JP2007501185A - C型肝炎を含むフラビウイルス関連疾患を治療するためのプリンヌクレオシド類似体 - Google Patents
C型肝炎を含むフラビウイルス関連疾患を治療するためのプリンヌクレオシド類似体 Download PDFInfo
- Publication number
- JP2007501185A JP2007501185A JP2006520940A JP2006520940A JP2007501185A JP 2007501185 A JP2007501185 A JP 2007501185A JP 2006520940 A JP2006520940 A JP 2006520940A JP 2006520940 A JP2006520940 A JP 2006520940A JP 2007501185 A JP2007501185 A JP 2007501185A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- alkenyl
- alkynyl
- acyl
- optionally substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 241000710831 Flavivirus Species 0.000 title claims abstract description 52
- 208000005176 Hepatitis C Diseases 0.000 title abstract description 17
- 201000010099 disease Diseases 0.000 title description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 7
- 150000003834 purine nucleoside derivatives Chemical class 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 121
- 239000000651 prodrug Substances 0.000 claims abstract description 74
- 229940002612 prodrug Drugs 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 62
- 241000710778 Pestivirus Species 0.000 claims abstract description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 662
- 125000000304 alkynyl group Chemical group 0.000 claims description 187
- 150000001875 compounds Chemical class 0.000 claims description 171
- 125000002252 acyl group Chemical group 0.000 claims description 168
- 125000003342 alkenyl group Chemical group 0.000 claims description 160
- 229910052736 halogen Inorganic materials 0.000 claims description 97
- -1 especially CF 3 Chemical class 0.000 claims description 94
- 150000002367 halogens Chemical class 0.000 claims description 81
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 55
- 125000003545 alkoxy group Chemical group 0.000 claims description 54
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 52
- 229910052760 oxygen Inorganic materials 0.000 claims description 50
- 229910052717 sulfur Inorganic materials 0.000 claims description 48
- 238000011282 treatment Methods 0.000 claims description 48
- 239000003814 drug Substances 0.000 claims description 46
- 229910019142 PO4 Inorganic materials 0.000 claims description 43
- 239000010452 phosphate Substances 0.000 claims description 43
- 229940079322 interferon Drugs 0.000 claims description 42
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 41
- 108010050904 Interferons Proteins 0.000 claims description 38
- 102000014150 Interferons Human genes 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 35
- 125000003282 alkyl amino group Chemical group 0.000 claims description 26
- 239000001226 triphosphate Substances 0.000 claims description 26
- 150000001540 azides Chemical class 0.000 claims description 25
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- 235000011178 triphosphate Nutrition 0.000 claims description 25
- 229910052794 bromium Inorganic materials 0.000 claims description 23
- 239000003112 inhibitor Substances 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 150000001350 alkyl halides Chemical class 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- 229910052740 iodine Inorganic materials 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 20
- 125000003729 nucleotide group Chemical group 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 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 18
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 18
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 229960000329 ribavirin Drugs 0.000 claims description 16
- 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 16
- 239000003085 diluting agent Substances 0.000 claims description 15
- 238000001727 in vivo Methods 0.000 claims description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 15
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 13
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 150000002632 lipids Chemical class 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 238000006467 substitution reaction Methods 0.000 claims description 12
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 11
- 235000014633 carbohydrates Nutrition 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 150000001720 carbohydrates Chemical class 0.000 claims description 10
- 235000012000 cholesterol Nutrition 0.000 claims description 10
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 9
- 235000001014 amino acid Nutrition 0.000 claims description 8
- 239000002775 capsule Substances 0.000 claims description 8
- 108010047761 Interferon-alpha Proteins 0.000 claims description 7
- 102000006992 Interferon-alpha Human genes 0.000 claims description 7
- 230000003441 anti-flavivirus Effects 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 150000003904 phospholipids Chemical class 0.000 claims description 7
- 108010005716 Interferon beta-1a Proteins 0.000 claims description 6
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 5
- 230000000692 anti-sense effect Effects 0.000 claims description 5
- 230000001419 dependent effect Effects 0.000 claims description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
- 108700027921 interferon tau Proteins 0.000 claims description 5
- 238000013519 translation Methods 0.000 claims description 5
- 102000053642 Catalytic RNA Human genes 0.000 claims description 4
- 108090000994 Catalytic RNA Proteins 0.000 claims description 4
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 4
- 108010080374 albuferon Proteins 0.000 claims description 4
- 229960004461 interferon beta-1a Drugs 0.000 claims description 4
- 229940046166 oligodeoxynucleotide Drugs 0.000 claims description 4
- 108091092562 ribozyme Proteins 0.000 claims description 4
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 3
- GVEZIHKRYBHEFX-MNOVXSKESA-N 13C-Cerulenin Natural products CC=CCC=CCCC(=O)[C@H]1O[C@@H]1C(N)=O GVEZIHKRYBHEFX-MNOVXSKESA-N 0.000 claims description 3
- YYVYAPXYZVYDHN-UHFFFAOYSA-N 9,10-phenanthroquinone Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CC=C3C2=C1 YYVYAPXYZVYDHN-UHFFFAOYSA-N 0.000 claims description 3
- 229940121759 Helicase inhibitor Drugs 0.000 claims description 3
- 108010074328 Interferon-gamma Proteins 0.000 claims description 3
- 102000008070 Interferon-gamma Human genes 0.000 claims description 3
- FIVPIPIDMRVLAY-UHFFFAOYSA-N aspergillin Natural products C1C2=CC=CC(O)C2N2C1(SS1)C(=O)N(C)C1(CO)C2=O FIVPIPIDMRVLAY-UHFFFAOYSA-N 0.000 claims description 3
- ZVSKZLHKADLHSD-UHFFFAOYSA-N benzanilide Chemical compound C=1C=CC=CC=1C(=O)NC1=CC=CC=C1 ZVSKZLHKADLHSD-UHFFFAOYSA-N 0.000 claims description 3
- GVEZIHKRYBHEFX-UHFFFAOYSA-N caerulein A Natural products CC=CCC=CCCC(=O)C1OC1C(N)=O GVEZIHKRYBHEFX-UHFFFAOYSA-N 0.000 claims description 3
- GVEZIHKRYBHEFX-NQQPLRFYSA-N cerulenin Chemical compound C\C=C\C\C=C\CCC(=O)[C@H]1O[C@H]1C(N)=O GVEZIHKRYBHEFX-NQQPLRFYSA-N 0.000 claims description 3
- 229950005984 cerulenin Drugs 0.000 claims description 3
- FIVPIPIDMRVLAY-RBJBARPLSA-N gliotoxin Chemical compound C1C2=CC=C[C@H](O)[C@H]2N2[C@]1(SS1)C(=O)N(C)[C@@]1(CO)C2=O FIVPIPIDMRVLAY-RBJBARPLSA-N 0.000 claims description 3
- 229940103893 gliotoxin Drugs 0.000 claims description 3
- 229930190252 gliotoxin Natural products 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 229960003130 interferon gamma Drugs 0.000 claims description 3
- 150000003548 thiazolidines Chemical class 0.000 claims description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims 4
- BCSVVFYGWBCDLM-UHFFFAOYSA-N 5-(4-aminoimidazo[4,5-d]triazin-7-yl)-2-(hydroxymethyl)thiolan-3-ol Chemical compound C1=NC=2C(N)=NN=NC=2N1C1CC(O)C(CO)S1 BCSVVFYGWBCDLM-UHFFFAOYSA-N 0.000 claims 2
- 101000749287 Clitocybe nebularis Clitocypin Proteins 0.000 claims 2
- 101000767029 Clitocybe nebularis Clitocypin-1 Proteins 0.000 claims 2
- 229940094664 Cysteine protease inhibitor Drugs 0.000 claims 2
- 102000015696 Interleukins Human genes 0.000 claims 2
- 108010063738 Interleukins Proteins 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 abstract description 140
- 125000003835 nucleoside group Chemical group 0.000 abstract description 56
- 150000003833 nucleoside derivatives Chemical class 0.000 abstract description 45
- XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical class N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 abstract description 17
- 239000003443 antiviral agent Substances 0.000 abstract description 13
- 241000711549 Hepacivirus C Species 0.000 description 105
- 0 *C([C@@]1N=CNC1N)=N* Chemical compound *C([C@@]1N=CNC1N)=N* 0.000 description 86
- 238000003786 synthesis reaction Methods 0.000 description 67
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 239000002585 base Substances 0.000 description 51
- 235000000346 sugar Nutrition 0.000 description 49
- 230000015572 biosynthetic process Effects 0.000 description 45
- 241000700605 Viruses Species 0.000 description 43
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 125000006239 protecting group Chemical group 0.000 description 32
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 229940079593 drug Drugs 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 21
- 239000003153 chemical reaction reagent Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 208000006454 hepatitis Diseases 0.000 description 20
- 239000002342 ribonucleoside Substances 0.000 description 20
- 101710144111 Non-structural protein 3 Proteins 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 208000015181 infectious disease Diseases 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 19
- 230000009467 reduction Effects 0.000 description 19
