UA125407C2 - Заміщені похідні індоліну як інгібітори реплікації вірусів денге - Google Patents
Заміщені похідні індоліну як інгібітори реплікації вірусів денге Download PDFInfo
- Publication number
- UA125407C2 UA125407C2 UAA201912024A UAA201912024A UA125407C2 UA 125407 C2 UA125407 C2 UA 125407C2 UA A201912024 A UAA201912024 A UA A201912024A UA A201912024 A UAA201912024 A UA A201912024A UA 125407 C2 UA125407 C2 UA 125407C2
- Authority
- UA
- Ukraine
- Prior art keywords
- ome
- compound
- mmol
- chiral
- mixture
- Prior art date
Links
- 241000725619 Dengue virus Species 0.000 title description 25
- 239000003112 inhibitor Substances 0.000 title description 4
- 230000029812 viral genome replication Effects 0.000 title description 4
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical class C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 310
- 206010012310 Dengue fever Diseases 0.000 claims abstract description 30
- 208000025729 dengue disease Diseases 0.000 claims abstract description 26
- 208000001490 Dengue Diseases 0.000 claims abstract description 21
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 230000002265 prevention Effects 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 172
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 64
- 239000002904 solvent Substances 0.000 claims description 51
- 241000700605 Viruses Species 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 241000396377 Tranes Species 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 229940126601 medicinal product Drugs 0.000 claims description 5
- 239000003443 antiviral agent Substances 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 218
- 238000000034 method Methods 0.000 abstract description 215
- 238000002360 preparation method Methods 0.000 abstract description 15
- 239000003814 drug Substances 0.000 abstract description 8
- 208000036142 Viral infection Diseases 0.000 abstract description 7
- 230000009385 viral infection Effects 0.000 abstract description 7
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 180
- 238000003786 synthesis reaction Methods 0.000 description 180
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 164
- 239000000243 solution Substances 0.000 description 114
- 238000000926 separation method Methods 0.000 description 101
- 238000005481 NMR spectroscopy Methods 0.000 description 85
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 84
- 239000000741 silica gel Substances 0.000 description 78
- 229910002027 silica gel Inorganic materials 0.000 description 78
- 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 74
- 239000012044 organic layer Substances 0.000 description 74
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 65
- 238000003818 flash chromatography Methods 0.000 description 63
- 239000012071 phase Substances 0.000 description 59
- 239000000047 product Substances 0.000 description 55
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 52
- 230000005526 G1 to G0 transition Effects 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 37
- -1 indoline derivative compounds Chemical class 0.000 description 35
- 238000000746 purification Methods 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 29
- 238000007711 solidification Methods 0.000 description 27
- 230000008023 solidification Effects 0.000 description 27
- 239000002253 acid Substances 0.000 description 26
- TXWOGHSRPAYOML-UHFFFAOYSA-M cyclobutanecarboxylate Chemical compound [O-]C(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-M 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 239000003054 catalyst Substances 0.000 description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- 230000003287 optical effect Effects 0.000 description 19
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 18
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 18
- 239000012298 atmosphere Substances 0.000 description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 150000004682 monohydrates Chemical class 0.000 description 17
- YETHUNXROLCEGJ-UHFFFAOYSA-N 3-methoxy-5-nitrophenol Chemical compound COC1=CC(O)=CC([N+]([O-])=O)=C1 YETHUNXROLCEGJ-UHFFFAOYSA-N 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- YMGUBTXCNDTFJI-UHFFFAOYSA-M cyclopropanecarboxylate Chemical compound [O-]C(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-M 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 230000014759 maintenance of location Effects 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 230000000840 anti-viral effect Effects 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 208000009714 Severe Dengue Diseases 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- 239000012065 filter cake Substances 0.000 description 7
- 238000004108 freeze drying Methods 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 6
- 229910004373 HOAc Inorganic materials 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000011877 solvent mixture Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 6
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 5
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 5
- 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 5
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 5
