EA016071B1 - Соединения и способы лечения или предотвращения флавивирусных инфекций - Google Patents

Info

Publication number

EA016071B1

EA016071B1 EA200702493A EA200702493A EA016071B1 EA 016071 B1 EA016071 B1 EA 016071B1 EA 200702493 A EA200702493 A EA 200702493A EA 200702493 A EA200702493 A EA 200702493A EA 016071 B1 EA016071 B1 EA 016071B1

Authority

EA

Eurasian Patent Office

Prior art keywords

trans

amino

thiophene

optionally substituted

methylcyclohexanecarbonyl

Prior art date

2005-05-13

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 302
• 238000000034 method Methods 0.000 title claims description 63
• 230000002265 prevention Effects 0.000 title description 4
• 206010054261 Flavivirus infection Diseases 0.000 title description 3
• 150000003839 salts Chemical class 0.000 claims abstract description 48
• 239000012453 solvate Substances 0.000 claims abstract description 36
• -1 -Ν ^ Κ ^^ ΝΚΟ-ΝΚ ^ Chemical group 0.000 claims description 467
• 125000000217 alkyl group Chemical group 0.000 claims description 288
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 203
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 133
• 125000000623 heterocyclic group Chemical group 0.000 claims description 118
• 125000003118 aryl group Chemical group 0.000 claims description 112
• 125000001072 heteroaryl group Chemical group 0.000 claims description 107
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 100
• 125000003342 alkenyl group Chemical group 0.000 claims description 74
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
• 125000000304 alkynyl group Chemical group 0.000 claims description 71
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 69
• 125000003545 alkoxy group Chemical group 0.000 claims description 67
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 65
• 229910052799 carbon Inorganic materials 0.000 claims description 61
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 60
• 229910052736 halogen Inorganic materials 0.000 claims description 60
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 58
• 150000002367 halogens Chemical class 0.000 claims description 51
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 49
• 229910052757 nitrogen Inorganic materials 0.000 claims description 49
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 47
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 46
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 46
• 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 43
• 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 43
• 230000003612 virological effect Effects 0.000 claims description 42
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 41
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 37
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 34
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 32
• 239000003795 chemical substances by application Substances 0.000 claims description 32
• 239000003112 inhibitor Substances 0.000 claims description 30
• 125000004043 oxo group Chemical group O=* 0.000 claims description 29
• 125000004104 aryloxy group Chemical group 0.000 claims description 28
• 238000002360 preparation method Methods 0.000 claims description 26
• 125000001424 substituent group Chemical group 0.000 claims description 26
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
• 208000015181 infectious disease Diseases 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
• 150000002923 oximes Chemical class 0.000 claims description 16
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 16
• 241000700605 Viruses Species 0.000 claims description 15
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 15
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 14
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 14
• 229920006395 saturated elastomer Polymers 0.000 claims description 14
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 14
• 229910052700 potassium Inorganic materials 0.000 claims description 13
• 108060004795 Methyltransferase Proteins 0.000 claims description 12
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 12
• 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 11
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 11
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 10
• 230000000694 effects Effects 0.000 claims description 10
• 229910052760 oxygen Inorganic materials 0.000 claims description 10
• 239000001301 oxygen Substances 0.000 claims description 10
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 239000003001 serine protease inhibitor Substances 0.000 claims description 9
• 125000004429 atom Chemical group 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 230000002401 inhibitory effect Effects 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
• AMOXNTAMLUCWJT-UHFFFAOYSA-N 5-(4,4-dimethylcyclohexyl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C(=O)C1CCC(C)CC1 AMOXNTAMLUCWJT-UHFFFAOYSA-N 0.000 claims description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 7
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• 230000002519 immonomodulatory effect Effects 0.000 claims description 7
• OSZNFYRPACBWAD-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(4-ethoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OCC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 OSZNFYRPACBWAD-UHFFFAOYSA-N 0.000 claims description 6
• MGIDOELNCIGRPO-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(O)CC1 MGIDOELNCIGRPO-UHFFFAOYSA-N 0.000 claims description 6
• HQUCUQJOQOFEQW-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(4-methylcyclohexanecarbonyl)-(4-oxocyclohexyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(=O)CC1 HQUCUQJOQOFEQW-UHFFFAOYSA-N 0.000 claims description 6
• HCTFEOYQHVJAEV-UAPYVXQJSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(C)CC1 HCTFEOYQHVJAEV-UAPYVXQJSA-N 0.000 claims description 6
• 108010047761 Interferon-alpha Proteins 0.000 claims description 6
• 102000006992 Interferon-alpha Human genes 0.000 claims description 6
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
• 230000000692 anti-sense effect Effects 0.000 claims description 6
• 239000003963 antioxidant agent Substances 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 239000011593 sulfur Chemical group 0.000 claims description 6
• JVSQRBKXYYHNAL-UHFFFAOYSA-N 3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-(4-phenoxycyclohexen-1-yl)thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)OC=1C=CC=CC=1)C(O)=O)C1CCC(O)CC1 JVSQRBKXYYHNAL-UHFFFAOYSA-N 0.000 claims description 5
• DHZRKGZVOWHWSR-UHFFFAOYSA-N 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCC2(CC=1)OCCO2)C(O)=O)C1CCC(O)CC1 DHZRKGZVOWHWSR-UHFFFAOYSA-N 0.000 claims description 5
• SNHOCYVWFCETLM-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[[4-(methoxymethoxy)cyclohexyl]-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OCOC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 SNHOCYVWFCETLM-UHFFFAOYSA-N 0.000 claims description 5
• 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 5
• 239000004599 antimicrobial Substances 0.000 claims description 5
• 239000003443 antiviral agent Substances 0.000 claims description 5
• 125000004122 cyclic group Chemical group 0.000 claims description 5
• WVIIMZNLDWSIRH-UHFFFAOYSA-N cyclohexylcyclohexane Chemical group C1CCCCC1C1CCCCC1 WVIIMZNLDWSIRH-UHFFFAOYSA-N 0.000 claims description 5
• 125000005879 dioxolanyl group Chemical group 0.000 claims description 5
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 5
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
• 229960000329 ribavirin Drugs 0.000 claims description 5
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 5
• 229940021747 therapeutic vaccine Drugs 0.000 claims description 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
• RWEPJHKNTQPJNB-UHFFFAOYSA-N 5-(2,6-difluorocyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1C(CCCC=1F)F)C(O)=O)C(=O)C1CCC(C)CC1 RWEPJHKNTQPJNB-UHFFFAOYSA-N 0.000 claims description 4
• OGBAPGFURAIVAC-UHFFFAOYSA-N 5-(3-hydroxycyclohexen-1-yl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCC(O)C=1)C(O)=O)C1CCC(O)CC1 OGBAPGFURAIVAC-UHFFFAOYSA-N 0.000 claims description 4
• OFOMFFOXKMZUIW-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-(n-(4-methylcyclohexanecarbonyl)anilino)thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C=1C=CC=CC=1)C1=C(C(O)=O)SC(C=2CCCCC=2)=C1 OFOMFFOXKMZUIW-UHFFFAOYSA-N 0.000 claims description 4
• AHQGMPPSKUDUDL-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(4-fluorocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(F)CC1 AHQGMPPSKUDUDL-UHFFFAOYSA-N 0.000 claims description 4
• NHRHXDMGFVGNRU-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[1,3-dioxan-5-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1COCOC1 NHRHXDMGFVGNRU-UHFFFAOYSA-N 0.000 claims description 4
• NRWYAVDHRVTITK-UPRSBDKSSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 NRWYAVDHRVTITK-UPRSBDKSSA-N 0.000 claims description 4
• LBFROQIFJOYWFA-HDRKRICHSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(Br)=C1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(Br)=C1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 LBFROQIFJOYWFA-HDRKRICHSA-N 0.000 claims description 4
• FBOBFRVOSFIYOQ-XHPGVBHPSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 FBOBFRVOSFIYOQ-XHPGVBHPSA-N 0.000 claims description 4
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 4
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 4
• 229960003805 amantadine Drugs 0.000 claims description 4
• 238000004891 communication Methods 0.000 claims description 4
