ES2881776T3 - Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus - Google Patents
Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus Download PDFInfo
- Publication number
- ES2881776T3 ES2881776T3 ES17711349T ES17711349T ES2881776T3 ES 2881776 T3 ES2881776 T3 ES 2881776T3 ES 17711349 T ES17711349 T ES 17711349T ES 17711349 T ES17711349 T ES 17711349T ES 2881776 T3 ES2881776 T3 ES 2881776T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- ring
- haloalkyl
- halo
- benzyloxy
- 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.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 173
- 208000009620 Orthomyxoviridae Infections Diseases 0.000 title description 4
- -1 hydroxy, amino Chemical group 0.000 claims abstract description 170
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 101
- 150000003839 salts Chemical class 0.000 claims abstract description 69
- 125000005843 halogen group Chemical group 0.000 claims abstract description 62
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 60
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 55
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 51
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 48
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims abstract description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 20
- 239000012453 solvate Substances 0.000 claims abstract description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 17
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 14
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 12
- 150000001345 alkine derivatives Chemical class 0.000 claims abstract description 12
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims abstract description 11
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 7
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 5
- 150000004292 cyclic ethers Chemical group 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 4
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 206010022000 influenza Diseases 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 9
- 229910005965 SO 2 Inorganic materials 0.000 claims description 5
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- 150000003536 tetrazoles Chemical class 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- 150000003852 triazoles Chemical class 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 33
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 146
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 107
- 239000000203 mixture Substances 0.000 description 105
- 238000006243 chemical reaction Methods 0.000 description 99
- 239000000243 solution Substances 0.000 description 93
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 92
- 235000019439 ethyl acetate Nutrition 0.000 description 75
- 238000000034 method Methods 0.000 description 74
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
- 239000000543 intermediate Substances 0.000 description 65
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 58
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 54
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- 238000005160 1H NMR spectroscopy Methods 0.000 description 45
- 239000011541 reaction mixture Substances 0.000 description 44
- 238000011282 treatment Methods 0.000 description 41
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 229910052938 sodium sulfate Inorganic materials 0.000 description 40
- 235000011152 sodium sulphate Nutrition 0.000 description 40
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 125000001424 substituent group Chemical group 0.000 description 33
- 239000000047 product Substances 0.000 description 32
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 239000012267 brine Substances 0.000 description 31
- 238000010898 silica gel chromatography Methods 0.000 description 31
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
- 239000010410 layer Substances 0.000 description 29
- 239000007787 solid Substances 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 238000000746 purification Methods 0.000 description 24
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
- 208000037797 influenza A Diseases 0.000 description 22
- 239000007832 Na2SO4 Substances 0.000 description 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 20
- 239000002585 base Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 19
- 239000003795 chemical substances by application Substances 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 0 C*C(C(C[n]1c(C(C(C(O)=CNC)=O)=N)nnc1*)O)I Chemical compound C*C(C(C[n]1c(C(C(C(O)=CNC)=O)=N)nnc1*)O)I 0.000 description 18
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 17
- 208000037798 influenza B Diseases 0.000 description 17
- 208000037799 influenza C Diseases 0.000 description 17
- 238000007792 addition Methods 0.000 description 16
- 229910052805 deuterium Inorganic materials 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 229940124597 therapeutic agent Drugs 0.000 description 15
- 230000009385 viral infection Effects 0.000 description 15
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 125000006413 ring segment Chemical group 0.000 description 12
- 241000712461 unidentified influenza virus Species 0.000 description 12
- 208000036142 Viral infection Diseases 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 229940015043 glyoxal Drugs 0.000 description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 229910000024 caesium carbonate Inorganic materials 0.000 description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 10
- 238000010348 incorporation Methods 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 9
- 239000005695 Ammonium acetate Substances 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- CUQZQRIIFNWQSJ-UHFFFAOYSA-N FC(F)(F)[Cu].c1cnc2c(c1)ccc1cccnc21 Chemical compound FC(F)(F)[Cu].c1cnc2c(c1)ccc1cccnc21 CUQZQRIIFNWQSJ-UHFFFAOYSA-N 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 229940043376 ammonium acetate Drugs 0.000 description 9