- 230000000694 effects Effects 0.000 description 18
- 238000001819 mass spectrum Methods 0.000 description 18
- 239000007858 starting material Substances 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 231100000283 hepatitis Toxicity 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 238000011160 research Methods 0.000 description 16
- 230000000840 anti-viral effect Effects 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 238000002560 therapeutic procedure Methods 0.000 description 15
- 239000012043 crude product Substances 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- 108060004795 Methyltransferase Proteins 0.000 description 13
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 13
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 12
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 12
- 239000007800 oxidant agent Substances 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 12
- 230000002441 reversible effect Effects 0.000 description 12
- 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 11
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 11
- 241000282412 Homo Species 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 230000010076 replication Effects 0.000 description 11
- 230000003612 virological effect Effects 0.000 description 11
- RHCSKNNOAZULRK-APZFVMQVSA-N 2,2-dideuterio-2-(3,4,5-trimethoxyphenyl)ethanamine Chemical compound NCC([2H])([2H])C1=CC(OC)=C(OC)C(OC)=C1 RHCSKNNOAZULRK-APZFVMQVSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 10
- 239000000969 carrier Substances 0.000 description 10
- 238000002648 combination therapy Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 206010054261 Flavivirus infection Diseases 0.000 description 9
- 102000035195 Peptidases Human genes 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 9
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 9
- 229940088598 enzyme Drugs 0.000 description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 9
- KCLJJGIWEJHHBV-UHFFFAOYSA-N 6-cyclopentyl-5h-imidazo[4,5-d]triazine Chemical compound C1CCCC1C1=NC2=NN=NC=C2N1 KCLJJGIWEJHHBV-UHFFFAOYSA-N 0.000 description 8
- 108700026244 Open Reading Frames Proteins 0.000 description 8
- 108091005804 Peptidases Proteins 0.000 description 8
- 108010022999 Serine Proteases Proteins 0.000 description 8
- 102000012479 Serine Proteases Human genes 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 208000010710 hepatitis C virus infection Diseases 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 241000283690 Bos taurus Species 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 7
- 101800001020 Non-structural protein 4A Proteins 0.000 description 7
- 108010076039 Polyproteins Proteins 0.000 description 7
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical class OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 description 7
- 239000005549 deoxyribonucleoside Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 229910052744 lithium Inorganic materials 0.000 description 7
- 150000008163 sugars Chemical class 0.000 description 7
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 7
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 7
- 230000029812 viral genome replication Effects 0.000 description 7
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 6
- 239000012027 Collins reagent Substances 0.000 description 6
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 6
- 239000005751 Copper oxide Substances 0.000 description 6
- 229910004373 HOAc Inorganic materials 0.000 description 6
- 239000003810 Jones reagent Substances 0.000 description 6
- 229910019093 NaOCl Inorganic materials 0.000 description 6
- 239000004365 Protease Substances 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229910052782 aluminium Inorganic materials 0.000 description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 6
- 239000011609 ammonium molybdate Substances 0.000 description 6
- 229910000431 copper oxide Inorganic materials 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 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 6
- 239000003937 drug carrier Substances 0.000 description 6
- 238000006345 epimerization reaction Methods 0.000 description 6
- 238000007429 general method Methods 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 6
- 150000002402 hexoses Chemical class 0.000 description 6
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 6
- 230000000977 initiatory effect Effects 0.000 description 6
- 150000002596 lactones Chemical class 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
- 239000003444 phase transfer catalyst Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 239000012286 potassium permanganate Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- NPRDHMWYZHSAHR-UHFFFAOYSA-N pyridine;trioxochromium Chemical compound O=[Cr](=O)=O.C1=CC=NC=C1.C1=CC=NC=C1 NPRDHMWYZHSAHR-UHFFFAOYSA-N 0.000 description 6
- 229910001927 ruthenium tetroxide Inorganic materials 0.000 description 6
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 description 5
- 241000710781 Flaviviridae Species 0.000 description 5
- 239000002841 Lewis acid Substances 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- PWGQHOJABIQOOS-UHFFFAOYSA-N copper;dioxido(dioxo)chromium Chemical compound [Cu+2].[O-][Cr]([O-])(=O)=O PWGQHOJABIQOOS-UHFFFAOYSA-N 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- CMMUKUYEPRGBFB-UHFFFAOYSA-L dichromic acid Chemical compound O[Cr](=O)(=O)O[Cr](O)(=O)=O CMMUKUYEPRGBFB-UHFFFAOYSA-L 0.000 description 5
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 150000007517 lewis acids Chemical class 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 235000020357 syrup Nutrition 0.000 description 5
- 239000006188 syrup Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000003813 thumb Anatomy 0.000 description 5
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 5
- CRWLATSHAHNVOV-XDTPYFJJSA-N (2r,3s,4r)-2-(hydroxymethyl)-5-(7h-purin-2-yl)oxolane-3,4-diol Chemical class O[C@@H]1[C@H](O)[C@@H](CO)OC1C1=NC=C(NC=N2)C2=N1 CRWLATSHAHNVOV-XDTPYFJJSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 241001227713 Chiron Species 0.000 description 4
- 238000006088 Dimroth rearrangement reaction Methods 0.000 description 4
- 241000764238 Isis Species 0.000 description 4
- 101800001019 Non-structural protein 4B Proteins 0.000 description 4
- 101710144121 Non-structural protein 5 Proteins 0.000 description 4
- 101800001014 Non-structural protein 5A Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 208000036142 Viral infection Diseases 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 239000007822 coupling agent Substances 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 210000003811 finger Anatomy 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 239000012038 nucleophile Substances 0.000 description 4
- 229940127073 nucleoside analogue Drugs 0.000 description 4
- 125000001979 organolithium group Chemical group 0.000 description 4
- 125000002524 organometallic group Chemical group 0.000 description 4
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 4
- 230000008707 rearrangement Effects 0.000 description 4
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229940021747 therapeutic vaccine Drugs 0.000 description 4
- 230000009385 viral infection Effects 0.000 description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- RTRQQBHATOEIAF-UHFFFAOYSA-N AICA riboside Natural products NC1=C(C(=O)N)N=CN1C1C(O)C(O)C(CO)O1 RTRQQBHATOEIAF-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241001118702 Border disease virus Species 0.000 description 3
- 102100040996 Cochlin Human genes 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 3
- 101000748988 Homo sapiens Cochlin Proteins 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 102100034349 Integrase Human genes 0.000 description 3
- 108010078049 Interferon alpha-2 Proteins 0.000 description 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 3
- 108091092724 Noncoding DNA Proteins 0.000 description 3
- 241000282579 Pan Species 0.000 description 3
- 241001494479 Pecora Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 108010067390 Viral Proteins Proteins 0.000 description 3
- 108020000999 Viral RNA Proteins 0.000 description 3
- 230000009102 absorption Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- RTRQQBHATOEIAF-UUOKFMHZSA-N acadesine Chemical compound NC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RTRQQBHATOEIAF-UUOKFMHZSA-N 0.000 description 3
- 239000011149 active material Substances 0.000 description 3
- 125000002877 alkyl aryl group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 125000001769 aryl amino group Chemical group 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 241001493065 dsRNA viruses Species 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 125000001475 halogen functional group Chemical group 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 108010010648 interferon alfacon-1 Proteins 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 3
- 229940106366 pegintron Drugs 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 150000003212 purines Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000003001 serine protease inhibitor Substances 0.000 description 3
- 238000009097 single-agent therapy Methods 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- OSGKKFFAACTJBG-SSQAQTMGSA-N (2r,3r,4r,5r)-2-(4-aminoimidazo[4,5-d]pyridazin-1-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=CN=NC(N)=C2N=C1 OSGKKFFAACTJBG-SSQAQTMGSA-N 0.000 description 2
