CA2890905A1 - Antiviral azasugar-containing nucleosides - Google Patents
Antiviral azasugar-containing nucleosides Download PDFInfo
- Publication number
- CA2890905A1 CA2890905A1 CA2890905A CA2890905A CA2890905A1 CA 2890905 A1 CA2890905 A1 CA 2890905A1 CA 2890905 A CA2890905 A CA 2890905A CA 2890905 A CA2890905 A CA 2890905A CA 2890905 A1 CA2890905 A1 CA 2890905A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- c6alkyl
- independently
- virus
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000002777 nucleoside Substances 0.000 title description 7
- 230000000840 anti-viral effect Effects 0.000 title description 5
- 125000003835 nucleoside group Chemical group 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 205
- 150000003839 salts Chemical class 0.000 claims abstract description 58
- 238000000034 method Methods 0.000 claims abstract description 41
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
- 208000036142 Viral infection Diseases 0.000 claims abstract description 10
- 230000009385 viral infection Effects 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- -1 OR0 Chemical group 0.000 claims description 274
- 229910052739 hydrogen Inorganic materials 0.000 claims description 202
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 128
- 125000003118 aryl group Chemical group 0.000 claims description 127
- 125000001072 heteroaryl group Chemical group 0.000 claims description 120
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 110
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 104
- 150000004820 halides Chemical class 0.000 claims description 94
- 241000700605 Viruses Species 0.000 claims description 87
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 68
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 61
- 150000001540 azides Chemical class 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 58
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims description 51
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 46
- 125000004001 thioalkyl group Chemical group 0.000 claims description 38
- 125000003342 alkenyl group Chemical group 0.000 claims description 34
- 125000000304 alkynyl group Chemical group 0.000 claims description 34
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 125000004414 alkyl thio group Chemical group 0.000 claims description 19
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000006691 (C2-C7) heterocyclyl group Chemical group 0.000 claims description 18
- 241000710772 Yellow fever virus Species 0.000 claims description 17
- 229940051021 yellow-fever virus Drugs 0.000 claims description 17
- 150000001413 amino acids Chemical class 0.000 claims description 16
- 241001115402 Ebolavirus Species 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 15
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 13
- 241000712079 Measles morbillivirus Species 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 241000712431 Influenza A virus Species 0.000 claims description 12
- 241000713196 Influenza B virus Species 0.000 claims description 12
- 241001115401 Marburgvirus Species 0.000 claims description 12
- 241000712890 Junin mammarenavirus Species 0.000 claims description 10
- 241000712910 Pichinde mammarenavirus Species 0.000 claims description 10
- 241000713126 Punta Toro virus Species 0.000 claims description 10
- 241000725643 Respiratory syncytial virus Species 0.000 claims description 10
- 241000713124 Rift Valley fever virus Species 0.000 claims description 10
- 241000315672 SARS coronavirus Species 0.000 claims description 10
- 241000712908 Tacaribe mammarenavirus Species 0.000 claims description 10
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 claims description 10
- 241000710886 West Nile virus Species 0.000 claims description 10
- 241001493065 dsRNA viruses Species 0.000 claims description 10
- 241000701161 unidentified adenovirus Species 0.000 claims description 10
- 241000709661 Enterovirus Species 0.000 claims description 9
- 230000010076 replication Effects 0.000 claims description 9
- 208000001490 Dengue Diseases 0.000 claims description 8
- 206010012310 Dengue fever Diseases 0.000 claims description 8
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 8
- 208000002606 Paramyxoviridae Infections Diseases 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 208000025729 dengue disease Diseases 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 241000710924 Togaviridae Species 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 241000712892 Arenaviridae Species 0.000 claims description 5
- 241000711573 Coronaviridae Species 0.000 claims description 5
- 241000711950 Filoviridae Species 0.000 claims description 5
- 241000710781 Flaviviridae Species 0.000 claims description 5
- 241000712464 Orthomyxoviridae Species 0.000 claims description 5
- 241000711504 Paramyxoviridae Species 0.000 claims description 5
- 241000150350 Peribunyaviridae Species 0.000 claims description 5
- 241000709664 Picornaviridae Species 0.000 claims description 5
- 241001493160 California encephalitis virus Species 0.000 claims description 4
- 241000709687 Coxsackievirus Species 0.000 claims description 4
- 241000710945 Eastern equine encephalitis virus Species 0.000 claims description 4
- 241000991587 Enterovirus C Species 0.000 claims description 4
- 241000190708 Guanarito mammarenavirus Species 0.000 claims description 4
- 241000711549 Hepacivirus C Species 0.000 claims description 4
- 241000709721 Hepatovirus A Species 0.000 claims description 4
- 241000710842 Japanese encephalitis virus Species 0.000 claims description 4
- 241000713102 La Crosse virus Species 0.000 claims description 4
- 241000712902 Lassa mammarenavirus Species 0.000 claims description 4
- 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 claims description 4
- 241000150452 Orthohantavirus Species 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 4
- 241000700647 Variola virus Species 0.000 claims description 4
- 241000710951 Western equine encephalitis virus Species 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical group [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 4
- 235000011180 diphosphates Nutrition 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 4
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical group [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 4
- 150000008300 phosphoramidites Chemical group 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical group C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 11
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 abstract description 8
- 108020000999 Viral RNA Proteins 0.000 abstract description 7
- 230000029812 viral genome replication Effects 0.000 abstract description 6
- 239000008186 active pharmaceutical agent Substances 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 159
