JP5820722B2 - シクロスポリン類似体及びｈｃｖ感染の治療におけるその使用 - Google Patents
シクロスポリン類似体及びｈｃｖ感染の治療におけるその使用 Download PDFInfo
- Publication number
- JP5820722B2 JP5820722B2 JP2011512478A JP2011512478A JP5820722B2 JP 5820722 B2 JP5820722 B2 JP 5820722B2 JP 2011512478 A JP2011512478 A JP 2011512478A JP 2011512478 A JP2011512478 A JP 2011512478A JP 5820722 B2 JP5820722 B2 JP 5820722B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- cyclosporin
- sar
- val
- acid
- 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.)
- Expired - Fee Related
Links
- 238000011282 treatment Methods 0.000 title description 60
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical class CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 title description 54
- 208000015181 infectious disease Diseases 0.000 title description 32
- 150000001875 compounds Chemical class 0.000 claims description 198
- 239000000203 mixture Substances 0.000 claims description 121
- 125000000217 alkyl group Chemical group 0.000 claims description 96
- 229960001265 ciclosporin Drugs 0.000 claims description 89
- 125000004432 carbon atom Chemical group C* 0.000 claims description 81
- -1 trans-4-benzyloxy-but-2-enyl Chemical group 0.000 claims description 72
- 238000000034 method Methods 0.000 claims description 67
- 229910052757 nitrogen Inorganic materials 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 55
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
- 150000002367 halogens Chemical class 0.000 claims description 53
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 47
- 239000008194 pharmaceutical composition Substances 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 239000002904 solvent Substances 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000001301 oxygen Substances 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 229910052717 sulfur Chemical group 0.000 claims description 16
- 239000011593 sulfur Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 9
- 239000012039 electrophile Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 150000001449 anionic compounds Chemical class 0.000 claims description 4
- 229920000447 polyanionic polymer Polymers 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- 208000010710 hepatitis C virus infection Diseases 0.000 claims description 2
- 241000894007 species Species 0.000 claims description 2
- 241000711549 Hepacivirus C Species 0.000 description 100
- 239000003795 chemical substances by application Substances 0.000 description 65
- 239000002552 dosage form Substances 0.000 description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- 239000003814 drug Substances 0.000 description 46
- 239000000243 solution Substances 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 36
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 34
- 229910001868 water Inorganic materials 0.000 description 33
- 239000004480 active ingredient Substances 0.000 description 32
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 31
- 230000000694 effects Effects 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 239000002253 acid Substances 0.000 description 27
- 239000002585 base Substances 0.000 description 26
- 229940079593 drug Drugs 0.000 description 26
- 102000014150 Interferons Human genes 0.000 description 25
- 108010050904 Interferons Proteins 0.000 description 25
- 229940079322 interferon Drugs 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000002560 therapeutic procedure Methods 0.000 description 24
- 108010036949 Cyclosporine Proteins 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- 201000010099 disease Diseases 0.000 description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 21
- 230000000069 prophylactic effect Effects 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 208000035475 disorder Diseases 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 17
- 239000000546 pharmaceutical excipient Substances 0.000 description 17
- 229960000329 ribavirin Drugs 0.000 description 17
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 17
- 229930105110 Cyclosporin A Natural products 0.000 description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- 125000000623 heterocyclic group Chemical group 0.000 description 16
- 229940124597 therapeutic agent Drugs 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 14
- 230000002265 prevention Effects 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 13
- 239000013543 active substance Substances 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 125000006413 ring segment Chemical group 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 238000013270 controlled release Methods 0.000 description 11
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
- 108010068682 Cyclophilins Proteins 0.000 description 10
- 102000001493 Cyclophilins Human genes 0.000 description 10
- 241000700605 Viruses Species 0.000 description 10
- 229930182912 cyclosporin Natural products 0.000 description 10
- 239000007884 disintegrant Substances 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000006186 oral dosage form Substances 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- 108010047761 Interferon-alpha Proteins 0.000 description 9
- 102000006992 Interferon-alpha Human genes 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 235000019698 starch Nutrition 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 108060001084 Luciferase Proteins 0.000 description 8
- 239000005089 Luciferase Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000006978 adaptation Effects 0.000 description 8
- 208000006673 asthma Diseases 0.000 description 8