- KUSVAFSNSFJGTK-GIWSHQQXSA-N (2r,3r,4r,5r)-2-(4-aminoimidazo[4,5-d]triazin-7-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=NN=NC(N)=C2N=C1 KUSVAFSNSFJGTK-GIWSHQQXSA-N 0.000 description 2
- JNGWKCBNKZBPLB-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(4-aminoimidazo[4,5-d]triazin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical class C1=NC=2C(N)=NN=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JNGWKCBNKZBPLB-UUOKFMHZSA-N 0.000 description 2
- SCVHJVCATBPIHN-SJCJKPOMSA-N (3s)-3-[[(2s)-2-[[2-(2-tert-butylanilino)-2-oxoacetyl]amino]propanoyl]amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)COC=1C(=C(F)C=C(F)C=1F)F)C(=O)C(=O)NC1=CC=CC=C1C(C)(C)C SCVHJVCATBPIHN-SJCJKPOMSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- YJQYHFMKGAVKDP-UHFFFAOYSA-N 3-butanoyl-1,8-dihydroxy-2-methylphenanthrene-9,10-dione Chemical compound C12=CC=CC(O)=C2C(=O)C(=O)C2=C1C=C(C(=O)CCC)C(C)=C2O YJQYHFMKGAVKDP-UHFFFAOYSA-N 0.000 description 2
- VJWXIRQLLGYIDI-UHFFFAOYSA-N 4,5-dichloro-1h-pyridazin-6-one Chemical compound OC1=NN=CC(Cl)=C1Cl VJWXIRQLLGYIDI-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- QHVZREGCOXMZPG-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazin-4-amine Chemical compound NC1=NN=NC2=C1NC=N2 QHVZREGCOXMZPG-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- AVSPYIVAVKYWSY-UHFFFAOYSA-N Cc1nnc2[n]1nnnc2C Chemical compound Cc1nnc2[n]1nnnc2C AVSPYIVAVKYWSY-UHFFFAOYSA-N 0.000 description 2
- 206010008631 Cholera Diseases 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- 241000710777 Classical swine fever virus Species 0.000 description 2
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 2
- 241000531123 GB virus C Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- FUTAPPOITCCWTH-WHFBIAKZSA-N Gly-Asp-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FUTAPPOITCCWTH-WHFBIAKZSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 206010061192 Haemorrhagic fever Diseases 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- 241000545744 Hirudinea Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000710842 Japanese encephalitis virus Species 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 101800001030 Non-structural protein 2A Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 230000006819 RNA synthesis Effects 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 108010046075 Thymosin Proteins 0.000 description 2
- 102000007501 Thymosin Human genes 0.000 description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
- 102000003929 Transaminases Human genes 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- GCZABPLTDYVJMP-CBUXHAPBSA-N [(2r,3r,4r,5s)-5-acetyloxy-3,4-dibenzoyloxyoxolan-2-yl]methyl benzoate Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1OC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)OC(=O)C)OC(=O)C1=CC=CC=C1 GCZABPLTDYVJMP-CBUXHAPBSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 238000011914 asymmetric synthesis Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 241000902900 cellular organisms Species 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- LXWYCLOUQZZDBD-LIYNQYRNSA-N csfv Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)[C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O)C1=CC=C(O)C=C1 LXWYCLOUQZZDBD-LIYNQYRNSA-N 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 229950000234 emricasan Drugs 0.000 description 2
- 206010014599 encephalitis Diseases 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229940029575 guanosine Drugs 0.000 description 2
- 108700012707 hepatitis C virus NS3 Proteins 0.000 description 2
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229940090438 infergen Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 238000011866 long-term treatment Methods 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 229940038850 rebif Drugs 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000000405 serological effect Effects 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 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 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000002723 toxicity assay Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- AXIVPWVQMWRRGH-HHXMPLFPSA-N (2r,3r,4r,5r)-2-(4,7-diaminoimidazo[4,5-d]pyridazin-3-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=C(N)N=NC(N)=C2N=C1 AXIVPWVQMWRRGH-HHXMPLFPSA-N 0.000 description 1
- MKKNDNXNWHPHKD-HHXMPLFPSA-N (2r,3r,4r,5r)-2-(4,7-dichloroimidazo[4,5-d]pyridazin-3-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=C(Cl)N=NC(Cl)=C2N=C1 MKKNDNXNWHPHKD-HHXMPLFPSA-N 0.000 description 1
- ZGWIXBYFKVZZNX-SSQAQTMGSA-N (2r,3r,4r,5r)-2-(4-chloroimidazo[4,5-d]pyridazin-1-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=CN=NC(Cl)=C2N=C1 ZGWIXBYFKVZZNX-SSQAQTMGSA-N 0.000 description 1
- PASOFFRBGIVJET-YRKGHMEHSA-N (2r,3r,4r,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 PASOFFRBGIVJET-YRKGHMEHSA-N 0.000 description 1
- QBIGTJDOMUFLBP-GWOFURMSSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-2-imidazo[4,5-d]pyridazin-3-yl-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=CN=NC=C2N=C1 QBIGTJDOMUFLBP-GWOFURMSSA-N 0.000 description 1
- MIJRQSBOVZHWDP-KAFVXXCXSA-N (2r,3r,4s,5r)-2-(4,7-diaminoimidazo[4,5-d]pyridazin-3-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NN=C(N)C=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O MIJRQSBOVZHWDP-KAFVXXCXSA-N 0.000 description 1
- ROKFJKIUAHNTIS-VPCXQMTMSA-N (2r,3r,4s,5r)-2-(4-aminoimidazo[4,5-d]pyridazin-1-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NN=CC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ROKFJKIUAHNTIS-VPCXQMTMSA-N 0.000 description 1
- IRFUDGZORANOFJ-KQYNXXCUSA-N (2r,3r,4s,5r)-2-(4-aminoimidazo[4,5-d]triazin-7-yl)-2,5-bis(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NN=NC=2N1[C@]1(CO)O[C@H](CO)[C@@H](O)[C@H]1O IRFUDGZORANOFJ-KQYNXXCUSA-N 0.000 description 1
- OZYLMFVIVZOBMO-TZQXKBMNSA-N (2r,3r,4s,5r)-2-(4-chloro-7-methoxyimidazo[4,5-d]pyridazin-1-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=2C(OC)=NN=C(Cl)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OZYLMFVIVZOBMO-TZQXKBMNSA-N 0.000 description 1
- KARZOEYKYREDRB-TZQXKBMNSA-N (2r,3r,4s,5r)-2-(4-chloro-7-methoxyimidazo[4,5-d]pyridazin-3-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(OC)=NN=C(Cl)C=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O KARZOEYKYREDRB-TZQXKBMNSA-N 0.000 description 1
- MXYRZDAGKTVQIL-IOSLPCCCSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)-2-methyloxolane-3,4-diol Chemical compound C1=NC2=C(N)N=CN=C2N1[C@]1(C)O[C@H](CO)[C@@H](O)[C@H]1O MXYRZDAGKTVQIL-IOSLPCCCSA-N 0.000 description 1
- OHMHMNDMISYDEY-PNHWDRBUSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(4-methoxyimidazo[4,5-d]pyridazin-1-yl)oxolane-3,4-diol Chemical compound C1=NC=2C(OC)=NN=CC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OHMHMNDMISYDEY-PNHWDRBUSA-N 0.000 description 1
- JHAGJNXFUFTCMR-PNHWDRBUSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(4-methoxyimidazo[4,5-d]pyridazin-3-yl)oxolane-3,4-diol Chemical compound C1=2C(OC)=NN=CC=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JHAGJNXFUFTCMR-PNHWDRBUSA-N 0.000 description 1
- ZZKNRXZVGOYGJT-VKHMYHEASA-N (2s)-2-[(2-phosphonoacetyl)amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CP(O)(O)=O ZZKNRXZVGOYGJT-VKHMYHEASA-N 0.000 description 1
- FAMIMCYLKYHILB-ZTXUJZEOSA-N (2s,3r,4r,5r)-2-(7-amino-4-azido-3h-imidazo[4,5-d]pyridazin-2-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1C1=NC2=C(N)N=NC(N=[N+]=[N-])=C2N1 FAMIMCYLKYHILB-ZTXUJZEOSA-N 0.000 description 1
- DIAVVJIYKDHXIR-TUINKIHRSA-N (2s,3r,4r,5r)-2-(7-azido-4-methoxy-3h-imidazo[4,5-d]pyridazin-2-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound N1C=2C(OC)=NN=C(N=[N+]=[N-])C=2N=C1[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O DIAVVJIYKDHXIR-TUINKIHRSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UWIAQFTYPNHYFU-VPCXQMTMSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2h-imidazo[4,5-d]pyridazin-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=CN=NC(=O)C2=NC1 UWIAQFTYPNHYFU-VPCXQMTMSA-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
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- UWZYICUGNHLGSA-UHFFFAOYSA-N 1h-imidazo[4,5-d]pyridazine Chemical compound N1=NC=C2NC=NC2=C1 UWZYICUGNHLGSA-UHFFFAOYSA-N 0.000 description 1
- XGDRLCRGKUCBQL-UHFFFAOYSA-N 1h-imidazole-4,5-dicarbonitrile Chemical compound N#CC=1N=CNC=1C#N XGDRLCRGKUCBQL-UHFFFAOYSA-N 0.000 description 1
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 1
- CEHJYEXLKQVWOT-UHFFFAOYSA-N 2,4,6-trihydroxy-3-nitrobenzamide Chemical class NC(=O)C1=C(O)C=C(O)C([N+]([O-])=O)=C1O CEHJYEXLKQVWOT-UHFFFAOYSA-N 0.000 description 1
- XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 1
- JXPDNDHCMMOJPC-UHFFFAOYSA-N 2-hydroxybutanedinitrile Chemical compound N#CC(O)CC#N JXPDNDHCMMOJPC-UHFFFAOYSA-N 0.000 description 1
- KIHAGWUUUHJRMS-JOCHJYFZSA-N 2-octadecanoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@H](CO)COP(O)(=O)OCCN KIHAGWUUUHJRMS-JOCHJYFZSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- FPJPTCHRIMPDSG-RRKCRQDMSA-N 4-amino-1-[(2S,4R,5R)-4-hydroxy-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)S[C@@H](CO)O1 FPJPTCHRIMPDSG-RRKCRQDMSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- BOBOFKFPBKUNDX-UHFFFAOYSA-N 5-(phenylmethoxymethyl)imidazo[4,5-d]pyridazine Chemical compound C1=C2N=CN=C2C=NN1COCC1=CC=CC=C1 BOBOFKFPBKUNDX-UHFFFAOYSA-N 0.000 description 1