- 235000019257 ammonium acetate Nutrition 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 8
- 102100031780 Endonuclease Human genes 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 239000011591 potassium Substances 0.000 description 8
- 238000002953 preparative HPLC Methods 0.000 description 8
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 230000002194 synthesizing effect Effects 0.000 description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 7
- 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 7
- 108010042407 Endonucleases Proteins 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 238000010511 deprotection reaction Methods 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 239000000460 chlorine Chemical group 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 125000001188 haloalkyl group Chemical group 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- 229910004298 SiO 2 Inorganic materials 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000000155 isotopic effect Effects 0.000 description 5
- 238000003328 mesylation reaction Methods 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- DZJJTSGLPYDYEU-XMMPIXPASA-N (8S)-8-benzhydryl-5-chloro-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)Cl)=C(C(C=C2)=O)OCC1=CC=CC=C1 DZJJTSGLPYDYEU-XMMPIXPASA-N 0.000 description 4
- MBXXNUIUYMJMSO-UHFFFAOYSA-N 3-amino-1,1-diphenylpropan-2-ol Chemical compound C=1C=CC=CC=1C(C(O)CN)C1=CC=CC=C1 MBXXNUIUYMJMSO-UHFFFAOYSA-N 0.000 description 4
- KTZAKTCBKGPDAH-UHFFFAOYSA-N 4-oxo-5-phenylmethoxy-1-(2-trimethylsilylethoxymethyl)pyridazine-3-carbaldehyde Chemical compound C(C1=CC=CC=C1)OC=1C(C(=NN(C=1)COCC[Si](C)(C)C)C=O)=O KTZAKTCBKGPDAH-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- LTNNWDJMVWKQNO-IUCAKERBSA-N [(2S,3S)-3-(4-fluorophenyl)oxiran-2-yl]methanol Chemical compound OC[C@@H]1O[C@H]1c1ccc(F)cc1 LTNNWDJMVWKQNO-IUCAKERBSA-N 0.000 description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 4
- 229940121357 antivirals Drugs 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 4
- RCWHHKPIJNSQLA-UHFFFAOYSA-N methyl 2-bromo-3-oxo-3-(4-oxo-3-phenylmethoxypyran-2-yl)propanoate Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C(C(C(=O)OC)Br)=O RCWHHKPIJNSQLA-UHFFFAOYSA-N 0.000 description 4
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- IEMLESBLQKSASJ-LSDHHAIUSA-N (1R,2R)-3-amino-1-(4-fluorophenyl)-1-phenylpropan-2-ol Chemical compound NC[C@H](O)[C@H](c1ccccc1)c1ccc(F)cc1 IEMLESBLQKSASJ-LSDHHAIUSA-N 0.000 description 3
- AMYMAANNWXYLLW-HSZRJFAPSA-N (8S)-8-[bis(4-fluorophenyl)methyl]-5-bromo-13-phenylmethoxy-3,6,9,10-tetrazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)OC1=C2N(N=CC1=O)[C@H](CN1C2=NC=C1Br)C(C1=CC=C(C=C1)F)C1=CC=C(C=C1)F AMYMAANNWXYLLW-HSZRJFAPSA-N 0.000 description 3
- OKRZGYAVUGPZGB-XMMPIXPASA-N (8S)-8-benzhydryl-5-bromo-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)Br)=C(C(C=C2)=O)OCC1=CC=CC=C1 OKRZGYAVUGPZGB-XMMPIXPASA-N 0.000 description 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 3
- BJVFNYWWCGKVNR-OWOJBTEDSA-N (e)-3-(4-fluorophenyl)prop-2-en-1-ol Chemical compound OC\C=C\C1=CC=C(F)C=C1 BJVFNYWWCGKVNR-OWOJBTEDSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 description 3
- UXAOGGJRVVGQFH-UHFFFAOYSA-N 1-amino-2-(1H-imidazol-2-yl)-3-phenylmethoxypyridin-4-one Chemical compound NN1C(=C(C(C=C1)=O)OCC1=CC=CC=C1)C=1NC=CN=1 UXAOGGJRVVGQFH-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- SBCFUXBYIWBKAC-UHFFFAOYSA-N 2-(1H-imidazol-2-yl)-3-phenylmethoxypyran-4-one Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C=1NC=CN=1 SBCFUXBYIWBKAC-UHFFFAOYSA-N 0.000 description 3
- UGXUZHYMLSXWAL-UHFFFAOYSA-N 2-[5-(hydrazinylmethyl)-1,3-thiazol-4-yl]-3-phenylmethoxypyran-4-one Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C=1N=CSC=1CNN UGXUZHYMLSXWAL-UHFFFAOYSA-N 0.000 description 3
- WBLMRAWHSSDVBB-UHFFFAOYSA-N 2-[5-(hydroxymethyl)-1,3-thiazol-4-yl]-3-phenylmethoxypyran-4-one Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C=1N=CSC=1CO WBLMRAWHSSDVBB-UHFFFAOYSA-N 0.000 description 3
- UXSBCFPBISLQOX-UHFFFAOYSA-N 3-[2-(2-hydroxy-3,3-diphenylpropyl)-1,2,4-triazol-3-yl]-5-phenylmethoxy-1-(2-trimethylsilylethoxymethyl)pyridazin-4-one Chemical compound C(C1=CC=CC=C1)OC=1C(C(=NN(C=1)COCC[Si](C)(C)C)C1=NC=NN1CC(C(C1=CC=CC=C1)C1=CC=CC=C1)O)=O UXSBCFPBISLQOX-UHFFFAOYSA-N 0.000 description 3
- VPKOSDBJWLHWIV-UHFFFAOYSA-N 3-hydrazinyl-1,1-diphenylpropan-2-ol Chemical compound N(N)CC(C(C1=CC=CC=C1)C1=CC=CC=C1)O VPKOSDBJWLHWIV-UHFFFAOYSA-N 0.000 description 3
- FPUHMWSJJFQMNU-UHFFFAOYSA-N 3-nitro-1,1-diphenylpropan-2-ol Chemical compound C=1C=CC=CC=1C(C(C[N+]([O-])=O)O)C1=CC=CC=C1 FPUHMWSJJFQMNU-UHFFFAOYSA-N 0.000 description 3
- ZCDPMEKAPGJOGP-UHFFFAOYSA-N 4-(4-oxo-3-phenylmethoxypyran-2-yl)-1,3-thiazole-5-carboxylic acid Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C=1N=CSC=1C(=O)O ZCDPMEKAPGJOGP-UHFFFAOYSA-N 0.000 description 3
- JBIHUDRUDVZFPT-UHFFFAOYSA-N 4-oxo-3-phenylmethoxypyran-2-carbaldehyde Chemical compound O1C=CC(=O)C(OCC=2C=CC=CC=2)=C1C=O JBIHUDRUDVZFPT-UHFFFAOYSA-N 0.000 description 3
- WBNOMQYTKXNCAR-UHFFFAOYSA-N 8-benzhydryl-13-hydroxy-3,6,9,10-tetrazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)C1CN2C(C=3N1N=CC(C=3O)=O)=NC=C2 WBNOMQYTKXNCAR-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical class [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- ZZAHEHWQNUVNEA-QGZVFWFLSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)Cl)=C(C(C=C2)=O)O Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)Cl)=C(C(C=C2)=O)O ZZAHEHWQNUVNEA-QGZVFWFLSA-N 0.000 description 3
- PNSZYGZIWVOPBV-GOSISDBHSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C=CN=3)=C(C(C=C2)=O)O Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C=CN=3)=C(C(C=C2)=O)O PNSZYGZIWVOPBV-GOSISDBHSA-N 0.000 description 3