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 105
- 239000000243 solution Substances 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 229960002429 proline Drugs 0.000 description 90
- 239000011541 reaction mixture Substances 0.000 description 87
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 80
- 238000002360 preparation method Methods 0.000 description 78
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 74
- 239000007787 solid Substances 0.000 description 67
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 63
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 58
- 238000005160 1H NMR spectroscopy Methods 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- 235000019439 ethyl acetate Nutrition 0.000 description 52
- 229940093499 ethyl acetate Drugs 0.000 description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 44
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 44
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 44
- 239000000203 mixture Substances 0.000 description 44
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 43
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- 235000019441 ethanol Nutrition 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 36
- 238000003818 flash chromatography Methods 0.000 description 32
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 29
- 239000000741 silica gel Substances 0.000 description 29
- 229910002027 silica gel Inorganic materials 0.000 description 29
- 238000003786 synthesis reaction Methods 0.000 description 29
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- 230000015572 biosynthetic process Effects 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- 238000010992 reflux Methods 0.000 description 25
- 238000012360 testing method Methods 0.000 description 25
- 230000000120 cytopathologic effect Effects 0.000 description 21
- 229910000104 sodium hydride Inorganic materials 0.000 description 21
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
- 239000011701 zinc Substances 0.000 description 20
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 238000003556 assay Methods 0.000 description 18
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 18
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 18
- 229910052725 zinc Inorganic materials 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 231100000135 cytotoxicity Toxicity 0.000 description 16
- 230000003013 cytotoxicity Effects 0.000 description 16
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 16
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 239000002609 medium Substances 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- UWMXUDUWVFWJPX-UHFFFAOYSA-N 1,5-dihydropyrrolo[3,2-d]pyrimidin-4-one Chemical compound OC1=NC=NC2=C1NC=C2 UWMXUDUWVFWJPX-UHFFFAOYSA-N 0.000 description 12
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229940024606 amino acid Drugs 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- 239000006188 syrup Substances 0.000 description 12
- 235000020357 syrup Nutrition 0.000 description 12
- 239000007788 liquid Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 101150041968 CDC13 gene Proteins 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 10
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 230000009466 transformation Effects 0.000 description 10
- 230000003612 virological effect Effects 0.000 description 10
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- KYPNNINGHKXOSL-UHFFFAOYSA-N n-(7-bromopyrrolo[2,1-f][1,2,4]triazin-4-yl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=NC=NN2C(Br)=CC=C12 KYPNNINGHKXOSL-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 230000001988 toxicity Effects 0.000 description 9
- 231100000419 toxicity Toxicity 0.000 description 9
- JCZPOYAMKJFOLA-ZXZARUISSA-N (3s,4r)-pyrrolidine-3,4-diol Chemical compound O[C@H]1CNC[C@H]1O JCZPOYAMKJFOLA-ZXZARUISSA-N 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- UUTYQBCAEWGFQL-UHFFFAOYSA-N 3-bromo-2,6-dimethoxypyridine Chemical compound COC1=CC=C(Br)C(OC)=N1 UUTYQBCAEWGFQL-UHFFFAOYSA-N 0.000 description 8
- BOUIZPWBFIVJPD-UHFFFAOYSA-N 3h-1,2,4-triazin-4-amine Chemical compound NN1CN=NC=C1 BOUIZPWBFIVJPD-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 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 8
- 229910015845 BBr3 Inorganic materials 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 108020004707 nucleic acids Proteins 0.000 description 7
- 102000039446 nucleic acids Human genes 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 7
- MAWUVEDTRZARNC-UHFFFAOYSA-N 5-bromo-2,4-bis[(2-methylpropan-2-yl)oxy]pyrimidine Chemical compound CC(C)(C)OC1=NC=C(Br)C(OC(C)(C)C)=N1 MAWUVEDTRZARNC-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- CUOKHACJLGPRHD-BXXZVTAOSA-N D-ribono-1,4-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H]1O CUOKHACJLGPRHD-BXXZVTAOSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- VFKYODDQOZLTQL-UHFFFAOYSA-N dimethyl 3-amino-1h-pyrrole-2,4-dicarboxylate Chemical compound COC(=O)C1=CNC(C(=O)OC)=C1N VFKYODDQOZLTQL-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical group 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- ZGJDDWOXVGDTSP-UHFFFAOYSA-N 4-chloro-5h-pyrrolo[3,2-d]pyrimidine Chemical compound ClC1=NC=NC2=C1NC=C2 ZGJDDWOXVGDTSP-UHFFFAOYSA-N 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- TZYQTWHRLVDYPL-UHFFFAOYSA-N 5h-pyrimidin-4-one Chemical compound O=C1CC=NC=N1 TZYQTWHRLVDYPL-UHFFFAOYSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 108060004795 Methyltransferase Proteins 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
- 235000011089 carbon dioxide Nutrition 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 210000003292 kidney cell Anatomy 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 5
- 239000007758 minimum essential medium Substances 0.000 description 5
- 150000002894 organic compounds Chemical class 0.000 description 5
- XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 5
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 4
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 4
- 241000282552 Chlorocebus aethiops Species 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 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
- 150000001371 alpha-amino acids Chemical class 0.000 description 4
- 235000008206 alpha-amino acids Nutrition 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- VSPXQZSDPSOPRO-UHFFFAOYSA-N pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound NC1=NC=NN2C=CC=C12 VSPXQZSDPSOPRO-UHFFFAOYSA-N 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- IBTGEEMBZJBBSH-UHFFFAOYSA-N 2,6-dimethoxypyridine Chemical compound COC1=CC=CC(OC)=N1 IBTGEEMBZJBBSH-UHFFFAOYSA-N 0.000 description 3
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 3