- 239000003085 diluting agent Substances 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 239000000314 lubricant Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000004806 packaging method and process Methods 0.000 description 8
- 239000006201 parenteral dosage form Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 7
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 7
- 102000002689 Toll-like receptor Human genes 0.000 description 7
- 108020000411 Toll-like receptor Proteins 0.000 description 7
- 239000000443 aerosol Substances 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 125000001072 heteroaryl group Chemical group 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 7
- 239000008108 microcrystalline cellulose Substances 0.000 description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 238000002054 transplantation Methods 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 6
- 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 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 108091005804 Peptidases Proteins 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000004365 Protease Substances 0.000 description 6
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 238000011461 current therapy Methods 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 125000001183 hydrocarbyl group Chemical group 0.000 description 6
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 6
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 6
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 6
- 125000004001 thioalkyl group Chemical group 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- 208000009137 Behcet syndrome Diseases 0.000 description 5
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 5
- 201000004624 Dermatitis Diseases 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 208000005176 Hepatitis C Diseases 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 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 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- 108060004795 Methyltransferase Proteins 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 125000001931 aliphatic group Chemical group 0.000 description 5
- 235000010323 ascorbic acid Nutrition 0.000 description 5
- 239000011668 ascorbic acid Substances 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
- 208000006454 hepatitis Diseases 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000012423 maintenance Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 4
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 229920000881 Modified starch Polymers 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 101710144111 Non-structural protein 3 Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 4
- 206010038997 Retroviral infections Diseases 0.000 description 4
- 108091027967 Small hairpin RNA Proteins 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000000840 anti-viral effect Effects 0.000 description 4
- 239000003125 aqueous solvent Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 4
- 239000007894 caplet Substances 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 235000015165 citric acid Nutrition 0.000 description 4
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 4
- 230000003111 delayed effect Effects 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 4
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 4
- GKTNLYAAZKKMTQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphinimyl]-n-methylmethanamine Chemical compound CN(C)P(=N)(N(C)C)N(C)C GKTNLYAAZKKMTQ-UHFFFAOYSA-N 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000002777 nucleoside Substances 0.000 description 4
- 150000003833 nucleoside derivatives Chemical class 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000011321 prophylaxis Methods 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 239000004055 small Interfering RNA Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 231100001274 therapeutic index Toxicity 0.000 description 4
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 101150065749 Churc1 gene Proteins 0.000 description 3
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 3
- 108010025815 Kanamycin Kinase Proteins 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 235000019483 Peanut oil Nutrition 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 102100038239 Protein Churchill Human genes 0.000 description 3
- 108010077895 Sarcosine Proteins 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- TVRCRTJYMVTEFS-ICGCPXGVSA-N [(2r,3r,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)-4-methyloxolan-3-yl] (2s)-2-amino-3-methylbutanoate Chemical group C[C@@]1(O)[C@H](OC(=O)[C@@H](N)C(C)C)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 TVRCRTJYMVTEFS-ICGCPXGVSA-N 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 3
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 229960001231 choline Drugs 0.000 description 3
- PJZPDFUUXKKDNB-KNINVFKUSA-N ciluprevir Chemical group 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 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 229940125797 compound 12 Drugs 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 230000005860 defense response to virus Effects 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000001033 ether group Chemical group 0.000 description 3
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 3
- 229940093471 ethyl oleate Drugs 0.000 description 3
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 150000002334 glycols Chemical class 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 210000004209 hair Anatomy 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 239000002955 immunomodulating agent Substances 0.000 description 3