• 229910052740 iodine Inorganic materials 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 150000003536 tetrazoles Chemical class 0.000 claims description 4
• AQBYCVVVNOZWPR-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(1-formylpiperidin-4-yl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(C=O)CC1 AQBYCVVVNOZWPR-UHFFFAOYSA-N 0.000 claims description 3
• GJNZQSSHAVNWFW-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(2,4-dichlorobenzoyl)-propan-2-ylamino]thiophene-2-carboxylic acid Chemical compound C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)C1=CC=C(Cl)C=C1Cl GJNZQSSHAVNWFW-UHFFFAOYSA-N 0.000 claims description 3
• YZBWRCKPMKZIKM-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(4-methylcyclohexanecarbonyl)-[1-(2-methylpropanoyl)piperidin-4-yl]amino]thiophene-2-carboxylic acid Chemical compound C1CN(C(=O)C(C)C)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 YZBWRCKPMKZIKM-UHFFFAOYSA-N 0.000 claims description 3
• VCJJWZOMFHUKMX-UHFFFAOYSA-N 5-cyclohexyl-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C1CCCCC1)C(O)=O)C1CCC(O)CC1 VCJJWZOMFHUKMX-UHFFFAOYSA-N 0.000 claims description 3
• GVYKMIALDJEPRQ-CPONINCNSA-N C1=C(C=2CCC(C)CC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 Chemical compound C1=C(C=2CCC(C)CC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 GVYKMIALDJEPRQ-CPONINCNSA-N 0.000 claims description 3
• HZCUBYGLTQHCPR-JCNLHEQBSA-N C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 Chemical compound C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 HZCUBYGLTQHCPR-JCNLHEQBSA-N 0.000 claims description 3
• FPARYJXWWMDFFU-KQEUCTNFSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1C=CCCC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1C=CCCC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 FPARYJXWWMDFFU-KQEUCTNFSA-N 0.000 claims description 3
• MMKZHFVOWJFVHI-KESTWPANSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C1CCN(C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C1CCN(C)CC1 MMKZHFVOWJFVHI-KESTWPANSA-N 0.000 claims description 3
• DRTQOSFDYDDNNA-YSXIEMCBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 DRTQOSFDYDDNNA-YSXIEMCBSA-N 0.000 claims description 3
• LMCDACUYZVUIFN-WXVWHJFISA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C1CCC2(C(N(C)C(=O)N2C)=O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C1CCC2(C(N(C)C(=O)N2C)=O)CC1 LMCDACUYZVUIFN-WXVWHJFISA-N 0.000 claims description 3
• WJGGHFVZSJUBRZ-YSXIEMCBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 WJGGHFVZSJUBRZ-YSXIEMCBSA-N 0.000 claims description 3
• XMHTZCKCUJIEIC-PPFQCUIHSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CC(C)CCC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CC(C)CCC1 XMHTZCKCUJIEIC-PPFQCUIHSA-N 0.000 claims description 3
• DTJARGIYIUHGII-KOMQPUFPSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CC1 DTJARGIYIUHGII-KOMQPUFPSA-N 0.000 claims description 3
• OSJUSKYSFLVNJA-SAABIXHNSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(F)(F)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(F)(F)CC1 OSJUSKYSFLVNJA-SAABIXHNSA-N 0.000 claims description 3
• XFFTZCJYAKZMAI-AFARHQOCSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(C=2C=CC=CC=2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(C=2C=CC=CC=2)CC1 XFFTZCJYAKZMAI-AFARHQOCSA-N 0.000 claims description 3
• GDLYEIAVXRHMTA-XUTJKUGGSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(C=2N=CC=CN=2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(C=2N=CC=CN=2)CC1 GDLYEIAVXRHMTA-XUTJKUGGSA-N 0.000 claims description 3
• QJEOKVNLHVLDLL-SAABIXHNSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCOCC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCOCC1 QJEOKVNLHVLDLL-SAABIXHNSA-N 0.000 claims description 3
• CEQRAOMBFIAWLT-SAABIXHNSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCSCC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCSCC1 CEQRAOMBFIAWLT-SAABIXHNSA-N 0.000 claims description 3
• AHQGMPPSKUDUDL-VJVRBHMKSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](F)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](F)CC1 AHQGMPPSKUDUDL-VJVRBHMKSA-N 0.000 claims description 3
• SATLBJQBKFNRNL-ICNBMTIMSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@H]1CC[C@@H](C#N)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@H]1CC[C@@H](C#N)CC1 SATLBJQBKFNRNL-ICNBMTIMSA-N 0.000 claims description 3
• OUUFVRBISAEUNT-YSXIEMCBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCCC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCCC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 OUUFVRBISAEUNT-YSXIEMCBSA-N 0.000 claims description 3
• BVXHTXRVCMTCJW-GONJQHFYSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)[C@H]1CC[C@@H](C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)[C@H]1CC[C@@H](C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 BVXHTXRVCMTCJW-GONJQHFYSA-N 0.000 claims description 3
• XLJOUVDPWPSXDM-VYUAXZJKSA-N C1C[C@@H](C)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 XLJOUVDPWPSXDM-VYUAXZJKSA-N 0.000 claims description 3
• XLJOUVDPWPSXDM-ICNBMTIMSA-N C1C[C@@H](C)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](C)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 XLJOUVDPWPSXDM-ICNBMTIMSA-N 0.000 claims description 3
• QOIHGTCVBFQWJO-DRLVJGDXSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(CC1)C(F)(F)F)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(CC1)C(F)(F)F)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 QOIHGTCVBFQWJO-DRLVJGDXSA-N 0.000 claims description 3
• JFUHFSBVZUPBIF-IKYFGSHTSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCC(CC=1)C(F)(F)F)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCC(CC=1)C(F)(F)F)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 JFUHFSBVZUPBIF-IKYFGSHTSA-N 0.000 claims description 3
• LNYKGELUODVSNS-YSXIEMCBSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 LNYKGELUODVSNS-YSXIEMCBSA-N 0.000 claims description 3
• GZPCNCMYPJUFCL-BIAGXBKMSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC=C1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC=C1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 GZPCNCMYPJUFCL-BIAGXBKMSA-N 0.000 claims description 3
• YUIXIDHCLFDQRR-XHPGVBHPSA-N C1C[C@@H](OCSC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OCSC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 YUIXIDHCLFDQRR-XHPGVBHPSA-N 0.000 claims description 3
• YRXSLMCVIZCAFE-XUTJKUGGSA-N C[C@H]1CC[C@@H](CC1)C(=O)N(C1CCN(CC1)c1cncnc1)c1cc(sc1C(O)=O)C1=CCCCC1 Chemical compound C[C@H]1CC[C@@H](CC1)C(=O)N(C1CCN(CC1)c1cncnc1)c1cc(sc1C(O)=O)C1=CCCCC1 YRXSLMCVIZCAFE-XUTJKUGGSA-N 0.000 claims description 3
• NYTDFZMGNVINAW-SAABIXHNSA-N C[C@H]1CC[C@@H](CC1)C(=O)N(C1CCNCC1)c1cc(sc1C(O)=O)C1=CCCCC1 Chemical compound C[C@H]1CC[C@@H](CC1)C(=O)N(C1CCNCC1)c1cc(sc1C(O)=O)C1=CCCCC1 NYTDFZMGNVINAW-SAABIXHNSA-N 0.000 claims description 3
• 102000053642 Catalytic RNA Human genes 0.000 claims description 3
• 108090000994 Catalytic RNA Proteins 0.000 claims description 3
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 3
• 229930105110 Cyclosporin A Natural products 0.000 claims description 3
• 108010036949 Cyclosporine Proteins 0.000 claims description 3
• 208000005176 Hepatitis C Diseases 0.000 claims description 3
• 102000013462 Interleukin-12 Human genes 0.000 claims description 3
• 108010065805 Interleukin-12 Proteins 0.000 claims description 3
• 241000320380 Silybum Species 0.000 claims description 3
• 235000010841 Silybum marianum Nutrition 0.000 claims description 3
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 229960001265 ciclosporin Drugs 0.000 claims description 3
• 229930182912 cyclosporin Natural products 0.000 claims description 3
• 229940117681 interleukin-12 Drugs 0.000 claims description 3
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• STUHQDIOZQUPGP-UHFFFAOYSA-N morpholin-4-ium-4-carboxylate Chemical compound OC(=O)N1CCOCC1 STUHQDIOZQUPGP-UHFFFAOYSA-N 0.000 claims description 3
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• IBBLRJGOOANPTQ-JKVLGAQCSA-N quinapril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 IBBLRJGOOANPTQ-JKVLGAQCSA-N 0.000 claims description 3
• 108091092562 ribozyme Proteins 0.000 claims description 3
• 229920002554 vinyl polymer Polymers 0.000 claims description 3
• YKLPAWHQHJTBDV-RXMQYKEDSA-N (2r)-2-amino-3-oxo-2-(sulfanylmethyl)butanoic acid Chemical compound CC(=O)[C@](N)(CS)C(O)=O YKLPAWHQHJTBDV-RXMQYKEDSA-N 0.000 claims description 2
• MERANRXZFXHYKZ-UHFFFAOYSA-N 5-(2,3-difluorocyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCCC(F)C=1F)C(O)=O)C(=O)C1CCC(C)CC1 MERANRXZFXHYKZ-UHFFFAOYSA-N 0.000 claims description 2
• FBOBFRVOSFIYOQ-UHFFFAOYSA-N 5-(4,4-dimethylcyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C(=O)C1CCC(C)CC1 FBOBFRVOSFIYOQ-UHFFFAOYSA-N 0.000 claims description 2
• CMBPRRDJOSJOPZ-UHFFFAOYSA-N 5-(4-tert-butylcyclohexen-1-yl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)C(C)(C)C)C(O)=O)C1CCC(O)CC1 CMBPRRDJOSJOPZ-UHFFFAOYSA-N 0.000 claims description 2
• VQNVTTOMIYUAAT-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(4-methylbenzoyl)-propan-2-ylamino]thiophene-2-carboxylic acid Chemical compound C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)C1=CC=C(C)C=C1 VQNVTTOMIYUAAT-UHFFFAOYSA-N 0.000 claims description 2
• PFOHWPCBSUQTAS-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[[4-[(1-methoxy-3-methyl-1-oxobutan-2-yl)carbamoyloxy]cyclohexyl]-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OC(=O)NC(C(=O)OC)C(C)C)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 PFOHWPCBSUQTAS-UHFFFAOYSA-N 0.000 claims description 2