- 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 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 3
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 3
- 229930182566 Gentamicin Natural products 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 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
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 3
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229910006124 SOCl2 Inorganic materials 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001299 aldehydes Chemical group 0.000 description 3
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 229910052796 boron Inorganic materials 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 description 3
- KTMGNAIGXYODKQ-VOTSOKGWSA-N ethyl (e)-2-cyano-3-ethoxyprop-2-enoate Chemical compound CCO\C=C(/C#N)C(=O)OCC KTMGNAIGXYODKQ-VOTSOKGWSA-N 0.000 description 3
- 229960002518 gentamicin Drugs 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229960003104 ornithine Drugs 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000000611 regression analysis Methods 0.000 description 3
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 241000114864 ssRNA viruses Species 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 210000002845 virion Anatomy 0.000 description 3
- CUOKHACJLGPRHD-PZGQECOJSA-N (3r,4s,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-one Chemical compound OC[C@@H]1OC(=O)[C@H](O)[C@@H]1O CUOKHACJLGPRHD-PZGQECOJSA-N 0.000 description 2
- BWKMGYQJPOAASG-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CNC(C(=O)O)CC2=C1 BWKMGYQJPOAASG-UHFFFAOYSA-N 0.000 description 2
- GRDXZRWCQWDLPG-UHFFFAOYSA-N 1,3,6-trimethylpyrimidine-2,4-dione Chemical compound CC1=CC(=O)N(C)C(=O)N1C GRDXZRWCQWDLPG-UHFFFAOYSA-N 0.000 description 2
- CMQXDMLOQZMKGG-UHFFFAOYSA-N 1,3-dimethyl-2,6-dioxopyrimidine-4-carbonitrile Chemical compound CN1C(C#N)=CC(=O)N(C)C1=O CMQXDMLOQZMKGG-UHFFFAOYSA-N 0.000 description 2
- GHMNEBMXJVXEPL-UHFFFAOYSA-N 1-(oxiran-2-yl)-3-phenylpropan-1-amine Chemical compound C1OC1C(N)CCC1=CC=CC=C1 GHMNEBMXJVXEPL-UHFFFAOYSA-N 0.000 description 2
- LXVCUAYQFAEUML-UHFFFAOYSA-N 2,2-dimethyl-n-pyrrolo[2,1-f][1,2,4]triazin-4-ylpropanamide Chemical compound CC(C)(C)C(=O)NC1=NC=NN2C=CC=C12 LXVCUAYQFAEUML-UHFFFAOYSA-N 0.000 description 2
- NQOZPTYIJQUKTJ-UHFFFAOYSA-N 2-[2-(3-methoxyphenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)quinazolin-3-yl]-n-propan-2-ylacetamide Chemical compound COC1=CC=CC(C=2N(C(=O)C3=CC(OCCCN4CCCCC4)=CC=C3N=2)CC(=O)NC(C)C)=C1 NQOZPTYIJQUKTJ-UHFFFAOYSA-N 0.000 description 2
- XMTQQYYKAHVGBJ-UHFFFAOYSA-N 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA Chemical compound CN(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XMTQQYYKAHVGBJ-UHFFFAOYSA-N 0.000 description 2
- BHPOOUUMRGOCIR-UHFFFAOYSA-N 3-bromo-2,6-bis(phenylmethoxy)pyridine Chemical compound N1=C(OCC=2C=CC=CC=2)C(Br)=CC=C1OCC1=CC=CC=C1 BHPOOUUMRGOCIR-UHFFFAOYSA-N 0.000 description 2
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 2
- PEXCIAYYXJNMLO-UHFFFAOYSA-N 6,6a-dihydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylic acid Chemical compound C1C2C(=CN1C(=O)O)OCO2 PEXCIAYYXJNMLO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 241000710815 Dengue virus 2 Species 0.000 description 2
- 239000012983 Dulbecco’s minimal essential medium Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical class FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- 101000594820 Homo sapiens Purine nucleoside phosphorylase Proteins 0.000 description 2
- 241000712003 Human respirovirus 3 Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- QEFRNWWLZKMPFJ-YGVKFDHGSA-N L-methionine S-oxide Chemical compound CS(=O)CC[C@H](N)C(O)=O QEFRNWWLZKMPFJ-YGVKFDHGSA-N 0.000 description 2
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- KBHCPIJKJQNHPN-UHFFFAOYSA-N N=NP(O)=O Chemical group N=NP(O)=O KBHCPIJKJQNHPN-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- WBTCZXYOKNRFQX-UHFFFAOYSA-N S1(=O)(=O)NC1=O Chemical group S1(=O)(=O)NC1=O WBTCZXYOKNRFQX-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 108010067390 Viral Proteins Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000000538 analytical sample Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 238000002832 anti-viral assay Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009697 arginine Nutrition 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical class O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 2
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007071 enzymatic hydrolysis Effects 0.000 description 2
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 235000004554 glutamine Nutrition 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 235000014304 histidine Nutrition 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000018977 lysine Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 2
- 235000019799 monosodium phosphate Nutrition 0.000 description 2
- 230000004660 morphological change Effects 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
- 229940127073 nucleoside analogue Drugs 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical group [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 239000011669 selenium Substances 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- XWHHYOYVRVGJJY-MRVPVSSYSA-N (2r)-2-amino-3-(4-fluorophenyl)propanoic acid Chemical compound OC(=O)[C@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-MRVPVSSYSA-N 0.000 description 1
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- OHONSQBTMHWXRV-PBXRRBTRSA-N (2r,3r,4s)-2-(hydroxymethyl)-4-methylpyrrolidine-3,4-diol Chemical compound C[C@]1(O)CN[C@H](CO)[C@H]1O OHONSQBTMHWXRV-PBXRRBTRSA-N 0.000 description 1
- FQRURPFZTFUXEZ-MRVPVSSYSA-N (2s)-2,3,3,3-tetrafluoro-2-(n-fluoroanilino)propanoic acid Chemical compound OC(=O)[C@](F)(C(F)(F)F)N(F)C1=CC=CC=C1 FQRURPFZTFUXEZ-MRVPVSSYSA-N 0.000 description 1
- AALYNABLSOHPQK-BYPYZUCNSA-N (2s)-2-(1,3-thiazol-4-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CSC=N1 AALYNABLSOHPQK-BYPYZUCNSA-N 0.000 description 1
- YPJJGMCMOHDOFZ-ZETCQYMHSA-N (2s)-2-(1-benzothiophen-3-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CSC2=C1 YPJJGMCMOHDOFZ-ZETCQYMHSA-N 0.000 description 1
- FDEWJJWPQXUJDU-NSHDSACASA-N (2s)-2-(anthracen-9-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=C(C=CC=C3)C3=CC2=C1 FDEWJJWPQXUJDU-NSHDSACASA-N 0.000 description 1
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
- VVDBQHCKPZBJPG-YFKPBYRVSA-N (2s)-2-(furan-2-ylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1=CC=CO1 VVDBQHCKPZBJPG-YFKPBYRVSA-N 0.000 description 1
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- RWLSBXBFZHDHHX-VIFPVBQESA-N (2s)-2-(naphthalen-2-ylamino)propanoic acid Chemical compound C1=CC=CC2=CC(N[C@@H](C)C(O)=O)=CC=C21 RWLSBXBFZHDHHX-VIFPVBQESA-N 0.000 description 1