- 229940121354 immunomodulator Drugs 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 239000008297 liquid dosage form Substances 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000000312 peanut oil Substances 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 3
- 230000000306 recurrent effect Effects 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000008159 sesame oil Substances 0.000 description 3
- 235000011803 sesame oil Nutrition 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000008247 solid mixture Substances 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- AYIYPHDKKVWZKI-LJTMIZJLSA-N (2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol;piperazine Chemical compound C1CNCCN1.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO AYIYPHDKKVWZKI-LJTMIZJLSA-N 0.000 description 2
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 2
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- OQCFWECOQNPQCG-UHFFFAOYSA-N 1,3,4,8-tetrahydropyrimido[4,5-c]oxazin-7-one Chemical compound C1CONC2=C1C=NC(=O)N2 OQCFWECOQNPQCG-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- QRKDOAWSBBGNLE-UHFFFAOYSA-N 2h-1,2,4-benzothiadiazine Chemical compound C1=CC=C2N=CNSC2=C1 QRKDOAWSBBGNLE-UHFFFAOYSA-N 0.000 description 2
- MLMQPDHYNJCQAO-UHFFFAOYSA-N 3,3-dimethylbutyric acid Chemical compound CC(C)(C)CC(O)=O MLMQPDHYNJCQAO-UHFFFAOYSA-N 0.000 description 2
- XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 2
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 2
- 125000006495 3-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 description 2
- PPUDLEUZKVJXSZ-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4r,5r)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 PPUDLEUZKVJXSZ-VPCXQMTMSA-N 0.000 description 2
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- 125000002528 4-isopropyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000007788 Acute Liver Failure Diseases 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 208000032467 Aplastic anaemia Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 2
- 0 CC(C)*CC(C)N(C)C Chemical compound CC(C)*CC(C)N(C)C 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 206010010144 Completed suicide Diseases 0.000 description 2
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 2
- 108010072220 Cyclophilin A Proteins 0.000 description 2
- 108010048028 Cyclophilin D Proteins 0.000 description 2
- 108010036941 Cyclosporins Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 2
- 208000015023 Graves' disease Diseases 0.000 description 2
- 206010018901 Haemoglobinaemia Diseases 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- 239000005639 Lauric acid Substances 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010029240 Neuritis Diseases 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 101800001020 Non-structural protein 4A Proteins 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 206010034277 Pemphigoid Diseases 0.000 description 2
- 102100034539 Peptidyl-prolyl cis-trans isomerase A Human genes 0.000 description 2
- 102100040283 Peptidyl-prolyl cis-trans isomerase B Human genes 0.000 description 2
- 102100034943 Peptidyl-prolyl cis-trans isomerase F, mitochondrial Human genes 0.000 description 2
- 208000037581 Persistent Infection Diseases 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000008156 Ringer's lactate solution Substances 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 208000002903 Thalassemia Diseases 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 102000044159 Ubiquitin Human genes 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 108020000999 Viral RNA Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- HTJGLYIJVSDQAE-VWNXEWBOSA-N [(1s,6s,7s,8r,8ar)-1,7,8-trihydroxy-1,2,3,5,6,7,8,8a-octahydroindolizin-6-yl] butanoate Chemical group O[C@H]1[C@H](O)[C@@H](OC(=O)CCC)CN2CC[C@H](O)[C@@H]21 HTJGLYIJVSDQAE-VWNXEWBOSA-N 0.000 description 2
- ZWELIJXAKMASLK-UGKPPGOTSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(5-amino-2-oxo-[1,3]thiazolo[4,5-d]pyrimidin-3-yl)-2-(hydroxymethyl)oxolan-3-yl] acetate Chemical group CC(=O)O[C@@H]1[C@H](OC(=O)C)[C@@H](CO)O[C@H]1N1C(=O)SC2=CN=C(N)N=C21 ZWELIJXAKMASLK-UGKPPGOTSA-N 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 229940072107 ascorbate Drugs 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 description 2
- 229940077388 benzenesulfonate Drugs 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 229940050390 benzoate Drugs 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 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
- 230000027455 binding Effects 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 238000005266 casting Methods 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 229950003414 celgosivir Drugs 0.000 description 2
- JWMLCCRPDOIBAV-UHFFFAOYSA-N chloro(methylsulfanyl)methane Chemical compound CSCCl JWMLCCRPDOIBAV-UHFFFAOYSA-N 0.000 description 2
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 2
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 2
- 229960002023 chloroprocaine Drugs 0.000 description 2
- 229940114081 cinnamate Drugs 0.000 description 2
- 235000013985 cinnamic acid Nutrition 0.000 description 2
- 229930016911 cinnamic acid Natural products 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- MRKZAZMYXYSBDG-UHFFFAOYSA-N cyclopentyl propanoate Chemical compound CCC(=O)OC1CCCC1 MRKZAZMYXYSBDG-UHFFFAOYSA-N 0.000 description 2
- 108010048032 cyclophilin B Proteins 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 229940043237 diethanolamine Drugs 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 2
