JP6209601B2 - フラビウイルス科ウイルスの大環状阻害剤 - Google Patents
フラビウイルス科ウイルスの大環状阻害剤 Download PDFInfo
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- JP6209601B2 JP6209601B2 JP2015516260A JP2015516260A JP6209601B2 JP 6209601 B2 JP6209601 B2 JP 6209601B2 JP 2015516260 A JP2015516260 A JP 2015516260A JP 2015516260 A JP2015516260 A JP 2015516260A JP 6209601 B2 JP6209601 B2 JP 6209601B2
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- alkyl
- aryl
- mmol
- alkoxy
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- TTZHDVOVKQGIBA-IQWMDFIBSA-N sofosbuvir Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@]2(F)C)O)CO[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC=2C=CC=CC=2)C=CC(=O)NC1=O TTZHDVOVKQGIBA-IQWMDFIBSA-N 0.000 claims description 3
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- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 285
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- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
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- TTZHDVOVKQGIBA-IAAJYNJHSA-N propan-2-yl (2s)-2-[[[(2r,3r,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@]2(F)C)O)COP(=O)(N[C@@H](C)C(=O)OC(C)C)OC=2C=CC=CC=2)C=CC(=O)NC1=O TTZHDVOVKQGIBA-IAAJYNJHSA-N 0.000 description 1
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- IYWRCNFZPNEADN-CXODAYGWSA-N tert-butyl n-[(2s)-1-[(2s,4r)-2-[[(1r,2s)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]-4-(6-methoxyisoquinolin-1-yl)oxypyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC=1C2=CC=C(C=C2C=CN=1)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C IYWRCNFZPNEADN-CXODAYGWSA-N 0.000 description 1
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- UIUWNILCHFBLEQ-NSCUHMNNSA-N trans-pent-3-enoic acid Chemical compound C\C=C\CC(O)=O UIUWNILCHFBLEQ-NSCUHMNNSA-N 0.000 description 1
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- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
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- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/18—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/504—Pyridazines; Hydrogenated pyridazines forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Families Citing this family (81)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AR091279A1 (es) | 2012-06-08 | 2015-01-21 | Gilead Sciences Inc | Inhibidores macrociclicos de virus flaviviridae |
| SG11201408047XA (en) | 2012-06-08 | 2015-01-29 | Gilead Sciences Inc | Macrocyclic inhibitors of flaviviridae viruses |
| US9090653B2 (en) | 2012-06-08 | 2015-07-28 | Gilead Sciences, Inc. | Macrocyclic inhibitors of flaviviridae viruses |
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| EP3722297A1 (en) | 2015-03-04 | 2020-10-14 | Gilead Sciences, Inc. | Toll-like receptor modulating 4,6-diamino-pyrido[3,2-d]pyrimidine compounds |
| US20170008785A1 (en) * | 2015-07-07 | 2017-01-12 | Nch Corporation | System and Method for Treating Water with a Biological Based Biocide |
| JP2018525412A (ja) | 2015-08-26 | 2018-09-06 | ギリアード サイエンシーズ， インコーポレイテッド | 重水素化トール様受容体調節因子 |
| EP4483875A3 (en) | 2016-05-10 | 2025-04-02 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
| EP3455218A4 (en) | 2016-05-10 | 2019-12-18 | C4 Therapeutics, Inc. | C3 CARBON-BASED GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN REDUCTION |
| CN109790143A (zh) | 2016-05-10 | 2019-05-21 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| CN109562107A (zh) | 2016-05-10 | 2019-04-02 | C4医药公司 | 用于靶蛋白降解的杂环降解决定子体 |
