OA20266A - - Google Patents
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- Publication number
- OA20266A OA20266A OA1202100252 OA20266A OA 20266 A OA20266 A OA 20266A OA 1202100252 OA1202100252 OA 1202100252 OA 20266 A OA20266 A OA 20266A
- Authority
- OA
- OAPI
- Prior art keywords
- compound
- independently selected
- compounds
- alkyl
- pharmaceutically acceptable
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 275
- 241000712891 Arenavirus Species 0.000 claims abstract description 62
- 102000003886 Glycoproteins Human genes 0.000 claims abstract description 33
- 108090000288 Glycoproteins Proteins 0.000 claims abstract description 33
- 201000009910 diseases by infectious agent Diseases 0.000 claims abstract description 21
- 241000700605 Viruses Species 0.000 claims description 42
- 230000002401 inhibitory effect Effects 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 239000003981 vehicle Substances 0.000 claims description 28
- 239000003937 drug carrier Substances 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 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 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 239000003112 inhibitor Substances 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 108020004459 Small Interfering RNA Proteins 0.000 claims description 9
- 229960005486 vaccines Drugs 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 6
- 229960000329 Ribavirin Drugs 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- ZCGNOVWYSGBHAU-UHFFFAOYSA-N Favipiravir Chemical compound NC(=O)C1=NC(F)=CNC1=O ZCGNOVWYSGBHAU-UHFFFAOYSA-N 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 229950008454 favipiravir Drugs 0.000 claims description 5
- 239000002955 immunomodulating agent Substances 0.000 claims description 5
- 230000002584 immunomodulator Effects 0.000 claims description 5
- 229940121354 immunomodulators Drugs 0.000 claims description 5
- 241000712892 Arenaviridae Species 0.000 claims description 3
- 229960000070 antineoplastic Monoclonal antibodies Drugs 0.000 claims description 3
- 229960000060 monoclonal antibodies Drugs 0.000 claims description 3
- 102000005614 monoclonal antibodies Human genes 0.000 claims description 3
- 108010045030 monoclonal antibodies Proteins 0.000 claims description 3
- 230000001404 mediated Effects 0.000 abstract description 7
- 206010047461 Viral infection Diseases 0.000 abstract description 2
- 208000001756 Virus Disease Diseases 0.000 abstract description 2
- 230000017613 viral reproduction Effects 0.000 abstract description 2
- -1 dilutant Substances 0.000 description 133
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
- 239000000203 mixture Substances 0.000 description 67
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 59
- 239000000243 solution Substances 0.000 description 48
- 210000004027 cells Anatomy 0.000 description 43
- 229910052805 deuterium Inorganic materials 0.000 description 29
- YZCKVEUIGOORGS-OUBTZVSYSA-N deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000002585 base Substances 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 23
- 241000124008 Mammalia Species 0.000 description 22
- 239000011780 sodium chloride Substances 0.000 description 22
- 238000004166 bioassay Methods 0.000 description 21
- 239000003085 diluting agent Substances 0.000 description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 21
- 150000003839 salts Chemical class 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 20
- 125000004432 carbon atoms Chemical group C* 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 239000000969 carrier Substances 0.000 description 17
- 239000003814 drug Substances 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 16
- 150000002148 esters Chemical group 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 229940079593 drugs Drugs 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 230000002194 synthesizing Effects 0.000 description 15
- ZADPBFCGQRWHPN-UHFFFAOYSA-N OBO Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 14
- 241000711975 Vesicular stomatitis virus Species 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 238000004113 cell culture Methods 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 230000003612 virological Effects 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 238000010348 incorporation Methods 0.000 description 13
- 229910052740 iodine Inorganic materials 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 241000282412 Homo Species 0.000 description 12
- 229910052794 bromium Inorganic materials 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 241000282414 Homo sapiens Species 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 125000004429 atoms Chemical group 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 239000002609 media Substances 0.000 description 11
- 239000012472 biological sample Substances 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 239000007832 Na2SO4 Substances 0.000 description 9
- 229940055764 Triaz Drugs 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 239000008079 hexane Substances 0.000 description 9
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 description 9
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 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 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- 229910002092 carbon dioxide Inorganic materials 0.000 description 8
- 239000006184 cosolvent Substances 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 235000015320 potassium carbonate Nutrition 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 108010010803 Gelatin Proteins 0.000 description 7