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 5
- ILTCFIIXWWUIPC-UHFFFAOYSA-N 3-amino-5-methoxyphenol Chemical compound COC1=CC(N)=CC(O)=C1 ILTCFIIXWWUIPC-UHFFFAOYSA-N 0.000 description 5
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 5
- 241000283725 Bos Species 0.000 description 5
- 229940126657 Compound 17 Drugs 0.000 description 5
- 241000255925 Diptera Species 0.000 description 5
- 101100301524 Drosophila melanogaster Reg-5 gene Proteins 0.000 description 5
- 241000710831 Flavivirus Species 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 229940126543 compound 14 Drugs 0.000 description 5
- 229940126142 compound 16 Drugs 0.000 description 5
- 229940125846 compound 25 Drugs 0.000 description 5
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 5
- 238000004925 denaturation Methods 0.000 description 5
- 230000036425 denaturation Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 150000002476 indolines Chemical class 0.000 description 5
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 235000019260 propionic acid Nutrition 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical compound CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 5
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 4
- MEQKSFQEPDRNEQ-UHFFFAOYSA-N 1-bromo-3-methoxy-5-nitrobenzene Chemical compound COC1=CC(Br)=CC([N+]([O-])=O)=C1 MEQKSFQEPDRNEQ-UHFFFAOYSA-N 0.000 description 4
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 4
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 4
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 4
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 229940125797 compound 12 Drugs 0.000 description 4
- 229940125758 compound 15 Drugs 0.000 description 4
- 229940125782 compound 2 Drugs 0.000 description 4
- 229940126086 compound 21 Drugs 0.000 description 4
- 229940125961 compound 24 Drugs 0.000 description 4
- 229940125898 compound 5 Drugs 0.000 description 4
- 201000002950 dengue hemorrhagic fever Diseases 0.000 description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- RUTOXMJIOZUHCR-UHFFFAOYSA-N methyl 4-(3-amino-5-methoxyphenoxy)-2,2-dimethylbutanoate Chemical compound NC=1C=C(OCCC(C(=O)OC)(C)C)C=C(C=1)OC RUTOXMJIOZUHCR-UHFFFAOYSA-N 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 230000006340 racemization Effects 0.000 description 4
- 238000010839 reverse transcription Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000013049 sediment Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 4
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 3
- UVNPEUJXKZFWSJ-LMTQTHQJSA-N (R)-N-[(4S)-8-[6-amino-5-[(3,3-difluoro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfanyl]pyrazin-2-yl]-2-oxa-8-azaspiro[4.5]decan-4-yl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@@H]1COCC11CCN(CC1)c1cnc(Sc2ccnc3NC(=O)C(F)(F)c23)c(N)n1 UVNPEUJXKZFWSJ-LMTQTHQJSA-N 0.000 description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 3
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 3
- OCABOAQENCPTSP-UHFFFAOYSA-N 5-fluoro-6-(trifluoromethoxy)-1H-indole Chemical compound FC=1C=C2C=CNC2=CC=1OC(F)(F)F OCABOAQENCPTSP-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 3
- 229940126639 Compound 33 Drugs 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000013592 cell lysate Substances 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 229940125810 compound 20 Drugs 0.000 description 3
- 229940125833 compound 23 Drugs 0.000 description 3
- 229940125851 compound 27 Drugs 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 229940125877 compound 31 Drugs 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 235000012907 honey Nutrition 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- VZYIYXOUATXYPL-UHFFFAOYSA-N tert-butyl 4-(3-amino-5-methoxyphenoxy)-2-methylbutanoate Chemical compound C(OC(=O)C(CCOC1=CC(=CC(N)=C1)OC)C)(C)(C)C VZYIYXOUATXYPL-UHFFFAOYSA-N 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 2
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 2
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 2
- WYRHXNFJTIEBOG-NSCUHMNNSA-N (E)-3-(3-methoxy-5-nitrophenyl)prop-2-en-1-ol Chemical compound COC=1C=C(C=C(C=1)[N+](=O)[O-])/C=C/CO WYRHXNFJTIEBOG-NSCUHMNNSA-N 0.000 description 2
- KGFADEJSZXEVMC-UHFFFAOYSA-N 1-methoxy-4-nitro-2-(trifluoromethyl)benzene Chemical compound COC1=CC=C([N+]([O-])=O)C=C1C(F)(F)F KGFADEJSZXEVMC-UHFFFAOYSA-N 0.000 description 2
- GZLKNDMDIICBFQ-UHFFFAOYSA-N 2-(4-chloro-2-methoxyphenyl)-1-[6-(trifluoromethoxy)-2,3-dihydroindol-1-yl]ethanone Chemical compound ClC1=CC(=C(C=C1)CC(=O)N1CCC2=CC=C(C=C12)OC(F)(F)F)OC GZLKNDMDIICBFQ-UHFFFAOYSA-N 0.000 description 2
- UXJIWCMQVOEXTG-UHFFFAOYSA-N 2-(4-chloro-2-methoxyphenyl)acetic acid Chemical compound COC1=CC(Cl)=CC=C1CC(O)=O UXJIWCMQVOEXTG-UHFFFAOYSA-N 0.000 description 2
- UHKXVRXZHGGOGP-UHFFFAOYSA-N 2-bromo-2-(4-chlorophenyl)-1-[6-(trifluoromethoxy)-2,3-dihydroindol-1-yl]ethanone Chemical compound BrC(C(=O)N1CCC2=CC=C(C=C12)OC(F)(F)F)C1=CC=C(C=C1)Cl UHKXVRXZHGGOGP-UHFFFAOYSA-N 0.000 description 2
- KKOAAWLOOHBFQP-UHFFFAOYSA-N 2-bromo-2-(4-chlorophenyl)acetic acid Chemical compound OC(=O)C(Br)C1=CC=C(Cl)C=C1 KKOAAWLOOHBFQP-UHFFFAOYSA-N 0.000 description 2