- HKUAWRVNDCVEHT-NSHDSACASA-N (2s)-2-(pyren-4-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC3=CC=CC4=CC=C1C2=C34 HKUAWRVNDCVEHT-NSHDSACASA-N 0.000 description 1
- CNMAQBJBWQQZFZ-LURJTMIESA-N (2s)-2-(pyridin-2-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=CC=N1 CNMAQBJBWQQZFZ-LURJTMIESA-N 0.000 description 1
- WTKYBFQVZPCGAO-LURJTMIESA-N (2s)-2-(pyridin-3-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=CN=C1 WTKYBFQVZPCGAO-LURJTMIESA-N 0.000 description 1
- SAAQPSNNIOGFSQ-LURJTMIESA-N (2s)-2-(pyridin-4-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=NC=C1 SAAQPSNNIOGFSQ-LURJTMIESA-N 0.000 description 1
- MRTPISKDZDHEQI-YFKPBYRVSA-N (2s)-2-(tert-butylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC(C)(C)C MRTPISKDZDHEQI-YFKPBYRVSA-N 0.000 description 1
- WRQSUCJAKAMYMQ-YFKPBYRVSA-N (2s)-2-(thiophen-3-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC=1C=CSC=1 WRQSUCJAKAMYMQ-YFKPBYRVSA-N 0.000 description 1
- NPDBDJFLKKQMCM-SCSAIBSYSA-N (2s)-2-amino-3,3-dimethylbutanoic acid Chemical compound CC(C)(C)[C@H](N)C(O)=O NPDBDJFLKKQMCM-SCSAIBSYSA-N 0.000 description 1
- PECGVEGMRUZOML-AWEZNQCLSA-N (2s)-2-amino-3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C([C@H](N)C(O)=O)C1=CC=CC=C1 PECGVEGMRUZOML-AWEZNQCLSA-N 0.000 description 1
- SWJFYJHCOWRRLR-QMMMGPOBSA-N (2s)-2-amino-3-(2,4,5-trifluorophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC(F)=C(F)C=C1F SWJFYJHCOWRRLR-QMMMGPOBSA-N 0.000 description 1
- ZEWXVRJSLTXWON-JTQLQIEISA-N (2s)-2-amino-3-(2,4-dimethylphenyl)propanoic acid Chemical compound CC1=CC=C(C[C@H](N)C(O)=O)C(C)=C1 ZEWXVRJSLTXWON-JTQLQIEISA-N 0.000 description 1
- JFVLNTLXEZDFHW-QMMMGPOBSA-N (2s)-2-amino-3-(2-bromophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1Br JFVLNTLXEZDFHW-QMMMGPOBSA-N 0.000 description 1
- QDQWGGPXZQIUPR-QMMMGPOBSA-N (2s)-2-amino-3-(2-carbamoylphenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1C(N)=O QDQWGGPXZQIUPR-QMMMGPOBSA-N 0.000 description 1
- NHBKDLSKDKUGSB-VIFPVBQESA-N (2s)-2-amino-3-(2-methylphenyl)propanoic acid Chemical compound CC1=CC=CC=C1C[C@H](N)C(O)=O NHBKDLSKDKUGSB-VIFPVBQESA-N 0.000 description 1
- NRCSJHVDTAAISV-QMMMGPOBSA-N (2s)-2-amino-3-(3,4-dichlorophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(Cl)C(Cl)=C1 NRCSJHVDTAAISV-QMMMGPOBSA-N 0.000 description 1
- GDMOHOYNMWWBAU-QMMMGPOBSA-N (2s)-2-amino-3-(3-bromophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(Br)=C1 GDMOHOYNMWWBAU-QMMMGPOBSA-N 0.000 description 1
- NUHHYFSZGZXEGU-QMMMGPOBSA-N (2s)-2-amino-3-(3-carbamoylphenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(C(N)=O)=C1 NUHHYFSZGZXEGU-QMMMGPOBSA-N 0.000 description 1
- PEMUHKUIQHFMTH-QMMMGPOBSA-N (2s)-2-amino-3-(4-bromophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(Br)C=C1 PEMUHKUIQHFMTH-QMMMGPOBSA-N 0.000 description 1
- OZVAXCWACWDNIQ-QMMMGPOBSA-N (2s)-2-amino-3-(4-carbamoylphenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(C(N)=O)C=C1 OZVAXCWACWDNIQ-QMMMGPOBSA-N 0.000 description 1
- DQLHSFUMICQIMB-VIFPVBQESA-N (2s)-2-amino-3-(4-methylphenyl)propanoic acid Chemical compound CC1=CC=C(C[C@H](N)C(O)=O)C=C1 DQLHSFUMICQIMB-VIFPVBQESA-N 0.000 description 1
- CSJZKSXYLTYFPU-NSHDSACASA-N (2s)-2-amino-3-(4-tert-butylphenyl)propanoic acid Chemical compound CC(C)(C)C1=CC=C(C[C@H](N)C(O)=O)C=C1 CSJZKSXYLTYFPU-NSHDSACASA-N 0.000 description 1
- RDAKEAJYLGZEEA-VIFPVBQESA-N (2s)-2-amino-3-[2-(aminomethyl)phenyl]propanoic acid Chemical compound NCC1=CC=CC=C1C[C@H](N)C(O)=O RDAKEAJYLGZEEA-VIFPVBQESA-N 0.000 description 1
- IOABLDGLYOGEHY-QMMMGPOBSA-N (2s)-2-amino-3-[2-(trifluoromethyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1C(F)(F)F IOABLDGLYOGEHY-QMMMGPOBSA-N 0.000 description 1
- YBVDQQQEPCEKPR-VIFPVBQESA-N (2s)-2-amino-3-[3-(aminomethyl)phenyl]propanoic acid Chemical compound NCC1=CC=CC(C[C@H](N)C(O)=O)=C1 YBVDQQQEPCEKPR-VIFPVBQESA-N 0.000 description 1
- BURBNIPKSRJAIQ-QMMMGPOBSA-N (2s)-2-amino-3-[3-(trifluoromethyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(C(F)(F)F)=C1 BURBNIPKSRJAIQ-QMMMGPOBSA-N 0.000 description 1
- GNVNKFUEUXUWDV-VIFPVBQESA-N (2s)-2-amino-3-[4-(aminomethyl)phenyl]propanoic acid Chemical compound NCC1=CC=C(C[C@H](N)C(O)=O)C=C1 GNVNKFUEUXUWDV-VIFPVBQESA-N 0.000 description 1
- SAQLLHDEEMZENJ-VIFPVBQESA-N (2s)-2-amino-3-[4-(phosphonomethyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(CP(O)(O)=O)C=C1 SAQLLHDEEMZENJ-VIFPVBQESA-N 0.000 description 1
- CRFFPDBJLGAGQL-QMMMGPOBSA-N (2s)-2-amino-3-[4-(trifluoromethyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(C(F)(F)F)C=C1 CRFFPDBJLGAGQL-QMMMGPOBSA-N 0.000 description 1
- VOIZSAUUYAGTMS-LURJTMIESA-N (2s)-2-amino-3-thiophen-3-ylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC=1C=CSC=1 VOIZSAUUYAGTMS-LURJTMIESA-N 0.000 description 1
- LLVUHQYJZJUDAM-ZETCQYMHSA-N (2s)-2-azaniumyl-3-(2,4-dinitrophenyl)propanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O LLVUHQYJZJUDAM-ZETCQYMHSA-N 0.000 description 1
- SDZGVFSSLGTJAJ-ZETCQYMHSA-N (2s)-2-azaniumyl-3-(2-nitrophenyl)propanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1[N+]([O-])=O SDZGVFSSLGTJAJ-ZETCQYMHSA-N 0.000 description 1
- YTHDRUZHNYKZGF-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(3-nitrophenyl)propanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=CC([N+]([O-])=O)=C1 YTHDRUZHNYKZGF-QMMMGPOBSA-N 0.000 description 1
- XGUXJMWPVJQIHI-YFKPBYRVSA-N (2s)-2-azaniumyl-3-cyclopropylpropanoate Chemical compound [O-]C(=O)[C@@H]([NH3+])CC1CC1 XGUXJMWPVJQIHI-YFKPBYRVSA-N 0.000 description 1
- ASKGBBKGACJSEL-SCZZXKLOSA-N (2s,3r)-2-(benzylamino)-3-phosphonooxybutanoic acid Chemical compound OP(=O)(O)O[C@H](C)[C@@H](C(O)=O)NCC1=CC=CC=C1 ASKGBBKGACJSEL-SCZZXKLOSA-N 0.000 description 1
- XTJDGOQYFKHEJR-ZJUUUORDSA-N (3r,4s)-4-phenylpyrrolidine-3-carboxylic acid Chemical compound OC(=O)[C@H]1CNC[C@@H]1C1=CC=CC=C1 XTJDGOQYFKHEJR-ZJUUUORDSA-N 0.000 description 1
- UAPQUOMPLVHDJP-DTWKUNHWSA-N (3s,4r)-4-(2-nitrophenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=CC=C1[N+]([O-])=O UAPQUOMPLVHDJP-DTWKUNHWSA-N 0.000 description 1
- FBFGHGLKHHVFCD-NWDGAFQWSA-N (3s,4r)-4-(3,5-dimethoxyphenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound COC1=CC(OC)=CC([C@H]2[C@@H](CNC2)C(O)=O)=C1 FBFGHGLKHHVFCD-NWDGAFQWSA-N 0.000 description 1
- BJGWYFRCQPUPCO-VHSXEESVSA-N (3s,4r)-4-(3-chlorophenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=CC(Cl)=C1 BJGWYFRCQPUPCO-VHSXEESVSA-N 0.000 description 1
- DPBJZZNRRNSKIH-WDEREUQCSA-N (3s,4r)-4-(3-methoxyphenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound COC1=CC=CC([C@H]2[C@@H](CNC2)C(O)=O)=C1 DPBJZZNRRNSKIH-WDEREUQCSA-N 0.000 description 1
- FQRPQUABFIUZMG-VHSXEESVSA-N (3s,4r)-4-(3-nitrophenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=CC([N+]([O-])=O)=C1 FQRPQUABFIUZMG-VHSXEESVSA-N 0.000 description 1