| AU2017271990B2 (en) | 2016-05-27 | 2019-12-19 | Gilead Sciences, Inc. | Methods for treating Hepatitis B virus infections using NS5A, NS5B or NS3 inhibitors |
| BR102017010009A2 (pt) | 2016-05-27 | 2017-12-12 | Gilead Sciences, Inc. | Compounds for the treatment of hepatitis b virus infection |
| JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
| PT3507276T (pt) | 2016-09-02 | 2022-01-11 | Gilead Sciences Inc | Compostos moduladores do recetor de tipo toll |
| EP3507288B1 (en) | 2016-09-02 | 2020-08-26 | Gilead Sciences, Inc. | 4,6-diamino-pyrido[3,2-d]pyrimidine derivaties as toll like receptor modulators |
| US10662416B2 (en) | 2016-10-14 | 2020-05-26 | Precision Biosciences, Inc. | Engineered meganucleases specific for recognition sequences in the hepatitis B virus genome |
| BR112019015231A2 (pt) | 2017-01-25 | 2020-04-14 | Basf Se | processos para a preparação de compostos e compostos |
| TW202510891A (zh) | 2017-01-31 | 2025-03-16 | 美商基利科學股份有限公司 | 替諾福韋埃拉酚胺(tenofovir alafenamide)之晶型 |
| JOP20180008A1 (ar) | 2017-02-02 | 2019-01-30 | Gilead Sciences Inc | مركبات لعلاج إصابة بعدوى فيروس الالتهاب الكبدي b |
| US20220235013A1 (en) | 2017-03-21 | 2022-07-28 | Bayer Pharma Aktiengesellschaft | 2-methyl-quinazolines |
| JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
| CN118440096A (zh) | 2017-06-20 | 2024-08-06 | C4医药公司 | 用于蛋白降解的n/o-连接的降解决定子和降解决定子体 |
| CN109384727B (zh) * | 2017-08-10 | 2023-07-28 | 中国科学院上海药物研究所 | 酞嗪酮类化合物、其制备方法、药物组合物及用途 |
| KR102891807B1 (ko) | 2017-08-22 | 2025-12-01 | 길리애드 사이언시즈, 인코포레이티드 | 치료 헤테로시클릭 화합물 |
| DK3706762T3 (da) | 2017-12-07 | 2024-12-16 | Univ Emory | N4-hydroxycytidin og derivater og antivirale anvendelser relateret dertil |
| CU24621B1 (es) | 2017-12-13 | 2022-09-08 | Lupin Ltd | Componentes heterocíclicos bicíclicos sustituidos como inhibidores de prmt5 |
| US11203610B2 (en) | 2017-12-20 | 2021-12-21 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2′3′ cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| CN111566120B (zh) | 2017-12-20 | 2023-09-29 | 捷克共和国有机化学与生物化学研究所 | 活化sting转接蛋白的具有膦酸酯键的3’3’环状二核苷酸 |
| CR20200347A (es) | 2018-02-13 | 2020-09-23 | Gilead Sciences Inc | Inhibidores pd-1/pd-l1 |
| US10836769B2 (en) | 2018-02-26 | 2020-11-17 | Gilead Sciences, Inc. | Substituted pyrrolizine compounds and uses thereof |
| US10870691B2 (en) | 2018-04-05 | 2020-12-22 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis B virus protein X |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | ２，２，─環二核苷酸 |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TW201945388A (zh) | 2018-04-12 | 2019-12-01 | 美商精密生物科學公司 | 對b型肝炎病毒基因體中之識別序列具有特異性之最佳化之經工程化巨核酸酶 |
| CA3097231A1 (en) | 2018-04-18 | 2019-10-24 | Bayer Pharma Aktiengesellschaft | 2-methyl-aza-quinazolines |
| KR102591947B1 (ko) | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| WO2019211799A1 (en) | 2018-05-03 | 2019-11-07 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide |
| US11186579B2 (en) | 2018-07-06 | 2021-11-30 | Gilead Sciences, Inc. | Therapeutic heterocyclic compounds |
| CA3103987C (en) | 2018-07-06 | 2023-08-01 | Gilead Sciences, Inc. | Therapeutic heterocyclic compounds |
| PT3820572T (pt) | 2018-07-13 | 2023-11-10 | Gilead Sciences Inc | Inibidores pd-1/pd-l1 |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ， インコーポレイテッド | Ｐｄ－１／ｐｄ－ｌ１阻害剤 |
| EP4371987B9 (en) | 2018-10-31 | 2025-11-26 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds as hpk1 inhibitors |
| KR102658602B1 (ko) | 2018-10-31 | 2024-04-19 | 길리애드 사이언시즈, 인코포레이티드 | Hpk1 억제 활성을 갖는 치환된 6-아자벤즈이미다졸 화합물 |