- NNYYXTHPUFLAOQ-UHFFFAOYSA-N 2-bromo-4-fluoro-5-(trifluoromethoxy)aniline Chemical compound BrC1=C(N)C=C(C(=C1)F)OC(F)(F)F NNYYXTHPUFLAOQ-UHFFFAOYSA-N 0.000 description 2
- BGWUXZLHDLNYHW-UHFFFAOYSA-N 3-methoxy-5-nitroaniline Chemical compound COC1=CC(N)=CC([N+]([O-])=O)=C1 BGWUXZLHDLNYHW-UHFFFAOYSA-N 0.000 description 2
- SBSFDYRKNUCGBZ-UHFFFAOYSA-N 4-bromo-2-fluoro-1-(trifluoromethoxy)benzene Chemical compound FC1=CC(Br)=CC=C1OC(F)(F)F SBSFDYRKNUCGBZ-UHFFFAOYSA-N 0.000 description 2
- CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 2
- MCNQUWLLXZZZAC-UHFFFAOYSA-N 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C#N)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MCNQUWLLXZZZAC-UHFFFAOYSA-N 0.000 description 2
- KNMAZUXTEPXPOM-UHFFFAOYSA-N 5-methoxy-6-(trifluoromethyl)-1h-indole Chemical compound C1=C(C(F)(F)F)C(OC)=CC2=C1NC=C2 KNMAZUXTEPXPOM-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- 241000256111 Aedes <genus> Species 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- PJHUUSIPDVULCT-UHFFFAOYSA-N BrC1=C(C=C(C(=C1)F)OC(F)(F)F)[N+](=O)[O-] Chemical compound BrC1=C(C=C(C(=C1)F)OC(F)(F)F)[N+](=O)[O-] PJHUUSIPDVULCT-UHFFFAOYSA-N 0.000 description 2
- 101100074836 Caenorhabditis elegans lin-22 gene Proteins 0.000 description 2
- 231100000491 EC50 Toxicity 0.000 description 2
- 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 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 2
- 241000077989 Hiradonta chi Species 0.000 description 2
- 244000308605 Irvingia smithii Species 0.000 description 2
- 235000002222 Irvingia smithii Nutrition 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010049771 Shock haemorrhagic Diseases 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 241000838698 Togo Species 0.000 description 2
- NOZCSQJFRSSGBP-UHFFFAOYSA-N [3-(dibenzylamino)-5-methoxyphenyl]methanol Chemical compound C(C1=CC=CC=C1)N(C=1C=C(C=C(C=1)OC)CO)CC1=CC=CC=C1 NOZCSQJFRSSGBP-UHFFFAOYSA-N 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 235000013405 beer Nutrition 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000013480 data collection Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
- MDWXTLNIZCHBJE-UHFFFAOYSA-N ethyl 2-formylcyclopropane-1-carboxylate Chemical compound CCOC(=O)C1CC1C=O MDWXTLNIZCHBJE-UHFFFAOYSA-N 0.000 description 2
- MIBSJZIXDXHQTL-UHFFFAOYSA-N ethyl 3-(3-methoxy-5-nitroanilino)cyclobutane-1-carboxylate Chemical compound COC=1C=C(C=C(C=1)[N+](=O)[O-])NC1CC(C1)C(=O)OCC MIBSJZIXDXHQTL-UHFFFAOYSA-N 0.000 description 2
- NETFSWBEMWQYFS-UHFFFAOYSA-N ethyl 3-(3-methoxy-5-nitrophenoxy)prop-2-enoate Chemical compound COC=1C=C(OC=CC(=O)OCC)C=C(C=1)[N+](=O)[O-] NETFSWBEMWQYFS-UHFFFAOYSA-N 0.000 description 2
- UUBYKQPQLBLTKH-UHFFFAOYSA-N ethyl 3-(4-methylphenyl)sulfonyloxycyclobutane-1-carboxylate Chemical compound C1C(C(=O)OCC)CC1OS(=O)(=O)C1=CC=C(C)C=C1 UUBYKQPQLBLTKH-UHFFFAOYSA-N 0.000 description 2
- SWIAMQXNLZLKSS-UHFFFAOYSA-N ethyl 3-[[3-(dibenzylamino)-5-methoxyphenyl]methoxy]propanoate Chemical compound C(C1=CC=CC=C1)N(C=1C=C(COCCC(=O)OCC)C=C(C=1)OC)CC1=CC=CC=C1 SWIAMQXNLZLKSS-UHFFFAOYSA-N 0.000 description 2
- KTVUZBJHOAPDGC-UHFFFAOYSA-N ethyl 3-hydroxycyclobutane-1-carboxylate Chemical compound CCOC(=O)C1CC(O)C1 KTVUZBJHOAPDGC-UHFFFAOYSA-N 0.000 description 2
- BXBRFSMPBOTZHJ-UHFFFAOYSA-N ethyl 3-oxocyclobutane-1-carboxylate Chemical compound CCOC(=O)C1CC(=O)C1 BXBRFSMPBOTZHJ-UHFFFAOYSA-N 0.000 description 2
- JGDVUJFJIFRNAX-UHFFFAOYSA-N ethyl 4-(3-amino-5-methoxyphenyl)butanoate Chemical compound NC=1C=C(C=C(C=1)OC)CCCC(=O)OCC JGDVUJFJIFRNAX-UHFFFAOYSA-N 0.000 description 2
- VUAMJAQNWQKOTC-UHFFFAOYSA-N ethyl 4-bromo-3-methylbutanoate Chemical compound CCOC(=O)CC(C)CBr VUAMJAQNWQKOTC-UHFFFAOYSA-N 0.000 description 2
- INKYXXACWOULNY-UHFFFAOYSA-N ethyl 5-(3-amino-5-methoxyphenyl)pentanoate Chemical compound NC=1C=C(C=C(C=1)OC)CCCCC(=O)OCC INKYXXACWOULNY-UHFFFAOYSA-N 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- JZANUKXGHGFYJI-ONEGZZNKSA-N methyl (E)-3-(3-methoxy-5-nitrophenyl)prop-2-enoate Chemical compound C(=C\C(=O)OC)/C1=CC(N(=O)=O)=CC(OC)=C1 JZANUKXGHGFYJI-ONEGZZNKSA-N 0.000 description 2
- APNITNSHOZKCGV-UHFFFAOYSA-N methyl 1-[2-(3-amino-5-methoxyphenoxy)ethyl]cyclopropane-1-carboxylate Chemical compound NC=1C=C(OCCC2(CC2)C(=O)OC)C=C(C=1)OC APNITNSHOZKCGV-UHFFFAOYSA-N 0.000 description 2
- RAVVJKCSZXAIQP-UHFFFAOYSA-N methyl 5-bromopentanoate Chemical compound COC(=O)CCCCBr RAVVJKCSZXAIQP-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 239000002245 particle Substances 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
- 238000001556 precipitation Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- ANVAROJPEJVBHI-UHFFFAOYSA-N tert-butyl 4-bromo-2-methylbutanoate Chemical compound BrCCC(C)C(=O)OC(C)(C)C ANVAROJPEJVBHI-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- AEVBPXDFDKBGLT-YOUFYPILSA-N (2s,3s,4r,5r)-n-[2-[4-(diethoxyphosphorylmethyl)anilino]-2-oxoethyl]-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolane-2-carboxamide Chemical compound C1=CC(CP(=O)(OCC)OCC)=CC=C1NC(=O)CNC(=O)[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 AEVBPXDFDKBGLT-YOUFYPILSA-N 0.000 description 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