- TZYVRXZQAWPIAB-FCLHUMLKSA-N 5-amino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4h-[1,3]thiazolo[4,5-d]pyrimidine-2,7-dione Chemical compound O=C1SC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O TZYVRXZQAWPIAB-FCLHUMLKSA-N 0.000 description 1
- MJQSRSOTRPMVKB-UHFFFAOYSA-N 5h-imidazo[4,5-c]pyridazine Chemical compound C1=NNC2=NC=NC2=C1 MJQSRSOTRPMVKB-UHFFFAOYSA-N 0.000 description 1
- SUPXSFXAMJPEPH-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]triazine Chemical compound N1=NC=C2NC=CC2=N1 SUPXSFXAMJPEPH-UHFFFAOYSA-N 0.000 description 1
- PVRBGBGMDLPYKG-UHFFFAOYSA-N 6-benzyl-7h-purine Chemical compound N=1C=NC=2N=CNC=2C=1CC1=CC=CC=C1 PVRBGBGMDLPYKG-UHFFFAOYSA-N 0.000 description 1
- DBCMWACNZJYUHS-UHFFFAOYSA-N 6-ethenyl-7h-purine Chemical compound C=CC1=NC=NC2=C1NC=N2 DBCMWACNZJYUHS-UHFFFAOYSA-N 0.000 description 1
- LSMBOEFDMAIXTM-UUOKFMHZSA-N 7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-imidazo[4,5-d]triazin-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NN=NC(O)=C2N=C1 LSMBOEFDMAIXTM-UUOKFMHZSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 102100022094 Acid-sensing ion channel 2 Human genes 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 241001167018 Aroa Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 229940096888 Beta tubulin inhibitor Drugs 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010051779 Bone marrow toxicity Diseases 0.000 description 1
- 241000710780 Bovine viral diarrhea virus 1 Species 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- QMORDZIHWOLWGE-IRTQWQCRSA-N C1=NC=2C(OC)=NN=C(N=[N+]=[N-])C=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O Chemical compound C1=NC=2C(OC)=NN=C(N=[N+]=[N-])C=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O QMORDZIHWOLWGE-IRTQWQCRSA-N 0.000 description 1
- AVFBNRXQKPXAFD-UHFFFAOYSA-N CCC1C(COC(C)=O)OC2(CC2)C1CC Chemical compound CCC1C(COC(C)=O)OC2(CC2)C1CC AVFBNRXQKPXAFD-UHFFFAOYSA-N 0.000 description 1
- LAFBXWXMJBNIMF-UHFFFAOYSA-N CCCC(C)c1c2nn[n](C)c2nnn1 Chemical compound CCCC(C)c1c2nn[n](C)c2nnn1 LAFBXWXMJBNIMF-UHFFFAOYSA-N 0.000 description 1
- CCVZZTPSIQDOSX-HHXMPLFPSA-N C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=C(N)N=NC(N=[N+]=[N-])=C2N=C1 Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=C(N)N=NC(N=[N+]=[N-])=C2N=C1 CCVZZTPSIQDOSX-HHXMPLFPSA-N 0.000 description 1
- FEFNLVNSFDKRND-SSQAQTMGSA-N C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=CN=NC(=O)C2=NC1 Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=CN=NC(=O)C2=NC1 FEFNLVNSFDKRND-SSQAQTMGSA-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
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- OKNAGYGKGIVKDJ-UHFFFAOYSA-N Cc1c2nn[n](C)c2nnn1 Chemical compound Cc1c2nn[n](C)c2nnn1 OKNAGYGKGIVKDJ-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000003858 Chymases Human genes 0.000 description 1
- 108090000227 Chymases Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 208000001490 Dengue Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 206010014596 Encephalitis Japanese B Diseases 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 101710121417 Envelope glycoprotein Proteins 0.000 description 1
- 241001125671 Eretmochelys imbricata Species 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 241000414862 GBV-A-like agents Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 241000711557 Hepacivirus Species 0.000 description 1
- 206010019791 Hepatitis post transfusion Diseases 0.000 description 1
- 101000901079 Homo sapiens Acid-sensing ion channel 2 Proteins 0.000 description 1
- 101000980898 Homo sapiens Cell division cycle-associated protein 4 Proteins 0.000 description 1
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010022004 Influenza like illness Diseases 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 201000005807 Japanese encephalitis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 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
- 206010023927 Lassa fever Diseases 0.000 description 1
- 241000712902 Lassa mammarenavirus Species 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 102000016397 Methyltransferase Human genes 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010053961 Mitochondrial toxicity Diseases 0.000 description 1
- 201000005805 Murray valley encephalitis Diseases 0.000 description 1
- RTGDFNSFWBGLEC-UHFFFAOYSA-N Mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1CC=C(C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-UHFFFAOYSA-N 0.000 description 1
- 241000288894 Myotis Species 0.000 description 1
- YTJAMOLQXDNLJC-UHFFFAOYSA-N N1N=CC=C2N=CC=C21 Chemical compound N1N=CC=C2N=CC=C21 YTJAMOLQXDNLJC-UHFFFAOYSA-N 0.000 description 1
- KUSWKYZAWVYWOK-UHFFFAOYSA-N N1N=NC=C2C1=CN=N2.N2=NN=CC=C2 Chemical compound N1N=NC=C2C1=CN=N2.N2=NN=CC=C2 KUSWKYZAWVYWOK-UHFFFAOYSA-N 0.000 description 1
- NNRMKZWOVZPCQC-HGJMQJFTSA-N NC(c1c(N)[n]([C@@H](C2=O)O[C@H](CO)C2=O)cn1)=O Chemical compound NC(c1c(N)[n]([C@@H](C2=O)O[C@H](CO)C2=O)cn1)=O NNRMKZWOVZPCQC-HGJMQJFTSA-N 0.000 description 1
- GBDQCLQBYCIKQT-LWOQYNTDSA-N NNC(c1c([NH2+2])[n](C(C2)O[C@H](CO)C2=O)cn1)=O Chemical compound NNC(c1c([NH2+2])[n](C(C2)O[C@H](CO)C2=O)cn1)=O GBDQCLQBYCIKQT-LWOQYNTDSA-N 0.000 description 1
- JNVJFXGVXWTSMV-UHFFFAOYSA-N Nc1c(C(NN)=O)nc[nH]1 Chemical compound Nc1c(C(NN)=O)nc[nH]1 JNVJFXGVXWTSMV-UHFFFAOYSA-N 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 208000011448 Omsk hemorrhagic fever Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 241000682990 Pegivirus A Species 0.000 description 1
- 241000228127 Penicillium griseofulvum Species 0.000 description 1
- 208000004571 Pestivirus Infections Diseases 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- ZEGRKMXCOCRTCS-UHFFFAOYSA-N Poppy acid Chemical class OC(=O)C1=CC(=O)C(O)=C(C(O)=O)O1 ZEGRKMXCOCRTCS-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101800003376 Protease-polymerase Proteins 0.000 description 1
- 101000774655 Protobothrops mucrosquamatus Snake venom metalloproteinase TM-1 Proteins 0.000 description 1
- 240000004604 Ptychosperma elegans Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 108020005161 RNA Caps Proteins 0.000 description 1
- 108010012974 RNA triphosphatase Proteins 0.000 description 1
- 241000538730 Rocio Species 0.000 description 1
- 208000032108 Russian spring-summer encephalitis Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 241000187180 Streptomyces sp. Species 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 108010078233 Thymalfasin Proteins 0.000 description 1
- 102400000800 Thymosin alpha-1 Human genes 0.000 description 1
- 208000004006 Tick-borne encephalitis Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 241000464917 Vieja Species 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 208000003152 Yellow Fever Diseases 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- VCOFHWVBJMASGS-BTKOSIOUSA-N [(2R,3R,4R,5R)-3,4-dibenzoyloxy-4-methyl-5-(4-oxo-2H-imidazo[4,5-d]pyridazin-1-yl)oxolan-2-yl]methyl benzoate Chemical compound O([C@@]1(C)[C@@H](O[C@H](COC(=O)C=2C=CC=CC=2)[C@H]1OC(=O)C=1C=CC=CC=1)N1C=2C(C(N=NC=2)=O)=NC1)C(=O)C1=CC=CC=C1 VCOFHWVBJMASGS-BTKOSIOUSA-N 0.000 description 1
- IEZRGOBHJRLXCZ-AELMIGOSSA-N [(2r,3r,4r,5r)-3,4-dibenzoyloxy-5-(4,7-diazidoimidazo[4,5-d]pyridazin-3-yl)-4-methyloxolan-2-yl]methyl benzoate Chemical compound O([C@@]1(C)[C@@H](O[C@H](COC(=O)C=2C=CC=CC=2)[C@H]1OC(=O)C=1C=CC=CC=1)N1C2=C(N=[N+]=[N-])N=NC(N=[N+]=[N-])=C2N=C1)C(=O)C1=CC=CC=C1 IEZRGOBHJRLXCZ-AELMIGOSSA-N 0.000 description 1
- DFSQFILPLZQGHP-AELMIGOSSA-N [(2r,3r,4r,5r)-3,4-dibenzoyloxy-5-(4,7-dichloroimidazo[4,5-d]pyridazin-3-yl)-4-methyloxolan-2-yl]methyl benzoate Chemical compound O([C@@]1(C)[C@@H](O[C@H](COC(=O)C=2C=CC=CC=2)[C@H]1OC(=O)C=1C=CC=CC=1)N1C2=C(Cl)N=NC(Cl)=C2N=C1)C(=O)C1=CC=CC=C1 DFSQFILPLZQGHP-AELMIGOSSA-N 0.000 description 1
- LQOVHNHWEYWONN-VGSCBBJJSA-N [(2r,3r,4r,5r)-3,4-dibenzoyloxy-5-(4,7-dichloroimidazo[4,5-d]pyridazin-3-yl)oxolan-2-yl]methyl benzoate Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1OC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)N1C=2C(Cl)=NN=C(C=2N=C1)Cl)OC(=O)C1=CC=CC=C1 LQOVHNHWEYWONN-VGSCBBJJSA-N 0.000 description 1
- SCLMKKXTAZAWOH-GTVIQNQPSA-N [(2r,3r,4r,5r)-3,4-dibenzoyloxy-5-(4-oxo-2h-imidazo[4,5-d]pyridazin-1-yl)oxolan-2-yl]methyl benzoate Chemical compound O([C@H]1[C@@H](O[C@@H]([C@H]1OC(=O)C=1C=CC=CC=1)COC(=O)C=1C=CC=CC=1)N1C=2C(C(N=NC=2)=O)=NC1)C(=O)C1=CC=CC=C1 SCLMKKXTAZAWOH-GTVIQNQPSA-N 0.000 description 1
- MHQZUMATDURSKH-YDXJMRNDSA-N [(2r,3r,4r,5r)-3,4-dibenzoyloxy-5-[4-oxo-5-(phenylmethoxymethyl)imidazo[4,5-d]pyridazin-1-yl]oxolan-2-yl]methyl benzoate Chemical compound O([C@H]1[C@@H](O[C@@H]([C@H]1OC(=O)C=1C=CC=CC=1)COC(=O)C=1C=CC=CC=1)N1C2=C(C(N(COCC=3C=CC=CC=3)N=C2)=O)N=C1)C(=O)C1=CC=CC=C1 MHQZUMATDURSKH-YDXJMRNDSA-N 0.000 description 1
- KBKCEYVQOVUCLA-AELMIGOSSA-N [(2r,3r,4r,5r)-5-(7-amino-4-azidoimidazo[4,5-d]pyridazin-1-yl)-3,4-dibenzoyloxy-4-methyloxolan-2-yl]methyl benzoate Chemical compound O([C@@]1(C)[C@@H](O[C@H](COC(=O)C=2C=CC=CC=2)[C@H]1OC(=O)C=1C=CC=CC=1)N1C2=C(N)N=NC(N=[N+]=[N-])=C2N=C1)C(=O)C1=CC=CC=C1 KBKCEYVQOVUCLA-AELMIGOSSA-N 0.000 description 1
- UZAQJUNXGUYOPM-AELMIGOSSA-N [(2r,3r,4r,5r)-5-(7-amino-4-azidoimidazo[4,5-d]pyridazin-3-yl)-3,4-dibenzoyloxy-4-methyloxolan-2-yl]methyl benzoate Chemical compound O([C@@]1(C)[C@@H](O[C@H](COC(=O)C=2C=CC=CC=2)[C@H]1OC(=O)C=1C=CC=CC=1)N1C2=C(N=[N+]=[N-])N=NC(N)=C2N=C1)C(=O)C1=CC=CC=C1 UZAQJUNXGUYOPM-AELMIGOSSA-N 0.000 description 1
- JRYQCEUTVAAQHC-SSGKUCQKSA-N [(2r,3r,4r,5r)-5-azido-3,4-dibenzoyloxyoxolan-2-yl]methyl benzoate Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1OC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)N=[N+]=[N-])OC(=O)C1=CC=CC=C1 JRYQCEUTVAAQHC-SSGKUCQKSA-N 0.000 description 1