- 229940043264 dodecyl sulfate Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000011194 food seasoning agent Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 229940050410 gluconate Drugs 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 229940049906 glutamate Drugs 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002489 hematologic effect Effects 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 230000003463 hyperproliferative effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 208000023589 ischemic disease Diseases 0.000 description 2
- 206010023332 keratitis Diseases 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 229940070765 laurate Drugs 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 208000007903 liver failure Diseases 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 2
- 239000000347 magnesium hydroxide Substances 0.000 description 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 2
- 229940049920 malate Drugs 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
- 229960002510 mandelic acid Drugs 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 201000006938 muscular dystrophy Diseases 0.000 description 2
- 201000005962 mycosis fungoides Diseases 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 2
- IFVGFQAONSKBCR-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]pyrimidin-2-amine Chemical compound C1CN1P(N1CC1)(=O)NC1=NC=CC=N1 IFVGFQAONSKBCR-UHFFFAOYSA-N 0.000 description 2
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 2
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 108010044156 peptidyl-prolyl cis-trans isomerase b Proteins 0.000 description 2
- 230000037050 permeability transition Effects 0.000 description 2
- NIXKBAZVOQAHGC-UHFFFAOYSA-N phenylmethanesulfonic acid Chemical class OS(=O)(=O)CC1=CC=CC=C1 NIXKBAZVOQAHGC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 229940075930 picrate Drugs 0.000 description 2
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 2
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 229960004919 procaine Drugs 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000001698 pyrogenic effect Effects 0.000 description 2
- 229940076788 pyruvate Drugs 0.000 description 2
- 229940107700 pyruvic acid Drugs 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 229960001860 salicylate Drugs 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 201000000306 sarcoidosis Diseases 0.000 description 2
- 229940043230 sarcosine Drugs 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 208000007056 sickle cell anemia Diseases 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 229940075554 sorbate Drugs 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229940086735 succinate Drugs 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 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
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 125000004665 trialkylsilyl group Chemical group 0.000 description 2
- 229940066528 trichloroacetate Drugs 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 2
- 229940007718 zinc hydroxide Drugs 0.000 description 2
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- IRZRJANZDIOOIF-GAJNKVMBSA-N (2r,3r,4r,5r)-2-(4-aminopyrrolo[2,3-d]pyrimidin-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=NC=NC(N)=C2C=C1 IRZRJANZDIOOIF-GAJNKVMBSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- RPALEGQGCGCFCX-FIWMUJSFSA-N (E)-2-Butenyl-4-methyl-threonine Chemical compound C\C=C\C[C@@H](C)[C@@H](O)[C@H](N)C(O)=O RPALEGQGCGCFCX-FIWMUJSFSA-N 0.000 description 1
- RMXLHIUHKIVPAB-OWOJBTEDSA-N (e)-1,4-dibromobut-2-ene Chemical compound BrC\C=C\CBr RMXLHIUHKIVPAB-OWOJBTEDSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- VBAJJNYVEFZPCW-UHFFFAOYSA-N 1-bromobut-2-enoxymethylbenzene Chemical compound CC=CC(Br)OCC1=CC=CC=C1 VBAJJNYVEFZPCW-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- VBRUONUESYTIDA-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-(methanesulfonamido)-n-methyl-5-propan-2-yloxy-1-benzofuran-3-carboxamide Chemical compound O1C2=CC(NS(C)(=O)=O)=C(OC(C)C)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 VBRUONUESYTIDA-UHFFFAOYSA-N 0.000 description 1
- JXZYSNWHGBGZAI-GOSISDBHSA-N 2-[(1r)-5-cyano-8-methyl-1-propyl-4,9-dihydro-3h-pyrano[3,4-b]indol-1-yl]acetic acid Chemical compound N1C2=C(C)C=CC(C#N)=C2C2=C1[C@@](CCC)(CC(O)=O)OCC2 JXZYSNWHGBGZAI-GOSISDBHSA-N 0.000 description 1
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-M 4-chlorobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-M 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- WTDWVLJJJOTABN-UHFFFAOYSA-N 5-cyclopropyl-2-(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-n-methyl-1-benzofuran-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC(N(CCO)S(C)(=O)=O)=C1C1CC1 WTDWVLJJJOTABN-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 201000010000 Agranulocytosis Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002065 Anaemia megaloblastic Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
- 239000004358 Butane-1, 3-diol Substances 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000006154 Chronic hepatitis C Diseases 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 206010009208 Cirrhosis alcoholic Diseases 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 206010054089 Depressive symptom Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 101100010343 Drosophila melanogaster lobo gene Proteins 0.000 description 1
- 208000003870 Drug Overdose Diseases 0.000 description 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