| EP3935065A1 (en) | 2019-03-07 | 2022-01-12 | Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. | 3'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| US20220143061A1 (en) | 2019-03-07 | 2022-05-12 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| CN113543851B (zh) | 2019-03-07 | 2025-03-18 | 捷克共和国有机化学与生物化学研究所 | 2’3’-环二核苷酸及其前药 |
| TWI751517B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TW202210480A (zh) | 2019-04-17 | 2022-03-16 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| WO2020237025A1 (en) | 2019-05-23 | 2020-11-26 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
| CA3140708A1 (en) | 2019-06-18 | 2020-12-24 | Helen Horton | Combination of hepatitis b virus (hbv) vaccines and pyridopyrimidine derivatives |
| WO2020263830A1 (en) | 2019-06-25 | 2020-12-30 | Gilead Sciences, Inc. | Flt3l-fc fusion proteins and methods of use |
| WO2021011891A1 (en) | 2019-07-18 | 2021-01-21 | Gilead Sciences, Inc. | Long-acting formulations of tenofovir alafenamide |
| EP4017476A1 (en) | 2019-08-19 | 2022-06-29 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
| CA3149557A1 (en) | 2019-09-30 | 2021-04-08 | Scott J. Balsitis | Hbv vaccines and methods treating hbv |
| CN114901366A (zh) * | 2019-11-04 | 2022-08-12 | 锐新医药公司 | Ras抑制剂 |
| PH12022550988A1 (en) * | 2019-11-04 | 2023-10-09 | Revolution Medicines Inc | Ras inhibitors |
| KR20220109408A (ko) | 2019-11-04 | 2022-08-04 | 레볼루션 메디슨즈, 인크. | Ras 억제제 |
| WO2021113765A1 (en) | 2019-12-06 | 2021-06-10 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome |
| AR121620A1 (es) | 2020-03-20 | 2022-06-22 | Gilead Sciences Inc | Profármacos de nucleósidos 4-c-sustituidos-2-halo-2-deoxiadenosina y métodos de preparación y uso de los mismos |
| WO2021198981A1 (en) | 2020-04-01 | 2021-10-07 | Janssen Biopharma, Inc. | Antiviral compounds and uses thereof |
| ES3054072T3 (en) | 2020-08-07 | 2026-01-29 | Gilead Sciences Inc | Prodrugs of phosphonamide nucleotide analogues and their pharmaceutical use |
| IL301298A (en) | 2020-09-15 | 2023-05-01 | Revolution Medicines Inc | Indole derivatives as RAS inhibitors in cancer therapy |
| CN116323623B (zh) | 2020-09-18 | 2025-09-26 | 拜耳公司 | 作为SOS1抑制剂的吡啶并[2,3-d]嘧啶-4-胺 |
| TWI815194B (zh) | 2020-10-22 | 2023-09-11 | 美商基利科學股份有限公司 | 介白素2-Fc融合蛋白及使用方法 |
| EP4074317A1 (en) | 2021-04-14 | 2022-10-19 | Bayer AG | Phosphorus derivatives as novel sos1 inhibitors |
| AR125787A1 (es) | 2021-05-05 | 2023-08-16 | Revolution Medicines Inc | Inhibidores de ras |
| JP2024518558A (ja) | 2021-05-13 | 2024-05-01 | ギリアード サイエンシーズ， インコーポレイテッド | ＴＬＲ８調節化合物と抗ＨＢＶ ｓｉＲＮＡ治療薬との組合せ |
| US11976072B2 (en) | 2021-06-23 | 2024-05-07 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| WO2022271659A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| EP4359413A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| US11932634B2 (en) | 2021-06-23 | 2024-03-19 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| CN114634421A (zh) * | 2022-02-24 | 2022-06-17 | 济宁晟泰药业有限公司 | 一种达沙替尼中间体的制备方法 |
| CN120019059A (zh) | 2022-07-29 | 2025-05-16 | 辉瑞公司 | 新型acc抑制剂 |
| WO2025240242A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| US20250345390A1 (en) | 2024-05-13 | 2025-11-13 | Gilead Sciences, Inc. | Combination therapies |
| US20250345389A1 (en) | 2024-05-13 | 2025-11-13 | Gilead Sciences, Inc. | Combination therapies |
| WO2025240246A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR006514A1 (es) * | 1995-07-04 | 1999-09-08 | Sandoz Ag | Un macrolido, sus usos, un proceso para producirlo, un aislado biologicamente puro capaz de producirlo, y una composicion farmaceutica quelo comprende |