- QJZSLTLDMBDKOU-VBHQRPIPSA-N [(2r,3r,4r,5s)-3,4,5-tribenzoyloxy-4-methyloxolan-2-yl]methyl benzoate Chemical compound O([C@]1(C)[C@@H]([C@@H](COC(=O)C=2C=CC=CC=2)O[C@H]1OC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 QJZSLTLDMBDKOU-VBHQRPIPSA-N 0.000 description 1
- GQJVBGYQFICEPS-UHFFFAOYSA-O [NH3+]C(C1N=CNC1C#N)=O Chemical compound [NH3+]C(C1N=CNC1C#N)=O GQJVBGYQFICEPS-UHFFFAOYSA-O 0.000 description 1
- HDRRAMINWIWTNU-NTSWFWBYSA-N [[(2s,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical class C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1CC[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HDRRAMINWIWTNU-NTSWFWBYSA-N 0.000 description 1
- QLDHWVVRQCGZLE-UHFFFAOYSA-N acetyl cyanide Chemical compound CC(=O)C#N QLDHWVVRQCGZLE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 108010027597 alpha-chymotrypsin Proteins 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 238000003353 bioavailability assay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 231100000366 bone marrow toxicity Toxicity 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001669 calcium Chemical class 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940107810 cellcept Drugs 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000020403 chronic hepatitis C virus infection Diseases 0.000 description 1
- PJZPDFUUXKKDNB-KNINVFKUSA-N ciluprevir Chemical compound N([C@@H]1C(=O)N2[C@H](C(N[C@@]3(C[C@H]3\C=C/CCCCC1)C(O)=O)=O)C[C@H](C2)OC=1C2=CC=C(C=C2N=C(C=1)C=1N=C(NC(C)C)SC=1)OC)C(=O)OC1CCCC1 PJZPDFUUXKKDNB-KNINVFKUSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000007821 culture assay Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 150000001944 cysteine derivatives Chemical class 0.000 description 1
- 239000002852 cysteine proteinase inhibitor Substances 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- OSBMXQIJLZOLET-UHFFFAOYSA-N ethyl 3-cyano-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=CC=1C#N OSBMXQIJLZOLET-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 150000002243 furanoses Chemical group 0.000 description 1
- 229940125777 fusion inhibitor Drugs 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000001279 glycosylating effect Effects 0.000 description 1
- 108010064833 guanylyltransferase Proteins 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 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
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229960004931 histamine dihydrochloride Drugs 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 102000044493 human CDCA4 Human genes 0.000 description 1
- 102000011749 human hepatitis C immune globulin Human genes 0.000 description 1
- 108010062138 human hepatitis C immune globulin Proteins 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 229950000038 interferon alfa Drugs 0.000 description 1
- 229960003521 interferon alfa-2a Drugs 0.000 description 1
- 108010006088 interferon alfa-n1 Proteins 0.000 description 1
- 229960003358 interferon alfacon-1 Drugs 0.000 description 1
- 229940028862 interferon gamma-1b Drugs 0.000 description 1
- 108010042414 interferon gamma-1b Proteins 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 210000001153 interneuron Anatomy 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229940065638 intron a Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 230000008384 membrane barrier Effects 0.000 description 1
- 201000011475 meningoencephalitis Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 231100000296 mitochondrial toxicity Toxicity 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 229940002988 pegasys Drugs 0.000 description 1
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 208000025858 pestivirus infectious disease Diseases 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 150000002993 phenylalanine derivatives Chemical class 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- NAYYNDKKHOIIOD-UHFFFAOYSA-N phthalamide Chemical compound NC(=O)C1=CC=CC=C1C(N)=O NAYYNDKKHOIIOD-UHFFFAOYSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 description 1
- 239000002212 purine nucleoside Substances 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 229940053146 rebetol Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000002821 scintillation proximity assay Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000012153 swine disease Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000012622 synthetic inhibitor Substances 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
- 229940095064 tartrate Drugs 0.000 description 1
- 102000013498 tau Proteins Human genes 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical class OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=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@@H](C)O)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@@H](C)O)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)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
- 229960004231 thymalfasin Drugs 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 239000008181 tonicity modifier Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- BSUNTQCMCCQSQH-UHFFFAOYSA-N triazine Chemical compound C1=CN=NN=C1.C1=CN=NN=C1 BSUNTQCMCCQSQH-UHFFFAOYSA-N 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 229940100050 virazole Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- 150000004799 α-ketoamides Chemical class 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/044—Pyrrole radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/052—Imidazole radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/056—Triazole or tetrazole radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/23—Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49021603P | 2003-07-25 | 2003-07-25 | |
| PCT/IB2004/002703 WO2005009418A2 (en) | 2003-07-25 | 2004-07-26 | Purine nucleoside analogues for treating diseases caused by flaviviridae including hepatitis c |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007501185A true JP2007501185A (ja) | 2007-01-25 |
| JP2007501185A5 JP2007501185A5 (https=) | 2007-09-20 |
Family
ID=34102969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006520940A Pending JP2007501185A (ja) | 2003-07-25 | 2004-07-26 | C型肝炎を含むフラビウイルス関連疾患を治療するためのプリンヌクレオシド類似体 |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US20050075309A1 (https=) |
| EP (1) | EP1658302B1 (https=) |
| JP (1) | JP2007501185A (https=) |
| KR (1) | KR20060084845A (https=) |
| CN (1) | CN1852915A (https=) |
| AT (1) | ATE478886T1 (https=) |
| AU (1) | AU2004258750A1 (https=) |
| BR (1) | BRPI0412849A (https=) |
| CA (1) | CA2533367C (https=) |
| DE (1) | DE602004028841D1 (https=) |
| DK (1) | DK1658302T3 (https=) |
| ES (1) | ES2351603T3 (https=) |
| NO (1) | NO20060914L (https=) |
| PL (1) | PL1658302T3 (https=) |
| PT (1) | PT1658302E (https=) |
| RU (1) | RU2006105640A (https=) |
| WO (1) | WO2005009418A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016138078A (ja) * | 2015-01-29 | 2016-08-04 | 学校法人日本大学 | 8−アザ−3,7−ジデアザアデニンヌクレオシド誘導体、8−アザ−3,7−ジデアザアデニンヌクレオチド誘導体及びポリヌクレオチド誘導体ならびにプローブ |
Families Citing this family (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2345657A1 (en) * | 2003-05-30 | 2011-07-20 | Pharmasset, Inc. | Modified fluorinated nucleoside analogues |
| EP1658302B1 (en) * | 2003-07-25 | 2010-08-25 | IDENIX Pharmaceuticals, Inc. | Purine nucleoside analogues for treating diseases caused by flaviviridae including hepatitis c |
| AU2005254057B2 (en) | 2004-06-15 | 2011-02-17 | Isis Pharmaceuticals, Inc. | C-purine nucleoside analogs as inhibitors of RNA-dependent RNA viral polymerase |
| CN101023094B (zh) * | 2004-07-21 | 2011-05-18 | 法莫赛特股份有限公司 | 烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备 |
| AU2005285045B2 (en) * | 2004-09-14 | 2011-10-13 | Gilead Sciences, Inc. | Preparation of 2'fluoro-2'- alkyl- substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
| JP2008535932A (ja) * | 2005-03-09 | 2008-09-04 | イデニクス(ケイマン)リミテツド | 抗ウィルス剤としての非天然塩基を有するヌクレオシド |
| WO2007041775A1 (en) * | 2005-10-10 | 2007-04-19 | The University Of Queensland | Cysteine protease inhibitors incorporating azide groups |
| MY150667A (en) | 2005-12-09 | 2014-02-28 | Gilead Pharmasset Llc | Antiviral nucleosides |
| JP2009532411A (ja) | 2006-04-04 | 2009-09-10 | エフ.ホフマン−ラ ロシュ アーゲー | Hcv治療のための3’,5’−ジ−o−アシル化ヌクレオシド |
| BRPI0715714A2 (pt) * | 2006-08-25 | 2014-03-11 | Wyeth Corp | Métodos para diminuir a frequência de emergência de uma infecção viral de hepatite c resistente ao tratamento, para atrasar a emergência de uma infecção viral de hepatite c resistente ao tratamento, para diminuir o nível de resistência de uma infecção viral de hepatite c resistente ao tratamento, para diminuir a emergência de uma infecção viral de hepatite c resistente a hcv-796, para identificar um indivíduo com uma probabilidade diminuída de responder a uma terapia viral anti-hepatite c, para monitorar, diagnosticar ou prognosticar a infecção viral de hepatite c resistente ao tratamento em um paciente, para monitorar o curso de tratamento de uma infecção viral de hepatite c em um paciente, para prognosticar o desenvolvimento de um ainfecção viral de hepatite c resistente ao tratamento em um paciente, para monitorar a infecção viral de hepatite c em um paciente e para diagnosticar o desenvolvimento de uma infecção viral de hepatite ao tratamento em um paciente |
| US8912321B2 (en) | 2006-10-10 | 2014-12-16 | Gilead Pharmasset Llc | Preparation of nucleosides ribofuranosyl pyrimidines |