- YATZLHXPQTZPOB-PXLXIMEGSA-N C(C1=CC=CC=C1)OC=1C(C(=NN(C=1)COCC[Si](C)(C)C)C(=O)/N=C/N(C)C)=O Chemical compound C(C1=CC=CC=C1)OC=1C(C(=NN(C=1)COCC[Si](C)(C)C)C(=O)/N=C/N(C)C)=O YATZLHXPQTZPOB-PXLXIMEGSA-N 0.000 description 3
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 229910004373 HOAc Inorganic materials 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- QNRRHYPPQFELSF-CNYIRLTGSA-N Laninamivir Chemical compound OC[C@@H](O)[C@@H](OC)[C@@H]1OC(C(O)=O)=C[C@H](N=C(N)N)[C@H]1NC(C)=O QNRRHYPPQFELSF-CNYIRLTGSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 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 3
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical class C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 3
- 229960003805 amantadine Drugs 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- 229940042406 direct acting antivirals neuraminidase inhibitors Drugs 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229950004244 laninamivir Drugs 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- NNNOWNACZNIRSN-UHFFFAOYSA-N methyl 2,3-dioxo-3-(4-oxo-3-phenylmethoxypyran-2-yl)propanoate Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C(C(C(=O)OC)=O)=O NNNOWNACZNIRSN-UHFFFAOYSA-N 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 229960003752 oseltamivir Drugs 0.000 description 3
- NENPYTRHICXVCS-YNEHKIRRSA-N oseltamivir acid Chemical compound CCC(CC)O[C@@H]1C=C(C(O)=O)C[C@H](N)[C@H]1NC(C)=O NENPYTRHICXVCS-YNEHKIRRSA-N 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229960001084 peramivir Drugs 0.000 description 3
- UGTYTOKVOXBJBZ-LINPMSLLSA-N peramivir hydrate Chemical compound O.O.O.O.CCC(CC)[C@H](NC(C)=O)[C@@H]1[C@H](O)[C@@H](C(O)=O)C[C@H]1NC(N)=N UGTYTOKVOXBJBZ-LINPMSLLSA-N 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 125000006684 polyhaloalkyl group Polymers 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 229960000888 rimantadine Drugs 0.000 description 3
- 239000002911 sialidase inhibitor Substances 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 3
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 3
- 229960001028 zanamivir Drugs 0.000 description 3
- 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 2
- CXRKANNFODZYQY-AREMUKBSSA-N (8S)-8-[bis(4-fluorophenyl)methyl]-5-ethenyl-13-phenylmethoxy-3,6,9,10-tetrazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)OC1=C2N(N=CC1=O)[C@H](CN1C2=NC=C1C=C)C(C1=CC=C(C=C1)F)C1=CC=C(C=C1)F CXRKANNFODZYQY-AREMUKBSSA-N 0.000 description 2
- RFMVLMZKMHTWAN-AREMUKBSSA-N (8S)-8-benzhydryl-5-(hydroxymethyl)-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)CO)=C(C(C=C2)=O)OCC1=CC=CC=C1 RFMVLMZKMHTWAN-AREMUKBSSA-N 0.000 description 2
- SWVIFKIUHWETIT-MUUNZHRXSA-N (8S)-8-benzhydryl-5-cyclopropyl-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)C1CC1)=C(C(C=C2)=O)OCC1=CC=CC=C1 SWVIFKIUHWETIT-MUUNZHRXSA-N 0.000 description 2
- IXGCYZIJQFUNDE-HHHXNRCGSA-N (8S)-8-benzhydryl-5-ethenyl-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)C=C)=C(C(C=C2)=O)OCC1=CC=CC=C1 IXGCYZIJQFUNDE-HHHXNRCGSA-N 0.000 description 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- LOZWAPSEEHRYPG-UHFFFAOYSA-N 1,4-dithiane Chemical compound C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 2
- ROAHPSWCFDZYBG-UHFFFAOYSA-N 1-benzyl-2-(1H-imidazol-2-yl)-3-methoxypyridin-4-one Chemical compound C(C1=CC=CC=C1)N1C(=C(C(C=C1)=O)OC)C=1NC=CN=1 ROAHPSWCFDZYBG-UHFFFAOYSA-N 0.000 description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- XEIGFCGUSUVQER-UHFFFAOYSA-N 1H-pyrazino[1,2-b]pyridazine-3-carbaldehyde Chemical compound C1=CN2C(=CC(=CN2)C=O)C=N1 XEIGFCGUSUVQER-UHFFFAOYSA-N 0.000 description 2
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 2
- ZYRANPXTICJYND-UHFFFAOYSA-N 2-(1H-imidazol-2-yl)-3-methoxypyran-4-one Chemical compound N1C(=NC=C1)C=1OC=CC(C=1OC)=O ZYRANPXTICJYND-UHFFFAOYSA-N 0.000 description 2
- ZRBYJWZTILYFBG-LEWJYISDSA-N 2-[(2R,3R)-3-(4-fluorophenyl)-2-hydroxy-3-phenylpropyl]isoindole-1,3-dione Chemical compound FC1=CC=C(C=C1)[C@H]([C@H](CN1C(C2=CC=CC=C2C1=O)=O)O)C1=CC=CC=C1 ZRBYJWZTILYFBG-LEWJYISDSA-N 0.000 description 2
- FBKMZJCAWAJGGP-XMMPIXPASA-N 2-[1-[(2S)-2-amino-3,3-diphenylpropyl]-5-bromoimidazol-2-yl]-3-phenylmethoxypyran-4-one Chemical compound N[C@H](CN1C(=NC=C1Br)C=1OC=CC(C=1OCC1=CC=CC=C1)=O)C(C1=CC=CC=C1)C1=CC=CC=C1 FBKMZJCAWAJGGP-XMMPIXPASA-N 0.000 description 2
- FOUJXBXZSAVWGN-UHFFFAOYSA-N 2-[5-(bromomethyl)-1,3-thiazol-4-yl]-3-phenylmethoxypyran-4-one Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C=1N=CSC=1CBr FOUJXBXZSAVWGN-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- DPGSPRJLAZGUBQ-UHFFFAOYSA-N 2-ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(C=C)OC1(C)C DPGSPRJLAZGUBQ-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- ARSFCBLRXPKYOS-UHFFFAOYSA-N 3-[1-(2-hydroxy-3,3-diphenylpropyl)imidazol-2-yl]-5-phenylmethoxy-1-(2-trimethylsilylethoxymethyl)pyridazin-4-one Chemical compound C(C1=CC=CC=C1)OC=1C(C(=NN(C=1)COCC[Si](C)(C)C)C=1N(C=CN=1)CC(C(C1=CC=CC=C1)C1=CC=CC=C1)O)=O ARSFCBLRXPKYOS-UHFFFAOYSA-N 0.000 description 2
- YMBRHIPRAZULJT-XDFJSJKPSA-N 3-[1-[(2R,3R)-3-(4-fluorophenyl)-2-hydroxy-3-phenylpropyl]imidazol-2-yl]-5-phenylmethoxy-1-(2-trimethylsilylethoxymethyl)pyridazin-4-one Chemical compound C(C1=CC=CC=C1)OC=1C(C(=NN(C=1)COCC[Si](C)(C)C)C=1N(C=CN=1)C[C@@H]([C@H](C1=CC=CC=C1)C1=CC=C(C=C1)F)O)=O YMBRHIPRAZULJT-XDFJSJKPSA-N 0.000 description 2
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 2
- PRXZMTOPRUVVCF-UHFFFAOYSA-N 4-oxo-3-phenylmethoxypyran-2-carbonyl chloride Chemical compound O1C=CC(=O)C(OCC=2C=CC=CC=2)=C1C(=O)Cl PRXZMTOPRUVVCF-UHFFFAOYSA-N 0.000 description 2
- UECSSTBMYRHFFX-UHFFFAOYSA-N 4-oxo-5-phenylmethoxy-1-(2-trimethylsilylethoxymethyl)pyridazine-3-carboxamide Chemical compound C(C1=CC=CC=C1)OC=1C(C(=NN(C=1)COCC[Si](C)(C)C)C(=O)N)=O UECSSTBMYRHFFX-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 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