- DWPVVZZGGGCRRM-UHFFFAOYSA-N (4-methoxyphenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N1CCN(C)CC1 DWPVVZZGGGCRRM-UHFFFAOYSA-N 0.000 description 1
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
- GQLDEKHYZGCPNQ-NSCUHMNNSA-N (E)-3-(3-methoxy-5-nitrophenyl)prop-2-enal Chemical compound COC=1C=C(C=C(C=1)[N+](=O)[O-])/C=C/C=O GQLDEKHYZGCPNQ-NSCUHMNNSA-N 0.000 description 1
- APJSHECCIRQQDV-ZRDIBKRKSA-N (e)-3-[4-hydroxy-3-(5,5,8,8-tetramethyl-3-pentoxy-6,7-dihydronaphthalen-2-yl)phenyl]prop-2-enoic acid Chemical compound CCCCCOC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C1=CC(\C=C\C(O)=O)=CC=C1O APJSHECCIRQQDV-ZRDIBKRKSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 1
- SZCBDIVMCGFVPW-UHFFFAOYSA-N 1-[4-(aminomethyl)-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OC)=C1 SZCBDIVMCGFVPW-UHFFFAOYSA-N 0.000 description 1
- ZFNNBIMQDHBELV-UHFFFAOYSA-N 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-[3-(3-cyclohexylpropoxy)phenyl]-2-oxo-1,8-naphthyridin-3-yl]urea;dihydrochloride Chemical compound Cl.Cl.CC(C)C=1C=C(N)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C(C=1)=CC=CC=1OCCCC1CCCCC1 ZFNNBIMQDHBELV-UHFFFAOYSA-N 0.000 description 1
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
- WXYYACUWOMKZQC-UHFFFAOYSA-N 1-benzyl-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound C1=CC(C(C)C)=CC=C1C(C1=CC(OCC#C)=CC=C11)=NC(=O)N1CC1=CC=CC=C1 WXYYACUWOMKZQC-UHFFFAOYSA-N 0.000 description 1
- YKYWUHHZZRBGMG-JWTNVVGKSA-N 1-methyl-2-[[(1r,5s)-6-[[5-(trifluoromethyl)pyridin-2-yl]methoxymethyl]-3-azabicyclo[3.1.0]hexan-3-yl]methyl]benzimidazole Chemical compound C1([C@@H]2CN(C[C@@H]21)CC=1N(C2=CC=CC=C2N=1)C)COCC1=CC=C(C(F)(F)F)C=N1 YKYWUHHZZRBGMG-JWTNVVGKSA-N 0.000 description 1
- DIZKLZKLNKQFGB-UHFFFAOYSA-N 1-methylcyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(C)CC1 DIZKLZKLNKQFGB-UHFFFAOYSA-N 0.000 description 1
- YUGDKEWUYZXXRU-UHFFFAOYSA-N 2-(4-chlorophenoxy)acetonitrile Chemical compound ClC1=CC=C(OCC#N)C=C1 YUGDKEWUYZXXRU-UHFFFAOYSA-N 0.000 description 1
- CJLZUKCACMUYFP-GOSISDBHSA-N 2-[(5R)-4-[2-[3-(3-methylbutanoyloxy)phenyl]acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid Chemical compound CC(C)CC(=O)OC1=CC=CC(CC(=O)N2[C@@H](C3=CC=C(N=C3NCC2)C(F)(F)F)CC(O)=O)=C1 CJLZUKCACMUYFP-GOSISDBHSA-N 0.000 description 1
- WGABOZPQOOZAOI-UHFFFAOYSA-N 2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenyl]acetic acid Chemical compound COC1=C(C)C(OC)=CC(C(=O)N(CCCC=2C=CC=CC=2)CC=2C=CC(CC(O)=O)=CC=2)=C1 WGABOZPQOOZAOI-UHFFFAOYSA-N 0.000 description 1
- IANAREFPKLOIAF-UHFFFAOYSA-N 2-[5-methoxy-2-nitro-4-(trifluoromethyl)phenyl]acetonitrile Chemical compound COC1=CC(CC#N)=C([N+]([O-])=O)C=C1C(F)(F)F IANAREFPKLOIAF-UHFFFAOYSA-N 0.000 description 1
- UUXWIOLRYXMDJP-UHFFFAOYSA-N 2-bromo-2-(4-chloro-2-methoxyphenyl)-1-[6-(trifluoromethoxy)-2,3-dihydroindol-1-yl]ethanone Chemical compound BrC(C(=O)N1CCC2=CC=C(C=C12)OC(F)(F)F)C1=C(C=C(C=C1)Cl)OC UUXWIOLRYXMDJP-UHFFFAOYSA-N 0.000 description 1
- AYHLFSWSYYENTK-UHFFFAOYSA-N 2-bromo-2-(4-chlorophenyl)-1-[5-methoxy-6-(trifluoromethyl)-2,3-dihydroindol-1-yl]ethanone Chemical compound BrC(C(=O)N1CCC2=CC(=C(C=C12)C(F)(F)F)OC)C1=CC=C(C=C1)Cl AYHLFSWSYYENTK-UHFFFAOYSA-N 0.000 description 1
- QAFBDGXIYRHBDO-UHFFFAOYSA-N 2-diazoethyl acetate Chemical compound CC(=O)OCC=[N+]=[N-] QAFBDGXIYRHBDO-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- JUTDHSGANMHVIC-UHFFFAOYSA-N 2-phenylpyrrolidine Chemical compound C1CCNC1C1=CC=CC=C1 JUTDHSGANMHVIC-UHFFFAOYSA-N 0.000 description 1
- NSFXVRRBGNORBD-UHFFFAOYSA-N 2h-benzo[f]benzotriazole Chemical compound C1=C2C=CC=CC2=CC2=NNN=C21 NSFXVRRBGNORBD-UHFFFAOYSA-N 0.000 description 1
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
- HNFMVVHMKGFCMB-UHFFFAOYSA-N 3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine Chemical compound NC1=NC=CC=C1C1=NC2=CC=C(C=3C=CC=CC=3)N=C2N1C1=CC=C(C2(N)CCC2)C=C1 HNFMVVHMKGFCMB-UHFFFAOYSA-N 0.000 description 1
- HCLQARMRCPEALF-DNQXCXABSA-N 3-[[(2r)-2-[(1r)-2-[[1-(1-benzothiophen-2-yl)-2-methylpropan-2-yl]amino]-1-hydroxyethyl]pyrrolidin-1-yl]methyl]benzonitrile Chemical compound C([C@@H]1[C@H](O)CNC(C)(CC=2SC3=CC=CC=C3C=2)C)CCN1CC1=CC=CC(C#N)=C1 HCLQARMRCPEALF-DNQXCXABSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MWDVCHRYCKXEBY-LBPRGKRZSA-N 3-chloro-n-[2-oxo-2-[[(1s)-1-phenylethyl]amino]ethyl]benzamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(Cl)=C1 MWDVCHRYCKXEBY-LBPRGKRZSA-N 0.000 description 1
- WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
- XDCOYBQVEVSNNB-UHFFFAOYSA-N 4-[(7-naphthalen-2-yl-1-benzothiophen-2-yl)methylamino]butanoic acid Chemical compound OC(=O)CCCNCc1cc2cccc(-c3ccc4ccccc4c3)c2s1 XDCOYBQVEVSNNB-UHFFFAOYSA-N 0.000 description 1
- XSQGCAYHVDTGSD-UHFFFAOYSA-N 4-[3-[[1-(4-chlorophenyl)-2-oxo-2-[6-(trifluoromethoxy)-2,3-dihydroindol-1-yl]ethyl]amino]-5-methoxyphenoxy]-2,2-dimethylbutanoic acid Chemical compound ClC1=CC=C(C=C1)C(C(N1CCC2=CC=C(C=C12)OC(F)(F)F)=O)NC=1C=C(OCCC(C(=O)O)(C)C)C=C(C=1)OC XSQGCAYHVDTGSD-UHFFFAOYSA-N 0.000 description 1
- UIADWSXPNFQQCZ-UHFFFAOYSA-N 4-[4-(3,4-dichlorophenyl)-5-phenyl-1,3-oxazol-2-yl]butanoic acid Chemical compound ClC=1C=C(C=CC=1Cl)C=1N=C(OC=1C1=CC=CC=C1)CCCC(=O)O UIADWSXPNFQQCZ-UHFFFAOYSA-N 0.000 description 1