- UOAQYJHCQPXLOP-VHSXEESVSA-N (3s,4r)-4-(4-chlorophenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=C(Cl)C=C1 UOAQYJHCQPXLOP-VHSXEESVSA-N 0.000 description 1
- NSAIUTIMXGDOKA-WDEREUQCSA-N (3s,4r)-4-(4-cyanophenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=C(C#N)C=C1 NSAIUTIMXGDOKA-WDEREUQCSA-N 0.000 description 1
- YXKAESVIGMPPNB-VHSXEESVSA-N (3s,4r)-4-(4-fluorophenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=C(F)C=C1 YXKAESVIGMPPNB-VHSXEESVSA-N 0.000 description 1
- IJVDKAOETNQRCC-VHSXEESVSA-N (3s,4r)-4-(4-hydroxyphenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=C(O)C=C1 IJVDKAOETNQRCC-VHSXEESVSA-N 0.000 description 1
- FQHFMERRNRYSDS-WDEREUQCSA-N (3s,4r)-4-(4-methoxyphenyl)pyrrolidin-1-ium-3-carboxylate Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@H](C(O)=O)CNC1 FQHFMERRNRYSDS-WDEREUQCSA-N 0.000 description 1
- MFKDNBMRBWNZTH-VHSXEESVSA-N (3s,4r)-4-[4-(trifluoromethyl)phenyl]pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=C(C(F)(F)F)C=C1 MFKDNBMRBWNZTH-VHSXEESVSA-N 0.000 description 1
- NLVXTQPLGJBYLL-UONOGXRCSA-N (3s,4r)-4-naphthalen-1-ylpyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=CC2=CC=CC=C12 NLVXTQPLGJBYLL-UONOGXRCSA-N 0.000 description 1
- FXFJYUXPFQIPNN-UONOGXRCSA-N (3s,4r)-4-naphthalen-2-ylpyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1CNC[C@H]1C1=CC=C(C=CC=C2)C2=C1 FXFJYUXPFQIPNN-UONOGXRCSA-N 0.000 description 1
- NQULSPPHDFWDLL-NKWVEPMBSA-N (3s,4s)-4-propan-2-ylpyrrolidin-1-ium-3-carboxylate Chemical compound CC(C)[C@@H]1CNC[C@H]1C(O)=O NQULSPPHDFWDLL-NKWVEPMBSA-N 0.000 description 1
- PNHBRYIAJCYNDA-VQCQRNETSA-N (4r)-6-[2-[2-ethyl-4-(4-fluorophenyl)-6-phenylpyridin-3-yl]ethyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1CCC=1C(CC)=NC(C=2C=CC=CC=2)=CC=1C1=CC=C(F)C=C1 PNHBRYIAJCYNDA-VQCQRNETSA-N 0.000 description 1
- UXKLQDCALAWFIU-VKNDCNMPSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-tetradecoxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCCCC)C1=CC=CC=C1 UXKLQDCALAWFIU-VKNDCNMPSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical class C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 description 1
- 150000005071 1,2,4-oxadiazoles Chemical class 0.000 description 1
- 150000000178 1,2,4-triazoles Chemical class 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- 150000005072 1,3,4-oxadiazoles Chemical class 0.000 description 1
- RGGLEJFUEMKQSH-UHFFFAOYSA-N 1,4-benzodiazepin-2-one Chemical class O=C1C=NC=C2C=CC=CC2=N1 RGGLEJFUEMKQSH-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- QOSOOKJVDRMBEP-UHFFFAOYSA-N 1-(oxiran-2-yl)-2-(4-phenylmethoxyphenyl)ethanamine Chemical compound C1OC1C(N)CC(C=C1)=CC=C1OCC1=CC=CC=C1 QOSOOKJVDRMBEP-UHFFFAOYSA-N 0.000 description 1
- CXNVJKVOLRRZLP-UHFFFAOYSA-N 1-(oxiran-2-yl)-2-phenylethanamine Chemical compound C1OC1C(N)CC1=CC=CC=C1 CXNVJKVOLRRZLP-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical class C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 1
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 1
- 150000004793 2,6-dihydroxypyridines Chemical class 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- QNLJZHVCGHSLIJ-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-1-(oxiran-2-yl)ethanamine Chemical compound C1OC1C(N)CC1=CC(F)=CC(F)=C1 QNLJZHVCGHSLIJ-UHFFFAOYSA-N 0.000 description 1
- ISXFTBSPRQHQOO-UHFFFAOYSA-N 2-(3-bromophenyl)-1-(oxiran-2-yl)ethanamine Chemical compound C1OC1C(N)CC1=CC=CC(Br)=C1 ISXFTBSPRQHQOO-UHFFFAOYSA-N 0.000 description 1
- SMHRZXLAAGVEFO-UHFFFAOYSA-N 2-(4-nitrophenyl)-1-(oxiran-2-yl)ethanamine Chemical compound C1OC1C(N)CC1=CC=C([N+]([O-])=O)C=C1 SMHRZXLAAGVEFO-UHFFFAOYSA-N 0.000 description 1
- DXQCCQKRNWMECV-UHFFFAOYSA-N 2-(cyclopropylazaniumyl)acetate Chemical compound OC(=O)CNC1CC1 DXQCCQKRNWMECV-UHFFFAOYSA-N 0.000 description 1
- GIUTUZDGHNZVIA-UHFFFAOYSA-N 2-(ethylamino)acetic acid;hydrochloride Chemical compound Cl.CCNCC(O)=O GIUTUZDGHNZVIA-UHFFFAOYSA-N 0.000 description 1
- UNQHGXLQKSZYQU-UHFFFAOYSA-N 2-(thiophen-2-ylamino)acetic acid Chemical compound OC(=O)CNC1=CC=CS1 UNQHGXLQKSZYQU-UHFFFAOYSA-N 0.000 description 1
- VJQOUHZVZWHSNW-UHFFFAOYSA-N 2-(thiophen-3-ylamino)acetic acid Chemical compound OC(=O)CNC=1C=CSC=1 VJQOUHZVZWHSNW-UHFFFAOYSA-N 0.000 description 1
- CZHCGMZJLLOYJW-UHFFFAOYSA-N 2-amino-2-propylpentanoic acid Chemical compound CCCC(N)(C(O)=O)CCC CZHCGMZJLLOYJW-UHFFFAOYSA-N 0.000 description 1
- VXCZUOGLGVWRIR-UCROKIRRSA-N 2-amino-5-[(2s,3s,4r,5r)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]-1h-pyrimidin-6-one Chemical compound O=C1NC(N)=NC=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)N1 VXCZUOGLGVWRIR-UCROKIRRSA-N 0.000 description 1
- DQSACLYOIBPCJU-UHFFFAOYSA-N 2-azaniumyl-2-(2-methoxyphenyl)acetate Chemical compound COC1=CC=CC=C1C(N)C(O)=O DQSACLYOIBPCJU-UHFFFAOYSA-N 0.000 description 1
- GWHQTNKPTXDNRM-UHFFFAOYSA-N 2-azaniumyl-3-(2,4-dichlorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC=C(Cl)C=C1Cl GWHQTNKPTXDNRM-UHFFFAOYSA-N 0.000 description 1
- PRAWYXDDKCVZTL-UHFFFAOYSA-N 2-azaniumyl-3-(3,4-difluorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC=C(F)C(F)=C1 PRAWYXDDKCVZTL-UHFFFAOYSA-N 0.000 description 1
- QFGMPXZFCIHYIR-UHFFFAOYSA-N 2-azaniumyl-3-(3,5-difluorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC(F)=CC(F)=C1 QFGMPXZFCIHYIR-UHFFFAOYSA-N 0.000 description 1
- WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical compound OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 description 1
- YTCSGBSYHNQHFD-UHFFFAOYSA-N 2-azaniumyl-4-bromopent-4-enoate Chemical compound OC(=O)C(N)CC(Br)=C YTCSGBSYHNQHFD-UHFFFAOYSA-N 0.000 description 1
- XOQZTHUXZWQXOK-UHFFFAOYSA-N 2-azaniumyl-5-phenylpentanoate Chemical compound OC(=O)C(N)CCCC1=CC=CC=C1 XOQZTHUXZWQXOK-UHFFFAOYSA-N 0.000 description 1
- GEWXKWHUHOUZHX-UHFFFAOYSA-N 2-cyclohexyl-1-(oxiran-2-yl)ethanamine Chemical compound C1OC1C(N)CC1CCCCC1 GEWXKWHUHOUZHX-UHFFFAOYSA-N 0.000 description 1
- NYCRCTMDYITATC-UHFFFAOYSA-N 2-fluorophenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1F NYCRCTMDYITATC-UHFFFAOYSA-N 0.000 description 1
- IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical class COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- VBHYLBSLCBCHAT-UHFFFAOYSA-N 2-pyrido[3,2-d]pyrimidin-2-ylacetamide Chemical class N1=CC=CC2=NC(CC(=O)N)=NC=C21 VBHYLBSLCBCHAT-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- MLLSSTJTARJLHK-UHFFFAOYSA-N 3-aminocyclopentane-1-carboxylic acid Chemical compound NC1CCC(C(O)=O)C1 MLLSSTJTARJLHK-UHFFFAOYSA-N 0.000 description 1
- IEDIKTABXQYWBL-UHFFFAOYSA-N 3-aminopropanoic acid Chemical compound NCCC(O)=O.NCCC(O)=O IEDIKTABXQYWBL-UHFFFAOYSA-N 0.000 description 1
- JJDJLFDGCUYZMN-QMMMGPOBSA-N 3-chloro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(Cl)=C1 JJDJLFDGCUYZMN-QMMMGPOBSA-N 0.000 description 1
- BXRLWGXPSRYJDZ-UHFFFAOYSA-N 3-cyanoalanine Chemical compound OC(=O)C(N)CC#N BXRLWGXPSRYJDZ-UHFFFAOYSA-N 0.000 description 1