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- GKWNZSOSFIRSHC-UHFFFAOYSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)C1CN2C(C=3N1N=CC(C=3O)=O)=NC=N2 Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)C1CN2C(C=3N1N=CC(C=3O)=O)=NC=N2 GKWNZSOSFIRSHC-UHFFFAOYSA-N 0.000 description 2
- WDEOCCJGFPKMSH-UHFFFAOYSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)N1N2C(C=3N(C1C1CC1)C=CN=3)=C(C(C=C2)=O)O Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)N1N2C(C=3N(C1C1CC1)C=CN=3)=C(C(C=C2)=O)O WDEOCCJGFPKMSH-UHFFFAOYSA-N 0.000 description 2
- MZLBCYKHGSUPSZ-UHFFFAOYSA-N C(C1=CC=CC=C1)OC=1C(C=CN2NC(N3C(C2=1)=NC=C3)C1CC1)=O Chemical compound C(C1=CC=CC=C1)OC=1C(C=CN2NC(N3C(C2=1)=NC=C3)C1CC1)=O MZLBCYKHGSUPSZ-UHFFFAOYSA-N 0.000 description 2
- QAKITEMAYFJJSO-UHFFFAOYSA-N C1(CC1)C1NN2C(C=3N1C=CN=3)=C(C(C=C2)=O)O Chemical compound C1(CC1)C1NN2C(C=3N1C=CN=3)=C(C(C=C2)=O)O QAKITEMAYFJJSO-UHFFFAOYSA-N 0.000 description 2
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 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
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241000712431 Influenza A virus Species 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
- 102000005348 Neuraminidase Human genes 0.000 description 2
- 108010006232 Neuraminidase Proteins 0.000 description 2
- 229910002666 PdCl2 Inorganic materials 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003302 alkenyloxy group Chemical group 0.000 description 2
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 2
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000005133 alkynyloxy group Chemical group 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- OQROAIRCEOBYJA-UHFFFAOYSA-N bromodiphenylmethane Chemical compound C=1C=CC=CC=1C(Br)C1=CC=CC=C1 OQROAIRCEOBYJA-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000012054 celltiter-glo Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000007541 cellular toxicity Effects 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 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 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([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
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 150000001975 deuterium Chemical group 0.000 description 2
- 125000006001 difluoroethyl group Chemical group 0.000 description 2
- 125000004982 dihaloalkyl group Chemical group 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- UNAXNPTZJKKUGO-VMPITWQZSA-N ethyl (e)-3-(4-fluorophenyl)prop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CC=C(F)C=C1 UNAXNPTZJKKUGO-VMPITWQZSA-N 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 229960002510 mandelic acid Drugs 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- ROLPCJWVGPPUNP-UHFFFAOYSA-N methyl 3-methyl-5-(4-oxo-3-phenylmethoxypyran-2-yl)imidazole-4-carboxylate Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C=1N=CN(C=1C(=O)OC)C ROLPCJWVGPPUNP-UHFFFAOYSA-N 0.000 description 2
- VDEWEKURAPGTCE-UHFFFAOYSA-N methyl 3-oxo-3-(4-oxo-3-phenylmethoxypyran-2-yl)propanoate Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C(CC(=O)OC)=O VDEWEKURAPGTCE-UHFFFAOYSA-N 0.000 description 2
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 125000006682 monohaloalkyl group Chemical group 0.000 description 2
- 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 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- YLACRFYIUQZNIV-UHFFFAOYSA-N o-(2,4-dinitrophenyl)hydroxylamine Chemical compound NOC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O YLACRFYIUQZNIV-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
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000012285 osmium tetroxide Substances 0.000 description 2
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- PJESVVYWPFAJCS-UHFFFAOYSA-N pyridazine-3-carbonitrile Chemical compound N#CC1=CC=CN=N1 PJESVVYWPFAJCS-UHFFFAOYSA-N 0.000 description 2
- 238000012131 rapid influenza diagnostic test Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000001476 sodium potassium tartrate Substances 0.000 description 2
- 229940054269 sodium pyruvate Drugs 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 125000004001 thioalkyl group Chemical group 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- HQJLDLYZGKONEB-HOTGVXAUSA-N (1S,2R)-3-amino-1-(4-fluorophenyl)-1-(3-methylsulfonylphenyl)propan-2-ol Chemical compound NC[C@@H]([C@H](C1=CC(=CC=C1)S(=O)(=O)C)C1=CC=C(C=C1)F)O HQJLDLYZGKONEB-HOTGVXAUSA-N 0.000 description 1
- JGPXDNKSIXAZEQ-SBBZOCNPSA-N (2s,3s)-3-[[5-fluoro-2-(5-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]bicyclo[2.2.2]octane-2-carboxylic acid Chemical compound C1=C(F)C=C2C(C=3N=C(C(=CN=3)F)N[C@H]3C4CCC(CC4)[C@@H]3C(=O)O)=CNC2=N1 JGPXDNKSIXAZEQ-SBBZOCNPSA-N 0.000 description 1
- LZCURSZQCLJGES-GOSISDBHSA-N (8S)-8-[bis(4-fluorophenyl)methyl]-13-hydroxy-12-oxo-3,6,9,10-tetrazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraene-5-carbonitrile Chemical compound FC1=CC=C(C=C1)C([C@H]1CN2C(C=3N1N=CC(C=3O)=O)=NC=C2C#N)C1=CC=C(C=C1)F LZCURSZQCLJGES-GOSISDBHSA-N 0.000 description 1
- CYVDNIFUERLGCM-HXUWFJFHSA-N (8S)-8-benzhydryl-13-hydroxy-4,5-dimethyl-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=C(N=3)C)C)=C(C(C=C2)=O)O CYVDNIFUERLGCM-HXUWFJFHSA-N 0.000 description 1
- BZNXSEXRGLMSIC-RZIURPKCSA-N (8S)-8-benzhydryl-5-(1-hydroxyethyl)-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)C(C)O)=C(C(C=C2)=O)OCC1=CC=CC=C1 BZNXSEXRGLMSIC-RZIURPKCSA-N 0.000 description 1
- UKCPPXOFJIIQSM-RUZDIDTESA-N (8S)-8-benzhydryl-5-(difluoromethyl)-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)C(F)F)=C(C(C=C2)=O)OCC1=CC=CC=C1 UKCPPXOFJIIQSM-RUZDIDTESA-N 0.000 description 1
- ZKAIZZOWSMNAJP-HHHXNRCGSA-N (8S)-8-benzhydryl-5-ethyl-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)CC)=C(C(C=C2)=O)OCC1=CC=CC=C1 ZKAIZZOWSMNAJP-HHHXNRCGSA-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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- UAVDKVLJDAKWHA-UHFFFAOYSA-N 1,4-dihydropyridazine-3-carboxamide Chemical compound N1N=C(CC=C1)C(=O)N UAVDKVLJDAKWHA-UHFFFAOYSA-N 0.000 description 1