• CHSWOVCXLYDIIY-UHFFFAOYSA-N 5-(cyclopenten-1-yl)-3-[(2,4-dichlorobenzoyl)-propan-2-ylamino]thiophene-2-carboxylic acid Chemical compound C1=C(C=2CCCC=2)SC(C(O)=O)=C1N(C(C)C)C(=O)C1=CC=C(Cl)C=C1Cl CHSWOVCXLYDIIY-UHFFFAOYSA-N 0.000 claims description 2
• NRWYAVDHRVTITK-UHFFFAOYSA-N 5-(cyclopenten-1-yl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCC=1)C(O)=O)C1CCC(O)CC1 NRWYAVDHRVTITK-UHFFFAOYSA-N 0.000 claims description 2
• OHWPNFAZTZGNKZ-SAABIXHNSA-N C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(COC)COC)C(=O)[C@H]1CC[C@H](C)CC1 Chemical compound C1=C(C=2CCCCC=2)SC(C(O)=O)=C1N(C(COC)COC)C(=O)[C@H]1CC[C@H](C)CC1 OHWPNFAZTZGNKZ-SAABIXHNSA-N 0.000 claims description 2
• TVNILQLSTHSMLT-ZCYMVKBSSA-N C1CC(=NOCC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1CC(=NOCC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 TVNILQLSTHSMLT-ZCYMVKBSSA-N 0.000 claims description 2
• YBQKQVZAEDDNAU-CTYIDZIISA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C)C1=C(C(O)=O)SC(C=2CCCCC=2)=C1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C)C1=C(C(O)=O)SC(C=2CCCCC=2)=C1 YBQKQVZAEDDNAU-CTYIDZIISA-N 0.000 claims description 2
• AIPXYNJQICQCPP-QFLLTADKSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1C2CCC(C2)C1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1C2CCC(C2)C1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 AIPXYNJQICQCPP-QFLLTADKSA-N 0.000 claims description 2
• QHSXCGCAECGORC-LWLBLJAOSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1C=CC(C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1C=CC(C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 QHSXCGCAECGORC-LWLBLJAOSA-N 0.000 claims description 2
• JZZHJWYJGBDGPG-BRWVVXTDSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CC=C(C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CC=C(C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 JZZHJWYJGBDGPG-BRWVVXTDSA-N 0.000 claims description 2
• JFNVYOKGZLDNAH-KQEUCTNFSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CC=CCC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CC=CCC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 JFNVYOKGZLDNAH-KQEUCTNFSA-N 0.000 claims description 2
• GTZZCRIWNBVETM-GUJRETQESA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@@H](N2N=NC=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@@H](N2N=NC=C2)CC1 GTZZCRIWNBVETM-GUJRETQESA-N 0.000 claims description 2
• BVXHTXRVCMTCJW-LWLBLJAOSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 BVXHTXRVCMTCJW-LWLBLJAOSA-N 0.000 claims description 2
• IUWYBOFGGDTQOR-KHBPEBPSSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(CC1)OC=1C=CC=CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(CC1)OC=1C=CC=CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 IUWYBOFGGDTQOR-KHBPEBPSSA-N 0.000 claims description 2
• NINQOJCMYBIHMF-KCFDPAHWSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 NINQOJCMYBIHMF-KCFDPAHWSA-N 0.000 claims description 2
• PAMOIOVTAUVDIT-PWZZDWAZSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)C=1C=CC=CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)C=1C=CC=CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 PAMOIOVTAUVDIT-PWZZDWAZSA-N 0.000 claims description 2
• CRLPSZXQCTYECG-KESTWPANSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(C)(C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC(C)(C)CC1 CRLPSZXQCTYECG-KESTWPANSA-N 0.000 claims description 2
• VRCATWVIEHHTHZ-UAPYVXQJSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCCCC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCCCC1 VRCATWVIEHHTHZ-UAPYVXQJSA-N 0.000 claims description 2
• AHIZAJIZSMUYKS-KESTWPANSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(CCF)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(CCF)CC1 AHIZAJIZSMUYKS-KESTWPANSA-N 0.000 claims description 2
• BZOWKCOXOYJPPR-XHPGVBHPSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](N2N=NC=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](N2N=NC=C2)CC1 BZOWKCOXOYJPPR-XHPGVBHPSA-N 0.000 claims description 2
• QPTQPRHLMQYGHB-ZULOPVSISA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@H](N2N=CN=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@H](N2N=CN=C2)CC1 QPTQPRHLMQYGHB-ZULOPVSISA-N 0.000 claims description 2
• BZOWKCOXOYJPPR-ZULOPVSISA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@H](N2N=NC=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@H](N2N=NC=C2)CC1 BZOWKCOXOYJPPR-ZULOPVSISA-N 0.000 claims description 2
• MGIDOELNCIGRPO-IXXJFMHHSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@H]1CC[C@@H](O)CC1 MGIDOELNCIGRPO-IXXJFMHHSA-N 0.000 claims description 2
• BVXHTXRVCMTCJW-XBFADQFBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)[C@@H]1CC[C@@H](C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)[C@@H]1CC[C@@H](C)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 BVXHTXRVCMTCJW-XBFADQFBSA-N 0.000 claims description 2
• OVTIYPJPKHHYCK-GUJRETQESA-N C1C[C@@H](NC(=O)C(C)C)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](NC(=O)C(C)C)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 OVTIYPJPKHHYCK-GUJRETQESA-N 0.000 claims description 2
• OVTIYPJPKHHYCK-FORLXOICSA-N C1C[C@@H](NC(=O)C(C)C)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](NC(=O)C(C)C)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 OVTIYPJPKHHYCK-FORLXOICSA-N 0.000 claims description 2
• LNYKGELUODVSNS-URYRSFGFSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 LNYKGELUODVSNS-URYRSFGFSA-N 0.000 claims description 2
• AMOXNTAMLUCWJT-ZULOPVSISA-N C1C[C@@H](OC)CC[C@H]1N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@H]1N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 AMOXNTAMLUCWJT-ZULOPVSISA-N 0.000 claims description 2
• LNYKGELUODVSNS-HMYFDTNDSA-N C1C[C@@H](OC)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 Chemical compound C1C[C@@H](OC)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 LNYKGELUODVSNS-HMYFDTNDSA-N 0.000 claims description 2
• OWAQWJZQHJWZPO-RSUHOQBUSA-N Cl.C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@H](N2N=CN=C2)CC1 Chemical compound Cl.C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@H](N2N=CN=C2)CC1 OWAQWJZQHJWZPO-RSUHOQBUSA-N 0.000 claims description 2
• SNLFZVXDVWBLJR-FFPCIGOZSA-N [Cl-].C1(=CCCCC1)C1=CC(=C(S1)C(=O)OC)N(C1CC[NH+](CC1)C)C(=O)[C@@H]1CC[C@H](CC1)C Chemical compound [Cl-].C1(=CCCCC1)C1=CC(=C(S1)C(=O)OC)N(C1CC[NH+](CC1)C)C(=O)[C@@H]1CC[C@H](CC1)C SNLFZVXDVWBLJR-FFPCIGOZSA-N 0.000 claims description 2
• WMQSAOFWTROXBO-AFFTWYSYSA-N [Cl-].C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OCOC(=O)C(C)(C)C)C1CC[NH+](C)CC1 Chemical compound [Cl-].C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OCOC(=O)C(C)(C)C)C1CC[NH+](C)CC1 WMQSAOFWTROXBO-AFFTWYSYSA-N 0.000 claims description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 125000004426 substituted alkynyl group Chemical group 0.000 claims 5
• 125000000547 substituted alkyl group Chemical group 0.000 claims 3
• 102000007501 Thymosin Human genes 0.000 claims 2
• 108010046075 Thymosin Proteins 0.000 claims 2
• 125000003107 substituted aryl group Chemical group 0.000 claims 2
• LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 claims 2
• QYCGBAJADAGLLK-UHFFFAOYSA-N 1-(cyclohepten-1-yl)cycloheptene Chemical group C1CCCCC=C1C1=CCCCCC1 QYCGBAJADAGLLK-UHFFFAOYSA-N 0.000 claims 1
• VSIYJQNFMOOGCU-UHFFFAOYSA-N 1-(cyclohexen-1-yl)cyclohexene Chemical group C1CCCC(C=2CCCCC=2)=C1 VSIYJQNFMOOGCU-UHFFFAOYSA-N 0.000 claims 1
• KQXCUMQUYNMNKA-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(2,4-dimethylphenyl)sulfonylamino]thiophene-2-carboxylic acid Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)NC1=C(C(O)=O)SC(C=2CCCCC=2)=C1 KQXCUMQUYNMNKA-UHFFFAOYSA-N 0.000 claims 1
• VRCATWVIEHHTHZ-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[cyclohexyl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCCCC1 VRCATWVIEHHTHZ-UHFFFAOYSA-N 0.000 claims 1
• 101100404726 Arabidopsis thaliana NHX7 gene Proteins 0.000 claims 1
• CMBPRRDJOSJOPZ-LBKZCYKOSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)C(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)C(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 CMBPRRDJOSJOPZ-LBKZCYKOSA-N 0.000 claims 1
• NTQRCGGRNOJNJD-UAPYVXQJSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(S(C)(=O)=O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(S(C)(=O)=O)CC1 NTQRCGGRNOJNJD-UAPYVXQJSA-N 0.000 claims 1
• QPTQPRHLMQYGHB-XHPGVBHPSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 QPTQPRHLMQYGHB-XHPGVBHPSA-N 0.000 claims 1
• PUWYENWRQJAVBI-AFARHQOCSA-N CC(C)OC(OCOC(C(SC(C1=CCCCC1)=C1)=C1N(C1CCN(C)CC1)C([C@H]1CC[C@H](C)CC1)=O)=O)=O Chemical compound CC(C)OC(OCOC(C(SC(C1=CCCCC1)=C1)=C1N(C1CCN(C)CC1)C([C@H]1CC[C@H](C)CC1)=O)=O)=O PUWYENWRQJAVBI-AFARHQOCSA-N 0.000 claims 1
• OWAQWJZQHJWZPO-OMWMBCDQSA-N Cl.C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 Chemical compound Cl.C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 OWAQWJZQHJWZPO-OMWMBCDQSA-N 0.000 claims 1
• WTACZFZEZRUUSR-OMWMBCDQSA-N Cl.C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 Chemical class Cl.C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 WTACZFZEZRUUSR-OMWMBCDQSA-N 0.000 claims 1
• 241000282324 Felis Species 0.000 claims 1
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims 1
• 102000057028 SOS1 Human genes 0.000 claims 1
• 108700022176 SOS1 Proteins 0.000 claims 1
• 101100197320 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) RPL35A gene Proteins 0.000 claims 1
• 101150100839 Sos1 gene Proteins 0.000 claims 1
• 229960004308 acetylcysteine Drugs 0.000 claims 1
• GNPOLXWLSIADMF-UHFFFAOYSA-N azanium thiophene-2-carboxylate Chemical compound [NH4+].[O-]C(=O)C1=CC=CS1 GNPOLXWLSIADMF-UHFFFAOYSA-N 0.000 claims 1
• 125000005605 benzo group Chemical group 0.000 claims 1