- JZRBSTONIYRNRI-VIFPVBQESA-N 3-methylphenylalanine Chemical compound CC1=CC=CC(C[C@H](N)C(O)=O)=C1 JZRBSTONIYRNRI-VIFPVBQESA-N 0.000 description 1
- IRZQDMYEJPNDEN-UHFFFAOYSA-N 3-phenyl-2-aminobutanoic acid Natural products OC(=O)C(N)C(C)C1=CC=CC=C1 IRZQDMYEJPNDEN-UHFFFAOYSA-N 0.000 description 1
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
- HUWDAIDFJPVODH-UHFFFAOYSA-N 4-[2-amino-2-(oxiran-2-yl)ethyl]benzamide Chemical compound C1OC1C(N)CC1=CC=C(C(N)=O)C=C1 HUWDAIDFJPVODH-UHFFFAOYSA-N 0.000 description 1
- NYPIRLYMDJMKGW-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one Chemical compound C[C@@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 NYPIRLYMDJMKGW-VPCXQMTMSA-N 0.000 description 1
- CMUHFUGDYMFHEI-QMMMGPOBSA-N 4-amino-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N)C=C1 CMUHFUGDYMFHEI-QMMMGPOBSA-N 0.000 description 1
- VTCHZFWYUPZZKL-UHFFFAOYSA-N 4-azaniumylcyclopent-2-ene-1-carboxylate Chemical compound NC1CC(C(O)=O)C=C1 VTCHZFWYUPZZKL-UHFFFAOYSA-N 0.000 description 1
- 125000002672 4-bromobenzoyl group Chemical group BrC1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- XWHHYOYVRVGJJY-QMMMGPOBSA-N 4-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-QMMMGPOBSA-N 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- GTVVZTAFGPQSPC-UHFFFAOYSA-N 4-nitrophenylalanine Chemical compound OC(=O)C(N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-UHFFFAOYSA-N 0.000 description 1
- XDOLZJYETYVRKV-UHFFFAOYSA-N 7-Aminoheptanoic acid Chemical compound NCCCCCCC(O)=O XDOLZJYETYVRKV-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 101000716807 Arabidopsis thaliana Protein SCO1 homolog 1, mitochondrial Proteins 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 101100431855 Bacillus subtilis (strain 168) yclH gene Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000776207 Bornaviridae Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101100205313 Caenorhabditis elegans nars-1 gene Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 241000122205 Chamaeleonidae Species 0.000 description 1
- 102100041023 Coronin-2A Human genes 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- WLTCKEHCTUYJGI-UHFFFAOYSA-N Diethyl aminomalonate Chemical compound CCOC(=O)C(N)C(=O)OCC WLTCKEHCTUYJGI-UHFFFAOYSA-N 0.000 description 1
- 102000004073 Dopamine D3 Receptors Human genes 0.000 description 1
- 108090000525 Dopamine D3 Receptors Proteins 0.000 description 1
- 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 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- NIGWMJHCCYYCSF-UHFFFAOYSA-N Fenclonine Chemical compound OC(=O)C(N)CC1=CC=C(Cl)C=C1 NIGWMJHCCYYCSF-UHFFFAOYSA-N 0.000 description 1
- 102000020897 Formins Human genes 0.000 description 1
- 108091022623 Formins Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 101000748858 Homo sapiens Coronin-2A Proteins 0.000 description 1
- 101001076715 Homo sapiens RNA-binding protein 39 Proteins 0.000 description 1
- 101000764872 Homo sapiens Transient receptor potential cation channel subfamily A member 1 Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 229930188970 Justin Natural products 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
- JTTHKOPSMAVJFE-VIFPVBQESA-N L-homophenylalanine Chemical compound OC(=O)[C@@H](N)CCC1=CC=CC=C1 JTTHKOPSMAVJFE-VIFPVBQESA-N 0.000 description 1
- JZKXXXDKRQWDET-QMMMGPOBSA-N L-m-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(O)=C1 JZKXXXDKRQWDET-QMMMGPOBSA-N 0.000 description 1
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
- DGYHPLMPMRKMPD-UHFFFAOYSA-N L-propargyl glycine Natural products OC(=O)C(N)CC#C DGYHPLMPMRKMPD-UHFFFAOYSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 101100440246 Mus musculus Ncaph gene Proteins 0.000 description 1
- 241000238367 Mya arenaria Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- NPKISZUVEBESJI-AWEZNQCLSA-N N-benzoyl-L-phenylalanine Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=CC=CC=1)C1=CC=CC=C1 NPKISZUVEBESJI-AWEZNQCLSA-N 0.000 description 1
- VPTRWECDZZUXIF-UHFFFAOYSA-N N1=NNC2=CC=NC2=C1N Chemical class N1=NNC2=CC=NC2=C1N VPTRWECDZZUXIF-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 229910019093 NaOCl Inorganic materials 0.000 description 1
- NPKISZUVEBESJI-UHFFFAOYSA-N Nalpha-benzoyl-L-phenylalanine Natural products C=1C=CC=CC=1C(=O)NC(C(=O)O)CC1=CC=CC=C1 NPKISZUVEBESJI-UHFFFAOYSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- GEYBMYRBIABFTA-UHFFFAOYSA-N O-methyltyrosine Chemical compound COC1=CC=C(CC(N)C(O)=O)C=C1 GEYBMYRBIABFTA-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 235000014676 Phragmites communis Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CNILNQMBAHKMFS-UHFFFAOYSA-M Pyrithiobac-sodium Chemical compound [Na+].COC1=CC(OC)=NC(SC=2C(=C(Cl)C=CC=2)C([O-])=O)=N1 CNILNQMBAHKMFS-UHFFFAOYSA-M 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100026634 Rattus norvegicus Nos1 gene Proteins 0.000 description 1
- 241000702247 Reoviridae Species 0.000 description 1
- 241000711931 Rhabdoviridae 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
- 102100023361 SAP domain-containing ribonucleoprotein Human genes 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 229910018162 SeO2 Inorganic materials 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102100026186 Transient receptor potential cation channel subfamily A member 1 Human genes 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 229940122423 Viral RNA polymerase inhibitor Drugs 0.000 description 1
- 108700002693 Viral Replicase Complex Proteins Proteins 0.000 description 1
- IEOBLYIISRDDST-GRYCIOLGSA-N [(3ar,4s,6as)-2,2-dimethyl-5-oxido-4,6a-dihydro-3ah-[1,3]dioxolo[4,5-c]pyrrol-5-ium-4-yl]methyl-tert-butyl-dimethylsilane Chemical compound O1C(C)(C)O[C@H]2C=[N+]([O-])[C@H](C[Si](C)(C)C(C)(C)C)[C@H]21 IEOBLYIISRDDST-GRYCIOLGSA-N 0.000 description 1
- GLYOPNLBKCBTMI-UHFFFAOYSA-N [2-chloro-2-(1-chloro-2-phenylethoxy)ethyl]benzene Chemical compound C=1C=CC=CC=1CC(Cl)OC(Cl)CC1=CC=CC=C1 GLYOPNLBKCBTMI-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 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 1
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001295 alanines Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000006307 alkoxy benzyl group Chemical group 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 description 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
- 239000011717 all-trans-retinol Substances 0.000 description 1
- 235000019169 all-trans-retinol Nutrition 0.000 description 1