- UPSRJSLSMXBDEF-UHFFFAOYSA-N 5-[3-[[1-(4-chlorophenyl)-2-oxo-2-[6-(trifluoromethoxy)-2,3-dihydroindol-1-yl]ethyl]amino]-5-methoxyphenyl]pentanoic acid Chemical compound ClC1=CC=C(C=C1)C(C(N1CCC2=CC=C(C=C12)OC(F)(F)F)=O)NC=1C=C(C=C(C=1)OC)CCCCC(=O)O UPSRJSLSMXBDEF-UHFFFAOYSA-N 0.000 description 1
- MCSWKSCZARDPJX-UHFFFAOYSA-N 5-methoxy-6-(trifluoromethyl)-2,3-dihydro-1h-indole Chemical compound C1=C(C(F)(F)F)C(OC)=CC2=C1NCC2 MCSWKSCZARDPJX-UHFFFAOYSA-N 0.000 description 1
- CZFUAUSGMISVFX-UHFFFAOYSA-N 6-(trifluoromethoxy)-2,3-dihydro-1h-indole Chemical compound FC(F)(F)OC1=CC=C2CCNC2=C1 CZFUAUSGMISVFX-UHFFFAOYSA-N 0.000 description 1
- RRELDGDKULRRDM-UHFFFAOYSA-N 6-[2-chloro-4-nitro-5-(oxan-4-yloxy)anilino]-3,4-dihydro-1H-quinolin-2-one Chemical compound [O-][N+](=O)c1cc(Cl)c(Nc2ccc3NC(=O)CCc3c2)cc1OC1CCOCC1 RRELDGDKULRRDM-UHFFFAOYSA-N 0.000 description 1
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241001279686 Allium moly Species 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- QCMHGCDOZLWPOT-FMNCTDSISA-N COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 Chemical compound COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 QCMHGCDOZLWPOT-FMNCTDSISA-N 0.000 description 1
- 101100512901 Caenorhabditis elegans mes-4 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 241000710829 Dengue virus group Species 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 101100512902 Drosophila melanogaster Mes-4 gene Proteins 0.000 description 1
- GLPZEHFBLBYFHN-UHFFFAOYSA-N Ethychlozate Chemical compound C1=CC(Cl)=CC2=C(CC(=O)OCC)NN=C21 GLPZEHFBLBYFHN-UHFFFAOYSA-N 0.000 description 1
- 101150019273 GATM gene Proteins 0.000 description 1
- 206010061192 Haemorrhagic fever Diseases 0.000 description 1
- 241000463109 Haloprofundus marisrubri Species 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 229910016001 MoSe Inorganic materials 0.000 description 1
- 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 1
- SUKXKLNDBLNTSW-UHFFFAOYSA-N N-(4-hydroxycyclohexyl)-6-phenylhexanamide Chemical compound OC1CCC(CC1)NC(CCCCCC1=CC=CC=C1)=O SUKXKLNDBLNTSW-UHFFFAOYSA-N 0.000 description 1
- NUGPIZCTELGDOS-QHCPKHFHSA-N N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclopentanecarboxamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CC[C@@H](C=1C=NC=CC=1)NC(=O)C1CCCC1)C NUGPIZCTELGDOS-QHCPKHFHSA-N 0.000 description 1
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 1
- ZNSPHKJFQDEABI-NZQKXSOJSA-N Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 Chemical compound Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 ZNSPHKJFQDEABI-NZQKXSOJSA-N 0.000 description 1
- 101800001775 Nuclear inclusion protein A Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000353355 Oreosoma atlanticum Species 0.000 description 1
- 101150024701 PPH3 gene Proteins 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 238000012341 Quantitative reverse-transcriptase PCR Methods 0.000 description 1
- 235000003976 Ruta Nutrition 0.000 description 1
- 240000005746 Ruta graveolens Species 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- OJFKUJDRGJSAQB-UHFFFAOYSA-N TAK-632 Chemical compound C1=C(NC(=O)CC=2C=C(C=CC=2)C(F)(F)F)C(F)=CC=C1OC(C(=C1S2)C#N)=CC=C1N=C2NC(=O)C1CC1 OJFKUJDRGJSAQB-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000007985 Tris NaCl EDTA buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-PWCQTSIFSA-N Tritiated water Chemical compound [3H]O[3H] XLYOFNOQVPJJNP-PWCQTSIFSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 241001377938 Yara Species 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229940074995 bromine Drugs 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000012733 comparative method Methods 0.000 description 1
- 229940125876 compound 15a Drugs 0.000 description 1
- 229940126212 compound 17a Drugs 0.000 description 1
- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940023605 dengue virus vaccine Drugs 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- BFXLJWUGRPGMFU-UHFFFAOYSA-N dipropoxyphosphinothioyl n,n-diethylcarbamodithioate;sulfane Chemical compound S.CCCOP(=S)(OCCC)SC(=S)N(CC)CC BFXLJWUGRPGMFU-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 235000001159 dosh Nutrition 0.000 description 1
- 244000245171 dosh Species 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000013504 emergency use authorization Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- VVYZCBNOQLSBGE-YDFGWWAZSA-N ethyl (2E,4E)-5-(3-methoxy-5-nitrophenyl)penta-2,4-dienoate Chemical compound COC=1C=C(C=C(C=1)[N+](=O)[O-])/C=C/C=C/C(=O)OCC VVYZCBNOQLSBGE-YDFGWWAZSA-N 0.000 description 1
- AOQBVPPEXCRXAW-UHFFFAOYSA-N ethyl 2-(hydroxymethyl)cyclopropane-1-carboxylate Chemical compound CCOC(=O)C1CC1CO AOQBVPPEXCRXAW-UHFFFAOYSA-N 0.000 description 1
- DBRMDPWHXKAPCD-UHFFFAOYSA-N ethyl 3-(3-amino-5-methoxyphenoxy)propanoate Chemical compound NC=1C=C(OCCC(=O)OCC)C=C(C=1)OC DBRMDPWHXKAPCD-UHFFFAOYSA-N 0.000 description 1
- JDPRQLJJXIQEHN-UHFFFAOYSA-N ethyl 3-[(3-amino-5-methoxyphenyl)methoxy]propanoate Chemical compound NC=1C=C(COCCC(=O)OCC)C=C(C=1)OC JDPRQLJJXIQEHN-UHFFFAOYSA-N 0.000 description 1
- MCTSVNGBDYPRPR-UHFFFAOYSA-N ethyl 4-(3-amino-5-methoxyphenoxy)-3-methylbutanoate Chemical compound NC=1C=C(OCC(CC(=O)OCC)C)C=C(C=1)OC MCTSVNGBDYPRPR-UHFFFAOYSA-N 0.000 description 1