• 125000004432 carbon atom Chemical group C* 0.000 claims 1
• 230000002759 chromosomal effect Effects 0.000 claims 1
• 208000010710 hepatitis C virus infection Diseases 0.000 claims 1
• 208000036142 Viral infection Diseases 0.000 abstract description 3
• 230000009385 viral infection Effects 0.000 abstract description 3
• 241000710781 Flaviviridae Species 0.000 abstract 1
• 239000000203 mixture Substances 0.000 description 258
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 170
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 148
• 239000000243 solution Substances 0.000 description 142
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 112
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 100
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
• 239000011541 reaction mixture Substances 0.000 description 63
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 60
• 239000007787 solid Substances 0.000 description 51
• 239000000741 silica gel Substances 0.000 description 50
• 229910002027 silica gel Inorganic materials 0.000 description 50
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 48
• 230000002829 reductive effect Effects 0.000 description 42
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 42
• 239000012267 brine Substances 0.000 description 41
• 239000003480 eluent Substances 0.000 description 41
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 39
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 39
• 238000004440 column chromatography Methods 0.000 description 38
• 150000004702 methyl esters Chemical class 0.000 description 37
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
• 239000002904 solvent Substances 0.000 description 25
• 239000000460 chlorine Substances 0.000 description 23
• 239000012299 nitrogen atmosphere Substances 0.000 description 22
• 238000000746 purification Methods 0.000 description 22
• 239000000543 intermediate Substances 0.000 description 21
• 239000000725 suspension Substances 0.000 description 20
• 229940047124 interferons Drugs 0.000 description 19
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 19
• 238000010992 reflux Methods 0.000 description 19
• 239000007864 aqueous solution Substances 0.000 description 18
• 239000012044 organic layer Substances 0.000 description 18
• 238000010898 silica gel chromatography Methods 0.000 description 18
• 108090000623 proteins and genes Proteins 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• 239000002253 acid Substances 0.000 description 15
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 15
• 239000010410 layer Substances 0.000 description 15
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
• 102000004169 proteins and genes Human genes 0.000 description 15
• 108010050904 Interferons Proteins 0.000 description 14
• 102000014150 Interferons Human genes 0.000 description 14
• 239000004480 active ingredient Substances 0.000 description 14
• 235000018102 proteins Nutrition 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
• 125000001624 naphthyl group Chemical group 0.000 description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 238000006243 chemical reaction Methods 0.000 description 12
• 238000004587 chromatography analysis Methods 0.000 description 12
• 239000013058 crude material Substances 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 12
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 11
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• 238000001914 filtration Methods 0.000 description 10
• 125000004076 pyridyl group Chemical group 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 239000012043 crude product Substances 0.000 description 9
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 9
• ODYARUXXIJYYNA-UHFFFAOYSA-N 4-methylcyclohexane-1-carbonyl chloride Chemical compound CC1CCC(C(Cl)=O)CC1 ODYARUXXIJYYNA-UHFFFAOYSA-N 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• 239000012298 atmosphere Substances 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 239000006260 foam Substances 0.000 description 8
• 239000012634 fragment Substances 0.000 description 8
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
• 150000002576 ketones Chemical class 0.000 description 8
• 239000012074 organic phase Substances 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 239000012047 saturated solution Substances 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 7
• 239000013612 plasmid Substances 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 6
• 229910017976 MgO 4 Inorganic materials 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 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
• RJGHQTVXGKYATR-UHFFFAOYSA-L dibutyl(dichloro)stannane Chemical compound CCCC[Sn](Cl)(Cl)CCCC RJGHQTVXGKYATR-UHFFFAOYSA-L 0.000 description 6
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
• 239000003921 oil Substances 0.000 description 6
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
• PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 6
• 238000002953 preparative HPLC Methods 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 229910000104 sodium hydride Inorganic materials 0.000 description 6
• 239000006188 syrup Substances 0.000 description 6
• 235000020357 syrup Nutrition 0.000 description 6
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 5
• 108060001084 Luciferase Proteins 0.000 description 5
• 239000005089 Luciferase Substances 0.000 description 5
• 102000012479 Serine Proteases Human genes 0.000 description 5
• 108010022999 Serine Proteases Proteins 0.000 description 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• 229940043279 diisopropylamine Drugs 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 239000000825 pharmaceutical preparation Substances 0.000 description 5
• 125000003386 piperidinyl group Chemical group 0.000 description 5
• 239000012312 sodium hydride Substances 0.000 description 5
• 125000001544 thienyl group Chemical group 0.000 description 5
• 238000005406 washing Methods 0.000 description 5
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 4
• VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 4
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
• QTDXSEZXAPHVBI-UHFFFAOYSA-N 4-methylcyclohexane-1-carboxylic acid Chemical compound CC1CCC(C(O)=O)CC1 QTDXSEZXAPHVBI-UHFFFAOYSA-N 0.000 description 4
• VSBSZSMJLXBCCV-SAABIXHNSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C1COCOC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C1COCOC1 VSBSZSMJLXBCCV-SAABIXHNSA-N 0.000 description 4
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
• WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 4
• 230000005587 bubbling Effects 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 238000009833 condensation Methods 0.000 description 4
• 230000005494 condensation Effects 0.000 description 4
• 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 4
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 239000011159 matrix material Substances 0.000 description 4
• GFOIAINHMGKDME-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(O)CC1 GFOIAINHMGKDME-UHFFFAOYSA-N 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• 230000010076 replication Effects 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 0.000 description 4
• 239000007921 spray Substances 0.000 description 4
• 239000000375 suspending agent Substances 0.000 description 4
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
• RNEQXUALSHFBCE-UHFFFAOYSA-N 3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-(4-oxocyclohexen-1-yl)thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCC(=O)CC=1)C(O)=O)C1CCC(O)CC1 RNEQXUALSHFBCE-UHFFFAOYSA-N 0.000 description 3
• CCFPXCANXFKCOE-UHFFFAOYSA-N 3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC=C1)C(O)=O)C1CCC(O)CC1 CCFPXCANXFKCOE-UHFFFAOYSA-N 0.000 description 3
• KHTGWQYWBVTUTI-UHFFFAOYSA-N 4-(1,2,4-triazol-1-yl)cyclohexan-1-one Chemical compound C1CC(=O)CCC1N1N=CN=C1 KHTGWQYWBVTUTI-UHFFFAOYSA-N 0.000 description 3
• JNFOVWRVUGBVAH-UHFFFAOYSA-N 8-methyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile Chemical compound C1CC(C)(C#N)CCC21OCCO2 JNFOVWRVUGBVAH-UHFFFAOYSA-N 0.000 description 3
• VJZBGDJWIYJHCU-UHFFFAOYSA-N 9,12-dioxa-2,4-diazadispiro[4.2.4^{8}.2^{5}]tetradecane-1,3-dione Chemical compound N1C(=O)NC(=O)C11CCC2(OCCO2)CC1 VJZBGDJWIYJHCU-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• YARFHYQWCPLHGK-VJVRBHMKSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(F)(F)CC1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(F)(F)CC1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 YARFHYQWCPLHGK-VJVRBHMKSA-N 0.000 description 3
• QVBYCKAQILQSKF-KESTWPANSA-N C[C@H](CC1)CC[C@@H]1C(N(C1CC[N+](C)(C)CC1)C1=C(C([O-])=O)SC(C2=CCCCC2)=C1)=O Chemical compound C[C@H](CC1)CC[C@@H]1C(N(C1CC[N+](C)(C)CC1)C1=C(C([O-])=O)SC(C2=CCCCC2)=C1)=O QVBYCKAQILQSKF-KESTWPANSA-N 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• 229940121759 Helicase inhibitor Drugs 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• PGBFYLVIMDQYMS-UHFFFAOYSA-N Methyl thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=CS1 PGBFYLVIMDQYMS-UHFFFAOYSA-N 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• 229940123066 Polymerase inhibitor Drugs 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 229940122055 Serine protease inhibitor Drugs 0.000 description 3
• 101710102218 Serine protease inhibitor Proteins 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 235000001014 amino acid Nutrition 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 239000004305 biphenyl Substances 0.000 description 3