- ZXOFAHRGRROAQR-UHFFFAOYSA-N 1-(isocyanomethylsulfonyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1S(=O)(=O)C[N+]#[C-] ZXOFAHRGRROAQR-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- MRIUJFCNKWWEEG-UHFFFAOYSA-N 1-amino-2-(1H-imidazol-2-yl)-3-methoxypyridin-4-one Chemical compound NN1C(=C(C(C=C1)=O)OC)C=1NC=CN=1 MRIUJFCNKWWEEG-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- GPISSSODMKTEJD-UHFFFAOYSA-N 13-methoxy-3,6,8,9-tetrazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound COc1c2-c3nccn3CNn2ccc1=O GPISSSODMKTEJD-UHFFFAOYSA-N 0.000 description 1
- VHVUTJZQFZBIRR-UHFFFAOYSA-N 1h-pyridazin-4-one Chemical compound OC1=CC=NN=C1 VHVUTJZQFZBIRR-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- HLLGFGBLKOIZOM-UHFFFAOYSA-N 2,2-diphenylacetaldehyde Chemical compound C=1C=CC=CC=1C(C=O)C1=CC=CC=C1 HLLGFGBLKOIZOM-UHFFFAOYSA-N 0.000 description 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- IWWLVWWEZSOTJH-UHFFFAOYSA-N 2,3-dihydroxy-4-(4-methylbenzoyl)oxy-4-oxobutanoic acid Chemical compound CC1=CC=C(C(=O)OC(=O)C(O)C(O)C(O)=O)C=C1 IWWLVWWEZSOTJH-UHFFFAOYSA-N 0.000 description 1
- 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- YFTHTJAPODJVSL-UHFFFAOYSA-N 2-(1-benzothiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(SC=C2)C2=C1 YFTHTJAPODJVSL-UHFFFAOYSA-N 0.000 description 1
- KUVHGSWUVYMYMR-UHFFFAOYSA-N 2-(1-benzyl-3-methoxy-4-oxopyridin-2-yl)imidazole-1-carboxylic acid Chemical compound COC1=C(N(C=CC1=O)CC2=CC=CC=C2)C3=NC=CN3C(=O)O KUVHGSWUVYMYMR-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BPRRVHWYVWUGFX-VXKWHMMOSA-N 2-[(2R,3S)-3-(4-fluorophenyl)-2-hydroxy-3-(3-methylsulfanylphenyl)propyl]isoindole-1,3-dione Chemical compound FC1=CC=C(C=C1)[C@H]([C@H](CN1C(C2=CC=CC=C2C1=O)=O)O)C1=CC(=CC=C1)SC BPRRVHWYVWUGFX-VXKWHMMOSA-N 0.000 description 1
- HJZYYFVNJLKHDI-VXKWHMMOSA-N 2-[(2R,3S)-3-(4-fluorophenyl)-2-hydroxy-3-(3-methylsulfonylphenyl)propyl]isoindole-1,3-dione Chemical compound FC1=CC=C(C=C1)[C@H]([C@H](CN1C(C2=CC=CC=C2C1=O)=O)O)C1=CC(=CC=C1)S(=O)(=O)C HJZYYFVNJLKHDI-VXKWHMMOSA-N 0.000 description 1
- MJJQTTFSWVMPSD-GJZGRUSLSA-N 2-[[(2S,3S)-3-(4-fluorophenyl)oxiran-2-yl]methyl]isoindole-1,3-dione Chemical compound FC1=CC=C(C=C1)[C@H]1[C@@H](O1)CN1C(C2=CC=CC=C2C1=O)=O MJJQTTFSWVMPSD-GJZGRUSLSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- CFCNTIFLYGKEIO-UHFFFAOYSA-M 2-isocyanoacetate Chemical compound [O-]C(=O)C[N+]#[C-] CFCNTIFLYGKEIO-UHFFFAOYSA-M 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- VLUWLNIMIAFOSY-UHFFFAOYSA-N 2-methylbenzenesulfinic acid Chemical compound CC1=CC=CC=C1S(O)=O VLUWLNIMIAFOSY-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 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
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NYGXVLPJRCGHAD-UHFFFAOYSA-N 2-trimethylsilylethoxy methanesulfonate Chemical compound CS(=O)(=O)OOCC[Si](C)(C)C NYGXVLPJRCGHAD-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KMFZMBMVIQBLMG-UHFFFAOYSA-N 3-methoxy-4-oxopyran-2-carbaldehyde Chemical compound COC1=C(C=O)OC=CC1=O KMFZMBMVIQBLMG-UHFFFAOYSA-N 0.000 description 1
- ISULZYQDGYXDFW-UHFFFAOYSA-N 3-methylbutanoyl chloride Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 1
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KKLCYBZPQDOFQK-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC=C1 KKLCYBZPQDOFQK-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- KJSJBKBZMGSIPT-UHFFFAOYSA-N 4-oxo-3-phenylmethoxypyran-2-carboxylic acid Chemical compound O1C=CC(=O)C(OCC=2C=CC=CC=2)=C1C(=O)O KJSJBKBZMGSIPT-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 compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- SHISIZVWEDLGHH-UHFFFAOYSA-N 8-[bis(4-fluorophenyl)methyl]-13-hydroxy-3,6,9,10-tetrazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound FC1=CC=C(C=C1)C(C1CN2C(C=3N1N=CC(C=3O)=O)=NC=C2)C1=CC=C(C=C1)F SHISIZVWEDLGHH-UHFFFAOYSA-N 0.000 description 1
- YNCXGUBKNGPNDS-UHFFFAOYSA-N 8-benzhydryl-13-hydroxy-3,6,8,9-tetrazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)N1N2C(C=3N(C1)C=CN=3)=C(C(C=C2)=O)O YNCXGUBKNGPNDS-UHFFFAOYSA-N 0.000 description 1
- CGCQXESLBSVBRQ-UHFFFAOYSA-N 8-benzhydryl-13-methoxy-3,6,8,9-tetrazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)N1N2C(C=3N(C1)C=CN=3)=C(C(C=C2)=O)OC CGCQXESLBSVBRQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- STTIFGVBIUURHQ-UHFFFAOYSA-N B(O)O.N1C=NN=C1 Chemical compound B(O)O.N1C=NN=C1 STTIFGVBIUURHQ-UHFFFAOYSA-N 0.000 description 1
- QUIFZHRJWHVNIF-XMMPIXPASA-N Bc1cnc2[n]1C[C@H](C(c1ccccc1)c1ccccc1)N(C=CC1=O)C2=C1OCc1ccccc1 Chemical compound Bc1cnc2[n]1C[C@H](C(c1ccccc1)c1ccccc1)N(C=CC1=O)C2=C1OCc1ccccc1 QUIFZHRJWHVNIF-XMMPIXPASA-N 0.000 description 1
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
- JAKCDBCAFBRJAW-UHFFFAOYSA-N BrCC1=C(C(OC=CC2)=C2OCC2=CC=CC=C2)N=CS1 Chemical compound BrCC1=C(C(OC=CC2)=C2OCC2=CC=CC=C2)N=CS1 JAKCDBCAFBRJAW-UHFFFAOYSA-N 0.000 description 1
- NNZBUNJJDXUUKW-QGZVFWFLSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)Br)=C(C(C=C2)=O)O Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)Br)=C(C(C=C2)=O)O NNZBUNJJDXUUKW-QGZVFWFLSA-N 0.000 description 1
- NQLDIEMVOXSJPL-LJQANCHMSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)C)=C(C(C=C2)=O)O Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)C)=C(C(C=C2)=O)O NQLDIEMVOXSJPL-LJQANCHMSA-N 0.000 description 1
- RFJUTKICRVWFQE-OAQYLSRUSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)C1CC1)=C(C(C=C2)=O)O Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)C1CC1)=C(C(C=C2)=O)O RFJUTKICRVWFQE-OAQYLSRUSA-N 0.000 description 1
- USFOAQVPHGMWRV-HXUWFJFHSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)CC)=C(C(C=C2)=O)O Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)CC)=C(C(C=C2)=O)O USFOAQVPHGMWRV-HXUWFJFHSA-N 0.000 description 1
- RVCDVHVLHSRTSR-RUZDIDTESA-N C(C1=CC=CC=C1)OC1=C2N(N=CC1=O)[C@H](CN1C2=NC=C1CO)C(C1=CC=C(C=C1)F)C1=CC=C(C=C1)F Chemical compound C(C1=CC=CC=C1)OC1=C2N(N=CC1=O)[C@H](CN1C2=NC=C1CO)C(C1=CC=C(C=C1)F)C1=CC=C(C=C1)F RVCDVHVLHSRTSR-RUZDIDTESA-N 0.000 description 1