- 208000011345 Duchenne and Becker muscular dystrophy Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 241000710188 Encephalomyocarditis virus Species 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 206010014954 Eosinophilic fasciitis Diseases 0.000 description 1
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010049466 Erythroblastosis Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 241000711557 Hepacivirus Species 0.000 description 1
- 208000027761 Hepatic autoimmune disease Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 108700039791 Hepatitis C virus nucleocapsid Proteins 0.000 description 1
- 206010019791 Hepatitis post transfusion Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000005100 Herpetic Keratitis Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 206010021074 Hypoplastic anaemia Diseases 0.000 description 1
- 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100040018 Interferon alpha-2 Human genes 0.000 description 1
- 108010079944 Interferon-alpha2b Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 201000002287 Keratoconus Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- GWNVDXQDILPJIG-SHSCPDMUSA-N Leukotriene C4 Natural products CCCCCC=C/CC=C/C=C/C=C/C(SCC(NC(=O)CCC(N)C(=O)O)C(=O)NCC(=O)O)C(O)CCCC(=O)O GWNVDXQDILPJIG-SHSCPDMUSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 description 1
- 208000001244 Linear IgA Bullous Dermatosis Diseases 0.000 description 1
- 208000012309 Linear IgA disease Diseases 0.000 description 1
- 208000000185 Localized scleroderma Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 208000000682 Megaloblastic Anemia Diseases 0.000 description 1
- 208000027530 Meniere disease Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 101710171731 Mono-ADP-ribosyltransferase Proteins 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010051606 Necrotising colitis Diseases 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- FZRKAZHKEDOPNN-UHFFFAOYSA-N Nitric oxide anion Chemical compound O=[N-] FZRKAZHKEDOPNN-UHFFFAOYSA-N 0.000 description 1
- 101800001019 Non-structural protein 4B Proteins 0.000 description 1
- 101800001014 Non-structural protein 5A Proteins 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010073938 Ophthalmic herpes simplex Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010033296 Overdoses Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 208000031845 Pernicious anaemia Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 206010036774 Proctitis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000006311 Pyoderma Diseases 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010039705 Scleritis Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 208000031709 Skin Manifestations Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000001106 Takayasu Arteritis Diseases 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 231100000579 Toxinosis Toxicity 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010064996 Ulcerative keratitis Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000035868 Vascular inflammations Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- REBYQQNHTPNLJS-SNAWJCMRSA-N [(e)-4-bromobut-2-enoxy]methylbenzene Chemical compound BrC\C=C\COCC1=CC=CC=C1 REBYQQNHTPNLJS-SNAWJCMRSA-N 0.000 description 1
- YSVZGWAJIHWNQK-UHFFFAOYSA-N [3-(hydroxymethyl)-2-bicyclo[2.2.1]heptanyl]methanol Chemical compound C1CC2C(CO)C(CO)C1C2 YSVZGWAJIHWNQK-UHFFFAOYSA-N 0.000 description 1
- WOMMBEYPWVELIE-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] 2,2,2-trifluoroacetate Chemical group CC(C)(C)[Si](C)(C)OC(=O)C(F)(F)F WOMMBEYPWVELIE-UHFFFAOYSA-N 0.000 description 1
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000010398 acute inflammatory response Effects 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 208000012761 aggressive behavior Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 238000003915 air pollution Methods 0.000 description 1
- 230000010085 airway hyperresponsiveness Effects 0.000 description 1
- 208000010002 alcoholic liver cirrhosis Diseases 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000005360 alkyl sulfoxide group Chemical group 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 150000007658 benzothiadiazines Chemical class 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- TXLDSFAKBTWJAQ-UHFFFAOYSA-N bis(methylperoxy)methane Chemical compound COOCOOC TXLDSFAKBTWJAQ-UHFFFAOYSA-N 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 208000000594 bullous pemphigoid Diseases 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000003683 cardiac damage Effects 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 201000006815 congenital muscular dystrophy Diseases 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- LTYZGLKKXZXSEC-UHFFFAOYSA-N copper dihydride Chemical compound [CuH2] LTYZGLKKXZXSEC-UHFFFAOYSA-N 0.000 description 1
- 229910000050 copper hydride Inorganic materials 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 201000007717 corneal ulcer Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000008356 dextrose and sodium chloride injection Substances 0.000 description 1
- 239000008355 dextrose injection Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- 238000005906 dihydroxylation reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 244000309457 enveloped RNA virus Species 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 description 1
- 210000000918 epididymis Anatomy 0.000 description 1