• 235000010290 biphenyl Nutrition 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 229910002092 carbon dioxide Inorganic materials 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 239000006071 cream Substances 0.000 description 3
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 3
• 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 235000011187 glycerol Nutrition 0.000 description 3
• 125000001188 haloalkyl group Chemical group 0.000 description 3
• 208000006454 hepatitis Diseases 0.000 description 3
• 231100000283 hepatitis Toxicity 0.000 description 3
• 125000004404 heteroalkyl group Chemical group 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 125000001041 indolyl group Chemical group 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 229910052744 lithium Inorganic materials 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000002773 nucleotide Substances 0.000 description 3
• 125000003729 nucleotide group Chemical group 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 125000004193 piperazinyl group Chemical group 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 125000000335 thiazolyl group Chemical group 0.000 description 3
• 241000701447 unidentified baculovirus Species 0.000 description 3
• 238000001262 western blot Methods 0.000 description 3
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• WDXCZWJQOFPQOS-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]dec-7-en-8-ylboronic acid Chemical compound C1CC(B(O)O)=CCC21OCCO2 WDXCZWJQOFPQOS-UHFFFAOYSA-N 0.000 description 2
• WZWQNWWFCHNJON-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decane-8-carbonitrile Chemical compound C1CC(C#N)CCC21OCCO2 WZWQNWWFCHNJON-UHFFFAOYSA-N 0.000 description 2
• FEWLNYSYJNLUOO-UHFFFAOYSA-N 1-Piperidinecarboxaldehyde Chemical compound O=CN1CCCCC1 FEWLNYSYJNLUOO-UHFFFAOYSA-N 0.000 description 2
• TVOYTVJWNZERGX-UHFFFAOYSA-N 2-[8-(nitromethyl)-1,4-dioxaspiro[4.5]decan-8-yl]acetic acid Chemical compound C1CC(CC(=O)O)(C[N+]([O-])=O)CCC21OCCO2 TVOYTVJWNZERGX-UHFFFAOYSA-N 0.000 description 2
• VDCZRVJPEUWFMI-UHFFFAOYSA-N 2-azaspiro[4.5]decane-3,8-dione Chemical compound C1NC(=O)CC21CCC(=O)CC2 VDCZRVJPEUWFMI-UHFFFAOYSA-N 0.000 description 2
• DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
• BLNSUWQSBBAVMD-UHFFFAOYSA-N 3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-(4-oxocyclohexyl)thiophene-2-carboxylic acid Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C1CCC(=O)CC1)C(O)=O)C(=O)C1CCC(C)CC1 BLNSUWQSBBAVMD-UHFFFAOYSA-N 0.000 description 2
• QODZHJFYKBFCAJ-UHFFFAOYSA-N 4-(triazol-1-yl)cyclohexan-1-one Chemical compound C1CC(=O)CCC1N1N=NC=C1 QODZHJFYKBFCAJ-UHFFFAOYSA-N 0.000 description 2
• DZZLGMLLNNTZKL-UHFFFAOYSA-N 4-phenoxycyclohexan-1-one Chemical compound C1CC(=O)CCC1OC1=CC=CC=C1 DZZLGMLLNNTZKL-UHFFFAOYSA-N 0.000 description 2
• OQJNOHVPDZQBCM-UHFFFAOYSA-N 5-(3-hydroxycyclohexen-1-yl)-3-[(4-methylcyclohexanecarbonyl)-[4-(oxan-2-yloxy)cyclohexyl]amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCC(O)C=1)C(O)=O)C1CCC(OC2OCCCC2)CC1 OQJNOHVPDZQBCM-UHFFFAOYSA-N 0.000 description 2
• QRKLHFIPRBGHGR-UHFFFAOYSA-N 5-(4,4-dimethylcyclohexen-1-yl)-3-[[4-(methoxymethoxy)cyclohexyl]-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OCOC)CCC1N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)C(=O)C1CCC(C)CC1 QRKLHFIPRBGHGR-UHFFFAOYSA-N 0.000 description 2
• QMPSPZPLWQPLNV-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[[1-(2,2-difluoroethyl)piperidin-4-yl]-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCN(CC(F)F)CC1 QMPSPZPLWQPLNV-UHFFFAOYSA-N 0.000 description 2
• XEQYTVWTBFZWLU-UHFFFAOYSA-N 8-azido-1,4-dioxaspiro[4.5]decane Chemical compound C1CC(N=[N+]=[N-])CCC21OCCO2 XEQYTVWTBFZWLU-UHFFFAOYSA-N 0.000 description 2
• GTHRCIGLVKMIOM-UHFFFAOYSA-N 8-phenoxy-1,4-dioxaspiro[4.5]decane Chemical compound O1CCOC11CCC(OC=2C=CC=CC=2)CC1 GTHRCIGLVKMIOM-UHFFFAOYSA-N 0.000 description 2
• NUPNYQFGLIQQGM-UHFFFAOYSA-N 9,12-dioxa-3-azadispiro[4.2.4^{8}.2^{5}]tetradecan-2-one Chemical compound C1NC(=O)CC21CCC1(OCCO1)CC2 NUPNYQFGLIQQGM-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
• UUEBOGSQUVQIEE-YSXIEMCBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@@H](F)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)[C@@H]1CC[C@@H](F)CC1 UUEBOGSQUVQIEE-YSXIEMCBSA-N 0.000 description 2
• YIBUSNKWAYXYIB-YSXIEMCBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCCCCC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCCCCC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 YIBUSNKWAYXYIB-YSXIEMCBSA-N 0.000 description 2
• OZNMZONMPKBECR-GFKXMWDQSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC2(C(N(C)C(=O)N2C)=O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CCC2(C(N(C)C(=O)N2C)=O)CC1 OZNMZONMPKBECR-GFKXMWDQSA-N 0.000 description 2
• KCFLNRBBFVETGB-VJVRBHMKSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](C=2NN=NN=2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](C=2NN=NN=2)CC1 KCFLNRBBFVETGB-VJVRBHMKSA-N 0.000 description 2
• ARGZTWUXBRUFQC-GUJRETQESA-N C1C[C@@H](OCOCC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OCOCC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 ARGZTWUXBRUFQC-GUJRETQESA-N 0.000 description 2
• JIAZOZWJVJSOKM-KESTWPANSA-N COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C1CCN(CC(F)F)CC1 Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C1CCN(CC(F)F)CC1 JIAZOZWJVJSOKM-KESTWPANSA-N 0.000 description 2
• HCPWLJURHZATCV-UAPYVXQJSA-N COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C1CCNCC1 Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C1CCNCC1 HCPWLJURHZATCV-UAPYVXQJSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 2
• 241000710777 Classical swine fever virus Species 0.000 description 2
• 108091026890 Coding region Proteins 0.000 description 2
• 108020004414 DNA Proteins 0.000 description 2
• 241000710831 Flavivirus Species 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 235000010469 Glycine max Nutrition 0.000 description 2
• 241000711549 Hepacivirus C Species 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• 235000019766 L-Lysine Nutrition 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 229930040373 Paraformaldehyde Natural products 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 108010090804 Streptavidin Proteins 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 125000003368 amide group Chemical group 0.000 description 2
• 239000001099 ammonium carbonate Substances 0.000 description 2
• 235000012501 ammonium carbonate Nutrition 0.000 description 2
• 125000003725 azepanyl group Chemical group 0.000 description 2
• QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
• 229940061627 chloromethyl methyl ether Drugs 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
• XZWQKJXJNKYMAP-UHFFFAOYSA-N cyclohexen-1-ylboronic acid Chemical compound OB(O)C1=CCCCC1 XZWQKJXJNKYMAP-UHFFFAOYSA-N 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 230000002708 enhancing effect Effects 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
• 238000004108 freeze drying Methods 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 125000006038 hexenyl group Chemical group 0.000 description 2
• 239000012535 impurity Substances 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 229940079322 interferon Drugs 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• CDOSHBSSFJOMGT-UHFFFAOYSA-N linalool Chemical compound CC(C)=CCCC(C)(O)C=C CDOSHBSSFJOMGT-UHFFFAOYSA-N 0.000 description 2
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• KMTPLRIOOJYJQD-UHFFFAOYSA-N methyl 3-(1,4-dioxaspiro[4.5]decan-8-ylamino)thiophene-2-carboxylate Chemical compound S1C=CC(NC2CCC3(CC2)OCCO3)=C1C(=O)OC KMTPLRIOOJYJQD-UHFFFAOYSA-N 0.000 description 2
• JEMOHNKXRFEUDT-UHFFFAOYSA-N methyl 3-[(2-methylpropan-2-yl)oxycarbonylamino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1NC(=O)OC(C)(C)C JEMOHNKXRFEUDT-UHFFFAOYSA-N 0.000 description 2
• XYRRRTDDQUCNQM-UHFFFAOYSA-N methyl 3-amino-5-(cyclohexen-1-yl)thiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2CCCCC=2)=C1 XYRRRTDDQUCNQM-UHFFFAOYSA-N 0.000 description 2
• RZYLOBBUEWSONL-UHFFFAOYSA-N methyl 3-amino-5-bromothiophene-2-carboxylate Chemical compound COC(=O)C=1SC(Br)=CC=1N RZYLOBBUEWSONL-UHFFFAOYSA-N 0.000 description 2
• JWGYYGHNONYRSO-UHFFFAOYSA-N methyl 5-bromo-3-(1,4-dioxaspiro[4.5]decan-8-ylamino)thiophene-2-carboxylate Chemical compound S1C(Br)=CC(NC2CCC3(CC2)OCCO3)=C1C(=O)OC JWGYYGHNONYRSO-UHFFFAOYSA-N 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 239000012452 mother liquor Substances 0.000 description 2
• 239000002777 nucleoside Substances 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 229920002866 paraformaldehyde Polymers 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 239000006072 paste Substances 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 125000006513 pyridinyl methyl group Chemical group 0.000 description 2
• 238000007127 saponification reaction Methods 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000002562 thickening agent Substances 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 2
• MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
• 125000003944 tolyl group Chemical group 0.000 description 2
• 238000013519 translation Methods 0.000 description 2
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
• DCGLONGLPGISNX-UHFFFAOYSA-N trimethyl(prop-1-ynyl)silane Chemical compound CC#C[Si](C)(C)C DCGLONGLPGISNX-UHFFFAOYSA-N 0.000 description 2
• 230000029812 viral genome replication Effects 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
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
• RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 description 1