- ZRTHHEDWEJVADA-UHFFFAOYSA-N CB(C1)C1C(C(C=C1)=O)=C2N1NC(C1CC1)[n]1c2ncc1 Chemical compound CB(C1)C1C(C(C=C1)=O)=C2N1NC(C1CC1)[n]1c2ncc1 ZRTHHEDWEJVADA-UHFFFAOYSA-N 0.000 description 1
- VZUZUTVMBMBVSW-MUUNZHRXSA-N CC(C)(C)OC(N[C@H](C[n]1c(C(OC=CC2=O)=C2OCc2ccccc2)ncc1)C(c1ccccc1)c1ccccc1)=O Chemical compound CC(C)(C)OC(N[C@H](C[n]1c(C(OC=CC2=O)=C2OCc2ccccc2)ncc1)C(c1ccccc1)c1ccccc1)=O VZUZUTVMBMBVSW-MUUNZHRXSA-N 0.000 description 1
- FDUPKPIVOCHQOC-OAQYLSRUSA-N CC(C)CC(OC1=C(c2ncc[n]2C[C@@H]2C(c(cc3)ccc3F)c(cc3)ccc3F)N2N=CC1=O)=O Chemical compound CC(C)CC(OC1=C(c2ncc[n]2C[C@@H]2C(c(cc3)ccc3F)c(cc3)ccc3F)N2N=CC1=O)=O FDUPKPIVOCHQOC-OAQYLSRUSA-N 0.000 description 1
- YJTMZQGIYVBHEP-UHFFFAOYSA-N CCC([n]1c2ncc1)N(C(C1=CC=CCC1)c1ccccc1)N(C=CC1=O)C2=C1O Chemical compound CCC([n]1c2ncc1)N(C(C1=CC=CCC1)c1ccccc1)N(C=CC1=O)C2=C1O YJTMZQGIYVBHEP-UHFFFAOYSA-N 0.000 description 1
- PLWHEEWHIXTMQT-UHFFFAOYSA-N CS(=O)(=O)OC(C(C1=CC=CC=C1)C1=CC=CC=C1)CN1C(=NC=C1)C1=NNC=C(C1=O)O Chemical compound CS(=O)(=O)OC(C(C1=CC=CC=C1)C1=CC=CC=C1)CN1C(=NC=C1)C1=NNC=C(C1=O)O PLWHEEWHIXTMQT-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 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
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- OEQXWXSFKDMNSH-GOSISDBHSA-N FC1=CC=C(C=C1)C([C@H]1CN2C(C=3N1N=CC(C=3O)=O)=NC=C2CO)C1=CC=C(C=C1)F Chemical compound FC1=CC=C(C=C1)C([C@H]1CN2C(C=3N1N=CC(C=3O)=O)=NC=C2CO)C1=CC=C(C=C1)F OEQXWXSFKDMNSH-GOSISDBHSA-N 0.000 description 1
- 229940124947 FluMist Quadrivalent Drugs 0.000 description 1
- 229940124896 Fluarix Drugs 0.000 description 1
- 229940124943 Flublok Drugs 0.000 description 1
- 229940124946 Flucelvax Drugs 0.000 description 1
- 229940124894 Fluzone Drugs 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 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 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 206010022005 Influenza viral infections Diseases 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- AWIJSMFVNDAWRA-KRWDZBQOSA-N OC1=C(c2ncc[n]2C[C@H]2C(c3cccc(Cl)c3)c3cc(Cl)ccc3)N2N=CC1=O Chemical compound OC1=C(c2ncc[n]2C[C@H]2C(c3cccc(Cl)c3)c3cc(Cl)ccc3)N2N=CC1=O AWIJSMFVNDAWRA-KRWDZBQOSA-N 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229940123066 Polymerase inhibitor Drugs 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- CVQUWLDCFXOXEN-UHFFFAOYSA-N Pyran-4-one Chemical compound O=C1C=COC=C1 CVQUWLDCFXOXEN-UHFFFAOYSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 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 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 101001039853 Sonchus yellow net virus Matrix protein Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 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
- 239000007983 Tris buffer Substances 0.000 description 1
- CTCBPRXHVPZNHB-VQFZJOCSSA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate;(2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O CTCBPRXHVPZNHB-VQFZJOCSSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 229960001456 adenosine triphosphate Drugs 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 125000005277 alkyl imino group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
- CTPOHARTNNSRSR-APJZLKAGSA-N beraprost Chemical compound O([C@H]1C[C@@H](O)[C@@H]([C@@H]21)/C=C/[C@@H](O)C(C)CC#CC)C1=C2C=CC=C1CCCC(O)=O CTPOHARTNNSRSR-APJZLKAGSA-N 0.000 description 1
- 229960002890 beraprost Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- HTJWUNNIRKDDIV-UHFFFAOYSA-N bis(1-adamantyl)-butylphosphane Chemical compound C1C(C2)CC(C3)CC2CC13P(CCCC)C1(C2)CC(C3)CC2CC3C1 HTJWUNNIRKDDIV-UHFFFAOYSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000003738 britelite plus Methods 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- PMHQVHHXPFUNSP-UHFFFAOYSA-M copper(1+);methylsulfanylmethane;bromide Chemical compound Br[Cu].CSC PMHQVHHXPFUNSP-UHFFFAOYSA-M 0.000 description 1
- WJYJULOBJLLPER-UHFFFAOYSA-N copper(1+);trifluoromethane Chemical compound [Cu+].F[C-](F)F WJYJULOBJLLPER-UHFFFAOYSA-N 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000012045 crude solution Substances 0.000 description 1
- 238000007333 cyanation reaction Methods 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 1
- 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- VSGYTOKLSWSEPK-UHFFFAOYSA-M diethyl-[3-(2-hydroxy-2,2-diphenylacetyl)oxypropyl]-methylazanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1C(O)(C(=O)OCCC[N+](C)(CC)CC)C1=CC=CC=C1 VSGYTOKLSWSEPK-UHFFFAOYSA-M 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 1
- XEBCWEDRGPSHQH-HTQZYQBOSA-N dipropan-2-yl (2r,3r)-2,3-dihydroxybutanedioate Chemical compound CC(C)OC(=O)[C@H](O)[C@@H](O)C(=O)OC(C)C XEBCWEDRGPSHQH-HTQZYQBOSA-N 0.000 description 1
- 229940042397 direct acting antivirals cyclic amines Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- QGBQGMHXBSLYLZ-UHFFFAOYSA-N ditert-butyl-(1-naphthalen-1-ylnaphthalen-2-yl)phosphane Chemical group C1=CC=C2C(C3=C4C=CC=CC4=CC=C3P(C(C)(C)C)C(C)(C)C)=CC=CC2=C1 QGBQGMHXBSLYLZ-UHFFFAOYSA-N 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 108700020302 erbB-2 Genes Proteins 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- ZCGNOVWYSGBHAU-UHFFFAOYSA-N favipiravir Chemical compound NC(=O)C1=NC(F)=CNC1=O ZCGNOVWYSGBHAU-UHFFFAOYSA-N 0.000 description 1
- 229950008454 favipiravir Drugs 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 125000005347 halocycloalkyl group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 description 1
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- JKYRBGSRNKUKPW-UHFFFAOYSA-N iodomethyl methyl carbonate Chemical compound COC(=O)OCI JKYRBGSRNKUKPW-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- UKTIJASCFRNWCB-RMIBSVFLSA-N laninamivir octanoate hydrate Chemical compound CCCCCCCC(=O)OC[C@@H](O)[C@@H](OC)[C@@H]1OC(C(O)=O)=C[C@H](N=C(N)N)[C@H]1NC(C)=O UKTIJASCFRNWCB-RMIBSVFLSA-N 0.000 description 1