- FZQYPZHBHLEJGH-UHFFFAOYSA-N ethyl 4-(3-methoxy-5-nitrophenyl)butanoate Chemical compound COC=1C=C(C=C(C=1)[N+](=O)[O-])CCCC(=O)OCC FZQYPZHBHLEJGH-UHFFFAOYSA-N 0.000 description 1
- NFPCIQADIIWXMO-UHFFFAOYSA-N ethyl 4-[3-[[1-(4-chlorophenyl)-2-oxo-2-[6-(trifluoromethoxy)-2,3-dihydroindol-1-yl]ethyl]amino]-5-methoxyphenoxy]-3-methylbutanoate Chemical compound ClC1=CC=C(C=C1)C(C(N1CCC2=CC=C(C=C12)OC(F)(F)F)=O)NC=1C=C(OCC(CC(=O)OCC)C)C=C(C=1)OC NFPCIQADIIWXMO-UHFFFAOYSA-N 0.000 description 1
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 1
- XWRLQRLQUKZEEU-UHFFFAOYSA-N ethyl(hydroxy)silicon Chemical class CC[Si]O XWRLQRLQUKZEEU-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000000540 fraction c Anatomy 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 241000238565 lobster Species 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- LSEMRAPWMAYTFA-UHFFFAOYSA-N methyl 4-bromo-2,2-dimethylbutanoate Chemical compound COC(=O)C(C)(C)CCBr LSEMRAPWMAYTFA-UHFFFAOYSA-N 0.000 description 1
- NVFROOBLMCOHAB-UHFFFAOYSA-N methyl 5-(3-amino-5-methoxyphenoxy)pentanoate Chemical compound NC=1C=C(OCCCCC(=O)OC)C=C(C=1)OC NVFROOBLMCOHAB-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- BODLESUVCQEUII-UHFFFAOYSA-N n-[4-[2-(hydroxyamino)-2-oxoethyl]piperidin-4-yl]-4-[(2-methylquinolin-4-yl)methoxy]benzamide Chemical compound C=12C=CC=CC2=NC(C)=CC=1COC(C=C1)=CC=C1C(=O)NC1(CC(=O)NO)CCNCC1 BODLESUVCQEUII-UHFFFAOYSA-N 0.000 description 1
- 238000004651 near-field scanning optical microscopy Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- PFGVNLZDWRZPJW-OPAMFIHVSA-N otamixaban Chemical compound C([C@@H](C(=O)OC)[C@@H](C)NC(=O)C=1C=CC(=CC=1)C=1C=C[N+]([O-])=CC=1)C1=CC=CC(C(N)=N)=C1 PFGVNLZDWRZPJW-OPAMFIHVSA-N 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- SDVVLIIVFBKBMG-UHFFFAOYSA-N penta-2,4-dienoic acid Chemical compound OC(=O)C=CC=C SDVVLIIVFBKBMG-UHFFFAOYSA-N 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920000128 polypyrrole Polymers 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000012256 powdered iron Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 235000005806 ruta Nutrition 0.000 description 1
- 238000002317 scanning near-field acoustic microscopy Methods 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- DVWOYOSIEJRHKW-UIRZNSHLSA-M sodium (2S)-2-[[(2S)-2-[[(4,4-difluorocyclohexyl)-phenylmethoxy]carbonylamino]-4-methylpentanoyl]amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate Chemical compound FC1(CCC(CC1)C(OC(=O)N[C@H](C(=O)N[C@H](C(S(=O)(=O)[O-])O)C[C@H]1C(NCC1)=O)CC(C)C)C1=CC=CC=C1)F.[Na+] DVWOYOSIEJRHKW-UIRZNSHLSA-M 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- MFLRJLAEJSOGAP-UHFFFAOYSA-N tert-butyl 4-(3-methoxy-5-nitrophenoxy)-2-methylbutanoate Chemical compound C(OC(=O)C(CCOC1=CC(=CC(N(=O)=O)=C1)OC)C)(C)(C)C MFLRJLAEJSOGAP-UHFFFAOYSA-N 0.000 description 1
- IMTUVQBBDUOVBI-UHFFFAOYSA-N tert-butyl 4-[3-[[1-(4-chloro-2-methoxyphenyl)-2-oxo-2-[6-(trifluoromethoxy)-2,3-dihydroindol-1-yl]ethyl]amino]-5-methoxyphenoxy]-2-methylbutanoate Chemical compound C(OC(=O)C(CCOC1=CC(NC(C(=O)N2C3=CC(OC(F)(F)F)=CC=C3CC2)C2=C(OC)C=C(Cl)C=C2)=CC(OC)=C1)C)(C)(C)C IMTUVQBBDUOVBI-UHFFFAOYSA-N 0.000 description 1
- JYRWUSXRTGACLY-UHFFFAOYSA-N tert-butyl 4-[[3-(4-methylsulfonylphenyl)-[1,2]oxazolo[4,5-d]pyrimidin-7-yl]oxy]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=NC=NC2=C1ON=C2C1=CC=C(S(C)(=O)=O)C=C1 JYRWUSXRTGACLY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
-
- 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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17172237 | 2017-05-22 | ||
| PCT/EP2018/063028 WO2018215315A1 (en) | 2017-05-22 | 2018-05-18 | Substituted indoline derivatives as dengue viral replication inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA125407C2 true UA125407C2 (uk) | 2022-03-02 |
Family
ID=58745157
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA201912024A UA125407C2 (uk) | 2017-05-22 | 2018-05-18 | Заміщені похідні індоліну як інгібітори реплікації вірусів денге |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US11407715B2 (https=) |
| EP (1) | EP3630723B1 (https=) |
| JP (1) | JP7203764B2 (https=) |
| KR (1) | KR102625988B1 (https=) |
| CN (1) | CN110691773B (https=) |
| AR (1) | AR111878A1 (https=) |
| AU (1) | AU2018274100B2 (https=) |
| BR (1) | BR112019024195A2 (https=) |
| CA (1) | CA3060583C (https=) |
| CL (1) | CL2019003294A1 (https=) |
| CO (1) | CO2019012035A2 (https=) |
| CR (1) | CR20190530A (https=) |
| EA (1) | EA201992782A1 (https=) |
| EC (1) | ECSP19083640A (https=) |
| ES (1) | ES2929667T3 (https=) |
| IL (1) | IL270726B2 (https=) |
| MA (1) | MA48943A (https=) |
| MX (1) | MX393586B (https=) |
| NI (1) | NI201900119A (https=) |
| PE (1) | PE20200604A1 (https=) |
| PH (1) | PH12019502559A1 (https=) |
| TW (1) | TWI758480B (https=) |
| UA (1) | UA125407C2 (https=) |
| UY (1) | UY37742A (https=) |
| WO (1) | WO2018215315A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201116559D0 (en) | 2011-09-26 | 2011-11-09 | Univ Leuven Kath | Novel viral replication inhibitors |