• 239000001490 (3R)-3,7-dimethylocta-1,6-dien-3-ol Substances 0.000 description 1
• PCXQRRQONBYBHO-UHFFFAOYSA-N (4-phenoxycyclohexen-1-yl) trifluoromethanesulfonate Chemical compound C1CC(OS(=O)(=O)C(F)(F)F)=CCC1OC1=CC=CC=C1 PCXQRRQONBYBHO-UHFFFAOYSA-N 0.000 description 1
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 description 1
• 230000006269 (delayed) early viral mRNA transcription Effects 0.000 description 1
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• VMFCTZUYOILUMY-UHFFFAOYSA-N 1,1-difluoro-2-iodoethane Chemical compound FC(F)CI VMFCTZUYOILUMY-UHFFFAOYSA-N 0.000 description 1
• OSQAYXCDJAOMDA-UHFFFAOYSA-N 1,2,5,6,8,8a-hexahydroindolizine-3,7-dione Chemical compound C1C(=O)CCN2C(=O)CCC21 OSQAYXCDJAOMDA-UHFFFAOYSA-N 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• SZVHDRLVQJXQBT-UHFFFAOYSA-N 1,3-dimethoxypropan-2-one Chemical compound COCC(=O)COC SZVHDRLVQJXQBT-UHFFFAOYSA-N 0.000 description 1
• HKQTYQDNCKMNHZ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)CCC21OCCO2 HKQTYQDNCKMNHZ-UHFFFAOYSA-N 0.000 description 1
• FTXBKFXPNSRBDW-UHFFFAOYSA-N 1-(1,4-dioxaspiro[4.5]decan-8-yl)-1,2,4-triazole Chemical compound O1CCOC11CCC(N2N=CN=C2)CC1 FTXBKFXPNSRBDW-UHFFFAOYSA-N 0.000 description 1
• VDNFJEDSFOJTFV-UHFFFAOYSA-N 1-(1,4-dioxaspiro[4.5]decan-8-yl)triazole Chemical compound O1CCOC11CCC(N2N=NC=C2)CC1 VDNFJEDSFOJTFV-UHFFFAOYSA-N 0.000 description 1
• IWUCXVSUMQZMFG-RGDLXGNYSA-N 1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 IWUCXVSUMQZMFG-RGDLXGNYSA-N 0.000 description 1
• 239000001074 1-methoxy-4-[(E)-prop-1-enyl]benzene Substances 0.000 description 1
• DDSBNJVJUCCGNO-UHFFFAOYSA-N 1-methyl-4-oxocyclohexane-1-carbonitrile Chemical compound N#CC1(C)CCC(=O)CC1 DDSBNJVJUCCGNO-UHFFFAOYSA-N 0.000 description 1
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• IIEQJSIHKZXTHY-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethoxymethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCOCOC(=O)C(C)(C)C IIEQJSIHKZXTHY-UHFFFAOYSA-N 0.000 description 1
• QVDOCNRIQLYHGK-UHFFFAOYSA-N 2,4-dimethyl-9,12-dioxa-2,4-diazadispiro[4.2.4^{8}.2^{5}]tetradecan-3-one Chemical compound CN1C(=O)N(C)CC11CCC2(OCCO2)CC1 QVDOCNRIQLYHGK-UHFFFAOYSA-N 0.000 description 1
• BIVITDRRVUSHJW-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-ylidene)acetic acid Chemical compound C1CC(=CC(=O)O)CCC21OCCO2 BIVITDRRVUSHJW-UHFFFAOYSA-N 0.000 description 1
• POQLVOYRGNFGRM-UHFFFAOYSA-N 2-Tetradecanone Chemical compound CCCCCCCCCCCCC(C)=O POQLVOYRGNFGRM-UHFFFAOYSA-N 0.000 description 1
• KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 1
• UOCKAJKVYAPUAJ-UHFFFAOYSA-N 2-pyrrolidin-1-yl-1H-azepine Chemical compound C1CCCN1C1=CC=CC=CN1 UOCKAJKVYAPUAJ-UHFFFAOYSA-N 0.000 description 1
• AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
• KHCXGFNZZRXOND-UHFFFAOYSA-N 3-(bromomethyl)pyridine Chemical compound BrCC1=CC=CN=C1 KHCXGFNZZRXOND-UHFFFAOYSA-N 0.000 description 1
• AKXYKVHNZQCHMF-UHFFFAOYSA-N 3-amino-4-methylthiophene-2-carboxylic acid Chemical compound CC1=CSC(C(O)=O)=C1N AKXYKVHNZQCHMF-UHFFFAOYSA-N 0.000 description 1
• PDZFCYUQPCIRNP-UHFFFAOYSA-N 3-amino-5-(cyclohexen-1-yl)thiophene-2-carboxylic acid Chemical compound C1(=CCCCC1)C1=CC(=C(S1)C(=O)O)N PDZFCYUQPCIRNP-UHFFFAOYSA-N 0.000 description 1
• VECHSBHMUYHDPV-UHFFFAOYSA-N 3-amino-5-bromo-4-methylthiophene-2-carboxylic acid Chemical compound CC=1C(=C(SC=1Br)C(=O)O)N VECHSBHMUYHDPV-UHFFFAOYSA-N 0.000 description 1
• OQEBBZSWEGYTPG-UHFFFAOYSA-N 3-aminobutanoic acid Chemical compound CC(N)CC(O)=O OQEBBZSWEGYTPG-UHFFFAOYSA-N 0.000 description 1
• AJKDUJRRWLQXHM-UHFFFAOYSA-N 3-bromocyclohexene Chemical compound BrC1CCCC=C1 AJKDUJRRWLQXHM-UHFFFAOYSA-N 0.000 description 1
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• WHGMHGPIJZTKTI-UHFFFAOYSA-N 3h-1,2-benzodithiole Chemical compound C1=CC=C2CSSC2=C1 WHGMHGPIJZTKTI-UHFFFAOYSA-N 0.000 description 1
• ZOLNSECVOZFNLU-UHFFFAOYSA-N 3h-1,2-benzoxathiole Chemical compound C1=CC=C2CSOC2=C1 ZOLNSECVOZFNLU-UHFFFAOYSA-N 0.000 description 1
• PXQMSTLNSHMSJB-UHFFFAOYSA-N 4,4-dimethylcyclohexan-1-one Chemical compound CC1(C)CCC(=O)CC1 PXQMSTLNSHMSJB-UHFFFAOYSA-N 0.000 description 1
• JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 1
• VMWOMVJNSSRZCP-UHFFFAOYSA-N 4-chloro-1,1-dimethylcyclohexane Chemical compound CC1(C)CCC(Cl)CC1 VMWOMVJNSSRZCP-UHFFFAOYSA-N 0.000 description 1
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
• VBLAAESAMSKCOO-UHFFFAOYSA-N 5-(1,2,4-triazol-1-yl)heptan-2-one Chemical compound CC(=O)CCC(CC)N1C=NC=N1 VBLAAESAMSKCOO-UHFFFAOYSA-N 0.000 description 1
• LNYKGELUODVSNS-UHFFFAOYSA-N 5-(cyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)C1CCC(C)CC1 LNYKGELUODVSNS-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 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 1
• AMQIRCLQGYEIQA-UHFFFAOYSA-N 9,12-dioxa-2,4-diazadispiro[4.2.4^{8}.2^{5}]tetradecan-3-one Chemical compound N1C(=O)NCC11CCC2(OCCO2)CC1 AMQIRCLQGYEIQA-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
• 108010082126 Alanine transaminase Proteins 0.000 description 1
• 208000002109 Argyria Diseases 0.000 description 1
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 241000710780 Bovine viral diarrhea virus 1 Species 0.000 description 1
• LIILLHPREYYFSJ-HAQNSBGRSA-N BrC1=CC(=C(S1)C(=O)O)N(C(=O)[C@@H]1CC[C@H](CC1)C)C1COC(OC1)(C)C Chemical compound BrC1=CC(=C(S1)C(=O)O)N(C(=O)[C@@H]1CC[C@H](CC1)C)C1COC(OC1)(C)C LIILLHPREYYFSJ-HAQNSBGRSA-N 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• XSKWKTVUQVYCKD-MUVNWNFZSA-N C1C(=NOCC)CCC(C=2SC(=C(N([C@@H]3CC[C@@H](O)CC3)C(=O)[C@@H]3CC[C@@H](C)CC3)C=2)C(O)=O)=C1 Chemical compound C1C(=NOCC)CCC(C=2SC(=C(N([C@@H]3CC[C@@H](O)CC3)C(=O)[C@@H]3CC[C@@H](C)CC3)C=2)C(O)=O)=C1 XSKWKTVUQVYCKD-MUVNWNFZSA-N 0.000 description 1
• KVIIFMHSHSIEHH-OSHZUIANSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(=O)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCC(=O)CC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 KVIIFMHSHSIEHH-OSHZUIANSA-N 0.000 description 1
• VCJJWZOMFHUKMX-VJVRBHMKSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCCCC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C1CCCCC1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 VCJJWZOMFHUKMX-VJVRBHMKSA-N 0.000 description 1
• KEFGYEBMBUZYLK-QEYNBREGSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1C2CCC(C2)C=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1C2CCC(C2)C=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 KEFGYEBMBUZYLK-QEYNBREGSA-N 0.000 description 1
• UFAKXAOJOPWWCD-GUJRETQESA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(C)(C)CC=1)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 UFAKXAOJOPWWCD-GUJRETQESA-N 0.000 description 1
• BWSQKLRZLXODAO-BOIGYYLYSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)=NOCC=1C=CC=CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)=NOCC=1C=CC=CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 BWSQKLRZLXODAO-BOIGYYLYSA-N 0.000 description 1
• JVSQRBKXYYHNAL-CUUIZVKISA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)OC=1C=CC=CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC(CC=1)OC=1C=CC=CC=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 JVSQRBKXYYHNAL-CUUIZVKISA-N 0.000 description 1
• DHZRKGZVOWHWSR-YSXIEMCBSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC2(CC=1)OCCO2)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical class C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC2(CC=1)OCCO2)C(O)=O)[C@@H]1CC[C@@H](O)CC1 DHZRKGZVOWHWSR-YSXIEMCBSA-N 0.000 description 1
• USXOSXKMNUPPNO-JOSYPBKRSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC2CCCCC2C=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCC2CCCCC2C=1)C(O)=O)[C@@H]1CC[C@@H](O)CC1 USXOSXKMNUPPNO-JOSYPBKRSA-N 0.000 description 1
• YWEUSNUNKANIKM-AFARHQOCSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OCOC(=O)C(C)(C)C)C1CCN(C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OCOC(=O)C(C)(C)C)C1CCN(C)CC1 YWEUSNUNKANIKM-AFARHQOCSA-N 0.000 description 1
• QMKHTEOIBBSGKN-WHLIJDCNSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CC(C2)CCC2C1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C1CC(C2)CCC2C1 QMKHTEOIBBSGKN-WHLIJDCNSA-N 0.000 description 1
• SATLBJQBKFNRNL-VYUAXZJKSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](C#N)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](C#N)CC1 SATLBJQBKFNRNL-VYUAXZJKSA-N 0.000 description 1
• CVBAQFSUNUPYPG-GUJRETQESA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](C(C)(C)C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@@H](C(C)(C)C)CC1 CVBAQFSUNUPYPG-GUJRETQESA-N 0.000 description 1
• CVBAQFSUNUPYPG-FORLXOICSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@H](C(C)(C)C)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@@H]1CC[C@H](C(C)(C)C)CC1 CVBAQFSUNUPYPG-FORLXOICSA-N 0.000 description 1
• AHQGMPPSKUDUDL-IXXJFMHHSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@H]1CC[C@@H](F)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)[C@H]1CC[C@@H](F)CC1 AHQGMPPSKUDUDL-IXXJFMHHSA-N 0.000 description 1
• JYVDRDYGGXJIDJ-KESTWPANSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCCC=1)C(O)=O)C1CCCCC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C=1CCCCCC=1)C(O)=O)C1CCCCC1 JYVDRDYGGXJIDJ-KESTWPANSA-N 0.000 description 1
• XEKVZZSSIVDXMJ-KESTWPANSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC=C1C=1CCCCC=1)C(O)=O)C1CCN(CCF)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC=C1C=1CCCCC=1)C(O)=O)C1CCN(CCF)CC1 XEKVZZSSIVDXMJ-KESTWPANSA-N 0.000 description 1
