA-N 0.000 description 1
- IFNMJBFIRKAQBT-UHFFFAOYSA-N FC(F)OC1=CC=C(CBr)C=C1 Chemical compound FC(F)OC1=CC=C(CBr)C=C1 IFNMJBFIRKAQBT-UHFFFAOYSA-N 0.000 description 1
- VWGUMIIBGQCOOM-UHFFFAOYSA-N FC1=C(Br)C=CC=C1C1=NC2=CN(CC3=CC=C(OC(F)(F)F)C=C3)C=CC2=N1 Chemical compound FC1=C(Br)C=CC=C1C1=NC2=CN(CC3=CC=C(OC(F)(F)F)C=C3)C=CC2=N1 VWGUMIIBGQCOOM-UHFFFAOYSA-N 0.000 description 1
- QBEHXDXQUVMEQX-UHFFFAOYSA-N FC1=C(C(F)(F)F)C=CC=C1CBr Chemical compound FC1=C(C(F)(F)F)C=CC=C1CBr QBEHXDXQUVMEQX-UHFFFAOYSA-N 0.000 description 1
- UCRQNOWRKSMNII-UHFFFAOYSA-N FC1=C(C2=NC3=CC=NC=C3N2)C=CC=C1.FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CCl)=C1 Chemical compound FC1=C(C2=NC3=CC=NC=C3N2)C=CC=C1.FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CCl)=C1 UCRQNOWRKSMNII-UHFFFAOYSA-N 0.000 description 1
- MFGIYKBXYDVRED-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC(Br)=CC(Br)=C4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC(Br)=CC(Br)=C4)C=CC3=N2)C=CC=C1 MFGIYKBXYDVRED-UHFFFAOYSA-N 0.000 description 1
- VDCSPIOVHPOVRE-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC(C5=CC=CC=C5)=NO4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC(C5=CC=CC=C5)=NO4)C=CC3=N2)C=CC=C1 VDCSPIOVHPOVRE-UHFFFAOYSA-N 0.000 description 1
- IVSVQAXOPVWVCS-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC(Cl)=C(OC(F)(F)F)C=C4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC(Cl)=C(OC(F)(F)F)C=C4)C=CC3=N2)C=CC=C1 IVSVQAXOPVWVCS-UHFFFAOYSA-N 0.000 description 1
- JNQFMJYSWQRJDS-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC(F)=C(C(F)(F)F)C=C4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC(F)=C(C(F)(F)F)C=C4)C=CC3=N2)C=CC=C1 JNQFMJYSWQRJDS-UHFFFAOYSA-N 0.000 description 1
- DBPANVAZWQTTNS-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC(OC(F)(F)F)=CC=C4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC(OC(F)(F)F)=CC=C4)C=CC3=N2)C=CC=C1 DBPANVAZWQTTNS-UHFFFAOYSA-N 0.000 description 1
- YUDKIMNDXYULCU-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC(OC5=CC=CC=C5)=CC=C4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC(OC5=CC=CC=C5)=CC=C4)C=CC3=N2)C=CC=C1 YUDKIMNDXYULCU-UHFFFAOYSA-N 0.000 description 1
- GRGRYTUYRKTPPO-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC5=C(Cl)C=C(C(F)(F)F)N=C5C=C4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC5=C(Cl)C=C(C(F)(F)F)N=C5C=C4)C=CC3=N2)C=CC=C1 GRGRYTUYRKTPPO-UHFFFAOYSA-N 0.000 description 1
- GWEBIYDJKYRXAE-ZHACJKMWSA-N FC1=C(C2=NC3=CN(CC4=CC=C(/C=C/C5=CC=CC=C5)C=C4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC=C(/C=C/C5=CC=CC=C5)C=C4)C=CC3=N2)C=CC=C1 GWEBIYDJKYRXAE-ZHACJKMWSA-N 0.000 description 1
- CGJNEQACAUWASF-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC=C(C(F)(F)F)O4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC=C(C(F)(F)F)O4)C=CC3=N2)C=CC=C1 CGJNEQACAUWASF-UHFFFAOYSA-N 0.000 description 1
- ZFRBUDRKYHYELO-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC=C(Cl)C(C(F)(F)F)=C4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC=C(Cl)C(C(F)(F)F)=C4)C=CC3=N2)C=CC=C1 ZFRBUDRKYHYELO-UHFFFAOYSA-N 0.000 description 1
- KRLUPHLITQQPMX-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CC=CC(C(F)(F)F)=C4F)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CC=CC(C(F)(F)F)=C4F)C=CC3=N2)C=CC=C1 KRLUPHLITQQPMX-UHFFFAOYSA-N 0.000 description 1
- BFHMHZFSLIWRHK-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CSC(C5=CC=CC=C5)=N4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CSC(C5=CC=CC=C5)=N4)C=CC3=N2)C=CC=C1 BFHMHZFSLIWRHK-UHFFFAOYSA-N 0.000 description 1
- OPJDJHQGAXGUJP-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=CSC(C5=CC=CS5)=N4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=CSC(C5=CC=CS5)=N4)C=CC3=N2)C=CC=C1 OPJDJHQGAXGUJP-UHFFFAOYSA-N 0.000 description 1
- OLJVPZSURZIPIC-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=NC(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=NC(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)C=CC=C1 OLJVPZSURZIPIC-UHFFFAOYSA-N 0.000 description 1
- ISMODQAOWBWRLA-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=NOC(C5=CC(C(F)(F)F)=CC=C5)=N4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=NOC(C5=CC(C(F)(F)F)=CC=C5)=N4)C=CC3=N2)C=CC=C1 ISMODQAOWBWRLA-UHFFFAOYSA-N 0.000 description 1
- JQNIXGOICVZFHE-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=NOC(C5=CC=C(C(F)(F)F)C=C5)=N4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=NOC(C5=CC=C(C(F)(F)F)C=C5)=N4)C=CC3=N2)C=CC=C1 JQNIXGOICVZFHE-UHFFFAOYSA-N 0.000 description 1
- YCABXPHEEFONAF-UHFFFAOYSA-N FC1=C(C2=NC3=CN(CC4=NOC(C5=CC=CC=C5)=N4)C=CC3=N2)C=CC=C1 Chemical compound FC1=C(C2=NC3=CN(CC4=NOC(C5=CC=CC=C5)=N4)C=CC3=N2)C=CC=C1 YCABXPHEEFONAF-UHFFFAOYSA-N 0.000 description 1
- RINUERVPFANASB-UHFFFAOYSA-N FC1=C(CBr)C(C(F)(F)F)=CC=C1 Chemical compound FC1=C(CBr)C(C(F)(F)F)=CC=C1 RINUERVPFANASB-UHFFFAOYSA-N 0.000 description 1
- NDKCGHLFWAVIFL-UHFFFAOYSA-N FC1=C(CBr)C(C(F)(F)F)=CC=C1Cl Chemical compound FC1=C(CBr)C(C(F)(F)F)=CC=C1Cl NDKCGHLFWAVIFL-UHFFFAOYSA-N 0.000 description 1
- DJXBUSVMEONVRS-UHFFFAOYSA-N FC1=C(CBr)C=C(Cl)C=C1 Chemical compound FC1=C(CBr)C=C(Cl)C=C1 DJXBUSVMEONVRS-UHFFFAOYSA-N 0.000 description 1
- UFCSSWZQROEFBZ-UHFFFAOYSA-N FC1=C(CBr)C=CC(Cl)=C1 Chemical compound FC1=C(CBr)C=CC(Cl)=C1 UFCSSWZQROEFBZ-UHFFFAOYSA-N 0.000 description 1
- UDKQGFMDBMYVHI-UHFFFAOYSA-N FC1=C(CCl)C=CC(Br)=C1 Chemical compound FC1=C(CCl)C=CC(Br)=C1 UDKQGFMDBMYVHI-UHFFFAOYSA-N 0.000 description 1
- YFSLAUMUBPWDNY-UHFFFAOYSA-N FC1=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C(Cl)C=C1 Chemical compound FC1=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C(Cl)C=C1 YFSLAUMUBPWDNY-UHFFFAOYSA-N 0.000 description 1
- GGTQWWTYUKXFPP-UHFFFAOYSA-N FC1=C(Cl)C=C(CBr)C=C1 Chemical compound FC1=C(Cl)C=C(CBr)C=C1 GGTQWWTYUKXFPP-UHFFFAOYSA-N 0.000 description 1
- BDTHJNYVMYYBCK-UHFFFAOYSA-N FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(Cl)C=C4Cl)=NO3)C=CC2=N1 Chemical compound FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(Cl)C=C4Cl)=NO3)C=CC2=N1 BDTHJNYVMYYBCK-UHFFFAOYSA-N 0.000 description 1
- IQVUPLRVCSBIMH-UHFFFAOYSA-N FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(OC(F)(F)F)C=C4)=NO3)C=CC2=N1 Chemical compound FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(OC(F)(F)F)C=C4)=NO3)C=CC2=N1 IQVUPLRVCSBIMH-UHFFFAOYSA-N 0.000 description 1
- ARDKXNJXSREKSB-UHFFFAOYSA-N FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC(C4=CC=CC=C4OC(F)F)=NO3)C=CC2=N1 Chemical compound FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC(C4=CC=CC=C4OC(F)F)=NO3)C=CC2=N1 ARDKXNJXSREKSB-UHFFFAOYSA-N 0.000 description 1
- UWVOMHHPUDTLLP-UHFFFAOYSA-N FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC=C(I)C=C3)C=CC2=N1 Chemical compound FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC=C(I)C=C3)C=CC2=N1 UWVOMHHPUDTLLP-UHFFFAOYSA-N 0.000 description 1
- UVQAXTOLGBMLLQ-UHFFFAOYSA-N FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC=C(OC(F)(F)F)C=C3)C=CC2=N1 Chemical compound FC1=C(Cl)C=CC=C1C1=NC2=CN(CC3=CC=C(OC(F)(F)F)C=C3)C=CC2=N1 UVQAXTOLGBMLLQ-UHFFFAOYSA-N 0.000 description 1
- NAQZLFOKFHJHQL-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CC=NC=C3N2)=CC=C1.NC1=CC=NC=C1N.O=C(O)C1=CC=CC(F)=C1F Chemical compound FC1=C(F)C(C2=NC3=CC=NC=C3N2)=CC=C1.NC1=CC=NC=C1N.O=C(O)C1=CC=CC(F)=C1F NAQZLFOKFHJHQL-UHFFFAOYSA-N 0.000 description 1
- SLEYRMXORZTBHZ-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=C(C(F)(F)F)C=CC=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=C(C(F)(F)F)C=CC=C5)=NO4)C=CC3=N2)=CC=C1 SLEYRMXORZTBHZ-UHFFFAOYSA-N 0.000 description 1
- WDRNMQHKIFALRP-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=C(F)C=CC=C5C(F)(F)F)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=C(F)C=CC=C5C(F)(F)F)=NO4)C=CC3=N2)=CC=C1 WDRNMQHKIFALRP-UHFFFAOYSA-N 0.000 description 1
- VFPSEJXKCVNPTE-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=C(OC(F)(F)F)C=CC=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=C(OC(F)(F)F)C=CC=C5)=NO4)C=CC3=N2)=CC=C1 VFPSEJXKCVNPTE-UHFFFAOYSA-N 0.000 description 1
- MGHGJCDWCSDHCE-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(C(F)(F)F)C=C5C(F)(F)F)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(C(F)(F)F)C=C5C(F)(F)F)=NO4)C=CC3=N2)=CC=C1 MGHGJCDWCSDHCE-UHFFFAOYSA-N 0.000 description 1
- KVQRITKPCZPOQI-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NN4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NN4)C=CC3=N2)=CC=C1 KVQRITKPCZPOQI-UHFFFAOYSA-N 0.000 description 1
- LXZADEDJJICMEM-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NO4)C=NC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NO4)C=NC3=N2)=CC=C1 LXZADEDJJICMEM-UHFFFAOYSA-N 0.000 description 1
- OZYPITLWYKHSLC-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OC(F)(F)F)C=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OC(F)(F)F)C=C5)=NO4)C=CC3=N2)=CC=C1 OZYPITLWYKHSLC-UHFFFAOYSA-N 0.000 description 1
- MXCHEWIPCCJTET-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OCC6CCCCC6)C=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OCC6CCCCC6)C=C5)=NO4)C=CC3=N2)=CC=C1 MXCHEWIPCCJTET-UHFFFAOYSA-N 0.000 description 1
- XHYZQFCYGDBCCV-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=COC=C5)=NO4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(C5=COC=C5)=NO4)C=CC3=N2)=CC=C1 XHYZQFCYGDBCCV-UHFFFAOYSA-N 0.000 description 1
- SDDFPVIODHDXDK-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC(OC(F)(F)F)=CC=C4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC(OC(F)(F)F)=CC=C4)C=CC3=N2)=CC=C1 SDDFPVIODHDXDK-UHFFFAOYSA-N 0.000 description 1
- JBLIXOZXGNTMRD-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC=C(Br)C=C4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC=C(Br)C=C4)C=CC3=N2)=CC=C1 JBLIXOZXGNTMRD-UHFFFAOYSA-N 0.000 description 1
- KIUQOSFBSZFJDS-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC=C(C(F)(F)F)C=C4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC=C(C(F)(F)F)C=C4)C=CC3=N2)=CC=C1 KIUQOSFBSZFJDS-UHFFFAOYSA-N 0.000 description 1
- GAABNSYPXLCZPR-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=CC=C(C5=CC=C(C6=CC=CS6)C=C5)C=C4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=CC=C(C5=CC=C(C6=CC=CS6)C=C5)C=C4)C=CC3=N2)=CC=C1 GAABNSYPXLCZPR-UHFFFAOYSA-N 0.000 description 1
- YHKBYTZEJNAKRV-UHFFFAOYSA-N FC1=C(F)C(C2=NC3=CN(CC4=NC5=CC(Cl)=CC=C5O4)C=CC3=N2)=CC=C1 Chemical compound FC1=C(F)C(C2=NC3=CN(CC4=NC5=CC(Cl)=CC=C5O4)C=CC3=N2)=CC=C1 YHKBYTZEJNAKRV-UHFFFAOYSA-N 0.000 description 1
- JQNQDDLNDKORCE-UHFFFAOYSA-N FC1=C(F)C(C2NC3=CN(CC4=CC=C(I)C=C4)C=CC3N2)=CC=C1.FC1=CC(F)=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C=C2)C=C1.OB(O)C1=CC=C(F)C=C1F Chemical compound FC1=C(F)C(C2NC3=CN(CC4=CC=C(I)C=C4)C=CC3N2)=CC=C1.FC1=CC(F)=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C=C2)C=C1.OB(O)C1=CC=C(F)C=C1F JQNQDDLNDKORCE-UHFFFAOYSA-N 0.000 description 1
- QPLUIZXBWYUFMY-UHFFFAOYSA-N FC1=CC(Br)=C(CBr)C=C1 Chemical compound FC1=CC(Br)=C(CBr)C=C1 QPLUIZXBWYUFMY-UHFFFAOYSA-N 0.000 description 1
- MUYUOBOAWAXJIN-UHFFFAOYSA-N FC1=CC(Br)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)=C1 Chemical compound FC1=CC(Br)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)=C1 MUYUOBOAWAXJIN-UHFFFAOYSA-N 0.000 description 1
- UUWDRNYJILYINV-UHFFFAOYSA-N FC1=CC(Br)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 Chemical compound FC1=CC(Br)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 UUWDRNYJILYINV-UHFFFAOYSA-N 0.000 description 1
- FQENPXMGHXVBCF-UHFFFAOYSA-N FC1=CC(Br)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)=C1 Chemical compound FC1=CC(Br)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)=C1 FQENPXMGHXVBCF-UHFFFAOYSA-N 0.000 description 1
- UYFPCRXZDFWHOA-UHFFFAOYSA-N FC1=CC(C(F)(F)F)=CC(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)=C1 Chemical compound FC1=CC(C(F)(F)F)=CC(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)=C1 UYFPCRXZDFWHOA-UHFFFAOYSA-N 0.000 description 1
- KJJWBNKNUGONLM-UHFFFAOYSA-N FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CCl)=C1 Chemical compound FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CCl)=C1 KJJWBNKNUGONLM-UHFFFAOYSA-N 0.000 description 1
- KQVDBXPGSXFQBQ-UHFFFAOYSA-N FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)=C1 Chemical compound FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)=C1 KQVDBXPGSXFQBQ-UHFFFAOYSA-N 0.000 description 1
- FMAUWPUNUMBFDU-UHFFFAOYSA-N FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)=C1 Chemical compound FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)=C1 FMAUWPUNUMBFDU-UHFFFAOYSA-N 0.000 description 1
- FNXNYXMKCKYQEH-UHFFFAOYSA-N FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 Chemical compound FC1=CC(C(F)(F)F)=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 FNXNYXMKCKYQEH-UHFFFAOYSA-N 0.000 description 1
- MQUCRCQNRDHRPL-UHFFFAOYSA-N FC1=CC(C(F)(F)F)=CC=C1CBr Chemical compound FC1=CC(C(F)(F)F)=CC=C1CBr MQUCRCQNRDHRPL-UHFFFAOYSA-N 0.000 description 1
- WNEKWFICDBOPIP-UHFFFAOYSA-N FC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=C(F)C=C1 Chemical compound FC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=C(F)C=C1 WNEKWFICDBOPIP-UHFFFAOYSA-N 0.000 description 1
- RAMAMVZRWURROP-UHFFFAOYSA-N FC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 Chemical compound FC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 RAMAMVZRWURROP-UHFFFAOYSA-N 0.000 description 1
- NELHIKIEFUXJMD-UHFFFAOYSA-N FC1=CC(C2=CC=CC=C2)=CC=C1CN1C=CC2=NC(C3=CC=CC(Cl)=C3F)=NC2=C1 Chemical compound FC1=CC(C2=CC=CC=C2)=CC=C1CN1C=CC2=NC(C3=CC=CC(Cl)=C3F)=NC2=C1 NELHIKIEFUXJMD-UHFFFAOYSA-N 0.000 description 1
- RZDVWRJIDHNVNM-UHFFFAOYSA-N FC1=CC(C2=CC=CC=C2)=CC=C1CN1C=CC2=NC(C3=CC=CC(F)=C3F)=NC2=C1 Chemical compound FC1=CC(C2=CC=CC=C2)=CC=C1CN1C=CC2=NC(C3=CC=CC(F)=C3F)=NC2=C1 RZDVWRJIDHNVNM-UHFFFAOYSA-N 0.000 description 1
- FATBYMYDKNKEEE-UHFFFAOYSA-N FC1=CC(C2=CC=CC=C2)=CC=C1CN1C=CC2=NC(C3=CC=CC=C3F)=NC2=C1 Chemical compound FC1=CC(C2=CC=CC=C2)=CC=C1CN1C=CC2=NC(C3=CC=CC=C3F)=NC2=C1 FATBYMYDKNKEEE-UHFFFAOYSA-N 0.000 description 1
- DZSJIJONJFISCS-UHFFFAOYSA-N FC1=CC(C2=CC=CC=C2C(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC(Cl)=C3F)=NC2=C1 Chemical compound FC1=CC(C2=CC=CC=C2C(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC(Cl)=C3F)=NC2=C1 DZSJIJONJFISCS-UHFFFAOYSA-N 0.000 description 1
- VWYJVWWVCGXDAP-UHFFFAOYSA-N FC1=CC(C2=CC=CC=C2C(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC(F)=C3F)=NC2=C1 Chemical compound FC1=CC(C2=CC=CC=C2C(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC(F)=C3F)=NC2=C1 VWYJVWWVCGXDAP-UHFFFAOYSA-N 0.000 description 1
- FQICSHMHRNSKDG-UHFFFAOYSA-N FC1=CC(C2=CC=CC=C2C(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC=C3F)=NC2=C1 Chemical compound FC1=CC(C2=CC=CC=C2C(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC=C3F)=NC2=C1 FQICSHMHRNSKDG-UHFFFAOYSA-N 0.000 description 1
- GEVXJZBIFGIVKZ-UHFFFAOYSA-N FC1=CC(C2=CC=CC=C2OC(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC=C3F)=NC2=C1 Chemical compound FC1=CC(C2=CC=CC=C2OC(F)(F)F)=CC=C1CN1C=CC2=NC(C3=CC=CC=C3F)=NC2=C1 GEVXJZBIFGIVKZ-UHFFFAOYSA-N 0.000 description 1
- MQZWBTRGSDOAIO-UHFFFAOYSA-N FC1=CC(CBr)=C(C(F)(F)F)C=C1 Chemical compound FC1=CC(CBr)=C(C(F)(F)F)C=C1 MQZWBTRGSDOAIO-UHFFFAOYSA-N 0.000 description 1
- AUVLFQDKJFSFIX-UHFFFAOYSA-N FC1=CC(CBr)=C(Cl)C=C1 Chemical compound FC1=CC(CBr)=C(Cl)C=C1 AUVLFQDKJFSFIX-UHFFFAOYSA-N 0.000 description 1
- LCVWAXYGYMZJER-UHFFFAOYSA-N FC1=CC(CBr)=CC(C(F)(F)F)=C1 Chemical compound FC1=CC(CBr)=CC(C(F)(F)F)=C1 LCVWAXYGYMZJER-UHFFFAOYSA-N 0.000 description 1
- ZWOGKGYLCHMEJO-UHFFFAOYSA-N FC1=CC(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1 Chemical compound FC1=CC(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1 ZWOGKGYLCHMEJO-UHFFFAOYSA-N 0.000 description 1
- GEDNDNXNCLQCKY-UHFFFAOYSA-N FC1=CC(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1OC(F)(F)F Chemical compound FC1=CC(CN2C=CC3=NC(C4=CC=CC(Cl)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1OC(F)(F)F GEDNDNXNCLQCKY-UHFFFAOYSA-N 0.000 description 1
- GADHRSNDAZQORZ-UHFFFAOYSA-N FC1=CC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1 Chemical compound FC1=CC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1 GADHRSNDAZQORZ-UHFFFAOYSA-N 0.000 description 1
- NUHKUMAZNIOZNK-UHFFFAOYSA-N FC1=CC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1C(F)(F)F Chemical compound FC1=CC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1C(F)(F)F NUHKUMAZNIOZNK-UHFFFAOYSA-N 0.000 description 1
- HQLFFTZKHWQOIV-UHFFFAOYSA-N FC1=CC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1OC(F)(F)F Chemical compound FC1=CC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1OC(F)(F)F HQLFFTZKHWQOIV-UHFFFAOYSA-N 0.000 description 1
- WXKUVYDZFLLRMZ-UHFFFAOYSA-N FC1=CC(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1OC(F)(F)F Chemical compound FC1=CC(CN2C=CC3=NC(C4=CC=CC=C4F)=NC3=C2)=CC=C1C1=CC=CC=C1OC(F)(F)F WXKUVYDZFLLRMZ-UHFFFAOYSA-N 0.000 description 1
- GAUUDQVOPUKGJD-UHFFFAOYSA-N FC1=CC(Cl)=C(CBr)C=C1 Chemical compound FC1=CC(Cl)=C(CBr)C=C1 GAUUDQVOPUKGJD-UHFFFAOYSA-N 0.000 description 1
- KYKUEAHGMDKVLF-UHFFFAOYSA-N FC1=CC(Cl)=CC(F)=C1CBr Chemical compound FC1=CC(Cl)=CC(F)=C1CBr KYKUEAHGMDKVLF-UHFFFAOYSA-N 0.000 description 1
- KOXDMZFESRZMFZ-UHFFFAOYSA-N FC1=CC(F)=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)N=N2)C=C1 Chemical compound FC1=CC(F)=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)N=N2)C=C1 KOXDMZFESRZMFZ-UHFFFAOYSA-N 0.000 description 1
- QLXCCENHQCCPNQ-UHFFFAOYSA-N FC1=CC(F)=C(C2=CN=CC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 Chemical compound FC1=CC(F)=C(C2=CN=CC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C=C1 QLXCCENHQCCPNQ-UHFFFAOYSA-N 0.000 description 1
- KBDCRWZKXDEQBE-UHFFFAOYSA-N FC1=CC(F)=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C(F)=C1 Chemical compound FC1=CC(F)=C(C2=NOC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C(F)=C1 KBDCRWZKXDEQBE-UHFFFAOYSA-N 0.000 description 1
- KVSVNRFSKRFPIL-UHFFFAOYSA-N FC1=CC(F)=CC(CBr)=C1 Chemical compound FC1=CC(F)=CC(CBr)=C1 KVSVNRFSKRFPIL-UHFFFAOYSA-N 0.000 description 1