- WNNNWFKQCKFSDK-UHFFFAOYSA-N allylglycine Chemical compound OC(=O)C(N)CC=C WNNNWFKQCKFSDK-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- WTOFYLAWDLQMBZ-LURJTMIESA-N beta(2-thienyl)alanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CS1 WTOFYLAWDLQMBZ-LURJTMIESA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000001721 carboxyacetyl group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- DDYAZDRFUVZBMM-UHFFFAOYSA-N chloro-[chloro-di(propan-2-yl)silyl]oxy-di(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)O[Si](Cl)(C(C)C)C(C)C DDYAZDRFUVZBMM-UHFFFAOYSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125872 compound 4d Drugs 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- GCFAUZGWPDYAJN-UHFFFAOYSA-N cyclohexyl 3-phenylprop-2-enoate Chemical compound C=1C=CC=CC=1C=CC(=O)OC1CCCCC1 GCFAUZGWPDYAJN-UHFFFAOYSA-N 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000002308 endothelin receptor antagonist Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000005908 glyceryl ester group Chemical group 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- FODONWGPMXPGNC-UHFFFAOYSA-N gtpl6346 Chemical compound C1=CC(Cl)=CC=C1N1C(=O)C(SC=2C3=C4NCCOC4=CN=2)=C3N=C1 FODONWGPMXPGNC-UHFFFAOYSA-N 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 238000005669 hydrocyanation reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
- 201000005264 laryngeal carcinoma Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000011981 lindlar catalyst Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- VWHRYODZTDMVSS-QMMMGPOBSA-N m-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(F)=C1 VWHRYODZTDMVSS-QMMMGPOBSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- JZKXXXDKRQWDET-UHFFFAOYSA-N meta-tyrosine Natural products OC(=O)C(N)CC1=CC=CC(O)=C1 JZKXXXDKRQWDET-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 229940073584 methylene chloride Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- HXRAMSFGUAOAJR-UHFFFAOYSA-N n,n,n',n'-tetramethyl-1-[(2-methylpropan-2-yl)oxy]methanediamine Chemical compound CN(C)C(N(C)C)OC(C)(C)C HXRAMSFGUAOAJR-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
- 125000003367 polycyclic group Polymers 0.000 description 1
- 208000030761 polycystic kidney disease Diseases 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- KGRPHHFLPMPUBB-UHFFFAOYSA-N pyrrolo[2,1-f][1,2,4]triazine Chemical compound C1=NC=NN2C=CC=C21 KGRPHHFLPMPUBB-UHFFFAOYSA-N 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 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
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 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
- 239000012363 selectfluor Substances 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261727468P | 2012-11-16 | 2012-11-16 | |
| US61/727,468 | 2012-11-16 | ||
| PCT/US2013/070537 WO2014078778A2 (en) | 2012-11-16 | 2013-11-18 | Antiviral azasugar-containing nucleosides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2890905A1 true CA2890905A1 (en) | 2014-05-22 |
Family
ID=50731836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2890905A Abandoned CA2890905A1 (en) | 2012-11-16 | 2013-11-18 | Antiviral azasugar-containing nucleosides |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US20150291596A1 (enExample) |
| EP (2) | EP3251674A3 (enExample) |
| JP (1) | JP2016504284A (enExample) |
| AU (1) | AU2013344422A1 (enExample) |
| CA (1) | CA2890905A1 (enExample) |
| HK (1) | HK1212235A1 (enExample) |
| IL (1) | IL238785A0 (enExample) |
| MX (1) | MX2015005949A (enExample) |
| WO (1) | WO2014078778A2 (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20130862T1 (hr) | 2009-09-21 | 2013-10-25 | Gilead Sciences, Inc. | Procesi i intermedijeri za pripravu analoga 1'-cijanokarbanukleozida |
| UA111163C2 (uk) | 2010-07-22 | 2016-04-11 | Гайлід Сайєнсіз, Інк. | Способи й сполуки для лікування вірусних інфекцій paramyxoviridae |
| TWI767201B (zh) | 2014-10-29 | 2022-06-11 | 美商基利科學股份有限公司 | 絲狀病毒科病毒感染之治療 |
| AU2016216673B2 (en) | 2015-03-04 | 2017-02-02 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| MA52371A (fr) * | 2015-09-16 | 2021-09-22 | Gilead Sciences Inc | Méthodes de traitement d'infections dues aux coronaviridae |
| TW201725203A (zh) | 2015-12-16 | 2017-07-16 | 必治妥美雅史谷比公司 | 作為ａｐｊ受體促效劑之雜芳基羥基嘧啶酮 |
| WO2017172596A1 (en) | 2016-03-28 | 2017-10-05 | Incyte Corporation | Pyrrolotriazine compounds as tam inhibitors |
| US10640499B2 (en) | 2016-09-02 | 2020-05-05 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| AU2017318601B2 (en) | 2016-09-02 | 2020-09-03 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| CA3056072C (en) | 2017-03-14 | 2022-08-23 | Gilead Sciences, Inc. | Methods of treating feline coronavirus infections |
| CN106834546A (zh) * | 2017-03-20 | 2017-06-13 | 杭州迪安医学检验中心有限公司 | 一种基于熔解曲线法单管同时检测多种呼吸道病毒的引物及其应用 |
| JP2020518578A (ja) | 2017-05-01 | 2020-06-25 | ギリアード サイエンシーズ， インコーポレイテッド | （Ｓ）−２−エチルブチル２−（（（Ｓ）−（（（２Ｒ，３Ｓ，４Ｒ，５Ｒ）−５−（４−アミノピロロ［２，１−ｆ］［１，２，４］トリアジン−７−イル）−５−シアノ−３，４−ジヒドロキシテトラヒドロフラン−２−イル）メトキシ）（フェノキシ）ホスホリル）アミノ）プロパノエートの結晶形態 |
| ES3000461T3 (en) | 2017-07-11 | 2025-02-28 | Gilead Sciences Inc | Compositions comprising an rna polymerase inhibitor and cyclodextrin for treating viral infections |
| CN109053788A (zh) * | 2018-09-20 | 2018-12-21 | 山东谛爱生物技术有限公司 | 一种吡唑类化合物的制备方法 |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI751516B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI879779B (zh) | 2019-06-28 | 2025-04-11 | 美商基利科學股份有限公司 | 類鐸受體調節劑化合物的製備方法 |
| JP2023512656A (ja) | 2020-01-27 | 2023-03-28 | ギリアード サイエンシーズ， インコーポレイテッド | ＳＡＲＳ ＣｏＶ－２感染を治療するための方法 |
| TWI890963B (zh) | 2020-03-12 | 2025-07-21 | 美商基利科學股份有限公司 | 1'-氰基核苷之製備方法 |
| AU2021251689B2 (en) | 2020-04-06 | 2024-06-13 | Gilead Sciences, Inc. | Inhalation formulations of 1'-cyano substituted carbanucleoside analogs |
| TW202532084A (zh) | 2020-05-29 | 2025-08-16 | 美商基利科學股份有限公司 | 瑞德西韋之治療方法 |
| IL299202A (en) | 2020-06-24 | 2023-02-01 | Gilead Sciences Inc | 1'-cyano nucleoside analogs and uses thereof |
| CN111704619B (zh) * | 2020-07-30 | 2021-10-19 | 四川大学 | 一种Forodesine的制备方法 |
| PE20231983A1 (es) | 2020-08-27 | 2023-12-12 | Gilead Sciences Inc | Compuestos y metodos para el tratamiento de infecciones virales |
| US12274700B1 (en) | 2020-10-30 | 2025-04-15 | Accencio LLC | Methods of treating symptoms of coronavirus infection with RNA polymerase inhibitors |
| CN114588159A (zh) * | 2020-12-07 | 2022-06-07 | 成都傲科新技术有限责任公司 | 一种治疗猫冠状病毒感染的化合物及其应用 |
| JPWO2022270628A1 (enExample) * | 2021-06-25 | 2022-12-29 | ||
| PE20240654A1 (es) * | 2021-08-20 | 2024-04-04 | Shionogi & Co | Derivados de nucleosido y profarmacos de los mismos que tienen accion inhibidora del crecimiento viral |
| CN113666941B (zh) * | 2021-09-01 | 2023-03-10 | 浙江珲达生物科技有限公司 | 一种2,3-O-异亚丙基-D-核糖酸-γ-内酯的重结晶方法 |
| CA3244278A1 (en) | 2022-03-02 | 2023-09-07 | Gilead Sciences Inc | COMPOUNDS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS |
| US12357577B1 (en) | 2024-02-02 | 2025-07-15 | Gilead Sciences, Inc. | Pharmaceutical formulations and uses thereof |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3719667A (en) | 1970-08-24 | 1973-03-06 | Lilly Co Eli | Epimerization of 6-acylamido and 6-imido penicillin sulfoxide esters |