• VNDXSTNPMCDMEN-SAABIXHNSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C=1C=C2OCOC2=CC=1)C1=C(C(O)=O)SC(C=2CCCCC=2)=C1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C=1C=C2OCOC2=CC=1)C1=C(C(O)=O)SC(C=2CCCCC=2)=C1 VNDXSTNPMCDMEN-SAABIXHNSA-N 0.000 description 1
• ZLRJZXOWDZQFFV-JOLHVKOESA-N C1C[C@@H](COC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](COC)CC[C@@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 ZLRJZXOWDZQFFV-JOLHVKOESA-N 0.000 description 1
• ZLRJZXOWDZQFFV-HUBIGZFNSA-N C1C[C@@H](COC)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](COC)CC[C@H]1N(C1=C(SC(=C1)C=1CCCCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 ZLRJZXOWDZQFFV-HUBIGZFNSA-N 0.000 description 1
• KMYHCFYNQQPOHB-GUJRETQESA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(=O)OC)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(=O)OC)C(=O)[C@@H]1CC[C@@H](C)CC1 KMYHCFYNQQPOHB-GUJRETQESA-N 0.000 description 1
• GQOLEXCMAPABGR-YSXIEMCBSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCCCC1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C1CCCCC1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 GQOLEXCMAPABGR-YSXIEMCBSA-N 0.000 description 1
• COSFOXLUNFUJIP-JOLHVKOESA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CC(C)(C)CCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C=1CC(C)(C)CCC=1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 COSFOXLUNFUJIP-JOLHVKOESA-N 0.000 description 1
• MPHNLRLRWAYJHT-GUJRETQESA-N C1C[C@@H](OCOC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OCOC)CC[C@@H]1N(C1=C(SC(=C1)C1CCC(C)(C)CC1)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 MPHNLRLRWAYJHT-GUJRETQESA-N 0.000 description 1
• OVTIYPJPKHHYCK-RPCDJPHFSA-N CC(C)C(=O)NC1CCC(CC1)N(C(=O)[C@H]1CC[C@H](C)CC1)c1cc(sc1C(O)=O)C1=CCCCC1 Chemical class CC(C)C(=O)NC1CCC(CC1)N(C(=O)[C@H]1CC[C@H](C)CC1)c1cc(sc1C(O)=O)C1=CCCCC1 OVTIYPJPKHHYCK-RPCDJPHFSA-N 0.000 description 1
• QLNGJSGLNHZLTP-UHFFFAOYSA-N CCCC(=O)NC1CCC(CC1)N(C2=C(SC(=C2)C3=CCCCC3)C(=O)O)C(=O)C4CCC(CC4)C Chemical compound CCCC(=O)NC1CCC(CC1)N(C2=C(SC(=C2)C3=CCCCC3)C(=O)O)C(=O)C4CCC(CC4)C QLNGJSGLNHZLTP-UHFFFAOYSA-N 0.000 description 1
• OLLBRPWLJACADW-UHFFFAOYSA-N CCCCCCCC(CC)OS(C)(=O)=O Chemical compound CCCCCCCC(CC)OS(C)(=O)=O OLLBRPWLJACADW-UHFFFAOYSA-N 0.000 description 1
• NRSKLCCINAQQQL-UHFFFAOYSA-N CCN(CC)S.F.F.F Chemical compound CCN(CC)S.F.F.F NRSKLCCINAQQQL-UHFFFAOYSA-N 0.000 description 1
• PRJPAKLDRJCJFQ-GVRPRLBFSA-N COC(=O)C=1SC(C=2CCC(C)(C)CC=2)=CC=1N(C(CO[Si](C(C)C)(C(C)C)C(C)C)CO[Si](C(C)C)(C(C)C)C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 Chemical compound COC(=O)C=1SC(C=2CCC(C)(C)CC=2)=CC=1N(C(CO[Si](C(C)C)(C(C)C)C(C)C)CO[Si](C(C)C)(C(C)C)C(C)C)C(=O)[C@H]1CC[C@H](C)CC1 PRJPAKLDRJCJFQ-GVRPRLBFSA-N 0.000 description 1
• SCTGGEQFOGRINW-RPCDJPHFSA-N COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C(CC1)CCC1N1C=NC=N1 Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C(CC1)CCC1N1C=NC=N1 SCTGGEQFOGRINW-RPCDJPHFSA-N 0.000 description 1
• MRYMMWAGVKALOS-AQYVVDRMSA-N COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C(CC1)CCN1C1=NC=CC=N1 Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C(CC1)CCN1C1=NC=CC=N1 MRYMMWAGVKALOS-AQYVVDRMSA-N 0.000 description 1
• DATGYICDXPCPFN-GARHLSDISA-N COCO[C@@H]1CC[C@H](CC1)N(C(=O)[C@@H]1CC[C@H](CC1)C)C1=C(SC=C1)C(=O)O Chemical compound COCO[C@@H]1CC[C@H](CC1)N(C(=O)[C@@H]1CC[C@H](CC1)C)C1=C(SC=C1)C(=O)O DATGYICDXPCPFN-GARHLSDISA-N 0.000 description 1
• MYUJTVLROYBVEP-JOCQHMNTSA-N C[C@@H]1CC[C@H](CC1)C(=O)N(C1=C(SC=C1)C(=O)O)C1CCNCC1 Chemical compound C[C@@H]1CC[C@H](CC1)C(=O)N(C1=C(SC=C1)C(=O)O)C1CCNCC1 MYUJTVLROYBVEP-JOCQHMNTSA-N 0.000 description 1
• QTDXSEZXAPHVBI-LJGSYFOKSA-N C[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound C[C@H]1CC[C@H](C(O)=O)CC1 QTDXSEZXAPHVBI-LJGSYFOKSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 101710132601 Capsid protein Proteins 0.000 description 1
• WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 description 1
• OSCRSGVQXQCKKP-FMMATFHQSA-N Cl.C[C@H]1CC[C@@H](CC1)C(=O)N([C@H]1CC[C@@H](CC1)n1cncn1)c1cc(sc1C(O)=O)C1=CCCCC1 Chemical compound Cl.C[C@H]1CC[C@@H](CC1)C(=O)N([C@H]1CC[C@@H](CC1)n1cncn1)c1cc(sc1C(O)=O)C1=CCCCC1 OSCRSGVQXQCKKP-FMMATFHQSA-N 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
• NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
• 208000001490 Dengue Diseases 0.000 description 1
• 206010012310 Dengue fever Diseases 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 108090000331 Firefly luciferases Proteins 0.000 description 1
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000031220 Hemophilia Diseases 0.000 description 1
• 208000009292 Hemophilia A Diseases 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 206010019799 Hepatitis viral Diseases 0.000 description 1
• 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
• 101000868422 Homo sapiens Sushi, nidogen and EGF-like domain-containing protein 1 Proteins 0.000 description 1
• 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 1
• 102100040019 Interferon alpha-1/13 Human genes 0.000 description 1
• 102100040018 Interferon alpha-2 Human genes 0.000 description 1
• 108010079944 Interferon-alpha2b Proteins 0.000 description 1
• 108010029660 Intrinsically Disordered Proteins Proteins 0.000 description 1
• 241000710842 Japanese encephalitis virus Species 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
• 229930064664 L-arginine Natural products 0.000 description 1
• 235000014852 L-arginine Nutrition 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• PPNFNPIBVRLCFC-MLRKGSHFSA-N N1([C@H]2CC[C@@H](CC2)N(C=2C=C(SC=2C(=O)OC)C2CCC(C)(C)CC2)C(=O)[C@@H]2CC[C@@H](C)CC2)C=CN=N1 Chemical compound N1([C@H]2CC[C@@H](CC2)N(C=2C=C(SC=2C(=O)OC)C2CCC(C)(C)CC2)C(=O)[C@@H]2CC[C@@H](C)CC2)C=CN=N1 PPNFNPIBVRLCFC-MLRKGSHFSA-N 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 238000012408 PCR amplification Methods 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 239000004952 Polyamide Substances 0.000 description 1
• 108010076039 Polyproteins Proteins 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 108091081024 Start codon Proteins 0.000 description 1
• 102100032853 Sushi, nidogen and EGF-like domain-containing protein 1 Human genes 0.000 description 1
• 108020005038 Terminator Codon Proteins 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 description 1
• 239000005844 Thymol Substances 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 108020000999 Viral RNA Proteins 0.000 description 1
• 241000710772 Yellow fever virus Species 0.000 description 1
• JBPUGFODGPKTDW-SFHVURJKSA-N [(3s)-oxolan-3-yl] n-[[3-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoylamino]phenyl]methyl]carbamate Chemical compound C=1C=C(C=2OC=NC=2)C(OC)=CC=1NC(=O)NC(C=1)=CC=CC=1CNC(=O)O[C@H]1CCOC1 JBPUGFODGPKTDW-SFHVURJKSA-N 0.000 description 1
• WFIHKLWVLPBMIQ-UHFFFAOYSA-N [1,3]thiazolo[5,4-b]pyridine Chemical compound C1=CN=C2SC=NC2=C1 WFIHKLWVLPBMIQ-UHFFFAOYSA-N 0.000 description 1
• UCAVIHWWIOYPML-UHFFFAOYSA-N [1-(1,4-dioxaspiro[4.5]decan-8-yl)triazol-4-yl]-trimethylsilane Chemical compound N1=NC([Si](C)(C)C)=CN1C1CCC2(OCCO2)CC1 UCAVIHWWIOYPML-UHFFFAOYSA-N 0.000 description 1
• HLLIYDVPIGSIJX-AFFTWYSYSA-N [Cl-].CC(C)OC(=O)OCOC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C1CC[NH+](C)CC1 Chemical compound [Cl-].CC(C)OC(=O)OCOC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)[C@@H]1CC[C@@H](C)CC1)C1CC[NH+](C)CC1 HLLIYDVPIGSIJX-AFFTWYSYSA-N 0.000 description 1
• KBXDAFWYJGKGSE-UHFFFAOYSA-N [Li].CC1(C)[SiH2][SiH]=NC(C)(C)C1(C)C Chemical compound [Li].CC1(C)[SiH2][SiH]=NC(C)(C)C1(C)C KBXDAFWYJGKGSE-UHFFFAOYSA-N 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000003929 acidic solution Substances 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• HSMPSHPWCOOUJH-UHFFFAOYSA-N anilinyl Chemical group [NH]C1=CC=CC=C1 HSMPSHPWCOOUJH-UHFFFAOYSA-N 0.000 description 1
• 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
• 239000012223 aqueous fraction Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 239000000305 astragalus gummifer gum Substances 0.000 description 1
• 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 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
• BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229960004424 carbon dioxide Drugs 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• RECUKUPTGUEGMW-UHFFFAOYSA-N carvacrol Chemical compound CC(C)C1=CC=C(C)C(O)=C1 RECUKUPTGUEGMW-UHFFFAOYSA-N 0.000 description 1
• HHTWOMMSBMNRKP-UHFFFAOYSA-N carvacrol Natural products CC(=C)C1=CC=C(C)C(O)=C1 HHTWOMMSBMNRKP-UHFFFAOYSA-N 0.000 description 1
• 235000007746 carvacrol Nutrition 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
• 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
• 125000004773 chlorofluoromethyl group Chemical group [H]C(F)(Cl)* 0.000 description 1
• GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 229940043350 citral Drugs 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 229940125961 compound 24 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 1
• XDRVAZAFNWDVOE-UHFFFAOYSA-N cyclohexylboronic acid Chemical compound OB(O)C1CCCCC1 XDRVAZAFNWDVOE-UHFFFAOYSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 208000025729 dengue disease Diseases 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
• 125000006003 dichloroethyl group Chemical group 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• 125000004188 dichlorophenyl group Chemical group 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• 125000006001 difluoroethyl group Chemical group 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