- 201000010063 epididymitis Diseases 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 208000024711 extrinsic asthma Diseases 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 244000053095 fungal pathogen Species 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000007897 gelcap Substances 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108010050669 glucosidase I Proteins 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)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)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 201000010884 herpes simplex virus keratitis Diseases 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 206010021198 ichthyosis Diseases 0.000 description 1
- 201000002597 ichthyosis vulgaris Diseases 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- IGUXCTSQIGAGSV-UHFFFAOYSA-K indium(iii) hydroxide Chemical compound [OH-].[OH-].[OH-].[In+3] IGUXCTSQIGAGSV-UHFFFAOYSA-K 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 201000006334 interstitial nephritis Diseases 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000003903 intestinal lesions Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 208000023569 ischemic bowel disease Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 239000012948 isocyanate Chemical class 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 201000010666 keratoconjunctivitis Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229940059904 light mineral oil Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- 231100001016 megaloblastic anemia Toxicity 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 230000008965 mitochondrial swelling Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- 229940100661 nasal inhalant Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 230000037125 natural defense Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 208000004995 necrotizing enterocolitis Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 229940041672 oral gel Drugs 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000001769 paralizing effect Effects 0.000 description 1
- 238000012753 partial hepatectomy Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940002988 pegasys Drugs 0.000 description 1
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 1
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
- 229940106366 pegintron Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 210000002379 periodontal ligament Anatomy 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 208000019629 polyneuritis Diseases 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000379 polypropylene carbonate Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003658 preventing hair loss Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 244000000040 protozoan parasite Species 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940071117 starch glycolate Drugs 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000009121 systemic therapy Methods 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
- 238000012360 testing method Methods 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical group 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- GWIKYPMLNBTJHR-UHFFFAOYSA-M thiosulfonate group Chemical group S(=S)(=O)[O-] GWIKYPMLNBTJHR-UHFFFAOYSA-M 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 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
- 229950002810 valopicitabine Drugs 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000008136 water-miscible vehicle Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- C07K7/645—Cyclosporins; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5964908P | 2008-06-06 | 2008-06-06 | |
| US61/059,649 | 2008-06-06 | ||
| PCT/US2009/003411 WO2010002428A2 (en) | 2008-06-06 | 2009-06-05 | Novel macrocyclic peptides |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011523952A JP2011523952A (ja) | 2011-08-25 |
| JP2011523952A5 JP2011523952A5 (enExample) | 2012-07-26 |
| JP5820722B2 true JP5820722B2 (ja) | 2015-11-24 |
Family
ID=41415358
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011512478A Expired - Fee Related JP5820722B2 (ja) | 2008-06-06 | 2009-06-05 | シクロスポリン類似体及びｈｃｖ感染の治療におけるその使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9090671B2 (enExample) |
| EP (1) | EP2280989B1 (enExample) |
| JP (1) | JP5820722B2 (enExample) |
| CN (1) | CN102083852A (enExample) |
| CA (1) | CA2724523A1 (enExample) |
| WO (1) | WO2010002428A2 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL1802650T3 (pl) * | 2004-10-01 | 2012-04-30 | Scynexis Inc | 3-Etero i 3-tioetero podstawione pochodne cyklosporyny do leczenia i zapobiegania zakażeniu wirusem zapalenia wątroby typu C |
| JP5322647B2 (ja) * | 2005-09-30 | 2013-10-23 | スシネキス インク | ウイルス感染の治療及び予防のためのシクロスポリンａのアリールアルキル及びヘテロアリールアルキル誘導体 |
| US8188052B2 (en) | 2006-05-19 | 2012-05-29 | Scynexis, Inc. | Method for the treatment and prevention of ocular disorders |
| KR101089112B1 (ko) * | 2006-06-02 | 2011-12-06 | 피씨 제스띠옹 에스.아.에스. | 활성 전자 관리 |
| US20090306033A1 (en) * | 2008-06-06 | 2009-12-10 | Keqiang Li | Novel cyclic peptides |
| CA2724523A1 (en) | 2008-06-06 | 2010-01-07 | Scynexis, Inc. | Novel macrocyclic peptides |
| WO2010076329A1 (en) | 2008-12-31 | 2010-07-08 | Scynexis, Inc. | Derivatives of cyclosporin a |
| US20140050728A1 (en) | 2011-01-28 | 2014-02-20 | Board Of Regents Of The University Of Nebraska | Methods and compositions for inhibiting cyclophilin d for the treatment and prevention of obesity and kidney indications |
| US9266927B2 (en) | 2012-06-01 | 2016-02-23 | Allergan, Inc. | Cyclosporin A analogs |
| US9914755B2 (en) | 2015-01-08 | 2018-03-13 | Allergan, Inc. | Cyclosporin derivatives wherein the MeBmt sidechain has been cyclized |
| CN109485771A (zh) * | 2018-10-30 | 2019-03-19 | 焦作中维特品药业股份有限公司 | 一种交联聚维酮的制备方法 |