| US6124453A (en) | 1995-07-04 | 2000-09-26 | Novartis Ag | Macrolides |
| DE10239042A1 (de) | 2002-08-21 | 2004-03-04 | Schering Ag | Makrozyclische Pyrimidine, deren Herstellung und Verwendung als Arzneimittel |
| US20050159345A1 (en) * | 2002-10-29 | 2005-07-21 | Boehringer Ingelheim International Gmbh | Composition for the treatment of infection by Flaviviridae viruses |
| CN101198608B (zh) | 2005-06-16 | 2011-04-27 | 吉利德帕洛阿尔托股份有限公司 | A2b腺苷受体拮抗剂的前药 |
| AR054778A1 (es) | 2005-06-17 | 2007-07-18 | Novartis Ag | Uso de sangliferina en hcv |
| EP2011786A1 (en) | 2007-07-05 | 2009-01-07 | Laboratorios del Dr. Esteve S.A. | Indane-amine derivatives, their preparation and use as medicaments |
| CL2008003384A1 (es) * | 2007-11-14 | 2009-12-11 | Enanta Pharm Inc | Compuestos derivados de quinoxalina macrocíclica, inhibidores de serina proteasa; composicion farmaceutica que los comprende; y su uso en el tratamiento de la hepatitis c. |
| WO2009088256A2 (ko) | 2008-01-09 | 2009-07-16 | Konkuk University Industrial Cooperation Corp | 배큘로바이러스-기반 백신 |
| US20100080770A1 (en) * | 2008-09-29 | 2010-04-01 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| KR101734507B1 (ko) * | 2008-12-23 | 2017-05-11 | 얀센 파마슈티칼스 인코포레이티드 | Ｈｃｖ의 마크로시클릭 프로테아제 억제제를 제조하기 위한 방법 및 중간체 |
| WO2011063233A1 (en) | 2009-11-23 | 2011-05-26 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| EP3219713A1 (en) * | 2010-01-15 | 2017-09-20 | Gilead Sciences, Inc. | Inhibitors of flaviviridae viruses |
| EP2525659B1 (en) | 2010-01-19 | 2019-02-27 | Merck Sharp & Dohme Corp. | PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS |
| WO2011098808A1 (en) | 2010-02-09 | 2011-08-18 | Biotica Technology Limited | Sanglifehrin based compounds |
| GB201008123D0 (en) * | 2010-05-17 | 2010-06-30 | Biotica Tech Ltd | Novel compounds |
| WO2012040040A1 (en) * | 2010-09-21 | 2012-03-29 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
| AR084217A1 (es) | 2010-12-10 | 2013-05-02 | Gilead Sciences Inc | Inhibidores macrociclicos de virus flaviviridae |
| SG11201408047XA (en) | 2012-06-08 | 2015-01-29 | Gilead Sciences Inc | Macrocyclic inhibitors of flaviviridae viruses |
| SG11201408093PA (en) | 2012-06-08 | 2015-01-29 | Glenmark Pharmaceuticals Sa | Amides of 2-amino-4-arylthiazole compounds and their salts |
| US9090653B2 (en) | 2012-06-08 | 2015-07-28 | Gilead Sciences, Inc. | Macrocyclic inhibitors of flaviviridae viruses |
| AR091279A1 (es) | 2012-06-08 | 2015-01-21 | Gilead Sciences Inc | Inhibidores macrociclicos de virus flaviviridae |
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| CA2875692A1 (en) | 2013-12-12 |
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| US9145441B2 (en) | 2015-09-29 |
| NZ703040A (en) | 2016-11-25 |
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| USRE47334E1 (en) | 2019-04-02 |
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| PT2861604T (pt) | 2017-05-05 |
| EA201492209A1 (ru) | 2015-05-29 |
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| AU2013270672B2 (en) | 2017-10-19 |
| EA026235B1 (ru) | 2017-03-31 |
| EP2861604A1 (en) | 2015-04-22 |
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| SI2861604T1 (sl) | 2017-05-31 |
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| PL2861604T3 (pl) | 2017-08-31 |
| IL236005A0 (en) | 2015-02-01 |
| MX2014014766A (es) | 2015-05-11 |
| ES2624223T3 (es) | 2017-07-13 |
| HK1211285A1 (en) | 2016-05-20 |
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