| US3840556A (en) | 1971-05-28 | 1974-10-08 | Lilly Co Eli | Penicillin conversion by halogen electrophiles and anti-bacterials derived thereby |
| US4559157A (en) | 1983-04-21 | 1985-12-17 | Creative Products Resource Associates, Ltd. | Cosmetic applicator useful for skin moisturizing |
| LU84979A1 (fr) | 1983-08-30 | 1985-04-24 | Oreal | Composition cosmetique ou pharmaceutique sous forme aqueuse ou anhydre dont la phase grasse contient un polyether oligomere et polyethers oligomeres nouveaux |
| US4820508A (en) | 1987-06-23 | 1989-04-11 | Neutrogena Corporation | Skin protective composition |
| US4992478A (en) | 1988-04-04 | 1991-02-12 | Warner-Lambert Company | Antiinflammatory skin moisturizing composition and method of preparing same |
| US4938949A (en) | 1988-09-12 | 1990-07-03 | University Of New York | Treatment of damaged bone marrow and dosage units therefor |
| EP0630904A4 (en) * | 1992-08-26 | 1995-01-04 | Japan Tobacco Inc. | Novel nicotine derivative. |
| US7098334B2 (en) * | 2002-03-25 | 2006-08-29 | Industrial Research Limited | 4-amino-5H-pyrrolo[3,2-d]pyrimidine inhibitors of nucleoside phosphorylases and nucleosidases |
| AU2003233667A1 (en) * | 2002-05-23 | 2003-12-12 | Biocryst Pharmaceuticals, Inc. | Enhancing the efficacy of reverse transcriptase and dna polymerase inhibitors (nucleoside analogs) using pnp inhibitors and/or 2'-deoxyguanosine and/or prodrug thereof |
| EP1544294B8 (en) * | 2002-07-17 | 2014-03-19 | Riken | Nucleosides or nucleotides having novel unnatural bases and use thereof |
| WO2004050676A1 (ja) | 2002-12-04 | 2004-06-17 | Mitsubishi Gas Chemical Company, Inc. | フッ素化方法 |
| US6780993B1 (en) * | 2003-02-19 | 2004-08-24 | Biocryst Pharmaceuticals, Inc. | Preparation of deazaguanine analog |
| MY139887A (en) | 2004-04-02 | 2009-11-30 | Mitsubishi Tanabe Pharma Corp | Tetrahydronaphthyridine derivatives and a process for preparing the same. |
| US7560434B2 (en) * | 2004-06-22 | 2009-07-14 | Biocryst Pharmaceuticals, Inc. | AZA nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases |
| KR20070100237A (ko) * | 2004-10-29 | 2007-10-10 | 바이오크리스트 파마수티컬즈, 인코퍼레이티드 | 치료용 푸로피리미딘 및 티에노피리미딘 |
| DK1891038T3 (da) * | 2005-05-13 | 2009-01-19 | Lilly Co Eli | Substituerede n-arylpyrrolidiner som selektive androgenreceptormodulatorer |
| CA2618335C (en) * | 2005-08-15 | 2015-03-31 | F.Hoffmann-La Roche Ag | Antiviral phosphoramidates of 4'-substituted pronucleotides |
| EP1951244A4 (en) * | 2005-11-22 | 2010-08-25 | Glaxosmithkline Llc | CALCILYTIC COMPOUNDS |
| MX2008007103A (es) | 2005-12-02 | 2008-09-12 | Bayer Healthcare Llc | Derivados 4-amino-pirrolotriazina sustituidos, útiles para tratar trastornos hiperproliferativos y enfermedades asociadas con angiogenesis. |
| US7829584B2 (en) | 2006-03-21 | 2010-11-09 | Janssen Pharmaceutica Nv | Pyridines and pyridine N-oxides as modulators of thrombin |
| US8030322B2 (en) | 2006-04-27 | 2011-10-04 | Glaxo Group Limited | Spirocompounds useful as modulators for dopamine D3 receptors |
| SG177974A1 (en) * | 2007-01-12 | 2012-02-28 | Biocryst Pharm Inc | Antiviral nucleoside analogs |
| CA2685520A1 (en) * | 2007-05-10 | 2008-11-20 | Biocryst Pharmaceuticals, Inc. | Tetrahydrofuro [3 4-d] dioxolane compounds for use in the treatment of viral infections and cancer |
| EP2313102A2 (en) * | 2008-07-03 | 2011-04-27 | Biota Scientific Management | Bycyclic nucleosides and nucleotides as therapeutic agents |
| EP2348854A4 (en) * | 2008-09-22 | 2012-03-14 | Einstein Coll Med | METHOD AND COMPOSITIONS FOR THE TREATMENT OF BACTERIAL INFECTIONS BY INHIBITING THE "QUORUM SENSING |
| WO2011094450A1 (en) | 2010-01-27 | 2011-08-04 | Anacor Pharmaceuticals, Inc | Boron-containing small molecules |
| WO2011132017A1 (en) | 2010-04-19 | 2011-10-27 | Glenmark Pharmaceuticals S.A. | Pyrido[3,4-d]pyrimidinyl acetamide derivatives as trpa1 modulators |
| EP2627334B1 (en) * | 2010-10-15 | 2015-04-29 | Biocryst Pharmaceuticals, Inc. | Compositions for use in the treatment of viral infections |
| AR090699A1 (es) * | 2012-04-18 | 2014-12-03 | Biocryst Pharm Inc | Compuestos inhibidores de la actividad de la arn polimerasa viral |
-
2013
- 2013-11-18 EP EP17162146.9A patent/EP3251674A3/en not_active Withdrawn
- 2013-11-18 AU AU2013344422A patent/AU2013344422A1/en not_active Abandoned
- 2013-11-18 EP EP13855441.5A patent/EP2919785A4/en not_active Withdrawn
- 2013-11-18 JP JP2015542870A patent/JP2016504284A/ja active Pending
- 2013-11-18 CA CA2890905A patent/CA2890905A1/en not_active Abandoned
- 2013-11-18 HK HK16100301.6A patent/HK1212235A1/xx unknown
- 2013-11-18 MX MX2015005949A patent/MX2015005949A/es unknown
- 2013-11-18 WO PCT/US2013/070537 patent/WO2014078778A2/en not_active Ceased
- 2013-11-18 US US14/441,762 patent/US20150291596A1/en not_active Abandoned
-
2015
- 2015-05-13 IL IL238785A patent/IL238785A0/en unknown
-
2017
- 2017-03-31 US US15/475,507 patent/US20170267681A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2013344422A1 (en) | 2015-07-02 |
| WO2014078778A2 (en) | 2014-05-22 |
| US20170267681A1 (en) | 2017-09-21 |
| WO2014078778A3 (en) | 2014-10-09 |
| US20150291596A1 (en) | 2015-10-15 |
| JP2016504284A (ja) | 2016-02-12 |
| EP2919785A2 (en) | 2015-09-23 |
| EP2919785A4 (en) | 2016-10-05 |
| EP3251674A2 (en) | 2017-12-06 |
| HK1212235A1 (en) | 2016-06-10 |
| EP3251674A3 (en) | 2018-02-21 |
| IL238785A0 (en) | 2015-06-30 |
| MX2015005949A (es) | 2015-09-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2890905A1 (en) | Antiviral azasugar-containing nucleosides | |
| CA2870722C (en) | Compositions and methods for inhibiting viral polymerase | |
| CA2788155C (en) | Polyheterocyclic compounds highly potent as hcv inhibitors | |
| RU2640582C2 (ru) | Производные витамина в6 нуклеотидов, ациклических нуклеотидов и ациклических нуклеозидных фосфонатов | |
| TR201906416T4 (tr) | Hiv inhibitörü bileşiklerin fosfonat analogları. | |
| JP2017530118A (ja) | ヌクレオチド類似体 | |
| PT1628685E (pt) | Análogos de fosfonatos antivirais | |
| KR20240121760A (ko) | Pd-l1을 표적화하기 위한 방법 및 조성물 | |
| ES2962774T3 (es) | Inhibidores de la replicación de virus de inmunodeficiencia humana | |
| CA3091950A1 (en) | 7-substituted sulfonimidoylpurinone compounds and derivatives for the treatment and prophylaxis of liver cancer | |
| EA036892B1 (ru) | Макрогетероциклические нуклеозидные производные и их аналоги, получение и применение | |
| ES2218216T3 (es) | Analogos de nucleosidos de dioxolano para el tratamiento o la prevencion de infecciones viricas. | |
| ES2357770T3 (es) | Análogos de fosfonatos antivirales. | |
| WO2025199273A1 (en) | Methods and compositions for targeting pd-l1 | |
| HK1206627B (en) | Compositions and methods for inhibiting viral polymerase |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20191119 |