- 229950005327 laninamivir octanoate hydrate Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical compound [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Chemical class 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- DVLGIQNHKLWSRU-UHFFFAOYSA-N methyl 1h-imidazole-5-carboxylate Chemical compound COC(=O)C1=CN=CN1 DVLGIQNHKLWSRU-UHFFFAOYSA-N 0.000 description 1
- FZSPLVPNADXESY-UHFFFAOYSA-N methyl 4-(4-oxo-3-phenylmethoxypyran-2-yl)-1H-imidazole-5-carboxylate Chemical compound C(C1=CC=CC=C1)OC1=C(OC=CC1=O)C=1N=CNC=1C(=O)OC FZSPLVPNADXESY-UHFFFAOYSA-N 0.000 description 1
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- PCUVYBUDIWDLNI-UHFFFAOYSA-N methyl n-(n'-chloro-n-methoxycarbonylcarbamimidoyl)carbamate Chemical compound COC(=O)NC(=NCl)NC(=O)OC PCUVYBUDIWDLNI-UHFFFAOYSA-N 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
- JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-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
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- IVMHDOBGNQOUHO-UHFFFAOYSA-N oxathiane Chemical compound C1CCSOC1 IVMHDOBGNQOUHO-UHFFFAOYSA-N 0.000 description 1
- OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 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
- 238000002600 positron emission tomography Methods 0.000 description 1
- 229940074439 potassium sodium tartrate Drugs 0.000 description 1
- ZRLVQFQTCMUIRM-UHFFFAOYSA-N potassium;2-methylbutan-2-olate Chemical compound [K+].CCC(C)(C)[O-] ZRLVQFQTCMUIRM-UHFFFAOYSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 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
- 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
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- 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 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 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
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- MOZWQQBSIREDQQ-UHFFFAOYSA-N tert-butyl 2-(1-benzyl-3-methoxy-4-oxopyridin-2-yl)imidazole-1-carboxylate Chemical compound C(C1=CC=CC=C1)N1C(=C(C(C=C1)=O)OC)C=1N(C=CN=1)C(=O)OC(C)(C)C MOZWQQBSIREDQQ-UHFFFAOYSA-N 0.000 description 1
- ZMMCWINSQBFPJN-UHFFFAOYSA-N tert-butyl 2-(3-methoxy-4-oxo-1H-pyridin-2-yl)imidazole-1-carboxylate Chemical compound COC1=C(NC=CC1=O)C=1N(C=CN=1)C(=O)OC(C)(C)C ZMMCWINSQBFPJN-UHFFFAOYSA-N 0.000 description 1
- TYSZETYVESRFNT-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)OC(C)(C)C TYSZETYVESRFNT-UHFFFAOYSA-N 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000012443 tonicity enhancing agent Substances 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 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
- 239000012096 transfection reagent Substances 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662305392P | 2016-03-08 | 2016-03-08 | |
| PCT/IB2017/051338 WO2017153919A1 (en) | 2016-03-08 | 2017-03-07 | Tricyclic compounds useful to treat orthomyxovirus infections |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2881776T3 true ES2881776T3 (es) | 2021-11-30 |
Family
ID=58347733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17711349T Active ES2881776T3 (es) | 2016-03-08 | 2017-03-07 | Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US10858366B2 (https=) |
| EP (1) | EP3426656B1 (https=) |
| JP (1) | JP6918819B2 (https=) |
| CN (1) | CN108699059B (https=) |
| ES (1) | ES2881776T3 (https=) |
| WO (1) | WO2017153919A1 (https=) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11201708721XA (en) | 2015-04-28 | 2017-11-29 | Shionogi & Co | Substituted polycyclic pyridone derivative and prodrug thereof |
| SG11201804348SA (en) | 2015-12-15 | 2018-06-28 | Shionogi & Co | Medicine for treating influenza characterized by comprising combination of cap-dependent endonuclease inhibitor with anti-influenza drug |
| KR102398439B1 (ko) | 2016-03-07 | 2022-05-16 | 이난타 파마슈티칼스, 인코포레이티드 | B형 간염 항바이러스제 |
| ES2881776T3 (es) * | 2016-03-08 | 2021-11-30 | Novartis Ag | Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus |
| KR20190018469A (ko) | 2016-08-10 | 2019-02-22 | 시오노기세야쿠 가부시키가이샤 | 치환된 다환성 피리돈 유도체 및 그의 프로드러그를 함유하는 의약 조성물 |
| JOP20170169A1 (ar) | 2016-08-29 | 2019-01-30 | Novartis Ag | مركبات بيريدازين ثلاثية الحلقة مندمجة تفيد في علاج العدوى بفيروس أورثوميكسو |
| SG11202001685TA (en) | 2017-08-28 | 2020-03-30 | Enanta Pharm Inc | Hepatitis b antiviral agents |
| US11058678B2 (en) | 2018-01-22 | 2021-07-13 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| CN118878544A (zh) * | 2018-02-28 | 2024-11-01 | 诺华股份有限公司 | 作为正粘病毒复制抑制剂用于治疗流感的化合物 |
| JP2022500466A (ja) | 2018-09-21 | 2022-01-04 | エナンタ ファーマシューティカルズ インコーポレイテッド | 抗ウイルス剤としての官能化複素環 |
| IL283190B2 (en) | 2018-11-21 | 2025-08-01 | Enanta Pharm Inc | Functionalized heterocycles as antiviral agents |
| CN111410661B (zh) * | 2019-01-04 | 2023-05-05 | 周雨恬 | 帽依赖性内切核酸酶抑制剂及其用途 |
| CN109912624B (zh) * | 2019-04-11 | 2021-05-11 | 杭州科巢生物科技有限公司 | 一种巴洛沙韦酯关键母核中间体的合成方法 |
| CN111909174B (zh) | 2019-05-08 | 2022-01-21 | 江西彩石医药科技有限公司 | 吡啶酮衍生物的晶型及制备方法和应用 |
| WO2020247444A1 (en) | 2019-06-03 | 2020-12-10 | Enanta Pharmaceuticals, Inc, | Hepatitis b antiviral agents |
| WO2020247561A1 (en) | 2019-06-04 | 2020-12-10 | Enanta Pharmaceuticals, Inc, | Hepatitis b antiviral agents |
| WO2020247575A1 (en) | 2019-06-04 | 2020-12-10 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| US11738019B2 (en) | 2019-07-11 | 2023-08-29 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| US11236108B2 (en) | 2019-09-17 | 2022-02-01 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| WO2021188414A1 (en) | 2020-03-16 | 2021-09-23 | Enanta Pharmaceuticals, Inc. | Functionalized heterocyclic compounds as antiviral agents |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8501542D0 (en) | 1985-01-22 | 1985-02-20 | Erba Farmitalia | 4 5 6 7-tetrahydro-imidazo(4 5-clpyridine derivatives |
| ES2572030T3 (es) * | 2001-08-10 | 2017-07-19 | Shionogi & Co., Ltd. | Agente antiviral |
| JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
| TW200510425A (en) | 2003-08-13 | 2005-03-16 | Japan Tobacco Inc | Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor |
| TW200526635A (en) * | 2003-12-22 | 2005-08-16 | Shionogi & Co | Hydroxypyrimidinone derivative having HIV integrase inhibitory activity |
| US20070161639A1 (en) | 2004-03-09 | 2007-07-12 | Philip Jones | Hiv integrase inhibitors |
| FR2901795A1 (fr) * | 2006-05-30 | 2007-12-07 | Fourtillan Snc | Derives de pyrimidino[1',6'-1,2]pyrido[3,4-b]indoles et leur utilisation en therapeutique |
| CN102203100B (zh) | 2008-10-31 | 2014-08-27 | 盐野义制药株式会社 | 具有邻苯二酚基团的头孢菌素 |
| EP2412708A4 (en) * | 2009-03-26 | 2014-07-23 | Shionogi & Co | SUBSTITUTED 3-HYDROXY-4-PYRIDONE DERIVATIVE |
| TWI518084B (zh) | 2009-03-26 | 2016-01-21 | 鹽野義製藥股份有限公司 | 哌喃酮與吡啶酮衍生物之製造方法 |
| US8927710B2 (en) | 2009-06-15 | 2015-01-06 | Shionogi & Co., Ltd. | Substituted polycyclic carbamoylpyridone derivative |
| TW201201813A (en) * | 2010-03-31 | 2012-01-16 | Arqule Inc | Substituted benzo-pyrido-triazolo-diazepine compounds |
| US20120195857A1 (en) | 2010-08-12 | 2012-08-02 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| DK2620436T3 (en) | 2010-09-24 | 2018-07-30 | Shionogi & Co | Substituted polycyclic carbamoylpyridone derivative prodrug |
| US9328075B2 (en) * | 2011-05-05 | 2016-05-03 | St. Jude Children's Research Hospital | Pyrimidinone compounds and methods for treating influenza |
| RU2014113230A (ru) | 2011-10-12 | 2015-11-20 | Шионоги Энд Ко., Лтд. | Полициклическое производное пиридона, обладающее ингибирующей активностью в отношении интегразы |
| JP6089108B2 (ja) | 2012-09-20 | 2017-03-01 | セルトリオン， インク． | ドラスタチン１０誘導体、その製造方法およびそれを含む抗癌剤組成物 |
| CA2894642A1 (en) * | 2013-01-08 | 2014-07-17 | Savira Pharmaceuticals Gmbh | Pyrimidone derivatives and their use in the treatment, amelioration or prevention of a viral disease |
| AU2014308991B2 (en) | 2013-08-21 | 2019-02-14 | Janssen Biopharma, Inc. | Antiviral compounds |
| US10098913B2 (en) | 2013-09-11 | 2018-10-16 | University Of Southern California | Composition of stem cells having highly expressed FAS ligand |
| SI3030549T1 (sl) | 2013-09-12 | 2019-08-30 | Janssen Biopharma, Inc. | Spojine piridazinona in njihove uporabe |
| MX377396B (es) | 2013-09-12 | 2025-03-10 | Janssen Biopharma Inc | Compuestos de azapiridona y usos de los mismos. |
| CN107074880A (zh) | 2014-07-07 | 2017-08-18 | 萨维拉制药有限公司 | 二氢吡啶并吡嗪‑1,8‑二酮和它们在治疗、改善或预防病毒疾病中的用途 |
| US10208045B2 (en) | 2015-03-11 | 2019-02-19 | Alios Biopharma, Inc. | Aza-pyridone compounds and uses thereof |
| ES2881776T3 (es) * | 2016-03-08 | 2021-11-30 | Novartis Ag | Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus |
| KR20190018469A (ko) | 2016-08-10 | 2019-02-22 | 시오노기세야쿠 가부시키가이샤 | 치환된 다환성 피리돈 유도체 및 그의 프로드러그를 함유하는 의약 조성물 |
| JOP20170169A1 (ar) | 2016-08-29 | 2019-01-30 | Novartis Ag | مركبات بيريدازين ثلاثية الحلقة مندمجة تفيد في علاج العدوى بفيروس أورثوميكسو |
| US11247993B2 (en) | 2018-01-17 | 2022-02-15 | Jiangxi Caishi Pharmaceutical Technology Co., Ltd. | Pyridone derivative, composition and use as antiviral drug thereof |
| CN118878544A (zh) | 2018-02-28 | 2024-11-01 | 诺华股份有限公司 | 作为正粘病毒复制抑制剂用于治疗流感的化合物 |
-
2017
- 2017-03-07 ES ES17711349T patent/ES2881776T3/es active Active
- 2017-03-07 JP JP2018547307A patent/JP6918819B2/ja active Active
- 2017-03-07 US US16/083,089 patent/US10858366B2/en active Active
- 2017-03-07 EP EP17711349.5A patent/EP3426656B1/en active Active
- 2017-03-07 CN CN201780015673.6A patent/CN108699059B/zh active Active
- 2017-03-07 WO PCT/IB2017/051338 patent/WO2017153919A1/en not_active Ceased
-
2020
- 2020-07-20 US US16/933,000 patent/US11453677B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| WO2017153919A1 (en) | 2017-09-14 |
| US10858366B2 (en) | 2020-12-08 |
| JP2019512485A (ja) | 2019-05-16 |
| CN108699059B (zh) | 2021-06-18 |
| CN108699059A (zh) | 2018-10-23 |
| US20200347072A1 (en) | 2020-11-05 |
| US11453677B2 (en) | 2022-09-27 |
| JP6918819B2 (ja) | 2021-08-11 |
| EP3426656A1 (en) | 2019-01-16 |
| US20190092780A1 (en) | 2019-03-28 |
| EP3426656B1 (en) | 2021-05-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2881776T3 (es) | Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus | |
| US20250223288A1 (en) | Amino acid compounds and methods of use | |
| ES2974494T3 (es) | Compuestos tricíclicos fusionados de piridazinona útiles para tratar las infecciones por ortomixovirus | |
| US20230117605A1 (en) | Dosage forms and regimens for amino acid compounds | |
| ES2760466T3 (es) | Derivados de pirazol útiles como inhibidores de la proteína activadora de 5-lipoxigenasa (FLAP) | |
| US12071441B2 (en) | 10-(di(phenyl)methyl)-4-hydroxy-8,9,9A,10-tetrahydro-7H-pyrrolo[1′,2′:4,5]pyrazino[1,2-b]pyridazine-3,5-dione derivatives and related compounds as inhibitors of the orthomyxovirus replication for treating influenza | |
| HK40119293A (en) | Fused tricyclic pyridazinone compounds and prodrugs thereof useful to treat orthomyxovirus infections | |
| BR122023025728A2 (pt) | Derivados de 10-(di(fenil)metil)-4-hidróxi-8,9,9a-10-tetra-hidro-7hpirrolo[1',2':4,5]pirazino[1,2-b]piridazina-3,5-diona e compostos relacionados como inibidores de da replicação de ortomixovírus, seus usos para tratamento de influenza, composição farmacêutica, e combinação | |
| HK40033744A (en) | Compounds as inhibitors of the orthomyxovirus replication for treating influenza | |
| HK40042824A (en) | 10-(di(phenyl)methyl)-4-hydroxy-8,9,9a,10-tetrahydro-7h-pyrrolo[1',2':4,5]pyrazino[1,2-b]pyridazine-3,5-dione derivatives and related compounds as inhibitors of the orthomyxovirus replication for treating influenza | |
| HK40042824B (en) | 10-(di(phenyl)methyl)-4-hydroxy-8,9,9a,10-tetrahydro-7h-pyrrolo[1',2':4,5]pyrazino[1,2-b]pyridazine-3,5-dione derivatives and related compounds as inhibitors of the orthomyxovirus replication for treating influenza | |
| HK40009791B (zh) | 用於治疗正粘病毒感染的稠合三环哒嗪酮化合物 |