| JOP20160086B1 (ar) | 2015-05-08 | 2021-08-17 | 2 Katholieke Univ Leuven Ku Leuven Research And Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20160198B1 (ar) | 2015-09-16 | 2022-03-14 | Janssen Pharmaceuticals Inc | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JO3633B1 (ar) | 2015-09-16 | 2020-08-27 | Katholieke Univ Leuven Ku Leuven Research & Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| MX2018011788A (es) | 2016-03-31 | 2019-05-20 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicacion virica de dengue. |
| HRP20210847T1 (hr) | 2016-03-31 | 2021-07-23 | Janssen Pharmaceuticals, Inc. | Supstituirani derivati indola kao inhibitori replikacije denga virusa |
| KR102359766B1 (ko) | 2016-04-01 | 2022-02-07 | 얀센 파마슈티칼즈, 인코포레이티드 | 뎅기 바이러스 복제 억제제로서 치환된 인돌 화합물 유도체 |
| JOP20170069B1 (ar) | 2016-04-01 | 2021-08-17 | 1 Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180026A1 (ar) | 2017-03-31 | 2019-01-30 | Univ Leuven Kath | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180025B1 (ar) | 2017-03-31 | 2021-08-17 | Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| CN110753682B (zh) | 2017-05-22 | 2023-06-30 | 杨森制药公司 | 作为登革热病毒复制抑制剂的经取代的吲哚啉衍生物 |
| PE20260044A1 (es) * | 2023-06-05 | 2026-01-09 | Zydus Lifesciences Ltd | Compuestos novedosos para tratar infecciones virales |
| WO2025248536A1 (en) * | 2024-05-29 | 2025-12-04 | Zydus Lifesciences Limited | Novel oxime derivatives to treat viral infections |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2241178T3 (es) | 1997-10-27 | 2005-10-16 | Eli Lilly And Company | Profarmacos de ester de morlino-n-etilo de inhibidores indolicos de spla 2. |
| GB0110832D0 (en) | 2001-05-03 | 2001-06-27 | Virogen Ltd | Antiviral compounds |
| US20050074457A1 (en) | 2001-12-12 | 2005-04-07 | Adeela Kamal | Assays and implements for determining and modulating hsp90 binding activity |
| GB0215293D0 (en) | 2002-07-03 | 2002-08-14 | Rega Foundation | Viral inhibitors |
| ZA200705872B (en) | 2005-01-14 | 2008-09-25 | Genelabs Tecnologies Inc | Indole derivatives for treating viral infections |
| JP2008530124A (ja) | 2005-02-09 | 2008-08-07 | ミジェニックス インコーポレイテッド | フラビウイルス感染症を処置または予防するための組成物および方法 |
| AU2009256390A1 (en) | 2008-06-03 | 2009-12-10 | Siga Technologies, Inc. | Small molecule inhibitors for the treatment or prevention of dengue virus infection |
| JP5559174B2 (ja) * | 2008-08-19 | 2014-07-23 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 冷感−メントール受容体拮抗剤 |
| TWI453207B (zh) | 2008-09-08 | 2014-09-21 | Signal Pharm Llc | 胺基三唑并吡啶，其組合物及使用其之治療方法 |
| EP2393359A4 (en) | 2009-02-09 | 2012-10-03 | Enanta Pharm Inc | COMPOUND DIBENZIMIDAZOLE DERIVATIVES |
| GB0910003D0 (en) | 2009-06-11 | 2009-07-22 | Univ Leuven Kath | Novel compounds for the treatment of neurodegenerative diseases |
| US8993604B2 (en) | 2009-06-30 | 2015-03-31 | Siga Technologies, Inc. | Treatment and prevention of dengue virus infections |
| US7948798B1 (en) | 2009-07-22 | 2011-05-24 | Marvell International Ltd. | Mixed multi-level cell and single level cell storage device |
| CA2785563C (en) | 2010-01-15 | 2019-05-14 | Gilead Sciences, Inc. | Inhibitors of flaviviridae viruses |
| EP2552211A4 (en) | 2010-03-26 | 2013-10-23 | Glaxo Group Ltd | INDAZOLYL-PYRIMIDINE AS KINASEHEMMER |
| JP5716205B2 (ja) | 2011-03-29 | 2015-05-13 | 学校法人日本大学 | グルコシダーゼ活性阻害用組成物及びそのスクリーニング方法 |
| GB201116559D0 (en) | 2011-09-26 | 2011-11-09 | Univ Leuven Kath | Novel viral replication inhibitors |
| EP2624519A4 (en) * | 2011-09-30 | 2014-04-23 | Huawei Tech Co Ltd | NETWORKING METHOD AND DEVICE |
| GB201305376D0 (en) | 2013-03-25 | 2013-05-08 | Univ Leuven Kath | Novel viral replication inhibitors |
| KR102290189B1 (ko) | 2013-10-23 | 2021-08-17 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 카르복스아미드 유도체 및 ｂ형 간염 치료용 의약으로서의 이의 용도 |
| CN116987080A (zh) | 2014-01-31 | 2023-11-03 | 百时美施贵宝公司 | 作为因子xia抑制剂的具有杂环p2′基团的大环化合物 |
| ME03344B (me) | 2014-10-01 | 2019-10-20 | Janssen Pharmaceuticals Inc | Mono- ili di-supstituisani indoli kao inнibitori replikacije denga virusa |
| NO2721243T3 (https=) | 2014-10-01 | 2018-10-20 | ||
| AU2015326930B2 (en) * | 2014-10-01 | 2020-03-26 | Janssen Pharmaceuticals, Inc. | Mono- or di-substituted indole derivatives as dengue viral replication inhibitors |
| PH12017501272B1 (en) | 2015-01-16 | 2023-01-11 | Janssen Pharmaceuticals Inc | Indole derivatives as dengue viral replication inhibitors |
| AR103680A1 (es) | 2015-02-23 | 2017-05-24 | Lilly Co Eli | Inhibidores selectivos de bace1 |
| JOP20160086B1 (ar) | 2015-05-08 | 2021-08-17 | 2 Katholieke Univ Leuven Ku Leuven Research And Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20160198B1 (ar) | 2015-09-16 | 2022-03-14 | Janssen Pharmaceuticals Inc | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JO3633B1 (ar) | 2015-09-16 | 2020-08-27 | Katholieke Univ Leuven Ku Leuven Research & Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| MX374683B (es) | 2015-11-03 | 2025-03-04 | Zoetis Services Llc | Compuestos polimericos sol-gel y sus usos. |
| HRP20210847T1 (hr) | 2016-03-31 | 2021-07-23 | Janssen Pharmaceuticals, Inc. | Supstituirani derivati indola kao inhibitori replikacije denga virusa |
| ES2804580T3 (es) | 2016-03-31 | 2021-02-08 | Takeda Pharmaceuticals Co | Compuesto heterocíclico |