| EP2091927B1 (en) | 2006-11-09 | 2011-07-20 | F. Hoffmann-La Roche AG | Thiazole and oxazole-substituted arylamides |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| TW200936146A (en) * | 2007-11-29 | 2009-09-01 | Metabasis Therapeutics Inc | Antiviral nucleoside compounds |
| EP2234989B1 (en) | 2007-12-17 | 2014-08-13 | F. Hoffmann-La Roche AG | Tetrazole-substituted arylamide derivatives and their use as p2x3 and/or p2x2/3 purinergic receptor antagonists |
| ES2542245T3 (es) | 2007-12-17 | 2015-08-03 | F. Hoffmann-La Roche Ag | Derivados de arilamida sustituido con triazol y su utilización como antagonistas del receptor purinérgico P2x3 y/o P2x2/3 |
| CA2708791C (en) | 2007-12-17 | 2016-06-21 | F. Hoffmann-La Roche Ag | Imidazole-substituted arylamides and uses thereof as p2x receptor antagonists |
| ES2417182T3 (es) | 2007-12-17 | 2013-08-06 | F. Hoffmann-La Roche Ag | Nuevas arilamidas sustituidas con pirazol |
| ES2398684T3 (es) | 2008-04-23 | 2013-03-21 | Gilead Sciences, Inc. | Análogos de carbanucleósido para el tratamiento antiviral |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| KR20110098849A (ko) | 2008-12-23 | 2011-09-01 | 파마셋 인코포레이티드 | 뉴클레오시드 유사체 |
| PT2376088T (pt) | 2008-12-23 | 2017-05-02 | Gilead Pharmasset Llc | Fosforamidatos de nucleósidos de 2-amino-purina 6-osubstituída |
| SG194404A1 (en) | 2008-12-23 | 2013-11-29 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| TWI598358B (zh) | 2009-05-20 | 2017-09-11 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| CN102574778B (zh) | 2009-06-22 | 2015-01-07 | 弗·哈夫曼-拉罗切有限公司 | 新的联苯基和苯基-吡啶酰胺类化合物 |
| US8476457B2 (en) | 2009-06-22 | 2013-07-02 | Roche Palo Alto Llc | Indole, indazole and benzimidazole arylamides as P2X3 and P2X2/3 antagonists |
| EP2445889B1 (en) | 2009-06-22 | 2016-08-10 | F.Hoffmann-La Roche Ag | Novel benzoxazolone -substituted arylamides |
| TWI483950B (zh) | 2009-09-21 | 2015-05-11 | Gilead Sciences Inc | 用於製備1’-取代碳核苷類似物之方法及中間物 |
| MX2012005528A (es) | 2009-11-14 | 2012-06-12 | Hoffmann La Roche | Biomarcadores para pronosticar rapida respuesta a tratamiento hcv. |
| MX2012005703A (es) | 2009-12-02 | 2012-06-12 | Hoffmann La Roche | Biomarcadores para pronosticar una respuesta prolongada al tratamiento contra el vhc. |
| PL3290428T3 (pl) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu |
| PT2609923T (pt) | 2010-03-31 | 2017-08-30 | Gilead Pharmasset Llc | Processo para a cristalização de 2-(((s)- (perfluorofenoxi)(fenoxi)fosforil)amino)propanoato de (s)-isopropilo |
| KR101995598B1 (ko) | 2010-07-19 | 2019-07-02 | 길리애드 사이언시즈, 인코포레이티드 | 부분입체 이성질성으로 순수한 포스포라미데이트 전구약물의 제조 방법 |
| BR122020020745B8 (pt) | 2010-07-22 | 2023-10-31 | Gilead Sciences Inc | Composto antiviral para o tratamento de infecções por paramyxoviridae e composição farmacêutica que o compreende |
| AU2011336632B2 (en) | 2010-11-30 | 2015-09-03 | Gilead Pharmasset Llc | Compounds |
| CN102850355B (zh) * | 2011-06-29 | 2015-02-11 | 四川大学 | 9-磺酰基-9h-嘌呤衍生物及其制备方法和用途 |
| PL2709613T5 (pl) | 2011-09-16 | 2020-12-14 | Gilead Pharmasset Llc | Metody leczenia hcv |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| SG11201407336PA (en) | 2012-05-25 | 2015-03-30 | Janssen Sciences Ireland Uc | Uracyl spirooxetane nucleosides |
| GEP201706757B (en) | 2012-12-21 | 2017-10-25 | Alios Biopharma Inc | Substituted nucleosides, nucleotides and analogs thereof |
| PT2950786T (pt) | 2013-01-31 | 2020-03-03 | Gilead Pharmasset Llc | Formulação de combinação de dois compostos antivirais |
| RU2534613C2 (ru) | 2013-03-22 | 2014-11-27 | Александр Васильевич Иващенко | Алкил 2-{ [(2r,3s,5r)-5-(4-амино-2-оксо-2н-пиримидин-1-ил)- -гидрокси-тетрагидро-фуран-2-илметокси]-фенокси-фосфориламино} -пропионаты, нуклеозидные ингибиторы рнк-полимеразы hcv ns5b, способы их получения и применения |
| EA201690473A1 (ru) | 2013-08-27 | 2017-03-31 | ГАЙЛИД ФАРМАССЕТ ЭлЭлСи | Комбинированный состав двух противовирусных соединений |
| EP3055319A4 (en) | 2013-10-11 | 2018-01-10 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| WO2015095419A1 (en) * | 2013-12-18 | 2015-06-25 | Idenix Pharmaceuticals, Inc. | 4'-or nucleosides for the treatment of hcv |
| JP2017512183A (ja) | 2014-02-13 | 2017-05-18 | リガンド・ファーマシューティカルズ・インコーポレイテッド | プロドラッグ化合物およびそれらの使用 |
| CN106687118A (zh) | 2014-07-02 | 2017-05-17 | 配体药物公司 | 前药化合物及其用途 |
| TWI767201B (zh) | 2014-10-29 | 2022-06-11 | 美商基利科學股份有限公司 | 絲狀病毒科病毒感染之治療 |
| CA3182565A1 (en) | 2015-03-06 | 2016-09-15 | Atea Pharmaceuticals, Inc. | .beta.-d-2'-deoxy-2'-.alpha.-fluoro-2'-.beta.-c-substituted-2-modified-n6-substituted purine nucleotides for hcv treatment |
| SI3349758T1 (sl) | 2015-09-16 | 2022-08-31 | Gilead Sciences, Inc. | Postopki za zdravljenje okužb z virusom arenaviridae |
| CN109790143A (zh) | 2016-05-10 | 2019-05-21 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| CN109641874A (zh) | 2016-05-10 | 2019-04-16 | C4医药公司 | 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体 |
| EP4491236A3 (en) | 2016-05-10 | 2025-04-02 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| EP3454862B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
| US10202412B2 (en) | 2016-07-08 | 2019-02-12 | Atea Pharmaceuticals, Inc. | β-D-2′-deoxy-2′-substituted-4′-substituted-2-substituted-N6-substituted-6-aminopurinenucleotides for the treatment of paramyxovirus and orthomyxovirus infections |
| US10711029B2 (en) | 2016-07-14 | 2020-07-14 | Atea Pharmaceuticals, Inc. | Beta-d-2′-deoxy-2′-alpha-fluoro-2′-beta-c-substituted-4′fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
| DK3512863T3 (da) | 2016-09-07 | 2022-03-07 | Atea Pharmaceuticals Inc | 2¿-substituerede-N6-substituerede purinnukleotider til behandling af RNA-virus |
| US10537590B2 (en) * | 2016-09-30 | 2020-01-21 | Boehringer Ingelheim International Gmbh | Cyclic dinucleotide compounds |
| CN115477679A (zh) | 2017-02-01 | 2022-12-16 | 阿堤亚制药公司 | 用于治疗丙型肝炎病毒的核苷酸半硫酸盐 |
| US10682368B2 (en) | 2017-03-14 | 2020-06-16 | Gilead Sciences, Inc. | Methods of treating feline coronavirus infections |
| AU2018262501B2 (en) | 2017-05-01 | 2020-12-10 | Gilead Sciences, Inc. | Crystalline forms of (S) 2 ethylbutyl 2 (((S) (((2R,3S,4R,5R) 5 (4 aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2 yl)methoxy)(phenoxy) phosphoryl)amino)propanoate |
| EP4717317A2 (en) | 2017-06-20 | 2026-04-01 | C4 Therapeutics, Inc. | N/o-linked degrons and degronimers for protein degradation |
| WO2019014247A1 (en) | 2017-07-11 | 2019-01-17 | Gilead Sciences, Inc. | COMPOSITIONS COMPRISING POLYMERASE RNA INHIBITOR AND CYCLODEXTRIN FOR THE TREATMENT OF VIRAL INFECTIONS |
| CN109384727B (zh) * | 2017-08-10 | 2023-07-28 | 中国科学院上海药物研究所 | 酞嗪酮类化合物、其制备方法、药物组合物及用途 |
| RU2020126177A (ru) | 2018-01-09 | 2022-02-10 | Лиганд Фармасьютикалз, Инк. | Ацетальные соединения и их терапевтическое применение |
| EP3773753A4 (en) | 2018-04-10 | 2021-12-22 | ATEA Pharmaceuticals, Inc. | TREATMENT OF PATIENTS INFECTED WITH THE HEPATITIS C VIRUS WITH CIRRHOSIS |
| US11660307B2 (en) | 2020-01-27 | 2023-05-30 | Gilead Sciences, Inc. | Methods for treating SARS CoV-2 infections |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| JP7554841B2 (ja) | 2020-03-12 | 2024-09-20 | ギリアード サイエンシーズ, インコーポレイテッド | 1’-シアノヌクレオシドを調製する方法 |
| WO2021207049A1 (en) | 2020-04-06 | 2021-10-14 | Gilead Sciences, Inc. | Inhalation formulations of 1'-cyano substituted carbanucleoside analogs |
| CA3179226A1 (en) | 2020-05-29 | 2021-12-02 | Tomas Cihlar | Remdesivir treatment methods |
| AU2021296841B2 (en) | 2020-06-24 | 2025-01-23 | Gilead Sciences, Inc. | 1'-cyano nucleoside analogs and uses thereof |
| SI4204421T1 (sl) | 2020-08-27 | 2024-07-31 | Gilead Sciences, Inc., | Spojine in postopki za zdravljenje virusnih okužb |
| KR20240022574A (ko) | 2021-06-17 | 2024-02-20 | 아테아 파마슈티컬즈, 인크. | 유리한 항-hcv 조합 요법 |
| IL315102A (en) | 2022-03-02 | 2024-10-01 | Gilead Sciences Inc | COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS |
| US12357577B1 (en) | 2024-02-02 | 2025-07-15 | Gilead Sciences, Inc. | Pharmaceutical formulations and uses thereof |
Family Cites Families (148)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US101535A (en) * | 1870-04-05 | Improvement in ornamental-scroll type | ||
| US28013A (en) * | 1860-04-24 | Improved bullet-ladle | ||
| US60400A (en) * | 1866-12-11 | Improved folding lounge | ||
| US77587A (en) * | 1868-05-05 | Let i h | ||
| US19363A (en) * | 1858-02-16 | Improved harpoon-and lance | ||
| US55483A (en) * | 1866-06-12 | Improvement in pruning-hooks | ||
| US83307A (en) * | 1868-10-20 | Improvement in wash-boilehs | ||
| US2479A (en) * | 1842-03-04 | Machine for sizing papek | ||
| US110717A (en) * | 1871-01-03 | Improvement in car-wheel molds | ||
| US6002A (en) * | 1849-01-02 | Screw-wrench for grasping cylindrical forms | ||
| US147160A (en) * | 1874-02-03 | Improvement in seed-planters | ||
| US72788A (en) * | 1867-12-31 | Charles d | ||
| US97461A (en) * | 1869-11-30 | Improvement in stump-extractors | ||
| US67877A (en) * | 1867-08-20 | Robert hitchcock | ||
| US67901A (en) * | 1867-08-20 | Washinoton | ||
| US110718A (en) * | 1871-01-03 | Improvement in harvesters | ||
| US63622A (en) * | 1867-04-09 | Improvement in power looms | ||
| US102414A (en) * | 1870-04-26 | Improvement in peat-machines | ||
| US225037A (en) * | 1880-03-02 | Apparatus for the manufacture of ice | ||
| US82574A (en) * | 1868-09-29 | Williams | ||
| US63658A (en) * | 1867-04-09 | bobbins | ||
| US87873A (en) * | 1869-03-16 | Perry prettyman | ||
| US97462A (en) * | 1869-11-30 | Improved rrttit-slicer | ||
| US50229A (en) * | 1865-10-03 | Improvement in cultivators | ||