- VNGSMSFVLAAOGK-UHFFFAOYSA-N FC1=CC(F)=CC(CCl)=C1 Chemical compound FC1=CC(F)=CC(CCl)=C1 VNGSMSFVLAAOGK-UHFFFAOYSA-N 0.000 description 1
- OORWOUINIITOHK-UHFFFAOYSA-N FC1=CC(OCC2=CC=C(C(F)(F)F)O2)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound FC1=CC(OCC2=CC=C(C(F)(F)F)O2)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 OORWOUINIITOHK-UHFFFAOYSA-N 0.000 description 1
- LIYYZRFBRZNUCT-UHFFFAOYSA-N FC1=CC(OCCC(F)=C(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound FC1=CC(OCCC(F)=C(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 LIYYZRFBRZNUCT-UHFFFAOYSA-N 0.000 description 1
- ZKJBZOJRPNKVSL-UHFFFAOYSA-N FC1=CC(OCCCN2C=CC=C2)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound FC1=CC(OCCCN2C=CC=C2)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 ZKJBZOJRPNKVSL-UHFFFAOYSA-N 0.000 description 1
- RPQMGBGIVWFDQL-UHFFFAOYSA-N FC1=CC(OCCN2C=CC=C2)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound FC1=CC(OCCN2C=CC=C2)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 RPQMGBGIVWFDQL-UHFFFAOYSA-N 0.000 description 1
- FMONGDHUPLQOCP-UHFFFAOYSA-N FC1=CC2=C(OCOC2)C(CCl)=C1 Chemical compound FC1=CC2=C(OCOC2)C(CCl)=C1 FMONGDHUPLQOCP-UHFFFAOYSA-N 0.000 description 1
- BYRMZRWUEAESEZ-UHFFFAOYSA-N FC1=CC=C(C(F)(F)F)C=C1CBr Chemical compound FC1=CC=C(C(F)(F)F)C=C1CBr BYRMZRWUEAESEZ-UHFFFAOYSA-N 0.000 description 1
- PLNPCPNYXUIECF-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C(F)=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C(F)=C1 PLNPCPNYXUIECF-UHFFFAOYSA-N 0.000 description 1
- BRICJUGMFWXHEL-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 BRICJUGMFWXHEL-UHFFFAOYSA-N 0.000 description 1
- FOQVHNCBKKWDNQ-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1Cl Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1Cl FOQVHNCBKKWDNQ-UHFFFAOYSA-N 0.000 description 1
- IDOXKRBDPDLCSB-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1F Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1F IDOXKRBDPDLCSB-UHFFFAOYSA-N 0.000 description 1
- ZTZRFJWSVFAAGV-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)C=N2)C(F)=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)C=N2)C(F)=C1 ZTZRFJWSVFAAGV-UHFFFAOYSA-N 0.000 description 1
- DSCWFNZXIUVATR-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)C=C2F)C(F)=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)C=C2F)C(F)=C1 DSCWFNZXIUVATR-UHFFFAOYSA-N 0.000 description 1
- UQTSTXJMUHYEMH-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C(C(F)(F)F)=C2)C(F)=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C(C(F)(F)F)=C2)C(F)=C1 UQTSTXJMUHYEMH-UHFFFAOYSA-N 0.000 description 1
- ZIIVVEOCFIWQGB-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C(F)=C2)C(F)=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C(F)=C2)C(F)=C1 ZIIVVEOCFIWQGB-UHFFFAOYSA-N 0.000 description 1
- PNRQYQHODWKDHH-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C=C2F)C(F)=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)C=C2F)C(F)=C1 PNRQYQHODWKDHH-UHFFFAOYSA-N 0.000 description 1
- DGAWRKUJLGEOHV-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C(F)=C2)C(F)=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C(F)=C2)C(F)=C1 DGAWRKUJLGEOHV-UHFFFAOYSA-N 0.000 description 1
- BPYORNQQLJGXBV-UHFFFAOYSA-N FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C=C2F)C(F)=C1 Chemical compound FC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)C=C2F)C(F)=C1 BPYORNQQLJGXBV-UHFFFAOYSA-N 0.000 description 1
- FIURQAITOHMATC-UHFFFAOYSA-N FC1=CC=C(C2=NOC(CCl)=C2)C(C(F)(F)F)=C1.FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C(C(F)(F)F)=C1.FC1=CC=CC=C1C1=NC2=CC=NC=C2N1 Chemical compound FC1=CC=C(C2=NOC(CCl)=C2)C(C(F)(F)F)=C1.FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C(C(F)(F)F)=C1.FC1=CC=CC=C1C1=NC2=CC=NC=C2N1 FIURQAITOHMATC-UHFFFAOYSA-N 0.000 description 1
- BEGFXJXYAQULIU-UHFFFAOYSA-N FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)=C2)C(C(F)(F)F)=C1 Chemical compound FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)=C2)C(C(F)(F)F)=C1 BEGFXJXYAQULIU-UHFFFAOYSA-N 0.000 description 1
- QNXOTFWAJSJIEJ-UHFFFAOYSA-N FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)=C2)C(F)=C1 Chemical compound FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(Cl)=C5F)=NC4=C3)=C2)C(F)=C1 QNXOTFWAJSJIEJ-UHFFFAOYSA-N 0.000 description 1
- JMXHUBVGSXJYRR-UHFFFAOYSA-N FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(C(F)(F)F)=C1 Chemical compound FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC(F)=C5F)=NC4=C3)=C2)C(C(F)(F)F)=C1 JMXHUBVGSXJYRR-UHFFFAOYSA-N 0.000 description 1
- SXVYISKQZNEQOI-UHFFFAOYSA-N FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C(F)=C1 Chemical compound FC1=CC=C(C2=NOC(CN3C=CC4=NC(C5=CC=CC=C5F)=NC4=C3)=C2)C(F)=C1 SXVYISKQZNEQOI-UHFFFAOYSA-N 0.000 description 1
- JMNOONULDANZRZ-UHFFFAOYSA-N FC1=CC=C(CBr)C(C(F)(F)F)=C1 Chemical compound FC1=CC=C(CBr)C(C(F)(F)F)=C1 JMNOONULDANZRZ-UHFFFAOYSA-N 0.000 description 1
- JVQDTRQMKZMBAU-UHFFFAOYSA-N FC1=CC=C(CBr)C=C1C(F)(F)F Chemical compound FC1=CC=C(CBr)C=C1C(F)(F)F JVQDTRQMKZMBAU-UHFFFAOYSA-N 0.000 description 1
- PEYAZTMGRXSTQM-UHFFFAOYSA-N FC1=CC=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1C(F)(F)F Chemical compound FC1=CC=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1C(F)(F)F PEYAZTMGRXSTQM-UHFFFAOYSA-N 0.000 description 1
- JGFSTQUUDSBQCO-UHFFFAOYSA-N FC1=CC=C(OC2=CC(CBr)=CC=C2)C=C1 Chemical compound FC1=CC=C(OC2=CC(CBr)=CC=C2)C=C1 JGFSTQUUDSBQCO-UHFFFAOYSA-N 0.000 description 1
- UEMHAHNLTLCLDB-UHFFFAOYSA-N FC1=CC=C(OC2=CC=CC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C=C1 Chemical compound FC1=CC=C(OC2=CC=CC(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)=C2)C=C1 UEMHAHNLTLCLDB-UHFFFAOYSA-N 0.000 description 1
- ZGGZGYLUVPYTHJ-UHFFFAOYSA-N FC1=CC=C(OC2=CC=CC(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)=C2)C=C1 Chemical compound FC1=CC=C(OC2=CC=CC(CN3C=CC4=NC(C5=C(F)C=CC=C5)=NC4=C3)=C2)C=C1 ZGGZGYLUVPYTHJ-UHFFFAOYSA-N 0.000 description 1
- AILQJFIRCWXTHG-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=C(Br)C(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=C(Br)C(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)=C1F AILQJFIRCWXTHG-UHFFFAOYSA-N 0.000 description 1
- SPXJMUPUSHERKI-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=C(C(F)(F)F)C=C(C(F)(F)F)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=C(C(F)(F)F)C=C(C(F)(F)F)C=C4)C=CC3=N2)=C1F SPXJMUPUSHERKI-UHFFFAOYSA-N 0.000 description 1
- HBQCXCUUPRATKN-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=C(Cl)C(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=C(Cl)C(C5=CC=C(Cl)C=C5)=NO4)C=CC3=N2)=C1F HBQCXCUUPRATKN-UHFFFAOYSA-N 0.000 description 1
- FAKGEMMKNVITAP-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC(Br)=CC(Br)=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC(Br)=CC(Br)=C4)C=CC3=N2)=C1F FAKGEMMKNVITAP-UHFFFAOYSA-N 0.000 description 1
- DNKPIDNBUPFLIN-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NO4)C=C(C(F)(F)F)C3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NO4)C=C(C(F)(F)F)C3=N2)=C1F DNKPIDNBUPFLIN-UHFFFAOYSA-N 0.000 description 1
- MXENRFUGAKGCAT-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC(C5=CC=CC=C5)=NO4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC(C5=CC=CC=C5)=NO4)C=CC3=N2)=C1F MXENRFUGAKGCAT-UHFFFAOYSA-N 0.000 description 1
- GFSCSAIEFOXVMR-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC(Cl)=C(OC(F)(F)F)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC(Cl)=C(OC(F)(F)F)C=C4)C=CC3=N2)=C1F GFSCSAIEFOXVMR-UHFFFAOYSA-N 0.000 description 1
- SLTADVOILXOWTR-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(/C5=C/C6=C(C=CC=C6)O5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(/C5=C/C6=C(C=CC=C6)O5)C=C4)C=CC3=N2)=C1F SLTADVOILXOWTR-UHFFFAOYSA-N 0.000 description 1
- UJRGERLRYKVZBP-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(/C5=C/C6=C(C=CC=C6)S5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(/C5=C/C6=C(C=CC=C6)S5)C=C4)C=CC3=N2)=C1F UJRGERLRYKVZBP-UHFFFAOYSA-N 0.000 description 1
- LFWXOGDFMODOLV-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6=CC=C(C(F)(F)F)O6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6=CC=C(C(F)(F)F)O6)C=C5)C=C4)C=CC3=N2)=C1F LFWXOGDFMODOLV-UHFFFAOYSA-N 0.000 description 1
- CMSKTYMAOORNKV-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6=NC=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6=NC=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F CMSKTYMAOORNKV-UHFFFAOYSA-N 0.000 description 1
- ZEQJWPQKJLKPCF-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6CC6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6CC6)C=C5)C=C4)C=CC3=N2)=C1F ZEQJWPQKJLKPCF-UHFFFAOYSA-N 0.000 description 1
- ROTKKLBVOKQSLN-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6CCC6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6CCC6)C=C5)C=C4)C=CC3=N2)=C1F ROTKKLBVOKQSLN-UHFFFAOYSA-N 0.000 description 1
- JYXZGXVZUOPZKC-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6CCCO6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCC6CCCO6)C=C5)C=C4)C=CC3=N2)=C1F JYXZGXVZUOPZKC-UHFFFAOYSA-N 0.000 description 1
- CCQBRHMCJYDWFE-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCCC6OCCCO6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCCC6OCCCO6)C=C5)C=C4)C=CC3=N2)=C1F CCQBRHMCJYDWFE-UHFFFAOYSA-N 0.000 description 1
- WXPNEBILZYHWSZ-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCCN6C=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(C(F)(F)F)C=C(OCCN6C=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F WXPNEBILZYHWSZ-UHFFFAOYSA-N 0.000 description 1
- RCIROZOZGCEETC-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(Cl)C=CC(Cl)=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=C(Cl)C=CC(Cl)=C5)C=C4)C=CC3=N2)=C1F RCIROZOZGCEETC-UHFFFAOYSA-N 0.000 description 1
- CAWLXKQLQHRVEG-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC(C(F)(F)F)=CC(C(F)(F)F)=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC(C(F)(F)F)=CC(C(F)(F)F)=C5)C=C4)C=CC3=N2)=C1F CAWLXKQLQHRVEG-UHFFFAOYSA-N 0.000 description 1
- CRHSMQLCJZITIY-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC(C(F)(F)F)=CC=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC(C(F)(F)F)=CC=C5)C=C4)C=CC3=N2)=C1F CRHSMQLCJZITIY-UHFFFAOYSA-N 0.000 description 1
- GJRMBAGSCSDHLM-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC(Cl)=CC(Cl)=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC(Cl)=CC(Cl)=C5)C=C4)C=CC3=N2)=C1F GJRMBAGSCSDHLM-UHFFFAOYSA-N 0.000 description 1
- PXCANDGYPULNMG-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC(OC(F)(F)F)=CC=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC(OC(F)(F)F)=CC=C5)C=C4)C=CC3=N2)=C1F PXCANDGYPULNMG-UHFFFAOYSA-N 0.000 description 1
- IUEDOEHSPAALIC-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC6=CC=CC=C6C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC6=CC=CC=C6C=C5)C=C4)C=CC3=N2)=C1F IUEDOEHSPAALIC-UHFFFAOYSA-N 0.000 description 1
- FSLNQKGUBQUSQB-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(C(F)(F)F)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(C(F)(F)F)C=C5)C=C4)C=CC3=N2)=C1F FSLNQKGUBQUSQB-UHFFFAOYSA-N 0.000 description 1
- WSSOIXJZVUKKMJ-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(C6=CN=CO6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(C6=CN=CO6)C=C5)C=C4)C=CC3=N2)=C1F WSSOIXJZVUKKMJ-UHFFFAOYSA-N 0.000 description 1
- XHSBOHRQSWDHGI-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(Cl)C(Cl)=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(Cl)C(Cl)=C5)C=C4)C=CC3=N2)=C1F XHSBOHRQSWDHGI-UHFFFAOYSA-N 0.000 description 1
- KHGXAWPYHQVEMQ-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(Cl)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(Cl)C=C5)C=C4)C=CC3=N2)=C1F KHGXAWPYHQVEMQ-UHFFFAOYSA-N 0.000 description 1
- YBQOCTKJQBVHDB-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(Cl)S5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(Cl)S5)C=C4)C=CC3=N2)=C1F YBQOCTKJQBVHDB-UHFFFAOYSA-N 0.000 description 1
- FMJKXPOETAYGSM-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OC(F)F)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OC(F)F)C=C5)C=C4)C=CC3=N2)=C1F FMJKXPOETAYGSM-UHFFFAOYSA-N 0.000 description 1
- YUOFRZMGWDABOA-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OC6=CC=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OC6=CC=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F YUOFRZMGWDABOA-UHFFFAOYSA-N 0.000 description 1
- IGVJNFWPZQAYQA-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCCC6OCCCO6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCCC6OCCCO6)C=C5)C=C4)C=CC3=N2)=C1F IGVJNFWPZQAYQA-UHFFFAOYSA-N 0.000 description 1
- ZORHDFZQFFPXTD-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCCN6C=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=C(OCCN6C=CC=C6)C=C5)C=C4)C=CC3=N2)=C1F ZORHDFZQFFPXTD-UHFFFAOYSA-N 0.000 description 1
- WHJUHHYZNFMPPC-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC(Cl)=C5Cl)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC(Cl)=C5Cl)C=C4)C=CC3=N2)=C1F WHJUHHYZNFMPPC-UHFFFAOYSA-N 0.000 description 1
- LOWJGBXTNKMVDG-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC(F)=C5F)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC(F)=C5F)C=C4)C=CC3=N2)=C1F LOWJGBXTNKMVDG-UHFFFAOYSA-N 0.000 description 1
- MBKVDCKABLVHAN-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC(OCC6=CC=CC=C6)=C5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC(OCC6=CC=CC=C6)=C5)C=C4)C=CC3=N2)=C1F MBKVDCKABLVHAN-UHFFFAOYSA-N 0.000 description 1
- ZYCDPNCUUTYXTH-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC=C5C(F)(F)F)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC=C5C(F)(F)F)C=C4)C=CC3=N2)=C1F ZYCDPNCUUTYXTH-UHFFFAOYSA-N 0.000 description 1
- CDLXYFIZGLUHNP-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC=C5Cl)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC=C5Cl)C=C4)C=CC3=N2)=C1F CDLXYFIZGLUHNP-UHFFFAOYSA-N 0.000 description 1
- MUBUNXXLLXPNRT-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC=C5OC(F)(F)F)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CC=C5OC(F)(F)F)C=C4)C=CC3=N2)=C1F MUBUNXXLLXPNRT-UHFFFAOYSA-N 0.000 description 1
- MPYXULIXVMAAEM-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CO5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CO5)C=C4)C=CC3=N2)=C1F MPYXULIXVMAAEM-UHFFFAOYSA-N 0.000 description 1
- RGSOPQBOVNUCRB-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CS5)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CC=CS5)C=C4)C=CC3=N2)=C1F RGSOPQBOVNUCRB-UHFFFAOYSA-N 0.000 description 1
- MOFWYBZNAJLGJM-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CSC6=C5C=CC=C6)C=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(C5=CSC6=C5C=CC=C6)C=C4)C=CC3=N2)=C1F MOFWYBZNAJLGJM-UHFFFAOYSA-N 0.000 description 1
- RSVWTIKCBDYWFZ-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(Cl)C(C(F)(F)F)=C4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(Cl)C(C(F)(F)F)=C4)C=CC3=N2)=C1F RSVWTIKCBDYWFZ-UHFFFAOYSA-N 0.000 description 1
- MXBNQHOLBRJUHB-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CC=C(Cl)C=C4Cl)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CC=C(Cl)C=C4Cl)C=CC3=N2)=C1F MXBNQHOLBRJUHB-UHFFFAOYSA-N 0.000 description 1
- DSRZJIXZMQTNHV-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CSC(C5=CC=C(C(F)(F)F)C=C5)=N4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CSC(C5=CC=C(C(F)(F)F)C=C5)=N4)C=CC3=N2)=C1F DSRZJIXZMQTNHV-UHFFFAOYSA-N 0.000 description 1
- QYFJASPQOCOBBG-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=CSC(C5=CC=CC=C5)=N4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=CSC(C5=CC=CC=C5)=N4)C=CC3=N2)=C1F QYFJASPQOCOBBG-UHFFFAOYSA-N 0.000 description 1
- XMNJIENMAXJEHF-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=NC(C5=CC=NC=C5)=NO4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=NC(C5=CC=NC=C5)=NO4)C=CC3=N2)=C1F XMNJIENMAXJEHF-UHFFFAOYSA-N 0.000 description 1
- GQFPBOLNYBIPHY-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=NC(C5=NC=CC=C5)=NO4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=NC(C5=NC=CC=C5)=NO4)C=CC3=N2)=C1F GQFPBOLNYBIPHY-UHFFFAOYSA-N 0.000 description 1
- WJANCEVSBKSUFP-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=NN=C(C5=CC=C(Cl)C=C5)O4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=NN=C(C5=CC=C(Cl)C=C5)O4)C=CC3=N2)=C1F WJANCEVSBKSUFP-UHFFFAOYSA-N 0.000 description 1
- RVUHBNXLECSELZ-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=NOC(C5=CC(C(F)(F)F)=CC=C5)=N4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=NOC(C5=CC(C(F)(F)F)=CC=C5)=N4)C=CC3=N2)=C1F RVUHBNXLECSELZ-UHFFFAOYSA-N 0.000 description 1
- HIXQAIHQRJUZMP-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=NOC(C5=CC=C(C(F)(F)F)C=C5)=N4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=NOC(C5=CC=C(C(F)(F)F)C=C5)=N4)C=CC3=N2)=C1F HIXQAIHQRJUZMP-UHFFFAOYSA-N 0.000 description 1
- DYWZBGURAPJRSZ-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=NOC(C5=CC=CC=C5)=N4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=NOC(C5=CC=CC=C5)=N4)C=CC3=N2)=C1F DYWZBGURAPJRSZ-UHFFFAOYSA-N 0.000 description 1
- OGCMNAGBKLIKFT-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=NOC(C5=CC=CS5)=N4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=NOC(C5=CC=CS5)=N4)C=CC3=N2)=C1F OGCMNAGBKLIKFT-UHFFFAOYSA-N 0.000 description 1
- CUGPDDDHOIKMES-UHFFFAOYSA-N FC1=CC=CC(C2=NC3=CN(CC4=NSC(Cl)=N4)C=CC3=N2)=C1F Chemical compound FC1=CC=CC(C2=NC3=CN(CC4=NSC(Cl)=N4)C=CC3=N2)=C1F CUGPDDDHOIKMES-UHFFFAOYSA-N 0.000 description 1
- VEZAAMCYMVBLFV-CMDGGOBGSA-N FC1=CC=CC(Cl)=C1/C=C/C1=CC=C(CBr)C=C1 Chemical compound FC1=CC=CC(Cl)=C1/C=C/C1=CC=C(CBr)C=C1 VEZAAMCYMVBLFV-CMDGGOBGSA-N 0.000 description 1
- RODKRSRUFYGGLG-UHFFFAOYSA-N FC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound FC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 RODKRSRUFYGGLG-UHFFFAOYSA-N 0.000 description 1
- RCCACVBEUDZULH-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=C(C(F)(F)F)C=CC=C4F)=NO3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=C(C(F)(F)F)C=CC=C4F)=NO3)C=CC2=N1 RCCACVBEUDZULH-UHFFFAOYSA-N 0.000 description 1