| JP7277222B2 (ja) | 2019-03-29 | 2023-05-18 | 出光興産株式会社 | 潤滑油組成物 |
| JP2022551161A (ja) * | 2019-10-12 | 2022-12-07 | ファーサイト メディカル テクノロジー （シャンハイ） カンパニー リミテッド | ネフロトキシン誘発性腎障害の処置及び予防 |
| CN114230498B (zh) * | 2021-12-30 | 2023-11-17 | 湖北华世通生物医药科技有限公司 | β-(二甲氨基)乙基对甲苯磺酸巯酯盐酸盐的制备方法 |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US496193A (en) * | 1893-04-25 | Hot-air furnace | ||
| EP0194972B1 (en) * | 1985-03-11 | 1992-07-29 | Sandoz Ag | Novel cyclosporins |
| US4814323A (en) * | 1986-03-25 | 1989-03-21 | Andrieu J M | Process for the treatment and the prevention of AIDS and other disorders induced by the LAV/HTLV III virus |
| US4798823A (en) * | 1987-06-03 | 1989-01-17 | Merck & Co., Inc. | New cyclosporin analogs with modified "C-9 amino acids" |
| US4885276A (en) * | 1987-06-03 | 1989-12-05 | Merck & Co., Inc. | Cyclosporin analogs with modified "C-9 amino acids" |
| US4996193A (en) | 1989-03-03 | 1991-02-26 | The Regents Of The University Of California | Combined topical and systemic method of administration of cyclosporine |
| DE69124459T3 (de) * | 1990-11-02 | 2001-05-31 | Novartis Ag, Basel | Zyklosporine |
| US5948693A (en) * | 1994-09-01 | 1999-09-07 | Wisconsin Alumni Research Foundation | Solid phase synthesis of immunosuppressive agents |
| HUP9900405A3 (en) * | 1995-07-17 | 2001-04-28 | Scynexis Inc Durham | Cyclosporin derivatives with anti-hiv effect |
| JP3089350B2 (ja) * | 1995-11-20 | 2000-09-18 | ギルフォード ファーマシューティカルズ インコーポレイテッド | シクロフィリンロタマーゼ活性の阻害剤 |
| FR2757522B1 (fr) * | 1996-12-24 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derives de cyclosporine, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2757520B1 (fr) * | 1996-12-24 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derive de cyclosporine, sa preparation et les compositions pharmaceutiques qui le contiennent |
| FR2757521B1 (fr) | 1996-12-24 | 1999-01-29 | Rhone Poulenc Rorer Sa | Nouveaux derives de cyclosporine, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2762843B1 (fr) | 1997-04-30 | 1999-12-10 | Rhone Poulenc Rorer Sa | Nouveaux derives de cyclosporine, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2772768B1 (fr) | 1997-12-19 | 2000-01-14 | Rhone Poulenc Rorer Sa | Nouveau procede de preparation de derives de cyclosporine |
| GB9811854D0 (en) * | 1998-06-02 | 1998-07-29 | Ciba Geigy Ag | Organic compounds |
| CN1205220C (zh) * | 1998-06-12 | 2005-06-08 | 斯－凯穆公司 | 新颖的环孢菌素 |
| FR2780061B1 (fr) | 1998-06-22 | 2001-09-07 | Rhone Poulenc Rorer Sa | Nouveau procede de preparation de derives de cyclosporine |
| BR9911724A (pt) | 1998-07-01 | 2001-03-20 | Debiopharm Sa | Ciclosporina que tem um perfil de atividade melhorado |
| US6521595B1 (en) * | 1999-11-19 | 2003-02-18 | Lg Chemical, Ltd. | Nonimmunosuppressive [γ-hydroxy-methylleucine4] cyclosporin A, hair growth stimulator and external composition for skin using the same |
| US7015499B1 (en) * | 1999-12-01 | 2006-03-21 | D-Wave Systems, Inc. | Permanent readout superconducting qubit |
| RU2223761C2 (ru) | 1999-12-27 | 2004-02-20 | Джапан Тобакко Инк. | Соединения с конденсированным кольцом и их использование в качестве лекарственных средств |
| MY139078A (en) * | 2000-07-21 | 2009-08-28 | Schering Corp | Peptides as ns3-serine protease inhibitors of hepatitis c virus |
| US7105499B2 (en) | 2001-01-22 | 2006-09-12 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| JP2004532184A (ja) | 2001-01-22 | 2004-10-21 | 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ウィルスポリメラーゼ阻害薬としてのヌクレオシド誘導体 |
| AR036081A1 (es) | 2001-06-07 | 2004-08-11 | Smithkline Beecham Corp | Compuesto de 1,2-dihidroquinolina, su uso para preparar una composicion farmaceutica, metodos para prepararlo y compuestos del acido 2-aminobenzoico n-alquilado de utilidad como intermediarios en dichos metodos |
| GEP20074099B (en) * | 2001-11-27 | 2007-05-10 | Anadys Pharmaceuticals Inc | 3-β-D-RIBOFURANO-SYLTHIAZOLO[4,5-d]PYRIDIMINE NUCLEOSIDES AND USES THEREOF |
| KR20040039622A (ko) | 2002-11-04 | 2004-05-12 | 주식회사 엘지생활건강 | 모발 성장 효과를 갖는 사이클로스포린 3 위치 유도체를유효성분으로 하는 모발 성장 촉진제 |
| US6987090B2 (en) * | 2002-05-09 | 2006-01-17 | Lg Household & Health Care Ltd. | Use of 3-position cyclosporin derivatives for hair growth |
| CA2488842A1 (en) | 2002-06-17 | 2003-12-24 | Merck & Co., Inc. | Carbocyclic nucleoside analogs as rna-antivirals |
| KR20050035194A (ko) * | 2002-06-28 | 2005-04-15 | 이데닉스 (케이만) 리미티드 | 플라비비리다에 감염 치료용 2'-ｃ-메틸-3'-ｏ-ｌ-발린에스테르 리보푸라노실 사이티딘 |
| WO2004007512A2 (en) | 2002-07-16 | 2004-01-22 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| US7148226B2 (en) | 2003-02-21 | 2006-12-12 | Agouron Pharmaceuticals, Inc. | Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same |
| GB0307891D0 (en) | 2003-04-04 | 2003-05-14 | Angeletti P Ist Richerche Bio | Chemical compounds,compositions and uses |
| WO2005000308A2 (en) | 2003-05-15 | 2005-01-06 | Rigel Pharmaceuticals, Inc. | Methods of identifying hcv ns5b polymerase inhibitors and use against hepatitis c |
| GB0320638D0 (en) * | 2003-09-03 | 2003-10-01 | Novartis Ag | Organic compounds |
| GB0323845D0 (en) | 2003-10-10 | 2003-11-12 | Angeletti P Ist Richerche Bio | Chemical compounds,compositions and uses |
| MXPA06009881A (es) | 2004-03-01 | 2007-11-20 | Viropharma Inc | Derivados de piranoindol y el uso de los mismos para el tratamiento de infeccion o enfermedad de virus de hepatitis c. |
| GB0413087D0 (en) | 2004-06-11 | 2004-07-14 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US20070265222A1 (en) | 2004-06-24 | 2007-11-15 | Maccoss Malcolm | Nucleoside Aryl Phosphoramidates for the Treatment of Rna-Dependent Rna Viral Infection |
| CN1984670A (zh) * | 2004-07-13 | 2007-06-20 | 诺瓦提斯公司 | 治疗阿尔茨海默病的环孢菌素 |