| US2476A (en) * | 1842-02-28 | Machine for cutting meat and other substances | ||
| US8841A (en) * | 1852-03-30 | Sice-httxieb | ||
| US6007A (en) * | 1849-01-09 | Improvement in plows | ||
| US225029A (en) * | 1880-03-02 | Magnetic grain-separator | ||
| US198171A (en) * | 1877-12-11 | Improvement in the mode of raising cream | ||
| US99072A (en) * | 1870-01-25 | Improvement in shoes for horses | ||
| USRE29835E (en) * | 1971-06-01 | 1978-11-14 | Icn Pharmaceuticals | 1,2,4-Triazole nucleosides |
| US4211771A (en) * | 1971-06-01 | 1980-07-08 | Robins Ronald K | Treatment of human viral diseases with 1-B-D-ribofuranosyl-1,2,4-triazole-3-carboxamide |
| US3798209A (en) * | 1971-06-01 | 1974-03-19 | Icn Pharmaceuticals | 1,2,4-triazole nucleosides |
| US4522811A (en) * | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US5055394A (en) * | 1983-10-13 | 1991-10-08 | The United States Of America As Represented By The Secretary Of The Army | Nucleic acid probe and method for the rapid detection of typhoid fever bacteria |
| US5223263A (en) | 1988-07-07 | 1993-06-29 | Vical, Inc. | Liponucleotide-containing liposomes |
| WO1988002785A2 (en) | 1986-10-14 | 1988-04-21 | Beckman Instruments, Inc. | Improved nucleic acid hybridization technique and kit therefor |
| AU2526188A (en) | 1987-09-22 | 1989-04-18 | Regents Of The University Of California, The | Liposomal nucleoside analogues for treating aids |
| US5705363A (en) * | 1989-03-02 | 1998-01-06 | The Women's Research Institute | Recombinant production of human interferon τ polypeptides and nucleic acids |
| US5194654A (en) * | 1989-11-22 | 1993-03-16 | Vical, Inc. | Lipid derivatives of phosphonoacids for liposomal incorporation and method of use |
| JPH03148278A (ja) | 1989-11-02 | 1991-06-25 | Nippon Kayaku Co Ltd | 新規ヌクレオシド及びその製造法 |
| US5026687A (en) * | 1990-01-03 | 1991-06-25 | The United States Of America As Represented By The Department Of Health And Human Services | Treatment of human retroviral infections with 2',3'-dideoxyinosine alone and in combination with other antiviral compounds |
| CA2079912C (en) * | 1990-04-06 | 2000-07-11 | Gregory Reyes | Hepatitis c virus epitopes |
| AU7872491A (en) | 1990-05-07 | 1991-11-27 | Vical, Inc. | Lipid prodrugs of salicylate and nonsteroidal anti-inflammatory drugs |
| EP0531452A4 (en) | 1990-05-29 | 1993-06-09 | Vical, Inc. | Synthesis of glycerol di- and triphosphate derivatives |
| ATE131825T1 (de) | 1990-06-13 | 1996-01-15 | Arnold Glazier | Phosphorylierte prodrugs |
| US5372808A (en) * | 1990-10-17 | 1994-12-13 | Amgen Inc. | Methods and compositions for the treatment of diseases with consensus interferon while reducing side effect |
| US5149794A (en) * | 1990-11-01 | 1992-09-22 | State Of Oregon | Covalent lipid-drug conjugates for drug targeting |
| US5256641A (en) | 1990-11-01 | 1993-10-26 | State Of Oregon | Covalent polar lipid-peptide conjugates for immunological targeting |
| US6100024A (en) * | 1991-02-08 | 2000-08-08 | Promega Corporation | Methods and compositions for nucleic acid detection by target extension and probe amplification |
| AU668873B2 (en) | 1991-07-12 | 1996-05-23 | Chimerix, Inc. | Antiviral liponucleosides: treatment of hepatitis B |
| TW224053B (https=) * | 1991-09-13 | 1994-05-21 | Paul B Chretien | |
| JPH05111389A (ja) | 1991-10-24 | 1993-05-07 | Sanyo Kokusaku Pulp Co Ltd | 新規な抗ウイルス剤 |
| US5676942A (en) * | 1992-02-10 | 1997-10-14 | Interferon Sciences, Inc. | Composition containing human alpha interferon species proteins and method for use thereof |
| US5610054A (en) * | 1992-05-14 | 1997-03-11 | Ribozyme Pharmaceuticals, Inc. | Enzymatic RNA molecule targeted against Hepatitis C virus |
| GB9226729D0 (en) * | 1992-12-22 | 1993-02-17 | Wellcome Found | Therapeutic combination |
| WO1994019012A2 (en) * | 1993-02-24 | 1994-09-01 | Wang Jui H | Compositions and methods of application of reactive antiviral polymers |
| PT698216E (pt) * | 1993-05-10 | 2005-03-31 | Chiron Corp | Metodos de tipificacao do virus da hepatite c e reagentes para utilizar nestes |
| EP0746319A4 (en) | 1993-05-12 | 1997-11-05 | Karl Y Hostetler | ACYCLOVIR DERIVATIVES FOR TOPICAL USE |
| WO1995003056A1 (en) * | 1993-07-19 | 1995-02-02 | Tokyo Tanabe Company Limited | Hepatitis c virus proliferation inhibitor |
| DE4415539C2 (de) * | 1994-05-03 | 1996-08-01 | Osama Dr Dr Med Omer | Pflanzen mit virustatischer und antiviraler Wirkung |
| DE4432623A1 (de) * | 1994-09-14 | 1996-03-21 | Huels Chemische Werke Ag | Verfahren zur Bleichung von wäßrigen Tensidlösungen |
| US5696277A (en) | 1994-11-15 | 1997-12-09 | Karl Y. Hostetler | Antiviral prodrugs |
| JP3786447B2 (ja) | 1995-03-31 | 2006-06-14 | エーザイ株式会社 | C型肝炎の予防・治療剤 |
| US5874565A (en) * | 1995-08-29 | 1999-02-23 | Washington University | Nucleic acids comprising a highly conserved novel 3 terminal sequence element of the hepatitis C virus |
| EP0859833B1 (en) | 1995-09-27 | 2006-03-01 | Emory University | Recombinant hepatitis c virus rna replicase |
| JP2000506010A (ja) * | 1996-02-29 | 2000-05-23 | イミューソル インコーポレイテッド | C型肝炎ウイルスリボザイム |
| US5830905A (en) | 1996-03-29 | 1998-11-03 | Viropharma Incorporated | Compounds, compositions and methods for treatment of hepatitis C |
| JP3715027B2 (ja) * | 1996-05-07 | 2005-11-09 | シスメックス株式会社 | C型肝炎ウイルス感染症診断薬 |
| US5990276A (en) * | 1996-05-10 | 1999-11-23 | Schering Corporation | Synthetic inhibitors of hepatitis C virus NS3 protease |
| US5891874A (en) * | 1996-06-05 | 1999-04-06 | Eli Lilly And Company | Anti-viral compound |
| US5837257A (en) * | 1996-07-09 | 1998-11-17 | Sage R&D | Use of plant extracts for treatment of HIV, HCV and HBV infections |
| JP3927630B2 (ja) | 1996-09-27 | 2007-06-13 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ウイルス感染症の予防・治療剤 |
| US5922757A (en) * | 1996-09-30 | 1999-07-13 | The Regents Of The University Of California | Treatment and prevention of hepatic disorders |
| IL129126A0 (en) * | 1996-10-16 | 2000-02-17 | Icn Pharmaceuticals | Monocyclic l-nucleosides analogs and uses thereof |
| ATE271063T1 (de) | 1996-10-16 | 2004-07-15 | Icn Pharmaceuticals | Purin-l-nukleoside, deren analoga und verwendungen |
| AU4904397A (en) * | 1996-10-17 | 1998-05-11 | Chiron Corporation | Protease regulator screening assay |
| AP1019A (en) | 1996-10-18 | 2001-10-16 | Vertex Pharma | Inhibitors of serinre proteases, particularly hepatitis C virus NS3 protease. |
| GB9623908D0 (en) | 1996-11-18 | 1997-01-08 | Hoffmann La Roche | Amino acid derivatives |
| IL119833A (en) * | 1996-12-15 | 2001-01-11 | Lavie David | Hypericum perforatum extracts for the preparation of pharmaceutical compositions for the treatment of hepatitis |
| JP2001514508A (ja) * | 1997-03-05 | 2001-09-11 | ユニバーシティー オブ ワシントン | C型肝炎ウイルスの複製を選択的に抑制する薬剤を同定するための新規なスクリーニング法 |
| US6004933A (en) * | 1997-04-25 | 1999-12-21 | Cortech Inc. | Cysteine protease inhibitors |
| UA61962C2 (uk) * | 1997-06-30 | 2003-12-15 | Мерц Фарма Гмбх Унд Ко. Кгаа | Сполука 1-аміноалкілциклогексану, фармацевтична композиція на її основі та спосіб лікування |
| EP1012180B1 (en) | 1997-08-11 | 2004-12-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor peptide analogues |
| KR100719606B1 (ko) * | 1998-02-25 | 2007-05-17 | 에모리 유니버시티 | 2'-플루오로뉴클레오사이드 |
| GB9806815D0 (en) | 1998-03-30 | 1998-05-27 | Hoffmann La Roche | Amino acid derivatives |
| US6833361B2 (en) * | 1998-05-26 | 2004-12-21 | Ribapharm, Inc. | Nucleosides having bicyclic sugar moiety |
| CA2333380A1 (en) * | 1998-05-26 | 1999-12-02 | Icn Pharmaceuticals, Inc. | Novel nucleosides having bicyclic sugar moiety |
| AU756627B2 (en) | 1998-07-27 | 2003-01-16 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Diketoacid-derivatives as inhibitors of polymerases |
| US6323180B1 (en) * | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
| AU777040B2 (en) * | 1999-02-22 | 2004-09-30 | Shire Biochem Inc. | (1,8) naphthyridine derivatives having antiviral activity |
| DE19915178A1 (de) | 1999-04-03 | 2000-10-05 | Univ Mainz Johannes Gutenberg | Hepatitis C Virus Zellkultursystem |
| CA2384407C (en) | 1999-08-30 | 2009-10-20 | Roche Diagnostics Gmbh | 2-azapurine compounds and their use |
| US6566365B1 (en) * | 1999-11-04 | 2003-05-20 | Biochem Pharma Inc. | Method for the treatment of Flaviviridea viral infection using nucleoside analogues |
| US6495677B1 (en) * | 2000-02-15 | 2002-12-17 | Kanda S. Ramasamy | Nucleoside compounds |
| CN1427722A (zh) * | 2000-02-18 | 2003-07-02 | 希拉生物化学股份有限公司 | 用核苷类似物治疗或预防黄病毒感染的方法 |
| EP1964569A3 (en) * | 2000-04-13 | 2009-07-22 | Pharmasset, Inc. | 3'-or 2'-hydroxymethyl substituted nucleoside derivatives for treatment of viral infections |
| MY164523A (en) * | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| KR20080021797A (ko) * | 2000-05-26 | 2008-03-07 | 이데닉스(케이만)리미티드 | 플라비바이러스 및 페스티바이러스의 치료방법 및 조성물 |
| UA72612C2 (en) | 2000-07-06 | 2005-03-15 | Pyrido[2.3-d]pyrimidine and pyrimido[4.5-d]pyrimidine nucleoside analogues, prodrugs and method for inhibiting growth of neoplastic cells | |
| GB0017676D0 (en) | 2000-07-19 | 2000-09-06 | Angeletti P Ist Richerche Bio | Inhibitors of viral polymerase |
| SK742003A3 (en) | 2000-07-21 | 2003-06-03 | Schering Corp | Novel peptides as NS3-serine protease inhibitors of hepatitis C virus |
| WO2002008251A2 (en) | 2000-07-21 | 2002-01-31 | Corvas International, Inc. | Peptides as ns3-serine protease inhibitors of hepatitis c virus |
| AR029851A1 (es) | 2000-07-21 | 2003-07-16 | Dendreon Corp | Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de hepatitis c |
| AR034127A1 (es) | 2000-07-21 | 2004-02-04 | Schering Corp | Imidazolidinonas como inhibidores de ns3-serina proteasa del virus de hepatitis c, composicion farmaceutica, un metodo para su preparacion, y el uso de las mismas para la manufactura de un medicamento |
| US20030008841A1 (en) * | 2000-08-30 | 2003-01-09 | Rene Devos | Anti-HCV nucleoside derivatives |
| KR20090089922A (ko) * | 2000-10-18 | 2009-08-24 | 파마셋 인코포레이티드 | 바이러스 감염 및 비정상적인 세포 증식의 치료를 위한 변형된 뉴클레오시드 |
| US6650614B1 (en) | 2000-10-30 | 2003-11-18 | Cirrus Logic, Inc. | Optical disk pickup using current mode signal exchanges and systems and methods using the same |
| ES2263687T3 (es) | 2000-11-20 | 2006-12-16 | Bristol-Myers Squibb Company | Inhibidores tripeptidicos de la hepatitis c. |
| AU3659102A (en) | 2000-12-12 | 2002-06-24 | Schering Corp | Diaryl peptides as ns3-serine protease inhibitors of hepatits c virus |
| WO2002048157A2 (en) | 2000-12-13 | 2002-06-20 | Bristol-Myers Squibb Pharma Company | Imidazolidinones and their related derivatives as hepatitis c virus ns3 protease inhibitors |
| WO2002048116A2 (en) | 2000-12-13 | 2002-06-20 | Bristol-Myers Squibb Pharma Company | Inhibitors of hepatitis c virus ns3 protease |
| WO2002048165A2 (en) * | 2000-12-15 | 2002-06-20 | Pharmasset Ltd. | Antiviral agents for treatment of flaviviridae infections |
| WO2002057425A2 (en) | 2001-01-22 | 2002-07-25 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| US7105499B2 (en) * | 2001-01-22 | 2006-09-12 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| GB0112617D0 (en) | 2001-05-23 | 2001-07-18 | Hoffmann La Roche | Antiviral nucleoside derivatives |
| GB0114286D0 (en) | 2001-06-12 | 2001-08-01 | Hoffmann La Roche | Nucleoside Derivatives |
| JP2005536440A (ja) * | 2001-09-28 | 2005-12-02 | イデニクス(ケイマン)リミテツド | 4’位が修飾されたヌクレオシドを使用するフラビウイルスおよびペスチウイルスの治療のための方法および組成物 |
| AU2002330154A1 (en) | 2001-09-28 | 2003-04-07 | Centre National De La Recherche Scientifique | Methods and compositions for treating hepatitis c virus using 4'-modified nucleosides |
| MY151199A (en) | 2001-11-02 | 2014-04-30 | Rigel Pharmaceuticals Inc | Substituted diphenyl heterocycles useful for treating hcv infection |
| AU2002353165A1 (en) | 2001-12-17 | 2003-06-30 | Ribapharm Inc. | Deazapurine nucleoside libraries and compounds |
| WO2003062255A2 (en) | 2002-01-17 | 2003-07-31 | Ribapharm Inc. | Sugar modified nucleosides as viral replication inhibitors |
| US7217815B2 (en) * | 2002-01-17 | 2007-05-15 | Valeant Pharmaceuticals North America | 2-beta -modified-6-substituted adenosine analogs and their use as antiviral agents |
| WO2003062256A1 (en) | 2002-01-17 | 2003-07-31 | Ribapharm Inc. | 2'-beta-modified-6-substituted adenosine analogs and their use as antiviral agents |
| WO2003061385A1 (en) | 2002-01-17 | 2003-07-31 | Ribapharm Inc. | Tricyclic nucleoside library compounds, synthesis, and use as antiviral agents |
| GB0201179D0 (en) | 2002-01-18 | 2002-03-06 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| KR20040094692A (ko) | 2002-02-14 | 2004-11-10 | 파마셋, 리미티드 | 변형된 불소화 뉴클레오사이드 유사체 |
| RU2004128943A (ru) | 2002-02-28 | 2005-04-20 | Байота, Инк. (Us) | Средства, имитирующие нуклеотиды, и их пролекарственные формы |
| EP1487459A4 (en) | 2002-03-12 | 2006-05-24 | Ariad Pharma Inc | PEPTIDE ANALOGUES AND USES |
| AU2003232071A1 (en) * | 2002-05-06 | 2003-11-17 | Genelabs Technologies, Inc. | Nucleoside derivatives for treating hepatitis c virus infection |
| US20070004669A1 (en) | 2002-06-21 | 2007-01-04 | Carroll Steven S | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| EP1572945A2 (en) | 2002-06-27 | 2005-09-14 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| BR0312271A (pt) | 2002-06-28 | 2007-11-06 | Idenix Cayman Ltd | compostos, composições e seus usos para o tratamento de infecções por flaviviridae |
| MXPA04012779A (es) | 2002-06-28 | 2005-08-19 | Idenix Cayman Ltd | Profarmacos de 2'- y 3'-nucleosido para tratar infecciones por flaviviridae. |
| PL374781A1 (en) | 2002-06-28 | 2005-10-31 | Idenix (Cayman) Limited | 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| JP2005533108A (ja) | 2002-07-16 | 2005-11-04 | メルク エンド カムパニー インコーポレーテッド | Rna依存性rnaウイルスポリメラーゼの阻害剤としてのヌクレオシド誘導体 |
| AU2003256619A1 (en) | 2002-07-24 | 2004-02-09 | Isis Pharmaceuticals, Inc. | Pyrrolopyrimidine thionucleoside analogs as antivirals |
| AU2003263978A1 (en) | 2002-08-01 | 2004-02-23 | Board Of Trustees Of The Leland Stanford Junior University | 2',3'-dideoxynucleoside analogues for the treatment or prevention of flavivitridae infections |
| JP2006507235A (ja) | 2002-08-01 | 2006-03-02 | フアーマセツト・インコーポレイテツド | フラビウイルス科ウイルス感染治療のためのビシクロ[4.2.1]ノナン系を有する化合物 |
| US20040067877A1 (en) * | 2002-08-01 | 2004-04-08 | Schinazi Raymond F. | 2', 3'-Dideoxynucleoside analogues for the treatment or prevention of Flaviviridae infections |
| HRP20050168A2 (en) | 2002-08-23 | 2005-10-31 | Rigel Pharmaceuticals | Pyridyl substituted heterocycles useful for treating or preventing hcv infection |
| AU2003279797B2 (en) | 2002-09-30 | 2009-10-22 | Genelabs Technologies, Inc. | Nucleoside derivatives for treating hepatitis C virus infection |
| WO2004037159A2 (en) * | 2002-10-23 | 2004-05-06 | Obetherapy Biotechnology | Compounds, compositions and methods for modulating fat metabolism |
| EP1562440B1 (en) | 2002-11-07 | 2011-01-12 | The Texas A & M Univsersity System | Process for solubilizing protein |
| HUE033832T2 (en) | 2002-11-15 | 2018-01-29 | Idenix Pharmaceuticals Llc | 2'-methyl nucleosides in combination with interferon and Flaviviridae mutation |
| RU2005121904A (ru) | 2002-12-12 | 2006-01-20 | Айденикс (Кайман) Лимитед (Ky) | Способ получения 2`-разветвленных нуклеозидов |
| EP1658302B1 (en) * | 2003-07-25 | 2010-08-25 | IDENIX Pharmaceuticals, Inc. | Purine nucleoside analogues for treating diseases caused by flaviviridae including hepatitis c |
-
2004
- 2004-07-26 EP EP04744307A patent/EP1658302B1/en not_active Expired - Lifetime
- 2004-07-26 PL PL04744307T patent/PL1658302T3/pl unknown
- 2004-07-26 US US10/900,008 patent/US20050075309A1/en not_active Abandoned
- 2004-07-26 AT AT04744307T patent/ATE478886T1/de active
- 2004-07-26 CN CNA2004800270217A patent/CN1852915A/zh active Pending
- 2004-07-26 ES ES04744307T patent/ES2351603T3/es not_active Expired - Lifetime
- 2004-07-26 PT PT04744307T patent/PT1658302E/pt unknown
- 2004-07-26 DE DE602004028841T patent/DE602004028841D1/de not_active Expired - Lifetime
- 2004-07-26 AU AU2004258750A patent/AU2004258750A1/en not_active Abandoned
- 2004-07-26 JP JP2006520940A patent/JP2007501185A/ja active Pending
- 2004-07-26 CA CA2533367A patent/CA2533367C/en not_active Expired - Fee Related
- 2004-07-26 DK DK04744307.2T patent/DK1658302T3/da active
- 2004-07-26 WO PCT/IB2004/002703 patent/WO2005009418A2/en not_active Ceased
- 2004-07-26 KR KR1020067001534A patent/KR20060084845A/ko not_active Withdrawn
- 2004-07-26 BR BRPI0412849-4A patent/BRPI0412849A/pt not_active IP Right Cessation
- 2004-07-26 RU RU2006105640/04A patent/RU2006105640A/ru not_active Application Discontinuation
-
2006
- 2006-02-24 NO NO20060914A patent/NO20060914L/no not_active Application Discontinuation
-
2008
- 2008-11-13 US US12/270,795 patent/US8742101B2/en not_active Expired - Lifetime
-
2014
- 2014-05-02 US US14/269,003 patent/US9186369B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016138078A (ja) * | 2015-01-29 | 2016-08-04 | 学校法人日本大学 | 8−アザ−3,7−ジデアザアデニンヌクレオシド誘導体、8−アザ−3,7−ジデアザアデニンヌクレオチド誘導体及びポリヌクレオチド誘導体ならびにプローブ |
Also Published As
| Publication number | Publication date |
|---|---|
| DE602004028841D1 (de) | 2010-10-07 |
| CA2533367A1 (en) | 2005-02-03 |
| WO2005009418A2 (en) | 2005-02-03 |
| US9186369B2 (en) | 2015-11-17 |
| ES2351603T3 (es) | 2011-02-08 |
| WO2005009418A3 (en) | 2005-04-07 |
| PT1658302E (pt) | 2010-10-25 |
| PL1658302T3 (pl) | 2011-03-31 |
| DK1658302T3 (da) | 2010-11-22 |
| US20090169507A1 (en) | 2009-07-02 |
| EP1658302B1 (en) | 2010-08-25 |
| AU2004258750A1 (en) | 2005-02-03 |
| BRPI0412849A (pt) | 2006-09-26 |
| NO20060914L (no) | 2006-04-25 |
| US8742101B2 (en) | 2014-06-03 |
| KR20060084845A (ko) | 2006-07-25 |
| US20140234251A1 (en) | 2014-08-21 |
| ATE478886T1 (de) | 2010-09-15 |
| US20050075309A1 (en) | 2005-04-07 |
| CN1852915A (zh) | 2006-10-25 |
| CA2533367C (en) | 2013-10-01 |
| EP1658302A2 (en) | 2006-05-24 |
| RU2006105640A (ru) | 2007-09-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9186369B2 (en) | Purine nucleoside analogues for treating flaviviridae including hepatitis C | |
| EP4032897B1 (en) | Modified fluorinated nucleoside analogues | |
| AU2003257157B2 (en) | Compounds with the bicyclo[4.2.1] nonane system for the treatment of Flaviviridae infections | |
| JP2008503562A (ja) | フラビウイルス科による感染症を治療するための5−アザ−7−デアザプリン誘導体 | |
| MXPA04012802A (es) | Ester 2'-c-metil-3'-o-l-valina de ribofuranosil-citidina para el tratamiento de infecciones por flaviviridae. | |
| JP2006526629A5 (https=) | ||
| JP2008535932A (ja) | 抗ウィルス剤としての非天然塩基を有するヌクレオシド | |
| MXPA06001017A (en) | Purin nucleoside analogues for treating flaviviridae including hepatitis c | |
| HK1187349B (en) | Modified fluorinated nucleoside analogues |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070724 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070724 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20090703 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110215 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110513 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110520 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110613 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110620 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20110920 |