| MX2018011788A (es) * | 2016-03-31 | 2019-05-20 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicacion virica de dengue. |
| MY210545A (en) | 2016-04-01 | 2025-09-30 | Kite Pharma Inc | Chimeric receptors to flt3 and methods of use thereof |
| PT3436079T (pt) | 2016-04-01 | 2021-10-06 | Kite Pharma Inc | Recetores de antigénios quiméricos e de células t e métodos de uso |
| EP3436457B1 (en) | 2016-04-01 | 2022-07-20 | Basf Se | Bicyclic compounds |
| KR102359766B1 (ko) | 2016-04-01 | 2022-02-07 | 얀센 파마슈티칼즈, 인코포레이티드 | 뎅기 바이러스 복제 억제제로서 치환된 인돌 화합물 유도체 |
| JOP20170069B1 (ar) | 2016-04-01 | 2021-08-17 | 1 Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| KR20200068750A (ko) | 2016-04-01 | 2020-06-15 | 카이트 파마 인코포레이티드 | 키메라 수용체 및 그의 사용 방법 |
| AU2017241837B2 (en) | 2016-04-01 | 2021-07-22 | Signal Pharmaceuticals, Llc | Substituted aminopurine compounds, compositions thereof, and methods of treatment therewith |
| JOP20180026A1 (ar) | 2017-03-31 | 2019-01-30 | Univ Leuven Kath | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180025B1 (ar) | 2017-03-31 | 2021-08-17 | Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| CN110753682B (zh) | 2017-05-22 | 2023-06-30 | 杨森制药公司 | 作为登革热病毒复制抑制剂的经取代的吲哚啉衍生物 |
-
2018
- 2018-05-18 EA EA201992782A patent/EA201992782A1/ru unknown
- 2018-05-18 CN CN201880033697.9A patent/CN110691773B/zh active Active
- 2018-05-18 UA UAA201912024A patent/UA125407C2/uk unknown
- 2018-05-18 AU AU2018274100A patent/AU2018274100B2/en active Active
- 2018-05-18 KR KR1020197036401A patent/KR102625988B1/ko active Active
- 2018-05-18 EP EP18728541.6A patent/EP3630723B1/en active Active
- 2018-05-18 PE PE2019002404A patent/PE20200604A1/es unknown
- 2018-05-18 MX MX2019013893A patent/MX393586B/es unknown
- 2018-05-18 WO PCT/EP2018/063028 patent/WO2018215315A1/en not_active Ceased
- 2018-05-18 TW TW107116924A patent/TWI758480B/zh not_active IP Right Cessation
- 2018-05-18 BR BR112019024195-7A patent/BR112019024195A2/pt active Search and Examination
- 2018-05-18 US US16/612,670 patent/US11407715B2/en active Active
- 2018-05-18 CR CR20190530A patent/CR20190530A/es unknown
- 2018-05-18 ES ES18728541T patent/ES2929667T3/es active Active
- 2018-05-18 JP JP2019564166A patent/JP7203764B2/ja active Active
- 2018-05-18 MA MA048943A patent/MA48943A/fr unknown
- 2018-05-18 CA CA3060583A patent/CA3060583C/en active Active
- 2018-05-21 AR ARP180101342A patent/AR111878A1/es not_active Application Discontinuation
- 2018-05-22 UY UY0001037742A patent/UY37742A/es unknown
-
2019
- 2019-10-28 CO CONC2019/0012035A patent/CO2019012035A2/es unknown
- 2019-11-15 CL CL2019003294A patent/CL2019003294A1/es unknown
- 2019-11-15 PH PH12019502559A patent/PH12019502559A1/en unknown
- 2019-11-18 IL IL270726A patent/IL270726B2/en unknown
- 2019-11-21 NI NI201900119A patent/NI201900119A/es unknown
- 2019-11-22 EC ECSENADI201983640A patent/ECSP19083640A/es unknown
-
2022
- 2022-06-16 US US17/842,367 patent/US11795149B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| UA125407C2 (uk) | Заміщені похідні індоліну як інгібітори реплікації вірусів денге | |
| UA122965C2 (uk) | Заміщені хромани і спосіб застосування | |
| EP3105228B1 (en) | Heterocyclic compounds useful in the treatment of diabetes and obesity | |
| EA020815B1 (ru) | Ингибиторы вируса гепатита с | |
| UA123002C2 (uk) | Похідні індолу як інгібітори реплікації вірусів денге | |
| UA118369C2 (uk) | Сполуки, що інгібують активність lrrk2 кінази | |
| UA125970C2 (uk) | Заміщені похідні індоліну як інгібітори реплікації вірусів денге | |
| EP3962601B1 (en) | 5-ht2a agonists for use in treatment of depression | |
| UA126288C2 (uk) | Заміщені похідні індоліну як інгібітори реплікації вірусів денге | |
| UA121119C2 (uk) | Похідні моно- або дизаміщених індолів як інгібітори реплікації вірусів денге | |
| UA128183C2 (uk) | Похідні моно- або дизаміщених індолів як інгібітори реплікації вірусів денге | |
| SG194526A1 (en) | Amide compound and pharmaceutical application therefor | |
| UA123672C2 (uk) | Похідні моно- або дизаміщених індолів як інгібітори реплікації вірусів денге | |
| EP1714965A1 (en) | Composition containing solifenacin succinate | |
| KR20140090996A (ko) | R(+)-n-폼일-프로파길-아미노인단 | |
| EP3294706B1 (en) | Cyclic compounds | |
| EP4635944A1 (en) | 2-azabicyclo[3.1.1]heptane compound | |
| EP3490975B1 (en) | O-substituted hydroxamic acids | |
| CN118791418A (zh) | 一种吲哚类化合物及其制备方法与应用 | |
| UA128346C2 (uk) | Комбінації, які містять позитивні алостеричні модулятори або ортостеричні агоністи метаботропного глутаматергічного рецептора 2 підтипу, та їх застосування | |
| EA041349B1 (ru) | Замещенные производные индолина в качестве ингибиторов репликации вирусов денге | |
| HK40023943B (en) | Substituted indoline derivatives as dengue viral replication inhibitors | |
| HK40023943A (en) | Substituted indoline derivatives as dengue viral replication inhibitors | |
| WO2023225625A2 (en) | Bifunctional degraders comprising electrophilic protacs that engage dcaf1 and pharmaceutical compositions comprising the same | |
| UA121965C2 (uk) | Комбінації, які містять позитивні алостеричні модулятори або ортостеричні агоністи метаботропного глутаматергічного рецептора 2 підтипу, та їх застосування |