• CXQRZKIIGJLWPJ-UHFFFAOYSA-N diphenylphosphane;1-naphthalen-1-ylnaphthalene Chemical group C=1C=CC=CC=1PC1=CC=CC=C1.C1=CC=C2C(C=3C4=CC=CC=C4C=CC=3)=CC=CC2=C1 CXQRZKIIGJLWPJ-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 241001493065 dsRNA viruses Species 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 238000001493 electron microscopy Methods 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 239000012149 elution buffer Substances 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 230000009088 enzymatic function Effects 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 125000005469 ethylenyl group Chemical group 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 239000003349 gelling agent Substances 0.000 description 1
• WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000005802 health problem Effects 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000005980 hexynyl group Chemical group 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
• WYXXLXHHWYNKJF-UHFFFAOYSA-N isocarvacrol Natural products CC(C)C1=CC=C(O)C(C)=C1 WYXXLXHHWYNKJF-UHFFFAOYSA-N 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 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 1
• 239000008101 lactose Substances 0.000 description 1
• 229930007744 linalool Natural products 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 229910003002 lithium salt Inorganic materials 0.000 description 1
• 159000000002 lithium salts Chemical group 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 238000003468 luciferase reporter gene assay Methods 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• WWOYCMCZTZTIGU-UHFFFAOYSA-L magnesium;2-carboxybenzenecarboperoxoate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].OOC(=O)C1=CC=CC=C1C([O-])=O.OOC(=O)C1=CC=CC=C1C([O-])=O WWOYCMCZTZTIGU-UHFFFAOYSA-L 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 210000004779 membrane envelope Anatomy 0.000 description 1
• 229940041616 menthol Drugs 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 229950003168 merimepodib Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• OGJDZVITLCFAII-UHFFFAOYSA-N methyl 2-(1,4-dioxaspiro[4.5]decan-8-ylidene)acetate Chemical compound C1CC(=CC(=O)OC)CCC21OCCO2 OGJDZVITLCFAII-UHFFFAOYSA-N 0.000 description 1
• NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
• CKHQMNWVACYRCJ-UHFFFAOYSA-N methyl 3-[(4-azidocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-(4,4-dimethylcyclohexyl)thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2CCC(C)(C)CC2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(N=[N+]=[N-])CC1 CKHQMNWVACYRCJ-UHFFFAOYSA-N 0.000 description 1
• BQQHXIZCAPCAQE-UHFFFAOYSA-N methyl 3-amino-5-(4,4-dimethylcyclohexen-1-yl)thiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2CCC(C)(C)CC=2)=C1 BQQHXIZCAPCAQE-UHFFFAOYSA-N 0.000 description 1
• TWEQNZZOOFKOER-UHFFFAOYSA-N methyl 3-aminothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1N TWEQNZZOOFKOER-UHFFFAOYSA-N 0.000 description 1
• UEARGZRWCIVDOO-UHFFFAOYSA-N methyl 3-anilino-5-(cyclohexen-1-yl)thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1NC1=CC=CC=C1 UEARGZRWCIVDOO-UHFFFAOYSA-N 0.000 description 1
• NKMNDFXAMGNIMF-UHFFFAOYSA-N methyl 3-bromo-5-(4,4-dimethylcyclohexen-1-yl)thiophene-2-carboxylate Chemical compound BrC1=C(C(=O)OC)SC(C=2CCC(C)(C)CC=2)=C1 NKMNDFXAMGNIMF-UHFFFAOYSA-N 0.000 description 1
• PEGSJNCGPSIJOX-UHFFFAOYSA-N methyl 3-bromothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1Br PEGSJNCGPSIJOX-UHFFFAOYSA-N 0.000 description 1
• RDMQJIFPUUUVAS-UHFFFAOYSA-N methyl 5-(1-hydroxycyclohexyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]thiophene-2-carboxylate Chemical compound CC(C)(C)OC(=O)NC1=C(C(=O)OC)SC(C2(O)CCCCC2)=C1 RDMQJIFPUUUVAS-UHFFFAOYSA-N 0.000 description 1
• LIXSQKKNCMTAOV-UHFFFAOYSA-N methyl 5-(2,6-difluorocyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1C(CCCC=1F)F)C(=O)OC)C(=O)C1CCC(C)CC1 LIXSQKKNCMTAOV-UHFFFAOYSA-N 0.000 description 1
• SWVLETVKMGFLHZ-UHFFFAOYSA-N methyl 5-(4,4-dimethylcyclohexyl)-3-[1,3-dioxan-5-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2CCC(C)(C)CC2)=CC=1N(C(=O)C1CCC(C)CC1)C1COCOC1 SWVLETVKMGFLHZ-UHFFFAOYSA-N 0.000 description 1
• OSUVFWFEGCZXCD-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OC)C(=O)C1CCC(C)CC1 OSUVFWFEGCZXCD-UHFFFAOYSA-N 0.000 description 1
• WUDQZNWCZNXVSM-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[1,3-dioxan-5-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1COCOC1 WUDQZNWCZNXVSM-UHFFFAOYSA-N 0.000 description 1
• CKAFQCCNBSOGEI-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[[4-(methoxymethoxy)cyclohexyl]-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OCOC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OC)C(=O)C1CCC(C)CC1 CKAFQCCNBSOGEI-UHFFFAOYSA-N 0.000 description 1
• AEJSNRFCXSRZNH-UHFFFAOYSA-N methyl 5-bromo-3-[(2,4-dioxo-1,3-diazaspiro[4.5]decan-8-yl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2CCC3(CC2)C(NC(=O)N3)=O)C(=O)C2CCC(C)CC2)=C1C(=O)OC AEJSNRFCXSRZNH-UHFFFAOYSA-N 0.000 description 1
• VONOFJWOVOTLIO-UHFFFAOYSA-N methyl 5-bromo-3-[(4-fluorocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2CCC(F)CC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC VONOFJWOVOTLIO-UHFFFAOYSA-N 0.000 description 1
• MXZRZTHTXZXYIZ-UHFFFAOYSA-N methyl 5-bromo-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2CCC(O)CC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC MXZRZTHTXZXYIZ-UHFFFAOYSA-N 0.000 description 1
• SVQDIBDRCYBDIN-UHFFFAOYSA-N methyl 5-bromo-3-[(4-methylcyclohexanecarbonyl)-(4-oxocyclohexyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2CCC(=O)CC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC SVQDIBDRCYBDIN-UHFFFAOYSA-N 0.000 description 1
• QRHBBGITAUTBKO-UHFFFAOYSA-N methyl 5-bromo-3-[1,3-dioxan-5-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2COCOC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC QRHBBGITAUTBKO-UHFFFAOYSA-N 0.000 description 1
• JOCAMKMEAASVJQ-UHFFFAOYSA-N methyl 5-bromo-3-[1,4-dioxaspiro[4.5]decan-8-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2CCC3(CC2)OCCO3)C(=O)C2CCC(C)CC2)=C1C(=O)OC JOCAMKMEAASVJQ-UHFFFAOYSA-N 0.000 description 1
• YMZBNCXRVMHBHA-UHFFFAOYSA-N methyl 5-cyclohex-2-en-1-yl-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2C=CCCC2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(O)CC1 YMZBNCXRVMHBHA-UHFFFAOYSA-N 0.000 description 1
• UODPHKFUTYRNDZ-UHFFFAOYSA-N methyl 5-cyclohex-2-en-1-yl-3-[(4-methylcyclohexanecarbonyl)-(4-oxocyclohexyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2C=CCCC2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(=O)CC1 UODPHKFUTYRNDZ-UHFFFAOYSA-N 0.000 description 1
• 125000004492 methyl ester group Chemical group 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 238000000465 moulding Methods 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
• AQFWNELGMODZGC-UHFFFAOYSA-N o-ethylhydroxylamine Chemical compound CCON AQFWNELGMODZGC-UHFFFAOYSA-N 0.000 description 1
• NUXCOKIYARRTDC-UHFFFAOYSA-N o-ethylhydroxylamine;hydron;chloride Chemical compound Cl.CCON NUXCOKIYARRTDC-UHFFFAOYSA-N 0.000 description 1
• 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 125000005561 phenanthryl group Chemical group 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 238000005498 polishing Methods 0.000 description 1
• 229920002647 polyamide Polymers 0.000 description 1
• 235000021395 porridge Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
• VZOPRCCTKLAGPN-ZFJVMAEJSA-L potassium;sodium;(2r,3r)-2,3-dihydroxybutanedioate;tetrahydrate Chemical class O.O.O.O.[Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VZOPRCCTKLAGPN-ZFJVMAEJSA-L 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 238000000611 regression analysis Methods 0.000 description 1
• 239000012266 salt solution Substances 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 150000003385 sodium Chemical class 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229940054269 sodium pyruvate Drugs 0.000 description 1
• 159000000000 sodium salts Chemical group 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
• 150000003463 sulfur Chemical class 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 description 1
• 229950006081 taribavirin Drugs 0.000 description 1
• 229960002935 telaprevir Drugs 0.000 description 1
• BBAWEDCPNXPBQM-GDEBMMAJSA-N telaprevir Chemical compound N([C@H](C(=O)N[C@H](C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1)C(C)(C)C)C1CCCCC1)C(=O)C1=CN=CC=N1 BBAWEDCPNXPBQM-GDEBMMAJSA-N 0.000 description 1
• 108010017101 telaprevir Proteins 0.000 description 1
• GFNMJSGQSWLTOR-UHFFFAOYSA-N tert-butyl 4-[[5-(cyclohexen-1-yl)-2-methoxycarbonylthiophen-3-yl]-(4-methylcyclohexanecarbonyl)amino]piperidine-1-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCN(C(=O)OC(C)(C)C)CC1 GFNMJSGQSWLTOR-UHFFFAOYSA-N 0.000 description 1
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 description 1
• BMWZMDDFCPGUSM-UHFFFAOYSA-N thiophene-2-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CS1 BMWZMDDFCPGUSM-UHFFFAOYSA-N 0.000 description 1
• 150000003577 thiophenes Chemical class 0.000 description 1
• 229960000790 thymol Drugs 0.000 description 1
• 229910052718 tin Inorganic materials 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• CMHHITPYCHHOGT-UHFFFAOYSA-N tributylborane Chemical compound CCCCB(CCCC)CCCC CMHHITPYCHHOGT-UHFFFAOYSA-N 0.000 description 1
• 125000006000 trichloroethyl group Chemical group 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 238000002604 ultrasonography Methods 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 201000001862 viral hepatitis Diseases 0.000 description 1
• 230000006514 viral protein processing Effects 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229940051021 yellow-fever virus Drugs 0.000 description 1