- 210000004185 Liver Anatomy 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 210000003501 Vero Cells Anatomy 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229910052681 coesite Inorganic materials 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 229910052906 cristobalite Inorganic materials 0.000 description 7
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000008273 gelatin Substances 0.000 description 7
- 229920000159 gelatin Polymers 0.000 description 7
- 235000019322 gelatine Nutrition 0.000 description 7
- 235000011852 gelatine desserts Nutrition 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- 229940002612 prodrugs Drugs 0.000 description 7
- 229910052904 quartz Inorganic materials 0.000 description 7
- 229910052682 stishovite Inorganic materials 0.000 description 7
- 229910052905 tridymite Inorganic materials 0.000 description 7
- CJUHQADBFQRIMC-UHFFFAOYSA-N (4-propan-2-yloxyphenyl)boronic acid Chemical compound CC(C)OC1=CC=C(B(O)O)C=C1 CJUHQADBFQRIMC-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N 1-[(1S,2R,3R,4S,5R,6R)-3-carbamimidamido-6-{[(2R,3R,4R,5S)-3-{[(2S,3S,4S,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy}-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy}-2,4,5-trihydroxycyclohexyl]guanidine Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- MLNFMFAMNBGAQT-UHFFFAOYSA-N 4-propan-2-yloxyaniline Chemical compound CC(C)OC1=CC=C(N)C=C1 MLNFMFAMNBGAQT-UHFFFAOYSA-N 0.000 description 6
- LWAVFLMXSGFCHY-UHFFFAOYSA-N 6-bromo-3-iodo-7-methylimidazo[1,2-a]pyridine Chemical compound C1=C(Br)C(C)=CC2=NC=C(I)N21 LWAVFLMXSGFCHY-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 206010053317 Hydrophobia Diseases 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- IIMIOEBMYPRQGU-UHFFFAOYSA-L Picoplatin Chemical compound N.[Cl-].[Cl-].[Pt+2].CC1=CC=CC=N1 IIMIOEBMYPRQGU-UHFFFAOYSA-L 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M Sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000002503 metabolic Effects 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 230000002829 reduced Effects 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 108060001084 Luciferase family Proteins 0.000 description 5
- 210000001853 Microsomes, Liver Anatomy 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 241001112090 Pseudovirus Species 0.000 description 5
- 108010012057 RNA Replicase Proteins 0.000 description 5
- DPIDNFWCDMXMDY-UHFFFAOYSA-N [4-(2-hydroxypropan-2-yl)phenyl]boronic acid Chemical compound CC(C)(O)C1=CC=C(B(O)O)C=C1 DPIDNFWCDMXMDY-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 238000007792 addition Methods 0.000 description 5
- 150000001642 boronic acid derivatives Chemical class 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 239000008298 dragée Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 4
- 241000282693 Cercopithecidae Species 0.000 description 4
- 231100000036 EC90 Toxicity 0.000 description 4
- 230000036499 Half live Effects 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N Imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N MeOtBu Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- 230000036740 Metabolism Effects 0.000 description 4
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- 206010037660 Pyrexia Diseases 0.000 description 4
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- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 150000001502 aryl halides Chemical class 0.000 description 4
- 238000006795 borylation reaction Methods 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 230000000875 corresponding Effects 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 238000011161 development Methods 0.000 description 4
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N 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 4
- 238000004020 luminiscence type Methods 0.000 description 4
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
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- OZAIFHULBGXAKX-UHFFFAOYSA-N precursor Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- 239000003638 reducing agent Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 125000004434 sulfur atoms Chemical group 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 230000001225 therapeutic Effects 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N β-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-Bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1,2,3-triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- WPHYPLYNIJVNDH-UHFFFAOYSA-N 6-bromoimidazo[1,2-a]pyridine-7-carbonitrile Chemical compound C1=C(C#N)C(Br)=CN2C=CN=C21 WPHYPLYNIJVNDH-UHFFFAOYSA-N 0.000 description 3
- 210000003050 Axons Anatomy 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 229960005069 Calcium Drugs 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
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- 125000005152 trihalomethanesulfonyl group Chemical group 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
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- HCHKCACWOHOZIP-UHFFFAOYSA-N zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- AEMOLEFTQBMNLQ-QIUUJYRFSA-N β-D-glucuronic acid Chemical compound O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-QIUUJYRFSA-N 0.000 description 1
Abstract
Compounds as exemplified by compound A are useful in the treatment of arenavirus infections and viral infections mediated by arenavirus glycoproteins.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62/776,390 | 2018-12-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA20266A true OA20266A (us) | 2022-04-14 |
Family
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