- RPAPMGMPJHGWLY-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(OC(F)(F)F)C=C4)=NO3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=C(OC(F)(F)F)C=C4)=NO3)C=CC2=N1 RPAPMGMPJHGWLY-UHFFFAOYSA-N 0.000 description 1
- GSCORPMLHZPROR-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=CC=C4OC(F)F)=NO3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC(C4=CC=CC=C4OC(F)F)=NO3)C=CC2=N1 GSCORPMLHZPROR-UHFFFAOYSA-N 0.000 description 1
- MSZBYSLTRYXXBB-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC=C(C(F)(F)F)C=C3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC=C(C(F)(F)F)C=C3)C=CC2=N1 MSZBYSLTRYXXBB-UHFFFAOYSA-N 0.000 description 1
- QSPPBANZYOKTMW-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC=C(OC(F)(F)F)C=C3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC=C(OC(F)(F)F)C=C3)C=CC2=N1 QSPPBANZYOKTMW-UHFFFAOYSA-N 0.000 description 1
- ZDRRLDUNXNDNSV-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC=C(OCC4=CC=CC=C4)C=C3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC=C(OCC4=CC=CC=C4)C=C3)C=CC2=N1 ZDRRLDUNXNDNSV-UHFFFAOYSA-N 0.000 description 1
- NGODFORGVOWCMK-UHFFFAOYSA-N FC1=CC=CC=C1C1=NC2=CN(CC3=CC=C(SC(F)(F)F)C=C3)C=CC2=N1 Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC3=CC=C(SC(F)(F)F)C=C3)C=CC2=N1 NGODFORGVOWCMK-UHFFFAOYSA-N 0.000 description 1
- JKGULHHIABGMRV-UHFFFAOYSA-N FC1=CN(CC2=CC(C3=CC=C(Cl)C=C3)=NO2)C=C2N=C(C3=C(F)C(F)=CC=C3)N=C12 Chemical compound FC1=CN(CC2=CC(C3=CC=C(Cl)C=C3)=NO2)C=C2N=C(C3=C(F)C(F)=CC=C3)N=C12 JKGULHHIABGMRV-UHFFFAOYSA-N 0.000 description 1
- GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
- 241000710831 Flavivirus 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
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000711557 Hepacivirus Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 201000006219 Herpangina Diseases 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 102100039350 Interferon alpha-7 Human genes 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 206010027201 Meningitis aseptic Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- LFFIEVAMVPCZNA-UHFFFAOYSA-N N#CC1=C(C2=CC=C(CBr)C=C2)C=CC=C1 Chemical compound N#CC1=C(C2=CC=C(CBr)C=C2)C=CC=C1 LFFIEVAMVPCZNA-UHFFFAOYSA-N 0.000 description 1
- KEKOXVGTYYQOTD-UHFFFAOYSA-N N#CC1=C(C2=CC=C(CN3C=CC4=NC(C5=CSC=C5)=NC4=C3)C=C2)C=CC=C1 Chemical compound N#CC1=C(C2=CC=C(CN3C=CC4=NC(C5=CSC=C5)=NC4=C3)C=C2)C=CC=C1 KEKOXVGTYYQOTD-UHFFFAOYSA-N 0.000 description 1
- UNDBGHRTAXQUCO-UHFFFAOYSA-N N#CC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 Chemical compound N#CC1=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=CC=C1 UNDBGHRTAXQUCO-UHFFFAOYSA-N 0.000 description 1
- GUUKPGIJZYZERR-UHFFFAOYSA-N N#CC1=CC(CBr)=CC=C1F Chemical compound N#CC1=CC(CBr)=CC=C1F GUUKPGIJZYZERR-UHFFFAOYSA-N 0.000 description 1
- MFCRFXIAZKUGGP-UHFFFAOYSA-N N#CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound N#CC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 MFCRFXIAZKUGGP-UHFFFAOYSA-N 0.000 description 1
- DJOXAJDFHGJTAP-UHFFFAOYSA-N N#CC1=CC=C(CBr)C=C1F Chemical compound N#CC1=CC=C(CBr)C=C1F DJOXAJDFHGJTAP-UHFFFAOYSA-N 0.000 description 1
- VGKOPXSPRBQORS-UHFFFAOYSA-N N#CC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound N#CC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 VGKOPXSPRBQORS-UHFFFAOYSA-N 0.000 description 1
- RHLCWKRSKNUSAK-UHFFFAOYSA-N N#CC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1 Chemical compound N#CC1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)C=C1 RHLCWKRSKNUSAK-UHFFFAOYSA-N 0.000 description 1
- CZJZWNQTZWNQDS-UHFFFAOYSA-N N#CCC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound N#CCC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 CZJZWNQTZWNQDS-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-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
- FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
- HDHYJNFQAMSFLC-UHFFFAOYSA-N NC(=O)COC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 Chemical compound NC(=O)COC1=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=CC(F)=C1 HDHYJNFQAMSFLC-UHFFFAOYSA-N 0.000 description 1
- UWWAHTLUURLTMA-UHFFFAOYSA-N NC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound NC(=O)COC1=CC(C(F)(F)F)=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 UWWAHTLUURLTMA-UHFFFAOYSA-N 0.000 description 1
- YCVRHFPJCZJQJL-UHFFFAOYSA-N NC(=O)COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 Chemical compound NC(=O)COC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1 YCVRHFPJCZJQJL-UHFFFAOYSA-N 0.000 description 1
- DJUIBEWQTCJDEP-UHFFFAOYSA-N NC1=C(N)C(=O)N(CC2=CC=C(C(F)(F)F)C=C2)C=C1.NC1=C([N+](=O)[O-])C(=O)N(CC2=CC=C(C(F)(F)F)C=C2)C=C1.O=C1C([N+](=O)[O-])=C(Cl)C=CN1CC1=CC=C(C(F)(F)F)C=C1.[H]N1C(C2=C(F)C(F)=CC=C2)=NC2=C1C(=O)N(CC1=CC=C(C(F)(F)F)C=C1)C=C2.[H]N1C=CC(Cl)=C([N+](=O)[O-])C1=O Chemical compound NC1=C(N)C(=O)N(CC2=CC=C(C(F)(F)F)C=C2)C=C1.NC1=C([N+](=O)[O-])C(=O)N(CC2=CC=C(C(F)(F)F)C=C2)C=C1.O=C1C([N+](=O)[O-])=C(Cl)C=CN1CC1=CC=C(C(F)(F)F)C=C1.[H]N1C(C2=C(F)C(F)=CC=C2)=NC2=C1C(=O)N(CC1=CC=C(C(F)(F)F)C=C1)C=C2.[H]N1C=CC(Cl)=C([N+](=O)[O-])C1=O DJUIBEWQTCJDEP-UHFFFAOYSA-N 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- QELAVTMDKHSMOP-UHFFFAOYSA-N O=C(C(=O)C1=CC=C(CBr)C=C1)C1=CC=CC=C1 Chemical compound O=C(C(=O)C1=CC=C(CBr)C=C1)C1=CC=CC=C1 QELAVTMDKHSMOP-UHFFFAOYSA-N 0.000 description 1
- SZJQXQICJDHRJE-UHFFFAOYSA-N O=C(C1=CC=CC=C1)C1=CC(CBr)=CC=C1 Chemical compound O=C(C1=CC=CC=C1)C1=CC(CBr)=CC=C1 SZJQXQICJDHRJE-UHFFFAOYSA-N 0.000 description 1
- MHWJWEIHCJSAIZ-UHFFFAOYSA-N O=C(C1=CC=CC=C1)C1=CC(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)=CC=C1 Chemical compound O=C(C1=CC=CC=C1)C1=CC(CN2C=CC3=NC(C4=C(F)C=CC=C4)=NC3=C2)=CC=C1 MHWJWEIHCJSAIZ-UHFFFAOYSA-N 0.000 description 1
- RYULULVJWLRDQH-UHFFFAOYSA-N O=C(C1=CC=CC=C1)C1=CC=C(CBr)C=C1 Chemical compound O=C(C1=CC=CC=C1)C1=CC=C(CBr)C=C1 RYULULVJWLRDQH-UHFFFAOYSA-N 0.000 description 1
- MCOQHIWZJUDQIC-UHFFFAOYSA-N O=C(NC1=CC(Cl)=CC=C1)OCC#CCCl Chemical compound O=C(NC1=CC(Cl)=CC=C1)OCC#CCCl MCOQHIWZJUDQIC-UHFFFAOYSA-N 0.000 description 1
- RJLDFNIDYBRLQN-UHFFFAOYSA-N O=C(NC1=CC(Cl)=CC=C1O)C1=CC=CC=C1CCl Chemical compound O=C(NC1=CC(Cl)=CC=C1O)C1=CC=CC=C1CCl RJLDFNIDYBRLQN-UHFFFAOYSA-N 0.000 description 1
- GJRILCBIHBFECH-UHFFFAOYSA-N O=C(NC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1)OCC1=CC=CC=C1 Chemical compound O=C(NC1=CC=C(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)C=C1)OCC1=CC=CC=C1 GJRILCBIHBFECH-UHFFFAOYSA-N 0.000 description 1
- SBINAJOLHPXTEC-UHFFFAOYSA-N O=C(O)C1=C(C(=O)C2=CC(F)=CC(F)=C2)C=CC=C1 Chemical compound O=C(O)C1=C(C(=O)C2=CC(F)=CC(F)=C2)C=CC=C1 SBINAJOLHPXTEC-UHFFFAOYSA-N 0.000 description 1
- FBRJYBGLCHWYOE-UHFFFAOYSA-N O=C(O)C1=C(C(F)(F)F)C=CC=C1 Chemical compound O=C(O)C1=C(C(F)(F)F)C=CC=C1 FBRJYBGLCHWYOE-UHFFFAOYSA-N 0.000 description 1
- XZNLSDPNMNWCRE-UHFFFAOYSA-N O=C(O)C1=C(C(F)(F)F)C=CC=C1C(F)(F)F Chemical compound O=C(O)C1=C(C(F)(F)F)C=CC=C1C(F)(F)F XZNLSDPNMNWCRE-UHFFFAOYSA-N 0.000 description 1
- MRUDNSFOFOQZDA-UHFFFAOYSA-N O=C(O)C1=C(Cl)C=CC=C1Cl Chemical compound O=C(O)C1=C(Cl)C=CC=C1Cl MRUDNSFOFOQZDA-UHFFFAOYSA-N 0.000 description 1
- XNTIGDVFBDJLTQ-UHFFFAOYSA-N O=C(O)C1=C(Cl)C=CC=C1F Chemical compound O=C(O)C1=C(Cl)C=CC=C1F XNTIGDVFBDJLTQ-UHFFFAOYSA-N 0.000 description 1
- MYAZXWFEMDJTFE-UHFFFAOYSA-N O=C(O)C1=C(Cl)C=NC=C1 Chemical compound O=C(O)C1=C(Cl)C=NC=C1 MYAZXWFEMDJTFE-UHFFFAOYSA-N 0.000 description 1
- OCIYTBZXTFPSPI-UHFFFAOYSA-N O=C(O)C1=C(F)C=C(C(F)(F)F)C=C1 Chemical compound O=C(O)C1=C(F)C=C(C(F)(F)F)C=C1 OCIYTBZXTFPSPI-UHFFFAOYSA-N 0.000 description 1
- ONOTYLMNTZNAQZ-UHFFFAOYSA-N O=C(O)C1=C(F)C=CC=C1F Chemical compound O=C(O)C1=C(F)C=CC=C1F ONOTYLMNTZNAQZ-UHFFFAOYSA-N 0.000 description 1
- RCPNLJLUIPTOPI-UHFFFAOYSA-N O=C(O)C1=C(NC(=O)C2=CC=CC(CCl)=C2)C=CS1 Chemical compound O=C(O)C1=C(NC(=O)C2=CC=CC(CCl)=C2)C=CS1 RCPNLJLUIPTOPI-UHFFFAOYSA-N 0.000 description 1
- PKRSYEPBQPFNRB-UHFFFAOYSA-N O=C(O)C1=C(OC2=CC=CC=C2)C=CC=C1 Chemical compound O=C(O)C1=C(OC2=CC=CC=C2)C=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
- HVFQJWGYVXKLTE-UHFFFAOYSA-N O=C(O)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 Chemical compound O=C(O)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HVFQJWGYVXKLTE-UHFFFAOYSA-N 0.000 description 1
- XQNXXNNXRWYNAS-UHFFFAOYSA-N O=C(O)C1=CC(C2=CN=CC=C2)=NC2=C1C=CC=C2 Chemical compound O=C(O)C1=CC(C2=CN=CC=C2)=NC2=C1C=CC=C2 XQNXXNNXRWYNAS-UHFFFAOYSA-N 0.000 description 1
- CXKCZFDUOYMOOP-UHFFFAOYSA-N O=C(O)C1=CC(Cl)=CC(Cl)=C1 Chemical compound O=C(O)C1=CC(Cl)=CC(Cl)=C1 CXKCZFDUOYMOOP-UHFFFAOYSA-N 0.000 description 1
- PODFNQCZFHLJPH-UHFFFAOYSA-N O=C(O)C1=CC(N2C=CC=C2)=CC=C1 Chemical compound O=C(O)C1=CC(N2C=CC=C2)=CC=C1 PODFNQCZFHLJPH-UHFFFAOYSA-N 0.000 description 1
- NXTDJHZGHOFSQG-UHFFFAOYSA-N O=C(O)C1=CC(OC2=CC=CC=C2)=CC=C1 Chemical compound O=C(O)C1=CC(OC2=CC=CC=C2)=CC=C1 NXTDJHZGHOFSQG-UHFFFAOYSA-N 0.000 description 1
- BIABIACQHKYEEB-UHFFFAOYSA-N O=C(O)C1=CC2=C(C=C1)CCC2=O Chemical compound O=C(O)C1=CC2=C(C=C1)CCC2=O BIABIACQHKYEEB-UHFFFAOYSA-N 0.000 description 1
- DMPZJACLHDWUFS-UHFFFAOYSA-N O=C(O)C1=CC2=C(C=C1)N=CS2 Chemical compound O=C(O)C1=CC2=C(C=C1)N=CS2 DMPZJACLHDWUFS-UHFFFAOYSA-N 0.000 description 1
- DYSJMQABFPKAQM-UHFFFAOYSA-N O=C(O)C1=CC2=C(C=CC=C2)S1 Chemical compound O=C(O)C1=CC2=C(C=CC=C2)S1 DYSJMQABFPKAQM-UHFFFAOYSA-N 0.000 description 1
- WXXVQWSDMOAHHV-UHFFFAOYSA-N O=C(O)C1=CC2=NC=CC=C2C=C1 Chemical compound O=C(O)C1=CC2=NC=CC=C2C=C1 WXXVQWSDMOAHHV-UHFFFAOYSA-N 0.000 description 1
- UTHDVFIFIMWTJQ-UHFFFAOYSA-N O=C(O)C1=CC=C(C2=CC=C(Br)C=C2)C=C1 Chemical compound O=C(O)C1=CC=C(C2=CC=C(Br)C=C2)C=C1 UTHDVFIFIMWTJQ-UHFFFAOYSA-N 0.000 description 1
- YOFXYDVYMHOXSY-UHFFFAOYSA-N O=C(O)C1=CC=C(C2=CC=C(F)C=C2)S1 Chemical compound O=C(O)C1=CC=C(C2=CC=C(F)C=C2)S1 YOFXYDVYMHOXSY-UHFFFAOYSA-N 0.000 description 1
- SLKZDWAZOKIEEU-UHFFFAOYSA-N O=C(O)C1=CC=C(C2=CC=CC=C2F)C=C1 Chemical compound O=C(O)C1=CC=C(C2=CC=CC=C2F)C=C1 SLKZDWAZOKIEEU-UHFFFAOYSA-N 0.000 description 1
- QCIWHVKGVVQHIY-UHFFFAOYSA-N O=C(O)C1=CC=C(C2CCCCC2)C=C1 Chemical compound O=C(O)C1=CC=C(C2CCCCC2)C=C1 QCIWHVKGVVQHIY-UHFFFAOYSA-N 0.000 description 1
- NLSIIPKSANRIGS-UHFFFAOYSA-N O=C(O)C1=CC=C(N2C=CC=C2)C=C1 Chemical compound O=C(O)C1=CC=C(N2C=CC=C2)C=C1 NLSIIPKSANRIGS-UHFFFAOYSA-N 0.000 description 1
- RATSANVPHHXDCT-UHFFFAOYSA-N O=C(O)C1=CC=C(OC(F)(F)F)C=C1 Chemical compound O=C(O)C1=CC=C(OC(F)(F)F)C=C1 RATSANVPHHXDCT-UHFFFAOYSA-N 0.000 description 1
- JGQDBVXRYDEWGM-UHFFFAOYSA-N O=C(O)C1=CC=C2N=CC=NC2=C1 Chemical compound O=C(O)C1=CC=C2N=CC=NC2=C1 JGQDBVXRYDEWGM-UHFFFAOYSA-N 0.000 description 1
- AMNVOFVBUORNRG-UHFFFAOYSA-N O=C(O)C1=CC=CC(C2=CC=C(F)C(F)=C2)=C1 Chemical compound O=C(O)C1=CC=CC(C2=CC=C(F)C(F)=C2)=C1 AMNVOFVBUORNRG-UHFFFAOYSA-N 0.000 description 1
- YUQPLNXKGVRIAJ-UHFFFAOYSA-N O=C(O)C1=CC=CC(C2=CC=C(F)C=C2)=C1 Chemical compound O=C(O)C1=CC=CC(C2=CC=C(F)C=C2)=C1 YUQPLNXKGVRIAJ-UHFFFAOYSA-N 0.000 description 1
- QRDZFPUVLYEQTA-UHFFFAOYSA-N O=C(O)C1=CC=CC2=CC=CN=C21 Chemical compound O=C(O)C1=CC=CC2=CC=CN=C21 QRDZFPUVLYEQTA-UHFFFAOYSA-N 0.000 description 1
- LLLVHTWJGWNRBD-UHFFFAOYSA-N O=C(O)C1=CC=CN=C1F Chemical compound O=C(O)C1=CC=CN=C1F LLLVHTWJGWNRBD-UHFFFAOYSA-N 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N O=C(O)C1=CC=CO1 Chemical compound O=C(O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- MIIQJAUWHSUTIT-UHFFFAOYSA-N O=C(O)C1=CC=NO1 Chemical compound O=C(O)C1=CC=NO1 MIIQJAUWHSUTIT-UHFFFAOYSA-N 0.000 description 1
- HHWABXGAQNCVFW-UHFFFAOYSA-N O=C(O)C1=CN=C(N2C=CN=C2)C=C1 Chemical compound O=C(O)C1=CN=C(N2C=CN=C2)C=C1 HHWABXGAQNCVFW-UHFFFAOYSA-N 0.000 description 1
- UPUZGXILYFKSGE-UHFFFAOYSA-N O=C(O)C1=CN=C2/C=C\C=C/C2=N1 Chemical compound O=C(O)C1=CN=C2/C=C\C=C/C2=N1 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 description 1
- IIVUJUOJERNGQX-UHFFFAOYSA-N O=C(O)C1=CN=CN=C1 Chemical compound O=C(O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 1
- JUSIWJONLKBPDU-UHFFFAOYSA-N O=C(O)C1=CN=NC=C1 Chemical compound O=C(O)C1=CN=NC=C1 JUSIWJONLKBPDU-UHFFFAOYSA-N 0.000 description 1
- IMBBXSASDSZJSX-UHFFFAOYSA-N O=C(O)C1=CNN=C1 Chemical compound O=C(O)C1=CNN=C1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 1
- YNVOMSDITJMNET-UHFFFAOYSA-N O=C(O)C1=CSC=C1 Chemical compound O=C(O)C1=CSC=C1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
- HMVYYTRDXNKRBQ-UHFFFAOYSA-N O=C(O)C1=CSC=N1 Chemical compound O=C(O)C1=CSC=N1 HMVYYTRDXNKRBQ-UHFFFAOYSA-N 0.000 description 1
- KVMMIDQDXZOPAB-UHFFFAOYSA-N O=C(O)C1=NC=C2C=CC=CC2=C1 Chemical compound O=C(O)C1=NC=C2C=CC=CC2=C1 KVMMIDQDXZOPAB-UHFFFAOYSA-N 0.000 description 1
- NIPZZXUFJPQHNH-UHFFFAOYSA-N O=C(O)C1=NC=CN=C1 Chemical compound O=C(O)C1=NC=CN=C1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 1
- YPOXGDJGKBXRFP-UHFFFAOYSA-N O=C(O)C1=NC=NC=C1 Chemical compound O=C(O)C1=NC=NC=C1 YPOXGDJGKBXRFP-UHFFFAOYSA-N 0.000 description 1
- KOPFEFZSAMLEHK-UHFFFAOYSA-N O=C(O)C1=NNC=C1 Chemical compound O=C(O)C1=NNC=C1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 1
- VCISPKNFQLGMJI-UHFFFAOYSA-N O=C1OC(C2=C(CCl)C=CC=C2)=NC2=C1C=CC(Cl)=C2 Chemical compound O=C1OC(C2=C(CCl)C=CC=C2)=NC2=C1C=CC(Cl)=C2 VCISPKNFQLGMJI-UHFFFAOYSA-N 0.000 description 1
- FXJZAEOUBNYPFD-UHFFFAOYSA-N O=C1OC(C2=CC=CC(CCl)=C2)=NC2=C1C=CC(Cl)=C2 Chemical compound O=C1OC(C2=CC=CC(CCl)=C2)=NC2=C1C=CC(Cl)=C2 FXJZAEOUBNYPFD-UHFFFAOYSA-N 0.000 description 1
- XOXXPRWSPVVUPS-UHFFFAOYSA-N O=N(O)C1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 Chemical compound O=N(O)C1=CC=CC=C1C1=CC=C(CN2C=CC3=NC(C4=C(F)C(F)=CC=C4)=NC3=C2)C=C1 XOXXPRWSPVVUPS-UHFFFAOYSA-N 0.000 description 1
- UESVJQOCOJRRAZ-UHFFFAOYSA-N O=N([O-])C1=CC=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=C1 Chemical compound O=N([O-])C1=CC=CC(C2=CC=C(CN3C=CC4=NC(C5=C(F)C(F)=CC=C5)=NC4=C3)C=C2)=C1 UESVJQOCOJRRAZ-UHFFFAOYSA-N 0.000 description 1
- SUJXGYBNXSVALG-UHFFFAOYSA-N O=S(=O)(C1=CC=CC=C1)N1C=C(CBr)C2=C1C=CC=C2 Chemical compound O=S(=O)(C1=CC=CC=C1)N1C=C(CBr)C2=C1C=CC=C2 SUJXGYBNXSVALG-UHFFFAOYSA-N 0.000 description 1
- WEPKKLRCOPTNLP-UHFFFAOYSA-N O=S(=O)(C1=CC=CC=C1)N1C=CC2=C1C=CC(CBr)=C2 Chemical compound O=S(=O)(C1=CC=CC=C1)N1C=CC2=C1C=CC(CBr)=C2 WEPKKLRCOPTNLP-UHFFFAOYSA-N 0.000 description 1
- MFEGTJBBLPXXDT-UHFFFAOYSA-N O=S(=O)(CC1=NOC(CCl)=N1)C1=NC=CC=C1 Chemical compound O=S(=O)(CC1=NOC(CCl)=N1)C1=NC=CC=C1 MFEGTJBBLPXXDT-UHFFFAOYSA-N 0.000 description 1
- SFYHVQBHPYZLHF-UHFFFAOYSA-N O=S(=O)(NC1=CC=C(F)C=C1)C1=CC=C(CBr)C=C1 Chemical compound O=S(=O)(NC1=CC=C(F)C=C1)C1=CC=C(CBr)C=C1 SFYHVQBHPYZLHF-UHFFFAOYSA-N 0.000 description 1
- PIDISHAWZWUURP-UHFFFAOYSA-N O=[N+]([O-])C1=C(SC2=CC=C(CBr)C=C2)C=CC(C(F)(F)F)=C1 Chemical compound O=[N+]([O-])C1=C(SC2=CC=C(CBr)C=C2)C=CC(C(F)(F)F)=C1 PIDISHAWZWUURP-UHFFFAOYSA-N 0.000 description 1
- CPZOCLCUJQJRBN-UHFFFAOYSA-N O=[N+]([O-])C1=CC=C(CBr)O1 Chemical compound O=[N+]([O-])C1=CC=C(CBr)O1 CPZOCLCUJQJRBN-UHFFFAOYSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- XRMPPHPGDRQJCF-UHFFFAOYSA-N ONc1ccccc1-c1ccc(CN2C=C3N=C(c(cccc4F)c4F)N=C3C=C2)cc1 Chemical compound ONc1ccccc1-c1ccc(CN2C=C3N=C(c(cccc4F)c4F)N=C3C=C2)cc1 XRMPPHPGDRQJCF-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000015731 Peptide Hormones Human genes 0.000 description 1
- 108010038988 Peptide Hormones Proteins 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 101100055332 Pseudomonas oleovorans alkN gene Proteins 0.000 description 1
- 229910019020 PtO2 Inorganic materials 0.000 description 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000031320 Teratogenesis Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- SGBCRPFFLFPPFV-UHFFFAOYSA-N [4-[[2-(2,3-difluorophenyl)imidazo[4,5-c]pyridin-5-yl]methyl]phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1CN1C=C2N=C(C=3C(=C(F)C=CC=3)F)N=C2C=C1 SGBCRPFFLFPPFV-UHFFFAOYSA-N 0.000 description 1
- MHKOVSRFDDLIFU-UHFFFAOYSA-N [4-hydroxy-2-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(O)C=C1C(F)(F)F MHKOVSRFDDLIFU-UHFFFAOYSA-N 0.000 description 1
- ZBUADPJKSIJZKN-UHFFFAOYSA-N [H]C(F)(F)OC1=CC=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 Chemical compound [H]C(F)(F)OC1=CC=CC=C1C1=NOC(CN2C=CC3=NC(C4=CC=CC(F)=C4F)=NC3=C2)=C1 ZBUADPJKSIJZKN-UHFFFAOYSA-N 0.000 description 1
- CELVYRSCZWBLPY-UHFFFAOYSA-N [H]C1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NN4)C=CC3=N2)=CC=C1 Chemical compound [H]C1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(Cl)C=C5)=NN4)C=CC3=N2)=CC=C1 CELVYRSCZWBLPY-UHFFFAOYSA-N 0.000 description 1
- QIIHQLMQGPJLLM-UHFFFAOYSA-N [H]C1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OC)C=C5)=NN4)C=CC3=N2)=CC=C1 Chemical compound [H]C1=C(F)C(C2=NC3=CN(CC4=CC(C5=CC=C(OC)C=C5)=NN4)C=CC3=N2)=CC=C1 QIIHQLMQGPJLLM-UHFFFAOYSA-N 0.000 description 1
- RZSHQAGBKHKVNT-GWXTXILRSA-N [H][C@@]12CS[C@H](CCCCC(=O)NCCCCCOC3=CC(C(F)(F)F)=C(C4=CC=C(CN5C=CC6=NC(C7=C(F)C(F)=CC=C7)=NC6=C5)C=C4)C=C3)[C@]1([H])CC(=O)N2 Chemical compound [H][C@@]12CS[C@H](CCCCC(=O)NCCCCCOC3=CC(C(F)(F)F)=C(C4=CC=C(CN5C=CC6=NC(C7=C(F)C(F)=CC=C7)=NC6=C5)C=C4)C=C3)[C@]1([H])CC(=O)N2 RZSHQAGBKHKVNT-GWXTXILRSA-N 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 208000023344 acute nonparalytic poliomyelitis Diseases 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 229960001040 ammonium chloride Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 150000001450 anions Chemical group 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 125000005015 aryl alkynyl group Chemical group 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000007998 bicine buffer Substances 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- CTZOPIRFQQMWGR-UHFFFAOYSA-N carboxyoxymethyl 2,2-dimethylpropanoate Chemical group CC(C)(C)C(=O)OCOC(O)=O CTZOPIRFQQMWGR-UHFFFAOYSA-N 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000001023 centrifugal evaporation Methods 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000017580 chronic wasting disease Diseases 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical class C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 231100000223 dermal penetration Toxicity 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical group OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 229940093476 ethylene glycol Drugs 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- ASKSDLRLUXEOOR-SUFRFZPQSA-N gbv-c Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=3C4=CC=CC=C4NC=3)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CC(C)C)=CNC2=C1 ASKSDLRLUXEOOR-SUFRFZPQSA-N 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
- 230000014509 gene expression Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 244000144980 herd Species 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
- 229960002885 histidine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- PPNFWYUJXHAZIN-UHFFFAOYSA-N imidazo[4,5-c]pyridin-4-one Chemical class O=C1N=CC=C2N=CN=C12 PPNFWYUJXHAZIN-UHFFFAOYSA-N 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 125000004926 indolenyl group Chemical group 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229960003521 interferon alfa-2a Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000012500 ion exchange media Substances 0.000 description 1
- 125000004936 isatinoyl group Chemical group N1(C(=O)C(=O)C2=CC=CC=C12)C(=O)* 0.000 description 1
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 229940078545 isocetyl stearate Drugs 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000003819 low-pressure liquid chromatography Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 229940071125 manganese acetate Drugs 0.000 description 1
- UOGMEBQRZBEZQT-UHFFFAOYSA-L manganese(2+);diacetate Chemical compound [Mn+2].CC([O-])=O.CC([O-])=O UOGMEBQRZBEZQT-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- SFJSKDLRXSUQQZ-UHFFFAOYSA-N molecular hydrogen pyridine Chemical compound [H][H].c1ccncc1 SFJSKDLRXSUQQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- VFBILHPIHUPBPZ-UHFFFAOYSA-N n-[[2-[4-(difluoromethoxy)-3-propan-2-yloxyphenyl]-1,3-oxazol-4-yl]methyl]-2-ethoxybenzamide Chemical compound CCOC1=CC=CC=C1C(=O)NCC1=COC(C=2C=C(OC(C)C)C(OC(F)F)=CC=2)=N1 VFBILHPIHUPBPZ-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
- DOWVMJFBDGWVML-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-(1-oxidopyridin-1-ium-3-yl)imidazole-1-carboxamide Chemical compound C1=NC(C=2C=[N+]([O-])C=CC=2)=CN1C(=O)N(C)C1CCCCC1 DOWVMJFBDGWVML-UHFFFAOYSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 201000006545 nonparalytic poliomyelitis Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
- UYDLBVPAAFVANX-UHFFFAOYSA-N octylphenoxy polyethoxyethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCO)C=C1 UYDLBVPAAFVANX-UHFFFAOYSA-N 0.000 description 1
- 150000002888 oleic acid derivatives Chemical class 0.000 description 1
- 125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid group Chemical group C(C(=O)O)(=O)O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
- 125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008251 pharmaceutical emulsion Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000004932 phenoxathinyl group Chemical group 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- PWXJULSLLONQHY-UHFFFAOYSA-N phenylcarbamic acid Chemical class OC(=O)NC1=CC=CC=C1 PWXJULSLLONQHY-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- AXIPBRXJGSXLHF-UHFFFAOYSA-N piperidine;pyrrolidine Chemical compound C1CCNC1.C1CCNCC1 AXIPBRXJGSXLHF-UHFFFAOYSA-N 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 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 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 238000003307 slaughter Methods 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
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid group Chemical class S(N)(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004927 thianaphthalenyl group Chemical group S1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000005000 thioaryl group Chemical group 0.000 description 1
- 229930192474 thiophene Chemical group 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a series of novel imidazo[4,5-c]pyridine compounds, processes for their preparation, their use to treat or prevent viral infections and their use to manufacture a medicine to treat or prevent viral infections, particularly infections with viruses belonging to the family of the Flaviviridae and Picornaviridae and more preferably infections with hepatitis-C-virus (HCV).
- HCV hepatitis-C-virus
- the family of the Flaviviridae consists of 3 genera, the pestiviruses, the flaviviruses and the hepaciviruses and also contains the hepatitis G virus (HGV/GBV-C) that has not yet been assigned to a genus.
- Pestiviruses such as the Classical Swine Fever Virus (CSFV), the Bovine Viral Diarrhea Virus (BVDV) and the Border Disease Virus (BDV) cause infections of domestic livestock (respectively pigs, cattle and sheep) and are responsible for significant economic losses world-wide.
- CSFV Classical Swine Fever Virus
- BVDV Bovine Viral Diarrhea Virus
- BDV Border Disease Virus
- BVDV the prototypic representative of the pestivirus genus is ubiquitous and causes a range of clinical manifestations, including abortion, teratogenesis, respiratory problems, chronic wasting disease, immune system dysfunction, and predisposition to secondary viral and bacterial infections and may also cause acute fatal disease. Fetuses of cattle can be infected persistently with BVDV, these animals remain viremic throughout life and serve as a continuous source for virus spread in herds.
- Vaccines are used in some countries with varying degrees of success to control pestivirus disease. In other countries, animal culling and slaughter are used to contain pestivirus disease outbreaks.
- HCV hepatitis C virus
- Coxsackie viruses belong to the group of the enteroviruses, family of the Picornaviridae. They cause a heterogeneous group of infections including herpangina, aseptic meningitis, a common-cold-like syndrome, a non-paralytic poliomyelitis-like syndrome, epidemic pleurodynia (an acute, febrile, infectious disease generally occurring in epidemics), hand-foot-mouth syndrome, pediatric and adult pancreatitis and serious myocarditis.
- WO 00/20416 WO 00/39127, WO 00/40583, WO 03/007945 A1, WO 03/010140 A2, WO 03/010141 A2, WO 93/02080, WO 93/14072, WO 96/11192, WO 96/12703, WO 99/27929, Akamatsu, et al., New Efficient Route for Solid-Phase Synthesis of Benzimidazole Derivatives”, 4:475-483 , J. COMB.
- An embodiment of the present invention provides compounds having the general formula (A), wherein:
- Another embodiment of the present invention provides compounds having the general formula (A), wherein:
- An embodiment of the present invention provides compounds having the general formula (A), wherein:
- An embodiment of the present invention provides compounds of the formula (B) wherein Y is a single bond, and R 1 is aryl.
- Another embodiment of the present invention provides compounds of formula (B) wherein X is C 1 -C 10 alkylene, C 2-10 alkenylene or C 2-10 alkynylene.
- Another embodiment of the present invention provides compounds of formula (B) wherein R 3 is heterocylic.
- Another embodiment of the present invention provides compounds of formula (B) wherein R 3 is heterocyclic substituted with R 17 where Q is a bond and M is aryl.
- Another embodiment of the present invention provides compounds of formula (B) wherein Y is a single bond, and R 1 is phenyl.
- Another embodiment of the present invention provides compounds of formula (B) wherein R 3 is isoxazole substituted with R 17 where Q is a bond and M is aryl.
- Another embodiment of the present invention provides compounds of formula (B) wherein R 3 is isoxazole substituted with R 17 where Q is a bond and M is phenyl.
- Yet another embodiment of the present invention provides compounds having the formula (C),
- An embodiment of the present invention provides compounds of the formula (C) wherein Y is a single bond, and R 1 is aryl.
- Another embodiment of the present invention provides compounds of formula (C) wherein X is C 1 -C 10 alkylene, C 2-10 alkenylene or C 2-10 alkynylene.
- Another embodiment of the present invention provides compounds of formula (C) wherein R 3 is heterocylic.
- Another embodiment of the present invention provides compounds of formula (C) wherein R 3 is heterocyclic substituted with R 17 where Q is a bond and M is aryl.
- Another embodiment of the present invention provides compounds of formula (C) wherein Y is a single bond, and R 1 is phenyl.
- Another embodiment of the present invention provides compounds of formula (C) wherein R 3 is isoxazole substituted with R 17 where Q is a bond and M is aryl.
- Another embodiment of the present invention provides compounds of formula (C) wherein R 3 is isoxazole substituted with R 17 where Q is a bond and M is phenyl.
- the compounds of formula (A) are optionally combined with pharmacologically acceptable excipients.
- the compounds of formula (A) are administered in therapeutically effective amounts to subjects (humans or animals) in need of antiviral therapy, in particular for inhibiting the infection, growth or replication of Flaviviridae and Picornaviridae, especially BVDV, HCV and Coxsackie virus.
- the invention further relates to a method of screening antiviral compounds which comprises providing a compound of formula (A) and determining the anti-viral activity of said compound.
- a metabolite of the compounds of formula (A) made by the process of administering a compound of formula (A) to a subject and recovering the metabolite from the subject.
- the invention also comprises a method for structure-activity determination of analogues of formula (A) compounds wherein the substituents are defined in WO 2004/005286, comprising
- Alkyl means saturated hydrocarbon moiety where the moiety may be cyclic, cyclic or a combination of acyclic and cyclic portions.
- the acyclic portion may contain 1 to 3 carbon atoms, and each ring may contain 3 to 6 carbon atoms (for example, 3-methylcyclohexyl).
- cycloalkyl refers to the saturated hydrocarbon moieties that are cyclic.
- alkyl examples include methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-methyl-1-propyl(i-Bu), 2-butyl (s-Bu) 2-methyl-2-propyl (t-Bu), 1-pentyl (n-pentyl), 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, cyclopropyl, cyclobutyl, cyclopenty
- Alkenyl means a hydrocarbon moiety with at least one site of double bond unsaturation where the moiety may be acyclic, cyclic or a combination of acyclic and cyclic portions.
- the acyclic portion may contain 1 to 3 carbon atoms, and each cyclic portion may contain 3 to 6 carbon atoms.
- a site of double bond unsaturation may be in a acyclic portion, a cyclic portion.
- cycloalkenyl refers to the double bond unsaturated hydrocarbon moieties that are cyclic.
- alkenyl include, but are not limited to, ethylene or vinyl (—CH ⁇ CH 2 ), allyl (—CH 2 CH ⁇ CH 2 ), cyclopentenyl (—C 5 H 7 ), 5-hexenyl (—CH 2 CH 2 CH 2 CH 2 CH ⁇ CH 2 ), 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, and 1-cyclohex-3-enyl.
- the double bond optionally is in the cis or trans configuration.
- Alkynyl means a hydrocarbon moiety with a least one site of triple bond unsaturation where the moiety may be acyclic, cyclic or a combination of acyclic and cyclic portions.
- the acyclic portion may contain contain 1 to 3 carbon atoms, and each cyclic portion may contain 7 or more carbon atoms.
- cycloalkynl refers to triple bond unsaturated hydrocarbon moieties that are cyclic. Examples of the term “alkynyl” include, but are not limited to, —C ⁇ CH, —CH 2 C ⁇ CH, —CH 2 C—C-cyclohexyl, or —CH 2 -cycloheptynyl.
- alkyl, alkenyl and alkynyl groups refers to such groups with at least 2 sites of substitution.
- polyvalent hydrocarbon radicals include, but are not limited to, methylene (—CH 2 —) 1,2-ethylene (—CH 2 CH 2 —), 1,3-propylene (—CH 2 CH 2 CH 2 —), 1,4-butylene (—CH 2 CH 2 CH 2 CH 2 —), 1,2-ethylene (—CH ⁇ CH—), —C ⁇ C—, propargyl (—CH 2 C ⁇ C—), and 4-pentynyl (—CH 2 CH 2 CH 2 C ⁇ CH—).
- Aryl means an aromatic hydrocarbon containing 1 or more rings, generally 1, 2 or 3, with 4 to 6 carbon atoms in each, ordinarily 5 or 6 carbon atoms.
- Arylalkyl means an alkyl, alkenyl or alkynyl radical, respectively, in which one of the hydrogen atoms, typically a terminal or sp3 carbon atom, is replaced with an aryl radical.
- Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-1-yl, 2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethan-1-yl, 2-naphthylethen-1-yl, naphthobenzyl, 2-naphthophenylethan-1-yl and the like.
- carbocycles optionally are found as single rings or multiple ring systems. Ordinarily the hydrocarbons of the compounds of formula (A) are single rings. Monocyclic carbocycles generally have 3 to 6 ring atoms, still more typically 5 or 6 ring atoms. Bicyclic carbocycles typically have 7 to 12 ring atoms, e.g. arranged as a bicyclo [4,5], [5,5], [5,6] or [6,6] system, or 9 or 10 ring atoms arranged as a bicyclo [5,6] or [6,6] system.
- the number of carbon atoms is unspecified for a hydrocarbon, typically the number of carbon atoms will range from 1 to 18, except that the number of carbons typically will range from 2 to 18 for unsaturated hydrocarbons and from 6 to 10 for aryl.
- Heterocyclic or “heterocycle” means any 4, 5, 6, 7, 8 or 9 membered single or fused ring system containing one or more heteroatoms selected from the group consisting of O, N or S. Heterocycles optionally are entirely aromatic, entirely saturated, or contain 1 or more intra-ring sites of unsaturation, typically double bonds. Multiple heterocyclic rings (one or more of which contains a heteroatom) are bridged or spiro. Generally, the heterocyclic rings will be aromatic, and usually they are single rings.
- heterocycles include oxazacyloalkyl, morpholinyl, dioxacycloalkyl, thiacycloalkenyl, pyridyl, dihydroypyridyl, tetrahydropyridyl (piperidyl), thiazolyl, tetrahydrothiophenyl, furanyl, thienyl, pyrrolyl, pyranyl, pyrazolyl, pyrazolidinyl, pyrazolinyl, imidazolyl, tetrazolyl, benzofuranyl, thianaphthalenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, piperazinyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, bis-tetrahydro
- Carbon bonded heterocycles typically are bonded at position 2, 3, 4, 5, or 6 of a pyridine, position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of a pyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5 of a furan, tetrahydrofuran, thiofuran, thiophene, pyrrole or tetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole or thiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole, position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine, position 2, 3, 4, 5, 6, 7, or 8 of a
- carbon bonded heterocycles include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 6-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl.
- Nitrogen containing heterocycles are bonded at nitrogen or a carbon, typically a carbon atom. These include, for example, position 1 of aziridine, 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, 1-piperidinyl, 2-pyrroline, 3-pyrroline, 2-imidazoline, 3-imidazoline, 9-carbazole, 4-morpholine, 9-alpha or 13-carboline, 2-isoindole, 2-pyrazoline and 3-pyrazoline, and by analogy, azetidine, pyrrole, pyrrolidine piperidine, piperazine, indole, pyrazoline, indoline, imidazole, imidazolidine, 1H-indazole and isoindoline. These and other N-containing heterocycles are well-known to those skilled in the art, and their linkage sites are a matter of discretion.
- Sulfur containing heterocycles are bonded through carbon or sulfur. They include oxidized states such as —S( ⁇ O)( ⁇ O). In general, they are linked in the compounds of formula (A) analogous to N-containing heterocycles.
- Alkoxy”, “cycloalkoxy”, “aryloxy”, “arylalkyloxy”, “oxy heterocycle”, “thioalkyl”, “thiocycloalkyl”, “arylthio”, and “arylalkylthio” means substituents wherein an alkyl, cycloalkyl, aryl, or arylalkyl, respectively, are attached to an oxygen atom or a sulfur atom through a single bond, such as but not limited to methoxy, ethoxy, propoxy, butoxy, thioethyl, thiomethyl, phenyloxy, benzyloxy, mercaptobenzyl and the like.
- the compounds of the invention may exist in many different protonation states, depending on, among other things, the pH of their environment. While the structural formulae provided herein depict the compounds in only one of several possible protonation states, it will be understood that these structures are illustrative only, and that the invention is not limited to any particular protonation state—any and all protonated forms of the compounds are intended to fall within the scope of the invention.
- Naturally-occurring amino acid residues are those residues found naturally in plants, animals or microbes, especially proteins thereof. Polypeptides most typically will be substantially composed of such naturally-occurring amino acid residues. These amino acids are glycine, alanine, valine, leucine, isoleucine, serine, threonine, cysteine, methionine, glutamic acid, aspartic acid, lysine, hydroxylysine, arginine, histidine, phenylalanine, tyrosine, tryptophan, proline, asparagine, glutamine and hydroxyproline. Additionally, unnatural amino acids, for example, valanine, phenylglycine and homoarginine are also included.
- any site in the parental molecule is substituted with an amino acid, although it is within the scope of this invention to introduce amino acids at more than one permitted site.
- the ⁇ -amino or ⁇ -carboxyl group of the amino acid are bonded to the remainder of the molecule, i.e., carboxyl or amino groups in the amino acid side chains generally are not used to form the amide bonds with the parental compound (although these groups may need to be protected during synthesis of the conjugates).
- amino acid esters optionally are hydrolyzable in vivo or in vitro under acidic (pH ⁇ 3) or basic (pH >10) conditions.
- they are substantially stable in the gastrointestinal tract of humans but are hydrolyzed enzymatically in blood or in intracellular environments.
- R 28 usually is C 1 -C 6 alkyl or C 1 -C 6 alkyl substituted with amino, carboxyl, amide, carboxyl (as well as esters, as noted above), hydroxyl, C 6 -C 7 aryl, guanidinyl, imidazolyl, indolyl, sulfhydryl, sulfoxide, and/or alkylphosphate.
- R 1 is generally aryl or aromatic heterocyle substituted with 1, 2 or 3 R 6 wherein R 6 is halogen, C 1-18 alkoxy; or C 1-18 haloalkyl. Typically, R 1 is phenyl substituted with 1, 2 or 3 halogens, usually fluoro.
- Y generally is a single bond, O, C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene or one of said groups containing 1 to 3, usually 1, heteroatoms selected from O, S or NR 11 .
- Examples include —O(CH 2 ) 1-5 —, —(CH 2 ) 1-4 —O—(CH 2 ) 1-4 —, —S—(CH 2 ) 1-5 —, —(CH 2 ) 1-4 —S—(CH 2 ) 1-4 —, —NR 11 —(CH 2 ) 1-5 —, —(CH 2 ) 1-4 —NR 11 —(CH 2 ) 1-4 or C 3-10 cycloalkylidene.
- Y is —OCH 2 —, —CH 2 O—, C 1-2 alkylene, C 2-3 alkenylene, C 2-3 alkynylene, 0 or a bond, but usually a bond.
- YR 1 is not any one of H, an unsubstituted C 3-10 cycloalkyl or C1-C6 alkyl.
- YR 1 is halo or halomethyl-substituted (typically trihalomethyl) phenyl (and usually 1 to 2 substituents in ortho or meta).
- R 17 is M-Q in some embodiments of the invention.
- M is a ring. This means any cyclic organic structure, whether carbocyclic or heterocyclic, and whether saturated, unsaturated or aromatic or single or fused ring systems. M is chosen from rings that are structurally stable in biological systems. In general, M is a aryl or aromatic heterocycle where heterocycle is defined above.
- Q is a spacer group, and is not critical. Typically it is not cyclic and contains from no to 3 atoms, generally C, O or S, usually C or 0.
- R 17 typically is selected from the group consisting of C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 7-10 cycloalkynyl, halogen, aryl, aryloxy, arylthio, arylsulfoxide, arylsulfone, arylsulfonamide, arylalkyl; arylalkyloxy (optionally an benzyloxy); arylalkylthio (optionally a benzylthio); a heterocycle; C 1-18 hydroxyalkyl, but typically is an aryl or a heterocycle, and where each of said aryl, aryloxy, arylthio, arylsulfoxide, arylsulfone, arylsulfonamide, arylalkyl, arylalkyloxy, arylalkylthio, or heterocycle is optionally substituted with 1 or more R 19 .
- R 17 generally is positioned dist
- R 9 and R 18 typically are H, OH or alkyl.
- R 18 optionally is not NR 15 R 16 .
- R 6 generally is halogen. Optionally, R 6 is not C(O)R 18 .
- R 7 , R 8 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , R 20 , R 21 , R 23 and R 24 typically are independently H or C 1-18 alkyl.
- R 12 and R 22 typically are independently OH or alkyl.
- R 19 usually is H; C 1-18 alkyl; C 2-18 alkenyl; C 2-18 alkynyl; C 1-18 alkoxy; alkenyloxy; alkynyloxy; C 1-18 alkylthio; C 3-10 cycloalkyl; C 4-10 cycloalkenyl; C 4-10 cycloalkynyl; halogen; OH; CN; cyanoalkyl; NO 2 ; NR 20 R 21 ; haloalkyl; haloalkyloxy; C( ⁇ O)R 18 ; C( ⁇ O)OR 18 ; OalkenylC(—O)OR 18 ; —OalkylC(—O)NR 20 R 21 ; aryl; heterocycle; —OalkylOC( ⁇ O)R 18 ; C( ⁇ O)N(C 1-6 alkyl), N(H)S(O)(O)(C 1-6 alkyl); arylalkyloxy; aryloxy; ary
- R 25 and R 26 usually are not present but if they are then typically they are cyclopentyl or cyclohexyl. If the compound is substituted at R 25 or R 26 , either R 2 or R 4 is selected from ( ⁇ O), (—S), and ( ⁇ NR 27 ), usually ⁇ O.
- M typically is an aromatic ring, usually single or two fused rings, and containing 4 to 10 atoms. Usually, M is hydrocarbon, but also optionally comprises 1 to 3 N, O and/or S heteroatoms.
- Q usually is a hydrocarbon chain, typically a normal or secondary alkylene, which optionally comprises at least one oxy or thio ester. Generally Q is 1 to 6 atoms, usually 1 to 3. Q typically is not substituted with R 19 , but if it is then typically it is substituted with one R 19 . R 19 as substituted on Q usually is halogen, nitro or cyano. Substituents optionally are designated with or without bonds. Regardless of bond indications, if a substituent is polyvalent (based on its position in the structure referred to), then any and all possible orientations of the substituent are intended.
- Haloalkyl or haloalkyloxy typically are —CF3 or —OCF3.
- prodrug refers to any compound that when administered to a biological system generates the drug substance, i.e. active ingredient, as a result of spontaneous chemical reaction(s), enzyme catalyzed chemical reaction(s), photolysis, and/or metabolic chemical reaction(s).
- a prodrug is thus a covalently modified analog or latent form of a therapeutically-active compound.
- prodrugs are capable of acting as prodrugs.
- prodrugs are labile functional groups which separate from an active inhibitory compound during metabolism, systemically, inside a cell, by hydrolysis, enzymatic cleavage, or by some other process.
- prodrug moieties can serve to enhance solubility, absorption and lipophilicity to optimize drug delivery, bioavailability and efficacy.
- a “prodrug” is thus a covalently modified analog of a therapeutically-active compound.
- a prodrug moiety of course can be therapeutically active in its own right.
- Exemplary prodrug moieties include the hydrolytically sensitive or labile esters (—CO 2 R′) of carboxylic acids (—CO 2 H) or other functional groups with an acidic proton which is bound to the imidazo[4,5-c]pyridine compounds of the invention.
- the R′ group of such hydrolytically sensitive or labile esters may include: (i) acyloxymethyl esters —CH 2 C( ⁇ O)R 9a ; and (ii) acyloxymethyl carbonates —CH 2 C( ⁇ O)OR 9a where R 9a is C 1 -C 6 alkyl, C 1 -C 6 substituted alkyl, C 6 -C 20 aryl or C 6 -C 20 substituted aryl.
- a close variant of the acyloxyalkyl ester, the alkoxycarbonyloxyalkyl ester (carbonate), may also enhance oral bioavailability as a prodrug moiety in the compounds of the invention.
- An exemplary acyloxymethyl ester R group is pivaloyloxymethoxy, (POM) —CH 2 C( ⁇ O)C(CH 3 ) 3 .
- An exemplary acyloxymethyl carbonate prodrug moiety is pivaloyloxymethylcarbonate (POC) —CH 2 C( ⁇ O)OC(CH 3 ) 3 .
- Cleavable moieties capable of acting as prodrug functionalities are optionally linked at any tolerant site on the compound of this invention, for example R 3 and any of its substituents.
- the present invention excludes all compounds expressly disclosed in any prior art reference (to the extent the reference is effective as novelty- or inventive step/obviousness-defeating as the case may be) set forth in this application (as well as any compounds disclosed in any reference patent family member) and and any other compounds over which the claims of this application are not novel or do not posses an inventive step or are obvious under applicable law.
- the present invention excludes, as required, compounds according to the general formula (A) where
- the compounds of the invention optionally exclude those compounds according to the general formula (A) as described above, wherein (a) Y R 1 is not phenyl para substituted with OH, or (b) is H, an unsubstituted C 3-10 cycloalkyl, or C 1-6 alkyl.
- the compounds of the invention optionally exclude those compounds according to the general formula (A) as described above, wherein R 1 is not H, Y is not NR 11 with R 11 C 1-6 alkyl or methyl, and/or YR 1 is not monomethylamino.
- the compounds of the invention optionally exclude those compounds according to the general formula (A) as described above, wherein R 1 is a phenyl substituted with 1R 6 , R 6 is C( ⁇ O)R 18 and R 18 is t-butoxy.
- the compounds of the invention optionally exclude those compounds according to the general formula (A) as described above, wherein R 1 is not piperidinyl and is not piperazinyl substituted with methyl.
- the compounds of this invention exclude those compounds disclosed by WO 2004/005286, in particular the compounds in table 8 thereof.
- the compounds of this invention optionally exclude those in which XR 3 is the definitional equivalent to the substructure —CH2)n—Y—C(O)—N(R1)(R2) set forth on column 1, line 49 to column 2 line 38 of U.S. Pat. No. 5,302,601 and the comparable disclosure in any member of the patent family of U.S. Pat. No. 5,302,601, which disclosure is herewith expressly incorporated by reference.
- the compounds of this invention optionally exclude those in which R 5 contains any of the substituents designated as ⁇ Ar>> in WO 00/39127, in particular aryl, aryl phenoxy, or benzyl.
- the compounds of this invention optionally do not include the compounds of Example 35 of U.S. Pat. No. 5,302,601, Example 6 of U.S. Pat. No. 4,990,518, Examples 1 to 5 of U.S. Pat. No. 4,988,707, Examples 1-5 of U.S. Pat. No. 5,208,241, Example 39 of U.S. Pat. No. 5,137,896, the azabenzimidazole compound of WO 99/27929, Examples 1-20 and 45 of U.S. Pat. No. 5,227,384, Examples 3 and/or 11 of WO 96/12703 and/or compounds 340A, 347C, 349C, 351C, 355C and/or 356 C of WO 96/11192.
- the compounds of this invention optionally exclude those in which XR 3 is equivalent to the substructure —(CH 2 )n-Het-C(O)—N(R 1 )(R 2 ) set forth on column 1, line 41 to column 2 line 24 of U.S. Pat. No. 4,990,518.
- the compounds of this invention do not include the compounds expressly disclosed in the patents listed in the Background of the Invention above, in Chemical Abstracts acc no. 1987:18435 and in Chemical Abstracts acc no. 1983:594812.
- the compounds of this invention do not include the compounds expressly disclosed in Justus Liebigs Annalen der Chemie (1971), 747, 158-171 or in the Journal of the Chemical Society [section B]: Physical Organic (1966), 4, 285-291.
- the compounds of this invention exclude the compounds found in any patent family member of any published or issued patent specifically recited in this application.
- the compounds of this invention optionally also exclude the methylene homologues of the foregoing known compounds excluded from the scope of this invention. It is understood that a compound optionally excluded also includes the salts thereof.
- the compounds of this invention or the metabolites produced from these compounds in vivo, have a large number of uses. They are useful in immunology, chromatography, diagnostics and therapeutics, among other fields.
- the compounds of formula (A) are conjugated to immunogenic polypeptides as a reagent for eliciting antibodies capable of binding specifically to the polypeptide, to the compounds or to their metabolic products which retain immunologically recognized epitopes (sites of antibody binding).
- immunogenic compositions therefore are useful as intermediates in the preparation of antibodies for use in diagnostics, quality control, or the like, or in assays for the compounds of formula (A) or their novel metabolic products.
- the compounds are useful for raising antibodies against otherwise non-immunogenic polypeptides, in that the compounds serve as haptenic sites stimulating an immune response which cross-reacts with the unmodified conjugated protein.
- Conjugates of the compounds of formula (A) with immunogenic polypeptides such as albumin or keyhole limpet hemocyanin generally are useful as immunogens.
- the polypeptides are conjugated at the same sites denoted for amino acids.
- the metabolic products described above may retain a substantial degree of immunological cross reactivity with the compounds of the invention.
- the antibodies of this invention will be capable of binding to the unprotected compounds of the invention without binding to the protected compounds.
- the metabolic products will be capable of binding to the protected compounds and/or the metabolitic products without binding to the protected compounds of the invention, or will be capable of binding specifically to any one or all three.
- the antibodies desirably will not substantially cross-react with naturally-occurring materials.
- Substantial cross-reactivity is reactivity under specific assay conditions for specific analytes sufficient to interfere with the assay results.
- the immunogens of this invention contain the compound of this invention presenting the desired epitope in association with an immunogenic substance.
- association means covalent bonding to form an immunogenic conjugate (when applicable) or a mixture of non-covalently bonded materials, or a combination of the above.
- Immunogenic substances include adjuvants such as Freund's adjuvant, immunogenic proteins such as viral, bacterial, yeast, plant and animal polypeptides, in particular keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin or soybean trypsin inhibitor, and immunogenic polysaccharides.
- the compound having the structure of the desired epitope is covalently conjugated to an immunogenic polypeptide or polysaccharide by the use of a polyfunctional (ordinarily bifunctional) cross-linking agent.
- a polyfunctional (ordinarily bifunctional) cross-linking agent for the manufacture of hapten immunogens are conventional per se, and any of the methods used heretofore for conjugating haptens to immunogenic polypeptides or the like are suitably employed here as well, taking into account the functional groups on the precursors or hydrolytic products which are available for cross-linking and the likelihood of producing antibodies specific to the epitope in question as opposed to the immunogenic substance.
- polypeptide is conjugated to a site on the compound of the invention distant from the epitope to be recognized.
- the conjugates are prepared in conventional fashion.
- the conjugates comprise a compound of the invention attached by a bond or a linking group of 1-100, typically, 1-25, more typically 1-10 carbon atoms to the immunogenic substance.
- the conjugates are separated from starting materials and by products using chromatography or the like, and then are sterile filtered and vialed for storage.
- Animals are typically immunized against the immunogenic conjugates or derivatives and antisera or monoclonal antibodies prepared in conventional fashion.
- the compounds of this invention are useful as linkers, spacers or affinity (typically hydrophobic) moieties in preparing affinity absorption matrices.
- the compounds of the invention optionally are bound covalently to an insoluble matrix and used for affinity chromatography separations, depending on the nature of the groups of the compounds, for example compounds with pendant aryl groups are useful in making hydrophobic affinity columns.
- the compounds herein contain functional groups that are suitable as sites for cross-linking desired substances.
- affinity reagents such as hormones, peptides, antibodies, drugs, and the like to insoluble substrates.
- affinity reagents such as hormones, peptides, antibodies, drugs, and the like
- immobilized enzymes are used to perform catalytic conversions with facile recovery of enzyme.
- Bifunctional compounds are commonly used to link analytes to detectable groups in preparing diagnostic reagents.
- the compounds of this invention are labeled with detectable moieties such biotin, radioisotopes, enzymes and the like for diagnostic purposes.
- detectable moieties such biotin, radioisotopes, enzymes and the like for diagnostic purposes.
- Suitable techniques for accomplishing the labeling of the compounds of formula (A) are well known and will be apparent to the artisan from consideration of this specification as a whole.
- one suitable site for labeling is R17 or R19.
- the compounds of the invention are employed for the treatment or prophylaxis of viral infections such as yellow fever virus, Dengue virus, hepatitis B virus, hepatitis G virus, Classical Swine Fever virus or the Border Disease Virus, but more particularly flaviviral or picornaviral infections, in particular, HCV and BVDV.
- viral infections such as yellow fever virus, Dengue virus, hepatitis B virus, hepatitis G virus, Classical Swine Fever virus or the Border Disease Virus, but more particularly flaviviral or picornaviral infections, in particular, HCV and BVDV.
- the therapeutic compound(s) of this invention are administered to a subject mammal (including a human) by any means well known in the art, i.e. orally, intranasally, subcutaneously, intramuscularly, intradermally, intravenously, intra-arterially, parenterally or by catheterization.
- the therapeutically effective amount of the compound(s) is a flaviviral or picornaviral growth inhibiting amount. More preferably, it is a flaviviral or picornaviral replication inhibiting amount or a flaviviral or picoruaviral enzyme inhibiting amount of the compounds of formula (A).
- the actual amount will depend upon many factors known to the artisan, including bioavailability of the compound, whether it contains a prodrug functionality, its metabolism and distribution in the subject and its potency, among others. It typically is necessary to determine the proper dosing in the clinical setting, and this is well within the skill of the ordinary artisan.
- the therapeutically effective amount of the compound(s) of this invention optionally are divided into several sub-units per day or are administered at daily or more than one day intervals, depending upon the pathologic condition to be treated, the patient's condition and the nature of the compound of this invention.
- the evaluation of a synergistic effect in a drug combination may be made by analyzing the quantification of the interactions between individual drugs, using the median effect principle described by Chou et al. in Adv. Enzyme Reg . (1984) 22:27 or tests such as, but not limited to, the isobologram method, as previously described by Elion et al. in J. Biol. Chem. (1954) 208:477-488 and by Baba et al. in Antimicrob. Agents Chemother. (1984) 25:515-517, using EC 50 for calculating the fractional inhibitory concentration.
- Suitable anti-viral agents for inclusion in combination antiviral compositions or for coadministration in a course of therapy include, for instance, interferon alpha, ribavirin, a compound falling within the scope of disclosure of EP 1162196, WO 03/010141, WO 03/007945 and WO 03/010140, a compound falling within the scope of disclosure of WO 00/204425, and other patents or patent applications within their patent families, in amounts of 1 to 99.9% by weight compound of this invention, preferably from 1 to 99% by weight, more preferably from 5 to 95% by weight as can be readily determined by one skilled in the art.
- Such co-administered agents need not be formulated in the same dosage form as the compound of the invention. They optionally are simply administered to the subject in the course of treatment along with a course of treatment with a compound of formula (A).
- the present invention further provides veterinary compositions comprising at least one active ingredient as above defined together with a veterinary carrier therefore, for example in the treatment of BVDV.
- Veterinary carriers are materials useful for the purpose of administering the composition and are excipients which are otherwise inert or acceptable in the veterinary art and are compatible with the compound of this invention. These veterinary compositions may be administered orally, parenterally or by any other desired route.
- salts as used herein means the therapeutically active non-toxic salt forms formed by the compounds of formula (A). Such salts may include those derived by combination of appropriate cations such as alkali and alkaline earth metal ions or ammonium and quaternary amino ions with an acid anion moiety, typically a carboxylic acid.
- the compounds of the invention may bear multiple positive or negative charges.
- the net charge of the compounds of the invention may be either positive or negative.
- Any associated counter ions are typically dictated by the synthesis and/or isolation methods by which the compounds are obtained.
- Typical counter ions include, but are not limited to ammonium, sodium, potassium, lithium, halides, acetate, trifluoroacetate, etc., and mixtures thereof. It will be understood that the identity of any associated counter ion is not a critical feature of the invention, and that the invention encompasses the compounds in association with any type of counter ion.
- the invention is intended to encompass not only forms of the compounds that are in association with counter ions (e.g., dry salts), but also forms that are not in association with counter ions (e.g., aqueous or organic solutions).
- counter ions e.g., dry salts
- counter ions e.g., aqueous or organic solutions
- Metal salts typically are prepared by reacting the metal hydroxide with a compound of this invention.
- metal salts which are prepared in this way are salts containing Li+, Na+, Ca+2 and Mg+2 and K+.
- a less soluble metal salt can be precipitated from the solution of a more soluble salt by addition of the suitable metal compound.
- salts may be formed from acid addition of certain organic and inorganic acids to basic centers, typically amines, or to acidic groups. Examples of such appropriate acids include, for instance, inorganic acids such as hydrohalogen acids, e.g.
- hydrochloric or hydrobromic acid sulfuric acid, nitric acid, phosphoric acid and the like; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, benzoic, 2-hydroxypropanoic, 2-oxopropanoic, lactic, fumaric, tartaric, pyruvic, maleic, malonic, malic, salicylic (i.e.
- 2-hydroxybenzoic 2-hydroxybenzoic
- p-aminosalicylic isethionic, lactobionic, succinic oxalic and citric acids
- organic sulfonic acids such as methanesulfonic, ethanesulfonic, benzenesulfonic and p-toluenesulfonic acids
- inorganic acids such as hydrochloric, sulfuric, phosphoric and sulfamic acids, C1-C6 alkylsulfonic, benzenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, and the like.
- Preferred salts include mesylate and HCl.
- the compounds of this invention include the solvates formed with the compounds of formula (A) and their salts, such as for example hydrates, alcoholates and the like.
- the compositions herein comprise compounds of the invention in their un-ionized, as well as zwitterionic form, and combinations with stoichiometric amounts of water as in hydrates.
- the amino acid typically is one bearing a side chain with a basic or acidic group, e.g., lysine, arginine or glutamic acid, or a neutral group such as glycine, serine, threonine, alanine, isoleucine, or leucine.
- a basic or acidic group e.g., lysine, arginine or glutamic acid, or a neutral group such as glycine, serine, threonine, alanine, isoleucine, or leucine.
- Salts of acids or bases which are not physiologically acceptable may also find use, for example, in the preparation or purification of a compound of formula (A). All salts, whether or not derived form; a physiologically acceptable acid or base, are within the scope of the present invention.
- isomers as used herein means all possible isomeric forms, including tautomeric and stereochemical forms, which the compounds of formula (A) may possess, but not including position isomers.
- the structures shown herein exemplify only one tautomeric or resonance form of the compounds, but the corresponding alternative configurations are contemplated as well.
- the chemical designation of compounds denotes the mixture of all possible stereochemically isomeric forms, said mixtures containing all diastereomets and enantiomers (since the compounds of formula (A) may have one or more chiral centers), as well as the stereochemically pure or enriched isomers. More particularly, stereogenic centers may have either the R- or S-configuration, and double or triple bonds optionally are in either the cis- or trans-configuration.
- Enriched isomeric forms of a compound of this invention are defined as a single isomer substantially free of the compound's other enantiomers or diastereomers.
- the term “stereoisomerically enriched” or “chirally enriched” relates to compounds having a single stereoisomeric proportion of at least about 80% (i.e. at least 90% of one isomer and at most 10% of the other possible isomers), preferably at least 90%, more preferably at least 94% and most preferably at least 97%.
- the terms “enantiomerically pure” and “diastereomerically pure” contain undetectable levels of any other isomer.
- stereoisomers Separation of stereoisomers is accomplished by standard methods known to those in the art.
- One enantiomer of a compound of the invention can be separated substantially free of its opposing enantiomer by a method such as formation of diastereomers using optically active resolving agents (“Stereochemistry of Carbon Compounds,” (1962) by E. L. Eliel, McGraw Hill; Lochmuller, C. H., (1975) J. Chromatogr., 113:(3) 283-302).
- Separation of isomers in a mixture can be accomplished by any suitable method, including: (1) formation of ionic, diastereomeric salts with chiral compounds and separation by fractional crystallization or other methods, (2) formation of diastereomeric compounds with chiral derivatizing reagents, separation of the diastereomers, and conversion to the pure enantiomers, or (3) enantiomers can be separated directly under chiral conditions.
- diastereomeric salts can be formed by reaction of enantiomerically pure chiral bases such as brucine, quinine, ephedrine, strychnine, a-methyl-b-phenylethylamine (amphetamine), and the like with asymmetric compounds bearing an acidic functionality, such as carboxylic acid and sulfonic acid.
- enantiomerically pure chiral bases such as brucine, quinine, ephedrine, strychnine, a-methyl-b-phenylethylamine (amphetamine), and the like
- an acidic functionality such as carboxylic acid and sulfonic acid.
- the diastereomeric salts optionally are induced to separate by fractional crystallization or ionic chromatography.
- addition of chiral carboxylic or sulfonic acids, such as camphorsulfonic acid, tartaric acid, mandelic acid, or lactic acid can result in formation of the diastereomeric salts.
- the substrate to-be resolved may be reacted with one enantiomer of a chiral compound to form a diastereomeric pair (Eliel, E. and Wilen, S. (1994). Stereochemistry of Organic Compounds, John Wiley & Sons, Inc., p. 322).
- Diastereomeric compounds can be formed by reacting asymmetric compounds with enantiomerically pure chiral derivatizing reagents, such as menthyl derivatives, followed by separation of the diastereomers and hydrolysis to yield the free, enantiomerically enriched xanthene.
- a method of determining optical purity involves making chiral esters, such as a menthyl ester or Mosher ester, a-methoxy-a-(trifluoromethyl)phenyl acetate (Jacob III. (1982) J. Org. Chem. 47:4165), of the racemic mixture, and analyzing the NMR spectrum for the presence of the two atropisomeric diastereomers.
- Stable diastereomers can be separated and isolated by normal- and reverse-phase chromatography following methods for separation of atropisomeric naphthyl-isoquinolines (Hoye, T., WO 96/15111).
- a racemic mixture of two asymmetric enantiomers is separated by chromatography using a chiral stationary phase.
- Suitable chiral stationary phases are, for example, polysaccharides, in particular cellulose or amylose derivatives.
- Commercially available polysaccharide based chiral stationary phases are ChiralCeITM CA, OA, OB5, OC5, OD, OF, OG, OJ and OK, and ChiralpakTM AD, AS, OP(+) and OT(+).
- eluents or mobile phases for use in combination with said polysaccharide chiral stationary phases are hexane and the like, modified with an alcohol such as ethanol, isopropanol and the like.
- an alcohol such as ethanol, isopropanol and the like.
- the present invention also provides the in vivo metabolic products of the compounds described herein, to the extent such products are novel and unobvious over the prior art. Such products may result for example from the oxidation, reduction, hydrolysis, amidation, esterification and the like of the administered compound, primarily due to enzymatic processes. Accordingly, the invention includes novel and unobvious compounds produced by a process comprising contacting a compound of this invention with a mammal for a period of time sufficient to yield a metabolic product thereof. Such products typically are identified by preparing a radiolabelled (e.g. C14 or H3) compound of the invention, administering it parenterally in a detectable dose (e.g.
- a radiolabelled e.g. C14 or H3
- metabolite structures are determined in conventional fashion, e.g. by MS or NMR analysis. In general, analysis of metabolites is done in the same way as conventional drug metabolism studies well-known to those skilled in the art.
- the conversion products so long as they are not otherwise found in vivo, are useful in diagnostic assays for therapeutic dosing of the compounds of the invention even if they possess no antiviral activity of their own.
- the compounds of the invention optionally are formulated with conventional pharmaceutical carriers and excipients, which will be selected in accord with ordinary practice. Tablets will contain excipients, glidants, fillers, binders and the like. Aqueous formulations are prepared in sterile form, and when intended for delivery by other than oral administration generally will be isotonic. Formulations optionally contain excipients such as those set forth in the “Handbook of Pharmaceutical Excipients” (1986) and include ascorbic acid and other antioxidants, chelating agents such as EDTA, carbohydrates such as dextrin, hydroxyalkylcellulose, hydroxyalkylmethylcellulose, stearic acid and the like.
- the term “pharmaceutically acceptable carrier” as used herein means any material or substance with which the active ingredient is formulated in order to facilitate its application or dissemination to the locus to be treated, for instance by dissolving, dispersing or diffusing the said composition, and/or to facilitate its storage, transport or handling without impairing its effectiveness.
- the pharmaceutically acceptable carrier may be a solid or a liquid or a gas which has been compressed to form a liquid, i.e. the compositions of this invention can suitably be used as concentrates, emulsions, solutions, granulates, dusts, sprays, aerosols, suspensions, ointments, creams, tablets, pellets or powders.
- Suitable pharmaceutical carriers for use in the said pharmaceutical compositions and their formulation are well known to those skilled in the art, and there is no particular restriction to their selection within the present invention. They may also include additives such as wetting agents, dispersing agents, stickers, adhesives, emulsifying agents, solvents, coatings, antibacterial and antiftungal agents (for example phenol, sorbic acid, chlorobutanol), isotonic agents (such as sugars or sodium chloride) and the like, provided the same are consistent with pharmaceutical practice, i.e. carriers and additives which do not create permanent damage to mammals.
- additives such as wetting agents, dispersing agents, stickers, adhesives, emulsifying agents, solvents, coatings, antibacterial and antiftungal agents (for example phenol, sorbic acid, chlorobutanol), isotonic agents (such as sugars or sodium chloride) and the like, provided the same are consistent with pharmaceutical practice, i.e. carriers and additives which do not create permanent damage to mammals.
- compositions of the present invention may be prepared in any known manner, for instance by homogeneously mixing, coating and/or grinding the active ingredients, in a one-step or multi-steps procedure, with the selected carrier material and, where appropriate, the other additives such as surface-active agents may also be prepared by micronisation, for instance in view to obtain them in the form of microspheres usually having a diameter of about 1 to 10 gm, namely for the manufacture of microcapsules for controlled or sustained release of the active ingredients.
- Suitable surface-active agents also known as emulgent or emulsifier, to be used in the pharmaceutical compositions of the present invention are non-ionic, cationic and/or anionic materials having good emulsifying, dispersing and/or wetting properties.
- Suitable anionic surfactants include both water-soluble soaps and water-soluble synthetic surface-active agents.
- Suitable soaps are alkaline or alkaline-earth metal salts, unsubstituted or substituted ammonium salts of higher fatty acids (C 10 -C 22 ), e.g. the sodium or potassium salts of oleic or stearic acid, or of natural fatty acid mixtures obtainable form coconut oil or tallow oil.
- Synthetic surfactants include sodium or calcium salts of polyacrylic acids; fatty sulphonates and sulphates; sulphonated benzimidazole derivatives and alkylarylsulphonates.
- Fatty sulphonates or sulphates are usually in the form of alkaline or alkaline-earth metal salts, unsubstituted ammonium salts or ammonium salts substituted with an alkyl or acyl radical having from 8 to 22 carbon atoms, e.g.
- Suitable sulphonated benzimidazole derivatives preferably contain 8 to 22 carbon atoms.
- alkylarylsulphonates are the sodium, calcium or alcoholamine salts of dodecylbenzene sulphonic acid or dibutyl-naphthalenesulphonic acid or a naphthalene-sulphonic acid/formaldehyde condensation product.
- corresponding phosphates e.g. salts of phosphoric acid ester and an adduct of p-nonylphenol with ethylene and/or propylene oxide, or phospholipids.
- Suitable phospholipids for this purpose are the natural (originating from animal or plant cells) or synthetic phospholipids of the cephalin or lecithin type such as e.g.
- phosphatidylethanolamine phosphatidylserine, phosphatidylglycerine, lysolecithin, cardiolipin, dioctanylphosphatidyl-choline, dipalritoylphoshatidyl-choline and their mixtures.
- Suitable non-ionic surfactants include polyethoxylated and polypropoxylated derivatives of alkylphenols, fatty alcohols, fatty acids, aliphatic amines or amides containing at least 12 carbon atoms in the molecule, alkylarenesulphonates and dialkylsulphosuccinates, such as polyglycol ether derivatives of aliphatic and cycloaliphatic alcohols, saturated and unsaturated fatty acids and alkylphenols, said derivatives preferably containing 3 to 10 glycol ether groups and 8 to 20 carbon atoms in the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms in the alkyl moiety of the alkylphenol.
- non-ionic surfactants are water-soluble adducts of polyethylene oxide with poylypropylene glycol, ethylenediaminopolypropylene glycol containing 1 to 10 carbon atoms in the alkyl chain, which adducts contain 20 to 250 ethyleneglycol ether groups and/or 10 to 100 propyleneglycol ether groups.
- Such compounds usually contain from 1 to 5 ethyleneglycol units per propyleneglycol unit.
- non-ionic surfactants are nonylphenol-polyethoxyethanol, castor oil polyglycolic ethers, polypropylene/polyethylene oxide adducts, tributylphenoxypolyethoxyethanol, polyethyleneglycol and octylphenoxypolyethoxyethanol.
- Fatty acid esters of polyethylene sorbitan such as polyoxyethylene sorbitan trioleate
- glycerol glycerol
- sorbitan sucrose and pentaerythritol are also suitable non-ionic surfactants.
- Suitable cationic surfactants include quaternary ammonium salts, particularly halides, having 4 hydrocarbon radicals optionally substituted with halo, phenyl, substituted phenyl or hydroxy; for instance quaternary ammonium salts containing as N-substituent at least one C8C22 alkyl radical (e.g. cetyl, lauryl, palmityl, myristyl, oleyl and the like) and, as further substituents, unsubstituted or halogenated lower alkyl, benzyl and/or hydroxy-lower alkyl radicals.
- C8C22 alkyl radical e.g. cetyl, lauryl, palmityl, myristyl, oleyl and the like
- Compounds of the invention and their physiologically acceptable salts may be administered by any route appropriate to the condition to be treated, suitable routes including oral, rectal, nasal, topical (including ocular, buccal and sublingual), vaginal and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural).
- suitable routes including oral, rectal, nasal, topical (including ocular, buccal and sublingual), vaginal and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural).
- the preferred route of administration may vary with for example the condition of the recipient.
- the formulations both for veterinary and for human use, of the present invention comprise at least one active ingredient, as above described, together with one or more pharmaceutically acceptable carriers therefore and optionally other therapeutic ingredients.
- the carrier(s) optimally are “acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
- the formulations include those suitable for oral, rectal, nasal, topical (including buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural) administration.
- the formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy.
- Such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more accessory ingredients.
- the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.
- Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion.
- the active ingredient may also be presented as a bolus, electuary or paste.
- a tablet may be made by compression or molding, optionally with one or more accessory ingredients.
- Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active or dispersing agent.
- Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.
- the tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein.
- For infections of the eye or other external tissues e.g.
- the formulations are optionally applied as a topical ointment or cream containing the active ingredient(s) in an amount of, for example, 0.075 to 20% w/w (including active ingredient(s) in a range between 0.1% and 20% in increments of 0.1% w/w such as 0.6% w/w, 0.7% w/w, etc), preferably 0.2 to 15% w/w and most preferably 0.5 to 10% w/w.
- the active ingredients may be employed with either a paraffinic or a water-miscible ointment base.
- the active ingredients may be formulated in a cream with an oil-in-water cream base.
- the aqueous phase of the cream base may include, for example, at least 30% w/w of a polyhydric alcohol, i.e. an alcohol having two or more hydroxyl groups such as propylene glycol, butane 1,3-diol, mannitol, sorbitol, glycerol and polyethylene glycol (including PEG400) and mixtures thereof.
- the topical formulations may desirably include a compound which enhances absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethylsulfoxide and related analogs.
- the oily phase of the emulsions of this invention may be constituted from known ingredients in a known manner. While the phase may comprise merely an emulsifier (otherwise known as an emulgent), it desirably comprises a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. Optionally, a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts as a stabilizer. It is also preferred to include both an oil and a fat.
- the emulsifier(s) with or without stabilizer(s) make up the so-called emulsifying wax
- the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations.
- oils or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the active compound in most oils likely to be used in pharmaceutical emulsion formulations is very low.
- the cream should optionally be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers.
- Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate or a blend of branched chain esters known as Crodamol CAP may be used, the last three being preferred esters. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and/or liquid paraffin or other mineral oils can be used.
- Formulations suitable for topical administration to the eye also include eye drops wherein the active ingredient is dissolved or suspended in a suitable carrier, especially an aqueous solvent for the active ingredient.
- the active ingredient is optionally present in such formulations in a concentration of 0.5 to 20%, advantageously 0.5 to 10% particularly about 1.5% w/w.
- Formulations suitable for topical administration in the mouth include lozenges comprising the active ingredient in a flavored basis, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.
- Formulations for rectal administration may be presented as a suppository with a suitable base comprising for example cocoa butter or a salicylate.
- Formulations suitable for nasal administration wherein the carrier is a solid include a coarse powder having a particle size for example in the range 20 to 500 microns (including particle sizes in a range between 20 and 500 microns in increments of 5 microns such as 30 microns, 35 microns, etc), which is administered in the manner in which snuff is taken, i.e. by rapid inhalation through the nasal passage from a container of the powder held close up to the nose.
- Suitable formulations wherein the carrier is a liquid, for administration as for example a nasal spray or as nasal drops include aqueous or oily solutions of the active ingredient.
- Formulations suitable for aerosol administration may be prepared according to conventional methods and may be delivered with other therapeutic agents.
- Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate.
- Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.
- the formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use.
- Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.
- Preferred unit dosage formulations are those containing a daily dose or unit daily sub-dose, as herein above recited, or an appropriate fraction thereof, of an active ingredient.
- formulations of this invention may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents.
- Controlled release formulations adapted for oral administration in which discrete units comprising one or more compounds of the invention can be prepared according to conventional methods.
- Control release compositions may thus be achieved by selecting appropriate polymer carriers such as for example polyesters, polyamino acids, polyvinyl pyrrolidone, ethylene-vinyl acetate copolymers, methylcellulose, carboxymethylcellulose, protamine sulfate and the like.
- the rate of drug release and duration of action may also be controlled by incorporating the active ingredient into particles, e.g. microcapsules, of a polymeric substance such as hydrogels, polylactic acid, hydroxymethylcellulose, polymethyl methacrylate and the other above-described polymers.
- Such methods include colloid drug delivery systems like liposomes, microspheres, microemulsions, nanoparticles, nanocapsules and so on.
- the pharmaceutical composition may require protective coatings.
- Pharmaceutical forms suitable for injectionable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation thereof. Typical carriers for this purpose therefore include biocompatible aqueous buffers, ethanol, glycerol, propylene glycol, polyethylene glycol and the like and mixtures thereof.
- each active ingredient may therefore be formulated in a way suitable for an administration route different from that of the other ingredient, e.g. one of them may be in the form of an oral or parenteral formulation whereas the other is in the form of an ampoule for intravenous injection or an aerosol.
- the compounds of formula (A) are prepared using a series of chemical reactions well known to those skilled in the art, altogether making up the process for preparing said compounds and exemplified further.
- the processes described further are only meant as examples and by no means are meant to limit the scope of the present invention.
- the invention also relates to methods of making the compositions of the invention.
- the compositions are prepared by any of the applicable techniques of organic synthesis. Many such techniques are well known in the art. However, many of the known techniques are elaborated in “Compendium of Organic Synthetic Methods” (John Wiley & Sons, New York), Vol. 1, Ian T. Harrison and Shuyen Harrison, 1971; Vol. 2, Ian T. Harrison and Shuyen Harrison, 1974; Vol. 3, Louis S. Hegedus and Leroy Wade, 1977; Vol. 4, Leroy G. Wade, Jr., 1980; Vol. 5, Leroy G. Wade, Jr., 1984; and Vol. 6, Michael B.
- reaction conditions such as temperature, reaction time solvents, workup procedures, and the like, will be those common in the art for the particular reaction to be performed.
- the cited reference material, together with material cited therein, contains detailed descriptions of such conditions.
- the temperatures will be ⁇ 100° C. to 200° C.
- solvents will be aprotic or protic
- reaction times will be 10 seconds to 10 days.
- Workup typically consists of quenching any unreacted reagents followed by partition between a water/organic layer system (extraction) and separating the layer containing the product.
- Oxidation and reduction reactions are typically carried out at temperatures near room temperature (about 20° C.), although for metal hydride reductions frequently the temperature is reduced to 0° C. to ⁇ 100° C.
- solvents are typically aprotic for reductions and may be either protic or aprotic for oxidations. Reaction times are adjusted to achieve desired conversions.
- Condensation reactions are typically carried out at temperatures near room temperature, although for non-equilibrating, kinetically controlled condensations reduced temperatures (0° C. to ⁇ 100° C.) are also common.
- Solvents can be either protic (common in equilibrating reactions) or aprotic (common in kinetically controlled reactions).
- Standard synthetic techniques such as azeotropic removal of reaction by-products and use of anhydrous reaction conditions (e.g. inert gas environments) are common in the art and will be applied when applicable.
- treated means contacting, mixing, reacting, allowing to react, bringing into contact, and other terms common in the art for indicating that one or more chemical entities is treated in such a manner as to convert it to one or more other chemical entities.
- treating compound one with compound two is synonymous with “allowing compound one to react with compound two”, “contacting compound one with compound two”, “reacting compound one with compound two”, and other expressions common in the art of organic synthesis for reasonably indicating that compound one was “treated”, “reacted”, “allowed to react”, etc., with compound two.
- “Treating” indicates the reasonable and usual manner in which organic chemicals are allowed to react. Normal concentrations (0.01M to 10M, typically 0.1M to 1M), temperatures ( ⁇ 100° C. to 250° C., typically ⁇ 78° C. to 150° C., more typically ⁇ 78° C. to 100° C., still more typically 0° C. to 100° C.), reaction vessels (typically glass, plastic, metal), solvents, pressures, atmospheres (typically air for oxygen and water insensitive reactions or nitrogen or argon for oxygen or water sensitive), etc., are intended unless otherwise indicated.
- the knowledge of similar reactions known in the art of organic synthesis is used in selecting the conditions and apparatus for “treating” in a given process. In particular, one of ordinary skill in the art of organic sysnthesis selects conditions and apparatus reasonably expected to successfully carry out the chemical reactions of the described processes based on the knowledge in the art.
- reaction products from one another and/or from starting materials.
- the desired products of each step or series of steps is separated and/or purified (hereinafter separated) to the desired degree of homogeneity by the techniques common in the art.
- separations involve multiphase extraction, crystallization from a solvent or solvent mixture, distillation, sublimation, or chromatography.
- Chromatography can involve any number of methods including, for example, size exclusion or ion exchange chromatography, high, medium, or low pressure liquid chromatography, small scale and preparative thin or thick layer chromatography, as well as techniques of small scale thin layer and flash chromatography.
- reagents selected to bind to or render otherwise separable a desired product, unreacted starting material, reaction by product, or the like.
- reagents include adsorbents or absorbents such as activated carbon, molecular sieves, ion exchange media, or the like.
- the reagents can be acids in the case of a basic material, bases in the case of an acidic material, binding reagents such as antibodies, binding proteins, selective chelators such as crown ethers, liquid/liquid ion extraction reagents (LIX), or the like.
- alkylating reagents which may be employed in the pyridyl alkylation reaction of Scheme 1.
- the residue of the alkylating agent is located at the X R 3 site of the compound of this invention.
- the remainder of the compound will be as found in any of the compounds of examples 2-7.
- Alkylating reagent MW 195.475 203.053 168.666 223.471 154.639 253.109 154.639 203.053 145.588 203.053 190.672 273.478 338.832 269.059 205.039 223.471 325.225 289.478 262.579 269.059 228.721 253.06 207.016 253.06 307.03 253.06 199.09 221.043 175.057 285.567 154.639 344.203 216.663 261.569 218.682 212.078 275.144 195.57 198.648 299.113 294.907 228.077 244.144 193.632 222.084 223.471 152.623 255.961 118.523 252.11 255.138 190.039 328.828 176.012 202.611 237.099 281.123 238.087 170.638 239.623 257.023 198.648 257.023 350.235 257.023 252.11 257.023 236.111 257.023 320.206 257.023 2
- Scheme 2 shows a synthetic route to 5-biarylmethyl-2-phenyl-5H-imidazo[4,5-c]pyridines and 5-benzyl-2-biaryl-5H-imidazo[4,5-c]pyridines.
- Scheme 3 shows a synthetic route to 5-(alkoxybenzyl)-2-phenyl-5H-imidazo[4,5-c]pyridines and 5-benzyl-2-alkoxybenzyl-5H-imidazo[4,5-c]pyridines.
- R, R′, and R′′ can be any alkyl, benzylic or heterobenzylic groups.
- Analogous compounds may be synthesized in the same fashion as in the foregoing schemes by varying the starting materials, intermediates, solvents and conditions as will be known by those skilled in the art.
- Phosphorous pentoxide 24.56 g was dissolved in methanesulfonic acid (165.8 mL) at 50° C. with stirring.
- methanesulfonic acid 165.8 mL
- 3,4-diaminopyridine (12.3 g, 0.1 mmoles) and 2,3-difluorobenzoic acid (19.4 g, 0.12 moles) were added.
- the reaction mixture was heated to 190° C. for 3 hours. The reaction was done three times.
- the reaction mixtures was cooled to 50° C. and poured into ice with stirring. At this stage, all three batches were combined.
- the reaction mixture was neutralized by the addition of NaOH with stirring until the pH is 8. Solid material precipitated out of solution, was collected by filtration and air-dried.
- the material was crystallized by dissolving the material in MeOH with heat, followed by precipitation with water. This crystallization process was then repeated yielding 5((3-(4-chlorophenyl)isoxazol-5-yl)methyl)-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine (15.385 g, 38 mmole) as white crystal at a yield of 74%.
- 2-(2,3-difluorophenyl)-3H-imidazo[4,5-c]pyridine (20 g, 86.6 mmole) was added to 430 mL of DMF; Some of the solid material did not dissolve.
- To this solution was added 43 mL of a 10% NaOH (w/v) solution. With vigorous stirring, the un-dissolved material went into solution.
- the resulting solution was divided into 30 equal portions of 16.3 mL, 3 mmole of 2-(2,3-difluorophenyl)-3H-imidazo[4,5-c]pyridine so as to fit into a microwave reaction vessel.
- reaction vessel To each reaction vessel was added of 11-(chloromethyl)-4-(trifluoromethoxy)benzene (693 mg, 3 mmole). Each reaction mixture was microwaved for 1 minute at 110° C. Following the completion of all the microwave reactions, all of the reaction vessels were combined (one was lost due to breakage of the vessel) into three batches for workup. For each batch, DMF was removed by vacuum, and the resulting material was washed three times with deionized water.
- 2,4-difluorophenylboronic acid (196 mg, 1.24 mmole) was added to a solution of 5-(4-iodobenzyl)-2-(2,3-difluorophenyl)-5H-imidazo[4,5-c]pyridine (460 mg, 1.03 mmole) in DMF (10 mL).
- Na 2 CO 3 was dissolved in H 2 O, added to the DMF solution and stirred.
- Pd(PPh3) 4 was then added to the DMF reaction mixture. The reaction mixture was heated in a microwave at 200° C. for 2 minutes.
- 2,4-(bis-trifluoromethyl)benzaldoxime (9.75 g, 0.038 mol) was suspended in CH 2 Cl 2 (45 mL, 0.85 M) and cooled to 4° C.
- Propargyl chloride (2.72 mL, 0.038 mol) was added to the reaction solution followed by dropwise addition of NaOCl (10-13. % free chlorine, 37.6 mL, 0.061 mol).
- the reaction mixture was stirred at 4° C. for 15 min then heated to reflux for 3 h. After cooling to room temperature, the reaction was partitioned between CH 2 Cl 2 and H 2 O. The organic layer was separated, washed with saturated aqueous NaCl, and dried over sodium sulfate. After removal of solvent, the crude product chloromethylisoxazole was purified by column chromatography on silica (10% CH 2 Cl 2 /hexanes)(6.5 g, 0.020 mol).
- the solid material was recrystallized from EtoAc/hexanes to obtain 5-((3-(2-trifluoromethy-4-fluorophenyl)isoxazol-5-yl)methyl)-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine in 69% yield.
- Example 7B Either salt of Example 7B was mixed 1:1 by weight in dry pregelatinized starch. 100 mg of the mixture was loaded into a hard gel capsule.
- the scaffold in this case 2-(2,3-Difluoro-phenyl)-3H-imidazo[4,5-c]pyridine
- the total amount of 2-(2,3-Difluoro-phenyl)-3H-imidazo[4,5-c]pyridine was dissolved in enough DMF to give 500 ul/reaction.
- To each solution was added 60 ⁇ L of 10% (w/v)NaOH/H 2 O.
- the alkylating agents were dissolved in DMF at a concentration 480 ⁇ mole/mL and 250 ⁇ L of these solutions were added to the respective reaction.
- Each reaction was then heated to 110° C. for 1 min using microwave irradiation.
- the aryl boronic acid (1.2 eq.) was added to a solution of 5-(4-iodobenzyl)-2-(2,3-difluorophenyl)-5H-imidazo[4,5-c]pyridine (1 eq.) in DMF.
- Na 2 CO 3 (2eq) was dissolved in H 2 O, added to the DMF solution and stirred.
- Pd(PPh3)4 was then added to the DMF reaction mixture.
- the reaction mixture was heated in a microwave at 200° C. for 2 minutes.
- the reaction mixture was applied to a 1 g solid phase extraction cartridge (C-18) and the column was washed with 3 ⁇ 2 mL of methanol.
- the eluents were filtered through a 0.45 um filter and then concentrated to dryness.
- the resulting material was redissolved in DMF, and purified by reverse phase HPLC/MS.
- Oxime was suspended in CH 2 Cl 2 and cooled to 4° C. Propargyl chloride (1 equiv.) was added to the reaction solution followed by dropwise addition of NaOCl (10-13% free chlorine, 1 equiv.). The reaction mixture was stirred at 4° C. for 15 min then heated to reflux for 3 h. After cooling to room temperature, the reaction was partitioned between CH 2 Cl 2 and H 2 O. The organic layer was separated, washed with saturated aqueous NaCl, and dried over sodium sulfate. After removal of solvent, the crude product was purified by trituration (hexanes) or by column chromatography on silica (10% CH 2 Cl 2 /hexanes).
- the aryl bromide (1.2 eq.) was added to a solution of 4-((2-(2,3-difluorophenyl)-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenylboronic acid (1 eq.) in DMF.
- Na 2 CO 3 (2eq) was dissolved in H 2 O, added to the DMF solution and stirred.
- Pd(PPh 3 ) 4 (5 mole %) was then added to the DMF reaction mixture.
- the reaction mixture was heated in a microwave at 200° C. for 2 minutes.
- the reaction mixture was applied to a 1 g solid phase extraction cartridge (C-18) and the column was washed with 3 ⁇ 2 mL of methanol.
- the eluents were filtered through a 0.45 um filter and then concentrated to dryness.
- the resulting material was redissolved in DMF, and purified by reverse phase HPLC/MS.
- the appropriately substituted 4′-[2-(2,3-Difluoro-phenyl)-imidazo[4,5-c]pyridin-5-ylmethyl]-biphenyl-4-ol (5) scaffold was prepared by first treating 2-(2,3-Difluoro-phenyl)-3H-imidazo[4,5-c]pyridine) (1) with 1-bromomethyl-4-iodobenzene (2) in DMF using aqueous sodium hydroxide as base.
- Example 9 95 387.340 388.340 A
- Example 10 90 395.440 396.440 A
- Example 11 90 413.431 414.431 A
- Example 12 92 404.451 405.451 A
- Example 13 95 407.451 408.451 A
- Example 14 85 405.479 406.479 A
- Example 15 90 389.331 390.331 A
- Example 16 90 431.418 432.418 A
- Example 17 93 404.834 405.834
- Example 18 90 370.389 371.389 A
- Example 19 95 389.331 390.331 A
- Example 20 95 389.331 390.331 A
- Example 21 95 389.331 390.331 A
- Example 22 97 355.777 356.777 A
- Example 23 90 407.451 408.451
- Example 24 90 461.134 462.134 A
- Example 25 90 401.404 402.404 A
- Example 26 95 371.377 372.377 A
- Example 27 95 439.375 440.375
- the final step was performed as described above. Recrystallized from ethyl acetate.
- MDBK Madin-Darbey Bovine Kidney cells were maintained in Dulbecco's modified Eagle medium (DMEM) supplemented with BVDV-free 5% fetal calf serum (DMEME-FCS) at 37° C. in a humidified, 5% CO 2 atmosphere.
- BVDV-1 strain PE5175 was used to assess the antiviral activity in MDBK cells.
- the 50% effective concentration (EC 50 ) value was defined as the concentration of compound that protects 50% of the cell monolayer from virus-induced cytopathic effect.
- Huh-5-2 cells [a cell line with a persistent HCV replicon 1389luc-ubi-neo/NS3-3′/5.1; replicon with firefly luciferase-ubiquitin-neomycin phosphotransferase fusion protein and EMCV-IRES driven NS3-5B HCV polyprotein] was cultured in RPMI medium (Gibco) supplemented with 10% fetal calf serum, 2 mM L-glutamine (Life Technologies), 1 ⁇ non-essential amino acids (Life Technologies); 100 IU/mL penicillin and 100 ug/ml streptomycin and 250 ug/mL G418 (Geneticin, Life Technologies).
- Cells were seeded at a density of 7000 cells per well in 96 well View PlateTM (Packard) in medium containing the same components as described above, except for G418. Cells were allowed to adhere and proliferate for 24 hr. At that time, culture medium was removed and serial dilutions of the test compounds were added in culture medium lacking G418. Interferon alfa 2a (500 IU) was included as a positive control. Plates were further incubated at 37° C. and 5% CO 2 for 72 hours. Replication of the HCV replicon in Huh-5 cells results in luciferase activity in the cells.
- Luciferase activity is measured by adding 50 ⁇ L of 1 ⁇ Glo-lysis buffer (Promega) for 15 minutes followed by 50 ⁇ L of the Steady-Glo Luciferase assay reagent (Promega). Luciferase activity is measured with a luminometer and the signal in each individual well is expressed as a percentage of the untreated cultures. Parallel cultures of Huh-5-2 cells, seeded at a density of 7000 cells/well of classical 96-well cell culture plates (Becton-Dickinson) are treated in a similar fashion except that no Glo-lysis buffer or Steady-Glo Luciferase reagent is added. Instead the density of the culture is measured by means of the MTS method (Promega).
- Replicon cells were plated at 7.5 ⁇ 10 3 cells per well in a 96-well plate plates at 37° C. and 5% CO 2 in Dulbecco's modified essential medium containing 10% fetal calf serum, 1% nonessential amino acids and 1 mg/ml Geneticin. After allowing 24 h for cell attachment, different dilutions of compound were added to the cultures. Plates were incubated for 5 days, at which time RNA was extracted using the Qiamp Rneazyi Kit (Qiagen, Hilden, Germany).
- a 50 ⁇ L PCR reaction contained TaqMan EZ buffer (50 mmol/L Bicine, 115 mmol/L potassium acetate, 0.01 mmol/L EDTA, 60 nmol/L 6-carboxy-X-rhodamine, and 8% glycerol, pH 8.2; Perkin Elmer Corp./Applied Biosystems), 300 mmol/L deoxyadenosine triphosphate, 300 ⁇ mol/L deoxyguanosine triphosphate, 300 mmol/L deoxycytidine triphosphate, 600 ⁇ mol/L deoxyuridine triphosphate, 200 ⁇ mol/L forward primer [5′-ccg gcT Acc Tgc ccA TTc], 200 ⁇ mol/L reverse primer [ccA GaT cAT ccT gAT cgA cAA G], 100 ⁇ mol/L TaqMan probe [6-FAM-AcA Tcg cAT cgA g Agc
- Ct-value is defined as the number of PCR cycles for which the signal exceeds the baseline, which defines a positive value. The sample was considered to be positive if the Ct-value was ⁇ 50. Results are expressed as genomic equivalents (GE).
- the effect of the drugs on exponentially growing MDBK cells was assessed as follows. Cells were seeded at a density of 5000 cell/well in 96 well plates in MEM medium (Gibco) supplemented with 10% fetal calf serum, 2 mM L-glutamine (Life Technologies) and bicarbonate (Life Technologies). Cells were cultured for 24 hr after which serial dilutions of the test compounds were added. Cultures were then again further incubated for 3 days after which the effect on cell growth was quantified by means of the MTS method (Promega). The concentration that results in 50% inhibition of cell growth is defined as the 50% cytostatic concentration (CC 50 ).
- the compounds of Examples 2, 3A, 4 and 5 were found to have an EC50 in Replicon assay 2 of, respectively in micromoles, 0.01, 0.02, 0.01 and 0.0039, and to have a CC50 in the CC50 assay protocol of, respectively in micromoles, 26, 34, 19 and 10.8 (replicate 13.4).
- Substantially all of the compounds in Table 1 demonstrated activity of at least 1 micromolar in an anti-HCV/Replicon assay system. In addition, a number of the compounds also exhibited anti-BVDV activity.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/019,830 US20050222198A1 (en) | 2003-12-22 | 2004-12-21 | Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment |
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US53229203P | 2003-12-22 | 2003-12-22 | |
US53396304P | 2004-01-02 | 2004-01-02 | |
US59102404P | 2004-07-26 | 2004-07-26 | |
US59106904P | 2004-07-26 | 2004-07-26 | |
US59099004P | 2004-07-26 | 2004-07-26 | |
US59098904P | 2004-07-26 | 2004-07-26 | |
US11/019,830 US20050222198A1 (en) | 2003-12-22 | 2004-12-21 | Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment |
Publications (1)
Publication Number | Publication Date |
---|---|
US20050222198A1 true US20050222198A1 (en) | 2005-10-06 |
Family
ID=34744004
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/583,814 Active 2025-12-27 US7648998B2 (en) | 2003-12-22 | 2004-12-21 | Imidazo 4,5-c pyridine compounds and methods of antiviral treatment |
US11/019,830 Abandoned US20050222198A1 (en) | 2003-12-22 | 2004-12-21 | Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment |
US12/577,865 Active 2026-03-25 US8329727B2 (en) | 2003-12-22 | 2009-10-13 | Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/583,814 Active 2025-12-27 US7648998B2 (en) | 2003-12-22 | 2004-12-21 | Imidazo 4,5-c pyridine compounds and methods of antiviral treatment |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/577,865 Active 2026-03-25 US8329727B2 (en) | 2003-12-22 | 2009-10-13 | Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment |
Country Status (18)
Country | Link |
---|---|
US (3) | US7648998B2 (fr) |
EP (3) | EP2161273B1 (fr) |
JP (3) | JP4970048B2 (fr) |
KR (1) | KR101131589B1 (fr) |
AT (1) | ATE544765T1 (fr) |
AU (2) | AU2004309390B2 (fr) |
CA (1) | CA2549606C (fr) |
CY (1) | CY1112733T1 (fr) |
DK (2) | DK2161273T3 (fr) |
ES (1) | ES2381890T3 (fr) |
HK (1) | HK1092793A1 (fr) |
IL (1) | IL176298A (fr) |
NZ (2) | NZ548074A (fr) |
PL (1) | PL1706403T3 (fr) |
PT (1) | PT1706403E (fr) |
SG (1) | SG149067A1 (fr) |
SI (1) | SI2161273T1 (fr) |
WO (1) | WO2005063744A2 (fr) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050239821A1 (en) * | 2002-07-03 | 2005-10-27 | Johan Neyts | Viral inhibitors |
US20060052602A1 (en) * | 2004-07-27 | 2006-03-09 | Gilead Sciences, Inc. | Imidazo[4,5-d]pyrimidines, their uses and methods of preparation |
US20060252791A1 (en) * | 2004-12-21 | 2006-11-09 | Gilead Sciences, Inc. | Imidazo[4,5-c]pyridine compound and method of antiviral treatment |
US20070244148A1 (en) * | 2003-12-22 | 2007-10-18 | Bondy Steven S | Imidazo 4,5-C Pyridine Compounds and Methods of Antiviral Treatment |
US20080199427A1 (en) * | 2006-07-07 | 2008-08-21 | Bondy Steven S | Novel pyridazine compound and use thereof |
US20090036460A1 (en) * | 2007-07-06 | 2009-02-05 | Gilead Sciences, Inc. | Crystalline pyridazine compound |
CN102427731A (zh) * | 2009-02-27 | 2012-04-25 | 英安塔制药有限公司 | 丙型肝炎病毒抑制剂 |
US8673954B2 (en) | 2009-02-27 | 2014-03-18 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
US8927739B2 (en) | 2011-05-18 | 2015-01-06 | Enanta Pharmaceuticals, Inc. | Processes for the preparation of 5-azaspiro[2.4]heptane-6-carboxylic acid and its derivatives |
US9765087B2 (en) | 2009-02-27 | 2017-09-19 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69932323T2 (de) | 1998-03-02 | 2006-11-23 | Anthony S. Ramona Ellsworth | Fahrradaufhängungsvorrichtung und entsprechendes verfahren |
US20070128625A1 (en) * | 2005-07-25 | 2007-06-07 | Gilead Sciences, Llc | Drug-resistant mutants of hepatitis C virus |
UA96296C2 (en) * | 2006-07-07 | 2011-10-25 | Гилиад Сайенсиз, Инк. | Pyridazine compounds and use thereof |
AU2011253901B2 (en) * | 2006-07-07 | 2013-08-29 | Gilead Sciences, Inc. | Novel pyridazine compound and use thereof |
CA2672298C (fr) | 2006-12-14 | 2015-02-03 | K.U.Leuven Research & Development | Composes fusionnes de pyridine utiles dans la prevention ou le traitement des infections virales |
TW200920372A (en) * | 2007-07-13 | 2009-05-16 | Genelabs Tech Inc | Anti-viral compounds, compositions, and methods of use |
US20090197880A1 (en) * | 2007-07-13 | 2009-08-06 | Genelabs Technologies, Inc. | Anti-viral compounds, compositions, and methods of use |
UY31685A (es) * | 2008-03-04 | 2009-11-10 | Smithkline Beecham Corp | Compuestos antivirales, composiciones y metodos para usarlos |
KR101220182B1 (ko) * | 2009-02-25 | 2013-01-11 | 에스케이바이오팜 주식회사 | 치환된 아졸 유도체 화합물, 이를 포함하는 약제학적 조성물 및 이를 이용한 파킨슨씨 병 치료방법 |
US10752611B2 (en) | 2009-02-27 | 2020-08-25 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
US8101643B2 (en) * | 2009-02-27 | 2012-01-24 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
CA2784646A1 (fr) | 2009-12-18 | 2011-06-23 | Boehringer Ingelheim International Gmbh | Polytherapie du vhc |
US8933110B2 (en) | 2010-01-25 | 2015-01-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
US8785487B2 (en) | 2010-01-25 | 2014-07-22 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
EP2555622A4 (fr) | 2010-04-09 | 2013-09-18 | Enanta Pharm Inc | Inhibiteurs du virus de l'hépatite c |
KR101799429B1 (ko) * | 2010-05-03 | 2017-11-21 | 에스케이바이오팜 주식회사 | 신경 세포 사멸 또는 신경 퇴화를 억제하기 위한 약학적 조성물 |
JP2013526581A (ja) * | 2010-05-21 | 2013-06-24 | ギリアード サイエンシーズ, インコーポレイテッド | ヘテロ環式フラビウイルス科ウイルス阻害剤 |
US8778938B2 (en) | 2010-06-04 | 2014-07-15 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
WO2012021704A1 (fr) | 2010-08-12 | 2012-02-16 | Enanta Pharmaceuticals, Inc. | Inhibiteurs du virus de l'hépatite c |
US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
ES2527544T1 (es) | 2011-10-21 | 2015-01-26 | Abbvie Inc. | Tratamiento mono (PSI-7977) o de combinación con AAD para su uso en el tratamiento del VHC |
US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
AR088463A1 (es) | 2011-10-21 | 2014-06-11 | Abbvie Inc | Metodos para el tratamiento de hcv |
RS62434B1 (sr) | 2014-12-26 | 2021-11-30 | Univ Emory | Antivirusni n4-hidroksicitidin derivati |
WO2017189978A1 (fr) | 2016-04-28 | 2017-11-02 | Emory University | Compositions thérapeutiques à base de nucléotides et nucléosides contenant un alcyne et utilisations associées |
EP3455218A4 (fr) | 2016-05-10 | 2019-12-18 | C4 Therapeutics, Inc. | Dégronimères de type glutarimide liés au carbone c3 pour la dégradation de protéines cibles |
EP3454856B1 (fr) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Dégronimères hétérocycliques pour la dégradation de protéines cibles |
WO2017197036A1 (fr) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Dégronimères spirocycliques pour la dégradation de protéines cibles |
CN111372592A (zh) | 2017-12-07 | 2020-07-03 | 埃默里大学 | N4-羟基胞苷及衍生物和与其相关的抗病毒用途 |
AU2021225333A1 (en) * | 2020-02-24 | 2022-08-11 | Katholieke Universiteit Leuven | Pyrrolopyridine and imidazopyridine antiviral compounds |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040171626A1 (en) * | 2003-01-22 | 2004-09-02 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US20040186125A1 (en) * | 2003-01-22 | 2004-09-23 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US6803374B2 (en) * | 2001-09-26 | 2004-10-12 | Bristol-Myers Squibb Company | Compounds useful for treating hepatitis C virus |
US20060229336A1 (en) * | 2002-12-13 | 2006-10-12 | Kazmierski Wieslaw M | Ccr5 antagonists as therapeutic agents |
US20070032497A1 (en) * | 1999-12-27 | 2007-02-08 | Japan Tobacco Inc. | Fused-ring compounds and use thereof as drugs |
US7285551B2 (en) * | 1999-12-27 | 2007-10-23 | Japan Tobacco Inc. | Fused-ring compounds and use thereof as drugs |
US7294457B2 (en) * | 2001-08-07 | 2007-11-13 | Boehringer Ingelheim (Canada) Ltd. | Direct binding assay for identifying inhibitors of HCV polymerase |
US20080188516A1 (en) * | 2004-12-21 | 2008-08-07 | Bondy Steven S | Imiadazo[4,5-c] pyridine compound and method of antiviral treatment |
Family Cites Families (105)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US462009A (en) * | 1891-10-27 | Four-hundred-day clock | ||
US232937A (en) * | 1880-10-05 | Pipe cutter and wrench | ||
US605836A (en) * | 1898-06-21 | George ashley | ||
US89588A (en) * | 1869-05-04 | Improved apparatus for making illuminating-gas from gasoline | ||
US510260A (en) * | 1893-12-05 | Electric-arc-lighting system | ||
US78019A (en) * | 1868-05-19 | Albert b | ||
US300726A (en) * | 1884-06-17 | Benjamin franklin opp | ||
US637615A (en) * | 1899-07-31 | 1899-11-21 | Dluarej Norwood Jerauld | Fire-escape. |
US658625A (en) * | 1899-08-16 | 1900-09-25 | John Eicher | Cream-ripening apparatus. |
US706795A (en) * | 1902-03-24 | 1902-08-12 | Internat Silver Co | Tilting vessel. |
US1048742A (en) * | 1912-04-17 | 1912-12-31 | Theodore Scherba | Trolley. |
US1162196A (en) * | 1913-07-05 | 1915-11-30 | Safety Car Heating & Lighting | Dynamo-mounting. |
US1400241A (en) * | 1919-04-09 | 1921-12-13 | Sholdebrand Henry Oliver | Stovepipe-cleaner |
US1386923A (en) * | 1920-01-02 | 1921-08-09 | Edward C Capper | Automatic fire-alarm device |
US2191978A (en) * | 1935-10-10 | 1940-02-27 | Ig Farbenindustrie Ag | Quaternary nitrogen compounds and process of preparing them |
US2264115A (en) * | 1939-01-14 | 1941-11-25 | T & T Vicars Ltd | Method and apparatus for treating dough |
US2411662A (en) * | 1943-05-13 | 1946-11-26 | Geigy Ag J R | Imino-di-fatty acid amide |
US2548863A (en) * | 1946-05-29 | 1951-04-17 | Wyeth Corp | Substituted glycinamides |
US2516674A (en) * | 1948-10-29 | 1950-07-25 | Wyeth Corp | Substituted glycinamide |
US3035207A (en) * | 1959-01-14 | 1962-05-15 | A E I Lamp And Lighting Compan | Circuit arrangement for operating electric discharge lamp |
US3985891A (en) * | 1973-02-03 | 1976-10-12 | Boehringer Ingelheim Gmbh | 2-Phenyl-imidazo (4,5-b)pyridines and salts thereof |
SU813921A1 (ru) | 1979-10-26 | 1986-12-23 | Институт физико-органической химии и углехимии АН УССР | Стирильные производные имидазо(4,5- @ )пиридиний иодида,обладающие фунгицидной активностью |
SU851940A1 (ru) | 1980-03-20 | 1988-04-30 | Институт физико-органической химии и углехимии АН УССР | Четвертичные соли имидазо @ 4,5-с @ пиридини ,обладающие антимикробной и фунгистатической активностью |
SU860463A1 (ru) | 1980-04-09 | 1998-05-27 | Институт физико-органической химии и углехимии АН Украинской ССР | Производные 4-амино-1,3-диметилимидазо [4,5-с] пиридин-2-она, обладающие акарицидным действием |
SU1048742A1 (ru) | 1981-03-30 | 1986-12-23 | Институт физико-органической химии и углехимии АН УССР | 2,4-Дистирилпроизводные имидазо-(4,5- @ )пиридини ,обладающие бактериостатической и фунгистатической активностью |
US4358387A (en) * | 1981-08-10 | 1982-11-09 | Texaco Inc. | Cylinder lubricating oil composition |
CA1183847A (fr) * | 1981-10-01 | 1985-03-12 | Georges Van Daele | N-(3-hydroxy-4-piperidinyl)benzamide; derives |
US5137896A (en) * | 1981-10-01 | 1992-08-11 | Janssen Pharmaceutica N.V. | N-(3-hydroxy-4-piperidinyl)benzamide derivatives |
FR2527608B1 (fr) * | 1982-05-28 | 1986-10-10 | Sandoz Sa | Nouveaux composes heterocycliques, leur preparation et leur utilisation comme medicaments |
GB2148289B (en) | 1983-10-17 | 1987-09-23 | Lilly Co Eli | 3-bicyclicpyridinium-methyl cephalosporins |
US4692443A (en) * | 1983-10-17 | 1987-09-08 | Eli Lilly And Company | 3-bicyclicpyridinium-methyl cephalosporins |
GB8501542D0 (en) * | 1985-01-22 | 1985-02-20 | Erba Farmitalia | 4 5 6 7-tetrahydro-imidazo(4 5-clpyridine derivatives |
GB8530602D0 (en) | 1985-12-12 | 1986-01-22 | Fujisawa Pharmaceutical Co | Heterocyclic compounds |
ES2052544T3 (es) | 1986-02-03 | 1994-07-16 | Janssen Pharmaceutica Nv | Composiciones anti-histaminicas que contienen n-heterociclil-4-piperidinaminas. |
US4804658A (en) * | 1986-09-15 | 1989-02-14 | G. D. Searle & Co. | Imidazopyridine derivatives and pharmaceutical compositions |
NZ225447A (en) | 1987-07-20 | 1991-12-23 | Merck & Co Inc | Piperazinyl derivatives of purine and purine isosteres and pharmaceutical compositions |
US5057517A (en) * | 1987-07-20 | 1991-10-15 | Merck & Co., Inc. | Piperazinyl derivatives of purines and isosteres thereof as hypoglycemic agents |
US5227384A (en) * | 1988-03-14 | 1993-07-13 | G. D. Searle & Co. | 5-substituted [4,5-c] imidazopyridines and pharmaceutical use thereof |
US4914108A (en) * | 1988-03-14 | 1990-04-03 | G. D. Searle & Co. | 5-substituted(4,5-c)imidazopyridine compounds which have useful platelet activating factor antagonistic activity |
US5019581A (en) * | 1988-03-14 | 1991-05-28 | G. D. Searle & Co. | 5-substituted (4,5-c) imidazopyridine compounds which have useful platelet activating factor antagonistic activity |
US5302601A (en) * | 1988-03-14 | 1994-04-12 | G. D. Searle & Co. | 5-substituted imidazo[4,5-c]pyridines |
US5332744A (en) * | 1989-05-30 | 1994-07-26 | Merck & Co., Inc. | Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists |
US4988707A (en) | 1989-09-13 | 1991-01-29 | G. D. Searle & Co. | Pharmacologically active phenylalkanoyl substituted imidazo (4,5-C) pyridines |
US4990518A (en) * | 1989-09-13 | 1991-02-05 | G. D. Searle & Co. | Pharmacologically active heteroaryl substituted imidazo (4,5-c) pyridines |
US5095873A (en) | 1989-09-13 | 1992-03-17 | Yamaha Hatsudoki Kabushiki Kaisha | Fuel injection system and method for engine |
FR2663332B1 (fr) | 1990-06-15 | 1997-11-07 | Roussel Uclaf | Nouvelles cephalosporines comportant en position 3 un radical propenyle substitue par un ammonium quaternaire, leur procede de preparation, leur application comme medicaments, les compositions les renfermant et les nouveaux intermediaires obtenus. |
US5011832A (en) * | 1990-06-26 | 1991-04-30 | Merck & Co., Inc. | 2-biphenyl-carbapenem antibacterial agents |
US5372808A (en) * | 1990-10-17 | 1994-12-13 | Amgen Inc. | Methods and compositions for the treatment of diseases with consensus interferon while reducing side effect |
JPH04327587A (ja) | 1991-04-26 | 1992-11-17 | Asahi Chem Ind Co Ltd | 6’−c−アルキル−3−デアザネプラノシンa誘導体、その製造法およびその用途 |
GB9116056D0 (en) * | 1991-07-24 | 1991-09-11 | British Bio Technology | Compounds |
US5587372A (en) * | 1991-12-12 | 1996-12-24 | Roussel Uclaf | Cephalosporins |
GB9200245D0 (en) | 1992-01-07 | 1992-02-26 | British Bio Technology | Compounds |
GB9202792D0 (en) | 1992-02-11 | 1992-03-25 | British Bio Technology | Compounds |
DE4211474A1 (de) | 1992-04-06 | 1993-10-07 | Merck Patent Gmbh | Imidazopyridine |
US5208242A (en) | 1992-08-26 | 1993-05-04 | G. D. Searle & Co. | 5-substituted-4-phenyl-5H-imidazo[4,5-c]pyridine derivatives |
DE4230464A1 (de) | 1992-09-11 | 1994-03-17 | Merck Patent Gmbh | Imidazolderivate |
DE4236026A1 (de) * | 1992-10-24 | 1994-04-28 | Merck Patent Gmbh | Imidazopyridine |
JP3115455B2 (ja) | 1992-12-18 | 2000-12-04 | 明治製菓株式会社 | 新規セファロスポリン誘導体 |
US5374638A (en) | 1993-03-19 | 1994-12-20 | Merck & Co., Inc. | Six membered ring fused imidazoles substituted with phenoxyphenylacetic acid derivatives used to treat asthma |
DE4309969A1 (de) | 1993-03-26 | 1994-09-29 | Bayer Ag | Substituierte heteroanellierte Imidazole |
DE4318813A1 (de) | 1993-06-07 | 1994-12-08 | Merck Patent Gmbh | Imidazopyridine |
DE4324580A1 (de) * | 1993-07-22 | 1995-01-26 | Thomae Gmbh Dr K | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
US5486525A (en) * | 1993-12-16 | 1996-01-23 | Abbott Laboratories | Platelet activating factor antagonists: imidazopyridine indoles |
US5563143A (en) | 1994-09-21 | 1996-10-08 | Pfizer Inc. | Catechol diether compounds as inhibitors of TNF release |
US6506876B1 (en) * | 1994-10-11 | 2003-01-14 | G.D. Searle & Co. | LTA4 hydrolase inhibitor pharmaceutical compositions and methods of use |
US5585492A (en) * | 1994-10-11 | 1996-12-17 | G. D. Searle & Co. | LTA4 Hydrolase inhibitors |
US5635514A (en) * | 1994-10-25 | 1997-06-03 | G. D. Searle & Company | Heteroaralkyl and heteroarylthioalkyl thiophenolic compounds as 5-lipoxgenase inhibitors |
US5880140A (en) * | 1996-04-03 | 1999-03-09 | Merck & Co., Inc. | Biheteroaryl inhibitors of farnesyl-protein transferase |
US5854265A (en) * | 1996-04-03 | 1998-12-29 | Merck & Co., Inc. | Biheteroaryl inhibitors of farnesyl-protein transferase |
US5874452A (en) * | 1996-04-03 | 1999-02-23 | Merck & Co., Inc. | Biheteroaryl inhibitors of farnesyl-protein transferase |
US6080870A (en) * | 1996-04-03 | 2000-06-27 | Merck & Co., Inc. | Biaryl substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
US5872136A (en) * | 1996-04-03 | 1999-02-16 | Merck & Co., Inc. | Arylheteroaryl inhibitors of farnesyl-protein transferase |
US5883105A (en) * | 1996-04-03 | 1999-03-16 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
US6063930A (en) * | 1996-04-03 | 2000-05-16 | Merck & Co., Inc. | Substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
US5859035A (en) * | 1996-04-03 | 1999-01-12 | Merck & Co., Inc. | Arylheteroaryl inhibitors of farnesyl-protein transferase |
US5939557A (en) * | 1996-04-03 | 1999-08-17 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
US6015817A (en) * | 1996-12-05 | 2000-01-18 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
NZ504800A (en) * | 1997-11-28 | 2001-10-26 | Sumitomo Pharma | 6-Amino-9-benzyl-8-hydroxy-purine derivatives and interferon inducers, antiviral agents, anticancer agents and therapeutic agents for immunologic diseases thereof |
DE19845153A1 (de) | 1998-10-01 | 2000-04-06 | Merck Patent Gmbh | Imidazo[4,5]-pyridin-4-on-derivate |
US6271380B1 (en) | 1998-12-30 | 2001-08-07 | Dupont Pharmaceuticals Company | 1H-imidazo[4,5-d]pyridazin-7-ones, 3H-imidazo-[4,5-c]pyridin-4-ones and corresponding thiones as corticotropin releasing factor (CRF) receptor ligands |
DE69932263T2 (de) * | 1999-01-08 | 2007-06-06 | Chisso Corp. | Borderivate und organische elektrolumineszierende verbindungen |
DE19900471A1 (de) | 1999-01-08 | 2000-07-13 | Merck Patent Gmbh | Imidazo[4,5c]-pyridin-4-on-derivate |
EP1182195A4 (fr) * | 1999-05-07 | 2003-03-26 | Takeda Chemical Industries Ltd | Composes cycliques et leurs utilisations |
US6844367B1 (en) * | 1999-09-17 | 2005-01-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
EP1259485B1 (fr) * | 2000-02-29 | 2005-11-30 | Millennium Pharmaceuticals, Inc. | Benzamides et inhibiteurs associes du facteur xa |
EP1132381A1 (fr) | 2000-03-08 | 2001-09-12 | Cermol S.A. | Derivés d'esters d'acide propionique et compositions pharmaceutiques les contenant |
US6448281B1 (en) * | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
KR100892614B1 (ko) | 2001-04-17 | 2009-04-09 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 신규 아데닌 유도체 |
AR035543A1 (es) * | 2001-06-26 | 2004-06-16 | Japan Tobacco Inc | Agente terapeutico para la hepatitis c que comprende un compuesto de anillo condensado, compuesto de anillo condensado, composicion farmaceutica que lo comprende, compuestos de benzimidazol, tiazol y bifenilo utiles como intermediarios para producir dichos compuestos, uso del compuesto de anillo con |
US20030073836A1 (en) * | 2001-07-05 | 2003-04-17 | Boehringer Ingelheim Pharma Kg | Heteroarylcarboxylic acid amides, the preparation thereof and their use as pharmaceutical compositions |
US6841566B2 (en) | 2001-07-20 | 2005-01-11 | Boehringer Ingelheim, Ltd. | Viral polymerase inhibitors |
EP2335700A1 (fr) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Inhibiteurs de la polymerase du virus hepatitis C avec une structure heterobicylic |
DE10140246A1 (de) * | 2001-08-09 | 2003-03-06 | Forsch Pigmente Und Lacke E V | Verfahren zur Behandlung von Oberflächen von Substraten |
AU2003205570A1 (en) | 2002-01-10 | 2003-07-24 | Boehringer Ingelheim Pharma Gmbh And Co. Kg | Combination of mtp inhibitors or apob secretion inhibitors with fibrates for use as drugs |
GB0215293D0 (en) * | 2002-07-03 | 2002-08-14 | Rega Foundation | Viral inhibitors |
SI1532149T1 (sl) | 2002-08-21 | 2010-05-31 | Boehringer Ingelheim Pharma | amino piperidin il ksantini njihova priprava in njihova uporaba kot zdravila |
US20040097574A1 (en) | 2002-08-29 | 2004-05-20 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
DE602004022633D1 (de) * | 2003-01-30 | 2009-10-01 | Boehringer Ingelheim Pharma | 2,4-diaminopyrimidinderivate, die sich als inhibitoren von pkc-theta eignen |
US7566707B2 (en) * | 2003-06-18 | 2009-07-28 | Boehringer Ingelheim International Gmbh | Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions |
AU2004291262C1 (en) * | 2003-11-05 | 2011-08-11 | F. Hoffmann-La Roche Ag | Phenyl derivatives as PPAR agonists |
US7648998B2 (en) * | 2003-12-22 | 2010-01-19 | K.U. Leuven Research & Development | Imidazo 4,5-c pyridine compounds and methods of antiviral treatment |
CA2574220C (fr) * | 2004-07-27 | 2014-09-16 | Gilead Sciences, Inc. | Imidazo[4,5-d]pyrimidines, procedes d'utilisation et de preparation correspondants |
CN101018843B (zh) | 2004-09-13 | 2011-05-11 | 西巴特殊化学品控股有限公司 | 烷基氨基乙酰胺润滑添加剂 |
WO2008005519A2 (fr) * | 2006-07-07 | 2008-01-10 | Gilead Sciences, Inc. | Nouveau composé à base de pyrizadine et son utilisation |
UA99466C2 (en) | 2007-07-06 | 2012-08-27 | Гилиад Сайенсиз, Инк. | Crystalline pyridazine compound |
-
2004
- 2004-12-21 US US10/583,814 patent/US7648998B2/en active Active
- 2004-12-21 AT AT04815224T patent/ATE544765T1/de active
- 2004-12-21 AU AU2004309390A patent/AU2004309390B2/en not_active Ceased
- 2004-12-21 NZ NZ548074A patent/NZ548074A/en not_active IP Right Cessation
- 2004-12-21 CA CA2549606A patent/CA2549606C/fr not_active Expired - Fee Related
- 2004-12-21 ES ES04815224T patent/ES2381890T3/es active Active
- 2004-12-21 DK DK09157035.8T patent/DK2161273T3/en active
- 2004-12-21 PT PT04815224T patent/PT1706403E/pt unknown
- 2004-12-21 NZ NZ595000A patent/NZ595000A/xx not_active IP Right Cessation
- 2004-12-21 US US11/019,830 patent/US20050222198A1/en not_active Abandoned
- 2004-12-21 SG SG200809590-3A patent/SG149067A1/en unknown
- 2004-12-21 KR KR1020067012554A patent/KR101131589B1/ko not_active IP Right Cessation
- 2004-12-21 EP EP09157035.8A patent/EP2161273B1/fr active Active
- 2004-12-21 PL PL04815224T patent/PL1706403T3/pl unknown
- 2004-12-21 EP EP12154571A patent/EP2546254A1/fr not_active Withdrawn
- 2004-12-21 WO PCT/US2004/043112 patent/WO2005063744A2/fr active Application Filing
- 2004-12-21 SI SI200432254T patent/SI2161273T1/sl unknown
- 2004-12-21 DK DK04815224.3T patent/DK1706403T3/da active
- 2004-12-21 JP JP2006547305A patent/JP4970048B2/ja not_active Expired - Fee Related
- 2004-12-21 EP EP04815224A patent/EP1706403B9/fr active Active
-
2006
- 2006-06-14 IL IL176298A patent/IL176298A/en not_active IP Right Cessation
- 2006-12-05 HK HK06113327.1A patent/HK1092793A1/xx not_active IP Right Cessation
-
2009
- 2009-10-13 US US12/577,865 patent/US8329727B2/en active Active
-
2011
- 2011-05-02 JP JP2011103307A patent/JP5395844B2/ja not_active Expired - Fee Related
- 2011-05-13 AU AU2011202214A patent/AU2011202214B2/en not_active Ceased
-
2012
- 2012-04-03 CY CY20121100329T patent/CY1112733T1/el unknown
-
2013
- 2013-07-19 JP JP2013150196A patent/JP2013221030A/ja not_active Withdrawn
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070032497A1 (en) * | 1999-12-27 | 2007-02-08 | Japan Tobacco Inc. | Fused-ring compounds and use thereof as drugs |
US7285551B2 (en) * | 1999-12-27 | 2007-10-23 | Japan Tobacco Inc. | Fused-ring compounds and use thereof as drugs |
US7294457B2 (en) * | 2001-08-07 | 2007-11-13 | Boehringer Ingelheim (Canada) Ltd. | Direct binding assay for identifying inhibitors of HCV polymerase |
US6803374B2 (en) * | 2001-09-26 | 2004-10-12 | Bristol-Myers Squibb Company | Compounds useful for treating hepatitis C virus |
US20060229336A1 (en) * | 2002-12-13 | 2006-10-12 | Kazmierski Wieslaw M | Ccr5 antagonists as therapeutic agents |
US20040171626A1 (en) * | 2003-01-22 | 2004-09-02 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US20040186125A1 (en) * | 2003-01-22 | 2004-09-23 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US7098231B2 (en) * | 2003-01-22 | 2006-08-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US7223785B2 (en) * | 2003-01-22 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US20080188516A1 (en) * | 2004-12-21 | 2008-08-07 | Bondy Steven S | Imiadazo[4,5-c] pyridine compound and method of antiviral treatment |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7737162B2 (en) | 2002-07-03 | 2010-06-15 | Gilead Sciences, Inc. | Viral inhibitors |
US8779141B2 (en) | 2002-07-03 | 2014-07-15 | Gilead Sciences, Inc. | Viral inhibitors |
US20050239821A1 (en) * | 2002-07-03 | 2005-10-27 | Johan Neyts | Viral inhibitors |
US20070244148A1 (en) * | 2003-12-22 | 2007-10-18 | Bondy Steven S | Imidazo 4,5-C Pyridine Compounds and Methods of Antiviral Treatment |
US8329727B2 (en) | 2003-12-22 | 2012-12-11 | Gilead Sciences, Inc. | Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment |
US7648998B2 (en) | 2003-12-22 | 2010-01-19 | K.U. Leuven Research & Development | Imidazo 4,5-c pyridine compounds and methods of antiviral treatment |
US20100028301A1 (en) * | 2003-12-22 | 2010-02-04 | Bondy Steven S | IMIDAZO[4,5-c]PYRIDINE COMPOUNDS AND METHODS OF ANTIVIRAL TREATMENT |
US20060052602A1 (en) * | 2004-07-27 | 2006-03-09 | Gilead Sciences, Inc. | Imidazo[4,5-d]pyrimidines, their uses and methods of preparation |
US7790730B2 (en) * | 2004-07-27 | 2010-09-07 | Gilead Sciences, Inc. | Imidazo[4,5-d]pyrimidines, their uses and methods of preparation |
US20090208456A1 (en) * | 2004-07-27 | 2009-08-20 | Gilead Sciences, Inc. | Imidazo[4,5-d]pyrimidines, their uses and methods of preparation |
US20080188516A1 (en) * | 2004-12-21 | 2008-08-07 | Bondy Steven S | Imiadazo[4,5-c] pyridine compound and method of antiviral treatment |
US7795276B2 (en) * | 2004-12-21 | 2010-09-14 | Gilead Sciences, Inc. | Imiadazo[4,5-c] pyridine compound and method of antiviral treatment |
US20060252791A1 (en) * | 2004-12-21 | 2006-11-09 | Gilead Sciences, Inc. | Imidazo[4,5-c]pyridine compound and method of antiviral treatment |
US20100063059A1 (en) * | 2006-07-07 | 2010-03-11 | Gerhard Puerstinger | Novel pyridazine compound and use thereof |
US20100152444A1 (en) * | 2006-07-07 | 2010-06-17 | Gilead Sciences, Inc. | Novel pyridazine compound and use thereof |
US7754720B2 (en) | 2006-07-07 | 2010-07-13 | Gilead Sciences, Inc. | Pyridazine compound and use thereof |
US20080199427A1 (en) * | 2006-07-07 | 2008-08-21 | Bondy Steven S | Novel pyridazine compound and use thereof |
US7956184B2 (en) | 2006-07-07 | 2011-06-07 | Gilead Sciences, Inc. | Pyridazine compound and use thereof |
US8569487B2 (en) | 2006-07-07 | 2013-10-29 | Gilead Sciences, Inc. | Pyridazine compound and use thereof |
US20090036460A1 (en) * | 2007-07-06 | 2009-02-05 | Gilead Sciences, Inc. | Crystalline pyridazine compound |
US8569488B2 (en) | 2007-07-06 | 2013-10-29 | Gilead Sciences, Inc. | Crystalline pyridazine compound |
US8106054B2 (en) | 2007-07-06 | 2012-01-31 | Gilead Sciences, Inc. | Crystalline pyridazine compound |
CN102427731A (zh) * | 2009-02-27 | 2012-04-25 | 英安塔制药有限公司 | 丙型肝炎病毒抑制剂 |
US8673954B2 (en) | 2009-02-27 | 2014-03-18 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
CN102427731B (zh) * | 2009-02-27 | 2015-05-13 | 英安塔制药有限公司 | 丙型肝炎病毒抑制剂 |
US9765087B2 (en) | 2009-02-27 | 2017-09-19 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
US8927739B2 (en) | 2011-05-18 | 2015-01-06 | Enanta Pharmaceuticals, Inc. | Processes for the preparation of 5-azaspiro[2.4]heptane-6-carboxylic acid and its derivatives |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8329727B2 (en) | Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment | |
US7790730B2 (en) | Imidazo[4,5-d]pyrimidines, their uses and methods of preparation | |
US8779141B2 (en) | Viral inhibitors | |
US9242983B2 (en) | Viral inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: GILEAD SCIENCES, INC., CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BONDY, STEVEN S.;DOWDY, ERIC DAVIS;KIM, CHOUNG U.;AND OTHERS;REEL/FRAME:019272/0061;SIGNING DATES FROM 20070427 TO 20070507 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |
|
AS | Assignment |
Owner name: K.U. LEUVEN RESEARCH & DEVELOPMENT, BELGIUM Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:NEYTS, JOHAN;REEL/FRAME:023392/0470 Effective date: 20070521 |
|
AS | Assignment |
Owner name: GILEAD SCIENCES, INC., CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GILEAD SCIENCES, INC.;K.U. LEUVEN RESEARCH & DEVELOPMENT;REEL/FRAME:023503/0684;SIGNING DATES FROM 20091029 TO 20091111 Owner name: GILEAD SCIENCES, INC., CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PUERSTINGER, GERHARD;REEL/FRAME:023503/0668 Effective date: 20091030 Owner name: K.U. LEUVEN RESEARCH & DEVELOPMENT, BELGIUM Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PUERSTINGER, GERHARD;REEL/FRAME:023503/0668 Effective date: 20091030 Owner name: PUERSTINGER, GERHARD, AUSTRIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PUERSTINGER, GERHARD;REEL/FRAME:023503/0668 Effective date: 20091030 Owner name: K.U. LEUVEN RESEARCH & DEVELOPMENT, BELGIUM Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GILEAD SCIENCES, INC.;K.U. LEUVEN RESEARCH & DEVELOPMENT;REEL/FRAME:023503/0684;SIGNING DATES FROM 20091029 TO 20091111 Owner name: PUERSTINGER, GERHARD, AUSTRIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GILEAD SCIENCES, INC.;K.U. LEUVEN RESEARCH & DEVELOPMENT;REEL/FRAME:023503/0684;SIGNING DATES FROM 20091029 TO 20091111 |
|
AS | Assignment |
Owner name: K.U. LEUVEN RESEARCH & DEVELOPMENT, BELGIUM Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:GILEAD SCIENCES, INC.;REEL/FRAME:036495/0004 Effective date: 20150314 |