| BRPI0513370A (pt) | 2004-07-14 | 2008-05-06 | Novartis Ag | uso de uma combinação de ciclosporina e interferonas peguilados para tratamento de hepatite c (hcv) |
| GB0416396D0 (en) | 2004-07-22 | 2004-08-25 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| GEP20094751B (en) | 2004-08-18 | 2009-08-10 | Pfizer | Inhibitors of hepatitis c virus rna-dependent rna polymerase, and compositions and treatments using the same |
| SG139750A1 (en) | 2004-10-01 | 2008-02-29 | Debiopharm Sa Ch | Use of [d-meala]3-[etval]4-cyclosporin for the treatment of hepatitis c infection and pharmaceutical composition comprising said [d-meala]3- [etval]4-cyclosporin |
| US7196161B2 (en) * | 2004-10-01 | 2007-03-27 | Scynexis Inc. | 3-ether and 3-thioether substituted cyclosporin derivatives for the treatment and prevention of hepatitis C infection |
| CN101068829B (zh) * | 2004-10-01 | 2012-05-30 | 西尼克斯公司 | 用于治疗和预防丙型肝炎病毒感染的3-醚和3-硫醚取代的环孢菌素衍生物 |
| PL1802650T3 (pl) * | 2004-10-01 | 2012-04-30 | Scynexis Inc | 3-Etero i 3-tioetero podstawione pochodne cyklosporyny do leczenia i zapobiegania zakażeniu wirusem zapalenia wątroby typu C |
| WO2006041631A2 (en) | 2004-10-06 | 2006-04-20 | Amr Technology, Inc. | Novel cyclosporin alkynes and their utility as pharmaceutical agents |
| WO2006065335A2 (en) | 2004-10-21 | 2006-06-22 | Merck & Co., Inc. | Fluorinated pyrrolo[2,3-d]pyrimidine nucleosides for the treatment of rna-dependent rna viral infection |
| JP2008517986A (ja) | 2004-10-26 | 2008-05-29 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー | 抗ウイルス薬としての四環式インドール誘導体 |
| KR20070087624A (ko) | 2004-12-23 | 2007-08-28 | 노파르티스 아게 | Ｈｃｖ 치료용 조성물 |
| US20090214464A1 (en) | 2004-12-23 | 2009-08-27 | Beat Weidmann | Compounds for flaviviridae treatment |
| GB0518390D0 (en) | 2005-09-09 | 2005-10-19 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US7473688B2 (en) * | 2005-09-13 | 2009-01-06 | Bristol-Myers Squibb Company | Indolobenzazepine HCV NS5B inhibitors |
| JP5322647B2 (ja) * | 2005-09-30 | 2013-10-23 | スシネキス インク | ウイルス感染の治療及び予防のためのシクロスポリンａのアリールアルキル及びヘテロアリールアルキル誘導体 |
| US7754685B2 (en) | 2005-09-30 | 2010-07-13 | Scynexis, Inc. | Methods and pharmaceutical compositions for the treatment and prevention of hepatitis C infection |
| US8188052B2 (en) | 2006-05-19 | 2012-05-29 | Scynexis, Inc. | Method for the treatment and prevention of ocular disorders |
| WO2008069917A2 (en) | 2006-11-20 | 2008-06-12 | Scynexis, Inc. | Novel cyclic peptides |
| WO2008127613A1 (en) | 2007-04-11 | 2008-10-23 | Scynexis, Inc. | New pharmaceutical compositions |
| WO2008143996A1 (en) | 2007-05-18 | 2008-11-27 | Scynexis, Inc. | New chemical processes |
| US20090306033A1 (en) * | 2008-06-06 | 2009-12-10 | Keqiang Li | Novel cyclic peptides |
| CA2724523A1 (en) | 2008-06-06 | 2010-01-07 | Scynexis, Inc. | Novel macrocyclic peptides |
| WO2010076329A1 (en) * | 2008-12-31 | 2010-07-08 | Scynexis, Inc. | Derivatives of cyclosporin a |
| MX2011007195A (es) | 2009-01-07 | 2013-07-12 | Scynexis Inc | Derivado de ciclosporina para el uso en el tratamiento de infección de virus de hepatitis c (vhc) y virus de inmunodeficiencia humana (vih). |
| CN102271688A (zh) | 2009-01-07 | 2011-12-07 | 西尼克斯公司 | 用于治疗hcv的环孢菌素衍生物和核苷的组合 |
| CA2782898A1 (en) | 2009-12-09 | 2011-06-16 | Scynexis, Inc. | Novel cyclic peptides |
-
2009
- 2009-06-05 CA CA2724523A patent/CA2724523A1/en not_active Abandoned
- 2009-06-05 JP JP2011512478A patent/JP5820722B2/ja not_active Expired - Fee Related
- 2009-06-05 EP EP09773881.9A patent/EP2280989B1/en not_active Not-in-force
- 2009-06-05 CN CN2009801261909A patent/CN102083852A/zh active Pending
- 2009-06-05 US US12/479,633 patent/US9090671B2/en not_active Expired - Fee Related
- 2009-06-05 WO PCT/US2009/003411 patent/WO2010002428A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010002428A2 (en) | 2010-01-07 |
| EP2280989B1 (en) | 2016-02-10 |
| CA2724523A1 (en) | 2010-01-07 |
| EP2280989A2 (en) | 2011-02-09 |
| JP2011523952A (ja) | 2011-08-25 |
| US9090671B2 (en) | 2015-07-28 |
| US20090312300A1 (en) | 2009-12-17 |
| CN102083852A (zh) | 2011-06-01 |
| WO2010002428A3 (en) | 2010-03-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5820722B2 (ja) | シクロスポリン類似体及びｈｃｖ感染の治療におけるその使用 | |
| JP5780969B2 (ja) | シクロスポリンａの誘導体 | |
| JP2013513595A (ja) | 新規環状ペプチド | |
| JP5322647B2 (ja) | ウイルス感染の治療及び予防のためのシクロスポリンａのアリールアルキル及びヘテロアリールアルキル誘導体 | |
| US7576057B2 (en) | Cyclic peptides | |
| US7718767B2 (en) | 3-ether and 3-thioether substituted cyclosporin derivatives for the treatment and prevention of hepatitis C infection | |
| JP5517454B2 (ja) | Ｃ型肝炎感染の治療及び予防のための方法及び医薬組成物 | |
| US20090306033A1 (en) | Novel cyclic peptides | |
| CN102834409A (zh) | 环孢菌素类似物 | |
| CN104870007A (zh) | 新的抗病毒大环化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120604 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120604 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131217 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140311 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140318 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140616 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20141028 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150225 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20150413 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150609 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150824 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150915 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20151005 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5820722 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |