MD4754C1 - Compuşi policiclici de carbamoilpiridonă şi utilizarea lor farmaceutică - Google Patents
Compuşi policiclici de carbamoilpiridonă şi utilizarea lor farmaceutică Download PDFInfo
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- MD4754C1 MD4754C1 MDA20170067A MD20170067A MD4754C1 MD 4754 C1 MD4754 C1 MD 4754C1 MD A20170067 A MDA20170067 A MD A20170067A MD 20170067 A MD20170067 A MD 20170067A MD 4754 C1 MD4754 C1 MD 4754C1
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- Moldova
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed 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
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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| PCT/US2013/076367 WO2014100323A1 (en) | 2012-12-21 | 2013-12-19 | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
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| MDA20200093A MD4841B1 (ro) | 2012-12-21 | 2013-12-19 | Compuşi policiclici de carbamoilpiridonă şi utilizarea lor farmaceutică |
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Families Citing this family (179)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2729448B1 (en) | 2011-07-06 | 2015-09-09 | Gilead Sciences, Inc. | Compounds for the treatment of hiv |
| BR112014026643B1 (pt) | 2012-04-26 | 2023-03-07 | Universite De Montreal | Derivados de imidazotiadiazol e imidazopirazina como inibidores de receptor 4 ativado por protease (par4) para o tratamento de agregação de plaqueta, seus usos e composição farmacêutica |
| TWI568722B (zh) | 2012-06-15 | 2017-02-01 | 葛蘭馬克製藥公司 | 作爲mPGES-1抑制劑之三唑酮化合物 |
| MX344879B (es) * | 2012-12-21 | 2017-01-11 | Gilead Sciences Inc | Compuestos de carbamoilpiridona policiclicos y su uso farmaceutico. |
| UA111305C2 (uk) | 2012-12-21 | 2016-04-11 | Пфайзер Інк. | Конденсовані лактами арилу та гетероарилу |
| JP6437452B2 (ja) | 2013-01-14 | 2018-12-12 | インサイト・ホールディングス・コーポレイションIncyte Holdings Corporation | Pimキナーゼ阻害剤として有用な二環式芳香族カルボキサミド化合物 |
| ME03780B (me) | 2013-01-15 | 2021-04-20 | Incyte Holdings Corp | Jedinjenja tiazolkarboksamida i piridinkarboksamida korisna kao inhibitori pim kinaze |
| LT3019503T (lt) | 2013-07-12 | 2017-11-27 | Gilead Sciences, Inc. | Policikliniai karbamoilpiridono junginiai ir jų panaudojimas živ infekcijų gydymui |
| NO2865735T3 (OSRAM) | 2013-07-12 | 2018-07-21 | ||
| EA201690458A1 (ru) | 2013-08-23 | 2016-07-29 | Инсайт Корпорейшн | Фуро- и тиенопиридинкарбоксамиды, используемые в качестве ингибиторов pim-киназы |
| WO2015177537A1 (en) * | 2014-05-20 | 2015-11-26 | Cipla Limited | Process for preparing polycyclic carbamoyl pyridone derivatives and intermediates thereof |
| AP2016009605A0 (en) | 2014-06-17 | 2016-12-31 | Pfizer | Substituted dihydroisoquinolinone compounds |
| TWI744723B (zh) * | 2014-06-20 | 2021-11-01 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
| TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
| NO2717902T3 (OSRAM) * | 2014-06-20 | 2018-06-23 | ||
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| US9822124B2 (en) | 2014-07-14 | 2017-11-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as Pim kinase inhibitors |
| WO2016027879A1 (ja) * | 2014-08-22 | 2016-02-25 | 塩野義製薬株式会社 | インテグラーゼ阻害活性を有する多環性ピリドン誘導体 |
| US20160067255A1 (en) | 2014-09-04 | 2016-03-10 | Gilead Sciences, Inc. | Methods of treating or preventing hiv in patients using a combination of tenofovir alafenamide and dolutegravir |
| WO2016090545A1 (en) * | 2014-12-09 | 2016-06-16 | Merck Sharp & Dohme Corp. | Spirocyclic heterocycle compounds useful as hiv integrate inhibitors |
| TWI738321B (zh) * | 2014-12-23 | 2021-09-01 | 美商基利科學股份有限公司 | 多環胺甲醯基吡啶酮化合物及其醫藥用途 |
| TWI699355B (zh) | 2014-12-24 | 2020-07-21 | 美商基利科學股份有限公司 | 喹唑啉化合物 |
| NZ733125A (en) | 2014-12-24 | 2018-06-29 | Gilead Sciences Inc | Isoquinoline compounds for the treatment of hiv |
| BR112017013491A2 (pt) | 2014-12-24 | 2018-01-09 | Gilead Sciences, Inc. | compostos de pirimidina fundida para o tratamento de hiv |
| LT3236972T (lt) | 2014-12-26 | 2021-11-10 | Emory University | Antivirusiniai n4-hidroksicitidino dariniai |
| EP3722297A1 (en) | 2015-03-04 | 2020-10-14 | Gilead Sciences, Inc. | Toll-like receptor modulating 4,6-diamino-pyrido[3,2-d]pyrimidine compounds |
| CA2980362C (en) * | 2015-04-02 | 2020-02-25 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| RU2712275C9 (ru) * | 2015-04-28 | 2020-03-19 | Сионоги Энд Ко., Лтд. | Замещенные полициклические производные пиридона и их пролекарства |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
| CA2995004A1 (en) | 2015-08-26 | 2017-03-02 | Gilead Sciences, Inc. | Deuterated toll-like receptor modulators |
| AR105967A1 (es) | 2015-09-09 | 2017-11-29 | Incyte Corp | Sales de un inhibidor de pim quinasa |
| CA2999516A1 (en) | 2015-09-30 | 2017-04-06 | Gilead Sciences, Inc. | Compounds and combinations for the treatment of hiv |
| WO2017059251A1 (en) | 2015-10-02 | 2017-04-06 | Incyte Corporation | Heterocyclic compounds useful as pim kinase inhibitors |
| KR102606625B1 (ko) | 2015-11-09 | 2023-11-27 | 길리애드 사이언시즈, 인코포레이티드 | 인간 면역결핍 바이러스의 치료를 위한 치료 조성물 |
| JP6732915B2 (ja) | 2015-12-15 | 2020-07-29 | ギリアード サイエンシーズ, インコーポレイテッド | ヒト免疫不全ウイルス中和抗体 |
| 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 |
| WO2017197055A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| EP3454862B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
| CN109641874A (zh) | 2016-05-10 | 2019-04-16 | C4医药公司 | 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体 |
| WO2017223280A2 (en) * | 2016-06-23 | 2017-12-28 | Viiv Healthcare Company | Compositions and methods for the delivery of therapeutics |
| WO2018005328A1 (en) * | 2016-06-27 | 2018-01-04 | Concert Pharmaceuticals, Inc. | Deuterated bictegravir |
| BR112018071678B1 (pt) | 2016-08-19 | 2021-01-26 | Gilead Sciences, Inc. | compostos terapêuticos úteis para o tratamento profilático ou terapêutico de uma infecção por vírus hiv e suas composições farmacêuticas |
| WO2018042331A1 (en) | 2016-08-31 | 2018-03-08 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations and uses and treatments thereof |
| WO2018042332A1 (en) | 2016-08-31 | 2018-03-08 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations and uses and treatments thereof |
| ES2906581T3 (es) | 2016-09-02 | 2022-04-19 | Gilead Sciences Inc | Compuestos moduladores de los receptores tipo Toll |
| US10640499B2 (en) | 2016-09-02 | 2020-05-05 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| WO2018051250A1 (en) | 2016-09-14 | 2018-03-22 | Viiv Healthcare Company | Combination comprising tenofovir alafenamide, bictegravir and 3tc |
| WO2018064071A1 (en) | 2016-09-27 | 2018-04-05 | Gilead Sciences, Inc. | Therapeutic compositions for treatment of human immunodeficiency virus |
| US10800772B2 (en) | 2016-09-28 | 2020-10-13 | Gilead Sciences, Inc. | Therapeutic compounds |
| US10407438B2 (en) | 2016-10-27 | 2019-09-10 | Gilead Sciences, Inc. | Crystalline forms of darunavir |
| JOP20190130A1 (ar) | 2016-12-02 | 2019-06-02 | Merck Sharp & Dohme | مركبات حلقية غير متجانسة رباعية الحلقات مفيدة كمثبطات إنزيم مدمج لفيروس نقص المناعة البشرية (hiv) |
| CN108250215B (zh) * | 2016-12-28 | 2022-04-19 | 华创合成制药股份有限公司 | 一种新型抗hiv药物及其制备方法和用途 |
| TWI714820B (zh) | 2017-01-31 | 2021-01-01 | 美商基利科學股份有限公司 | 替諾福韋艾拉酚胺(tenofovir alafenamide)之晶型 |
| JOP20180009A1 (ar) | 2017-02-06 | 2019-01-30 | Gilead Sciences Inc | مركبات مثبط فيروس hiv |
| CN106860464A (zh) * | 2017-02-16 | 2017-06-20 | 江苏艾迪药业有限公司 | 用于联合抗病毒治疗的药物组合物及应用 |
| CN106860414B (zh) * | 2017-02-16 | 2019-12-24 | 江苏艾迪药业股份有限公司 | 一种用于抗hiv的复方制剂及其制备方法与应用 |
| ZA201803942B (en) | 2017-06-13 | 2021-05-26 | Cipla Ltd | Novel processes for preparation of integrase inhibitor |
| CN110769822A (zh) | 2017-06-20 | 2020-02-07 | 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 |
| WO2018237148A1 (en) | 2017-06-21 | 2018-12-27 | Gilead Sciences, Inc. | Multispecific antibodies that target hiv gp120 and cd3 |
| RU2755710C2 (ru) | 2017-06-30 | 2021-09-20 | Вайв Хелткер Компани | Комбинация, ее применение и способы лечения с использованием указанной комбинации |
| EP3661937B1 (en) | 2017-08-01 | 2021-07-28 | Gilead Sciences, Inc. | Crystalline forms of ethyl ((s)-((((2r,5r)-5-(6-amino-9h-purin-9-yl)-4-fluoro-2,5-dihydrofuran-2-yl)oxy)methyl)(phenoxy)phosphoryl)-l-alaninate (gs-9131) for treating viral infections |
| WO2019030625A1 (en) * | 2017-08-09 | 2019-02-14 | Viiv Healthcare Company | COMBINATIONS, USES AND CORRESPONDING TREATMENTS |
| WO2019030626A1 (en) * | 2017-08-09 | 2019-02-14 | Viiv Healthcare Company | COMBINATIONS, USES AND CORRESPONDING TREATMENTS |
| AR112413A1 (es) | 2017-08-17 | 2019-10-23 | Gilead Sciences Inc | Formas sólidas de un inhibidor de la cápside del vih |
| AR112412A1 (es) | 2017-08-17 | 2019-10-23 | Gilead Sciences Inc | Formas de sal de colina de un inhibidor de la cápside del vih |
| CN111386276B (zh) * | 2017-10-06 | 2023-06-23 | 盐野义制药株式会社 | 制备取代的多环吡啶酮衍生物的立体选择性方法 |
| JOP20180092A1 (ar) | 2017-10-13 | 2019-04-13 | Gilead Sciences Inc | مثبطات hiv بروتياز |
| EP3700573A1 (en) | 2017-10-24 | 2020-09-02 | Gilead Sciences, Inc. | Methods of treating patients co-infected with a virus and tuberculosis |
| LT3706762T (lt) | 2017-12-07 | 2024-12-27 | Emory University | N4-hidroksicitidinas ir jo dariniai bei susiję naudojimo prieš virusus būdai |
| WO2019113487A1 (en) | 2017-12-08 | 2019-06-13 | Incyte Corporation | Low dose combination therapy for treatment of myeloproliferative neoplasms |
| EP3728282B1 (en) | 2017-12-20 | 2023-11-22 | 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 |
| WO2019144015A1 (en) * | 2018-01-19 | 2019-07-25 | Gilead Sciences, Inc. | Metabolites of bictegravir |
| DK3749673T3 (da) | 2018-02-09 | 2022-06-20 | Sandoz Ag | Krystallinsk form af bictegravir-natrium |
| KR102587510B1 (ko) | 2018-02-15 | 2023-10-11 | 길리애드 사이언시즈, 인코포레이티드 | 피리딘 유도체 및 hiv 감염을 치료하기 위한 그의 용도 |
| CA3281991A1 (en) | 2018-02-16 | 2025-11-29 | Gilead Sciences, Inc. | Methods and intermediates for preparing therapeutic compounds useful in the treatment of retroviridae viral infection |
| WO2019159199A1 (en) | 2018-02-16 | 2019-08-22 | Cipla Limited | Continues flow process for the preparation of active pharmaceutical ingredients - polycyclic carbamoyl pyridone derivatives and intermediates thereof |
| 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 |
| 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 |
| 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 |
| CN109020911B (zh) * | 2018-04-16 | 2022-06-28 | 常州制药厂有限公司 | 用于制备bictegravir的中间体及其制备方法 |
| WO2019207602A1 (en) | 2018-04-26 | 2019-10-31 | Mylan Laboratories Limited | Polymorphic forms of bictegravir and its sodium salt |
| 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 |
| CN110526930B (zh) | 2018-05-23 | 2022-06-03 | 莫云芬 | 抗hiv病毒的含硫多环-羟基吡啶酮甲酰胺类似物及其应用 |
| SG11202011386QA (en) | 2018-05-31 | 2020-12-30 | Shionogi & Co | Polycyclic pyridone derivative |
| AU2019277548B2 (en) | 2018-05-31 | 2023-12-14 | Shionogi & Co., Ltd. | Polycyclic carbamoylpyridone derivative |
| WO2020004443A1 (ja) | 2018-06-27 | 2020-01-02 | 国立大学法人北海道大学 | 多環性カルバモイルピリドン誘導体を含有するアレナウイルス増殖阻害剤 |
| WO2020003151A1 (en) | 2018-06-28 | 2020-01-02 | Honour Lab Limited | Process for the preparation of sodium (2r,5s,13ar)-7,9-dioxo-10-((2,4,6-trifluorobenzyl)carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1', 2':4,5]pyrazino[2,1-b] [1,3] oxazepin-8-olate and its polymorphic form |
| SG11202012043RA (en) | 2018-07-03 | 2021-01-28 | Gilead Sciences Inc | Antibodies that target hiv gp120 and methods of use |
| US11634431B2 (en) | 2018-07-12 | 2023-04-25 | Laurus Labs Limited | Process for purification of protected polycyclic carbamoylpyridone derivatives |
| JP2021530523A (ja) | 2018-07-16 | 2021-11-11 | ギリアード サイエンシーズ, インコーポレイテッド | Hivの処置のためのカプシド阻害剤 |
| TWI766172B (zh) | 2018-07-30 | 2022-06-01 | 美商基利科學股份有限公司 | 抗hiv化合物 |
| CN112996517A (zh) | 2018-09-19 | 2021-06-18 | 吉利德科学公司 | 预防hiv的整合酶抑制剂 |
| US11179397B2 (en) | 2018-10-03 | 2021-11-23 | Gilead Sciences, Inc. | Imidazopyrimidine derivatives |
| MY207622A (en) | 2018-10-22 | 2025-03-06 | Univ Nebraska | Antiviral prodrugs and nanoformulations thereof |
| CN117105933A (zh) | 2018-10-31 | 2023-11-24 | 吉利德科学公司 | 具有hpk1抑制活性的取代的6-氮杂苯并咪唑化合物 |
| CN113227089B (zh) | 2018-10-31 | 2024-07-05 | 吉利德科学公司 | 作为hpk1抑制剂的取代的6-氮杂苯并咪唑化合物 |
| EP3653629A1 (en) * | 2018-11-16 | 2020-05-20 | Sandoz AG | Acid addition salts of an integrase strand transfer inhibitor |
| CN118873676A (zh) | 2018-11-29 | 2024-11-01 | 内布拉斯加大学董事会 | 抗病毒前药及其纳米制剂 |
| US12195480B2 (en) | 2019-02-07 | 2025-01-14 | Cipla Limited | Polymorphs of integrase inhibitor |
| WO2020176505A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
| WO2020176510A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
| EP3934757B1 (en) | 2019-03-07 | 2023-02-22 | Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. | 2'3'-cyclic dinucleotides and prodrugs thereof |
| 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 |
| 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 |
| SI3938047T1 (sl) | 2019-03-22 | 2022-10-28 | Gilead Sciences, Inc. | Premoščene triciklične karbamoilpiridonske spojine in njihova farmacevtska uporaba |
| TWI751516B (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 |
| WO2020214647A1 (en) | 2019-04-17 | 2020-10-22 | Gilead Sciences, Inc. | Solid forms of an hiv protease inhibitor |
| TW202104210A (zh) | 2019-04-17 | 2021-02-01 | 美商基利科學股份有限公司 | Hiv蛋白酶抑制劑 |
| 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 |
| TW202231277A (zh) | 2019-05-21 | 2022-08-16 | 美商基利科學股份有限公司 | 鑑別對使用gp120 v3聚醣導向之抗體的治療敏感之hiv病患的方法 |
| CN110229174A (zh) * | 2019-05-22 | 2019-09-13 | 博诺康源(北京)药业科技有限公司 | Bictegravir原料药基因毒性杂质的合成方法 |
| EP3972695A1 (en) | 2019-05-23 | 2022-03-30 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
| RU2717101C1 (ru) | 2019-06-03 | 2020-03-18 | Андрей Александрович Иващенко | Анелированные 9-гидрокси-1,8-диоксо-1,3,4,8-тетрагидро-2Н-пиридо[1,2-a]пиразин-7-карбоксамиды - ингибиторы интегразы ВИЧ, способы их получения и применения |
| CN110263404B (zh) * | 2019-06-12 | 2023-03-21 | 江苏大学 | 一种基于dpm模型的一体化预制泵站沉积特性的计算方法 |
| CA3140708A1 (en) | 2019-06-18 | 2020-12-24 | Helen Horton | Combination of hepatitis b virus (hbv) vaccines and pyridopyrimidine derivatives |
| EP3993797A4 (en) * | 2019-06-18 | 2023-10-25 | Laurus Labs Limited | Process and polymorphic forms of bictegravir and its pharmaceutically acceptable salts or co-crystals thereof |
| US20200398978A1 (en) | 2019-06-20 | 2020-12-24 | Bell Helicopter Textron Inc. | Low-drag rotor blade extension |
| JP7295283B2 (ja) | 2019-06-25 | 2023-06-20 | ギリアード サイエンシーズ, インコーポレイテッド | Flt3l-fc融合タンパク質及び使用方法 |
| US11248005B2 (en) | 2019-07-08 | 2022-02-15 | Lupin Limited | Process for preparation of intermediates used for the synthesis of HIV integrase inhibitor |
| JP7454645B2 (ja) | 2019-07-16 | 2024-03-22 | ギリアード サイエンシーズ, インコーポレイテッド | Hivワクチン並びにその作製方法及び使用方法 |
| 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 |
| CN110698473B (zh) * | 2019-10-08 | 2020-12-18 | 浙江大学 | 哌嗪酮并羟基吡啶酮-5-羧基类化合物及制备和应用 |
| EP4643882A2 (en) | 2019-11-26 | 2025-11-05 | Gilead Sciences, Inc. | Capsid inhibitors for the prevention of hiv |
| JPWO2021107066A1 (OSRAM) | 2019-11-28 | 2021-06-03 | ||
| US20230058677A1 (en) * | 2019-11-28 | 2023-02-23 | Shionogi & Co., Ltd. | Polycyclic pyridopyrazine derivative |
| CN117736207A (zh) | 2019-12-24 | 2024-03-22 | 卡尔那生物科学株式会社 | 二酰基甘油激酶调节化合物 |
| WO2021173522A1 (en) | 2020-02-24 | 2021-09-02 | Gilead Sciences, Inc. | Tetracyclic compounds for treating hiv infection |
| TWI845826B (zh) | 2020-03-20 | 2024-06-21 | 美商基利科學股份有限公司 | 4'-c-經取代-2-鹵基-2'-去氧腺苷核苷之前藥及其製造與使用方法 |
| EP4153181A1 (en) | 2020-05-21 | 2023-03-29 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising bictegravir |
| CN113698420A (zh) * | 2020-05-22 | 2021-11-26 | 上海迪赛诺生物医药有限公司 | 比克替拉韦钠的新晶型及其制备方法 |
| CA3181690A1 (en) | 2020-06-25 | 2021-12-30 | Chienhung CHOU | Capsid inhibitors for the treatment of hiv |
| MX2023001507A (es) | 2020-08-07 | 2023-03-06 | Gilead Sciences Inc | Profarmacos de analogos de nucleotidos de fosfonamida y su uso farmaceutico. |
| KR20230079137A (ko) | 2020-09-30 | 2023-06-05 | 길리애드 사이언시즈, 인코포레이티드 | 가교된 트리사이클릭 카르바모일피리돈 화합물 및 이의 용도 |
| 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 |
| CN114426540B (zh) * | 2020-10-29 | 2024-04-26 | 上海拓界生物医药科技有限公司 | 吡啶并[1,2-a]吡嗪-1,8-二酮类前药衍生物、其制备方法及其应用 |
| TW202227445A (zh) * | 2020-10-30 | 2022-07-16 | 大陸商上海拓界生物醫藥科技有限公司 | 抑制基因缺陷的hiv病毒的用途 |
| US20220144923A1 (en) | 2020-11-11 | 2022-05-12 | Gilead Sciences, Inc. | METHODS OF IDENTIFYING HIV PATIENTS SENSITIVE TO THERAPY WITH gp120 CD4 BINDING SITE-DIRECTED ANTIBODIES |
| PT4196479T (pt) | 2021-01-19 | 2024-01-03 | Gilead Sciences Inc | Compostos de piridotriazinas substituídos e suas utilizações |
| WO2022157561A1 (en) * | 2021-01-22 | 2022-07-28 | Laurus Labs Limited | Processes for purification of bictegravir intermediates |
| CN114835730A (zh) * | 2021-02-02 | 2022-08-02 | 齐鲁制药有限公司 | 一种制备多环氨基甲酰基吡啶酮化合物的方法 |
| WO2022224120A1 (en) | 2021-04-19 | 2022-10-27 | Honour Lab Limited | Polymorphic forms of bictegravir potassium |
| WO2022245671A1 (en) | 2021-05-18 | 2022-11-24 | Gilead Sciences, Inc. | Methods of using flt3l-fc fusion proteins |
| JP7686091B2 (ja) | 2021-06-23 | 2025-05-30 | ギリアード サイエンシーズ, インコーポレイテッド | ジアシルグリセロールキナーゼ調節化合物 |
| CN117377671A (zh) | 2021-06-23 | 2024-01-09 | 吉利德科学公司 | 二酰基甘油激酶调节化合物 |
| CN117480155A (zh) | 2021-06-23 | 2024-01-30 | 吉利德科学公司 | 二酰基甘油激酶调节化合物 |
| EP4359415A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2023006087A1 (zh) * | 2021-07-30 | 2023-02-02 | 南京明德新药研发有限公司 | 大环吡啶酮类化合物及其应用 |
| CN114230579A (zh) * | 2021-11-12 | 2022-03-25 | 南京艾迪医药科技有限公司 | 多环氨基甲酰基吡啶酮衍生物及其制备方法和药物组合物 |
| FI4445900T3 (fi) | 2021-12-03 | 2025-08-05 | Gilead Sciences Inc | Terapeuttisia yhdisteitä hiv-virusinfektiota varten |
| WO2023102523A1 (en) | 2021-12-03 | 2023-06-08 | Gilead Sciences, Inc. | Therapeutic compounds for hiv virus infection |
| CN118355020A (zh) | 2021-12-03 | 2024-07-16 | 吉利德科学公司 | Hiv病毒感染的治疗性化合物 |
| CN114605437A (zh) * | 2022-04-01 | 2022-06-10 | 遵义医科大学 | 连续一锅法制备三个替拉韦药物的合成工艺 |
| TWI856796B (zh) | 2022-04-06 | 2024-09-21 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
| WO2023248240A1 (en) | 2022-06-21 | 2023-12-28 | Mylan Laboratories Limited | Polymorphic forms of bictegravir sodium |
| EP4547659A1 (en) | 2022-07-01 | 2025-05-07 | Gilead Sciences, Inc. | Therapeutic compounds useful for the prophylactic or therapeutic treatment of an hiv virus infection |
| EP4554628A1 (en) | 2022-07-12 | 2025-05-21 | Gilead Sciences, Inc. | Hiv immunogenic polypeptides and vaccines and uses thereof |
| CA3265134A1 (en) | 2022-08-26 | 2024-02-29 | Gilead Sciences, Inc. | DOSING AND PLANNING REGIMEN FOR BROADLY NEUTRALIZING ANTIBODIES |
| CN120379998A (zh) * | 2022-09-20 | 2025-07-25 | 吉斯凯(苏州)制药有限公司 | 多环氮杂环酮类化合物及其应用 |
| WO2024076915A1 (en) | 2022-10-04 | 2024-04-11 | Gilead Sciences, Inc. | 4'-thionucleoside analogues and their pharmaceutical use |
| AU2024259111A1 (en) | 2023-04-19 | 2025-10-16 | Gilead Sciences, Inc. | Dosing regimen of capsid inhibitor |
| WO2024249517A1 (en) | 2023-05-31 | 2024-12-05 | Gilead Sciences, Inc. | Anti-hiv compounds |
| US20250042926A1 (en) | 2023-05-31 | 2025-02-06 | Gilead Sciences, Inc. | Therapeutic compounds for hiv |
| US20250011352A1 (en) | 2023-05-31 | 2025-01-09 | Gilead Sciences, Inc. | Solid forms |
| WO2025029247A1 (en) | 2023-07-28 | 2025-02-06 | Gilead Sciences, Inc. | Weekly regimen of lenacapavir for the treatment and prevention of hiv |
| US20250073172A1 (en) | 2023-08-15 | 2025-03-06 | Gilead Sciences, Inc. | Pharmaceutical formulations of bictegravir and lenacapavir |
| EP4529922A1 (en) | 2023-09-29 | 2025-04-02 | Gilead Sciences, Inc. | Pharmaceutical formulations of bictegravir and lenacapavir |
| WO2025042394A1 (en) | 2023-08-23 | 2025-02-27 | Gilead Sciences, Inc. | Dosing regimen of hiv capsid inhibitor |
| WO2025076542A1 (en) | 2023-10-05 | 2025-04-10 | Jones R Brad | Atovaquone as an ros inducer for use in the elimination of hiv-infected t-cells |
| US20250127801A1 (en) | 2023-10-11 | 2025-04-24 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| WO2025080863A1 (en) | 2023-10-11 | 2025-04-17 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| US20250120989A1 (en) | 2023-10-11 | 2025-04-17 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| WO2025137245A1 (en) | 2023-12-22 | 2025-06-26 | Gilead Sciences, Inc. | Solid forms of hiv integrase inhibitors |
| WO2025184452A1 (en) | 2024-03-01 | 2025-09-04 | Gilead Sciences, Inc. | Solid forms of hiv integrase inhibitors |
| WO2025184447A1 (en) | 2024-03-01 | 2025-09-04 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising hiv integrase inhibitors |
| WO2025184609A1 (en) | 2024-03-01 | 2025-09-04 | Gilead Sciences, Inc. | Antiviral compounds |
| US20250326779A1 (en) | 2024-04-03 | 2025-10-23 | Gilead Sciences, Inc. | Anti-hiv compounds |
| WO2025260028A1 (en) | 2024-06-14 | 2025-12-18 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising hiv integrase inhibitors |
Family Cites Families (135)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE788516A (fr) | 1971-09-10 | 1973-03-07 | Lonza Ag | Procede de fabrication d'esters alcoxyacetylacetiques |
| GB1528382A (en) | 1974-12-26 | 1978-10-11 | Teijin Ltd | Cyclopentene diols and acyl esters thereof and processes for their preparation |
| DE2658401A1 (de) | 1976-12-23 | 1978-07-06 | Merck Patent Gmbh | Cyclopentan-1-amine, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
| US4575694A (en) | 1984-03-05 | 1986-03-11 | Allied Corporation | Coaxial connector |
| DE3900735A1 (de) | 1989-01-12 | 1990-07-26 | Hoechst Ag | Neue mehrfunktionelle (alpha)-diazo-(beta)-ketoester, verfahren zu ihrer herstellung und deren verwendung |
| US6703396B1 (en) | 1990-02-01 | 2004-03-09 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nuclesoside enantiomers |
| US5204466A (en) | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| US6642245B1 (en) | 1990-02-01 | 2003-11-04 | Emory University | Antiviral activity and resolution of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane |
| DE4014649A1 (de) | 1990-05-08 | 1991-11-14 | Hoechst Ag | Neue mehrfunktionelle verbindungen mit (alpha)-diazo-ss-ketoester- und sulfonsaeureester-einheiten, verfahren zu ihrer herstellung und deren verwendung |
| GB9301000D0 (en) | 1993-01-20 | 1993-03-10 | Glaxo Group Ltd | Chemical compounds |
| US5922695A (en) | 1996-07-26 | 1999-07-13 | Gilead Sciences, Inc. | Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability |
| SE9702772D0 (sv) | 1997-07-22 | 1997-07-22 | Astra Pharma Prod | Novel compounds |
| US5935946A (en) | 1997-07-25 | 1999-08-10 | Gilead Sciences, Inc. | Nucleotide analog composition and synthesis method |
| WO1999025345A1 (en) | 1997-11-14 | 1999-05-27 | Merck & Co., Inc. | Alpha-1a adrenergic receptor antagonists |
| EP1178969B1 (en) | 1998-11-09 | 2005-07-13 | James Black Foundation Limited | Gastrin and cholecystokinin receptor ligands |
| GB2345058A (en) | 1998-12-01 | 2000-06-28 | Cerebrus Pharm Ltd | Hydroxypyridone compounds useful in the treatment of oxidative damage to the central nervous system |
| NZ512184A (en) | 1998-12-25 | 2003-08-29 | Shionogi & Co | Aromatic heterocycle compounds having HIV integrase inhibiting activities |
| EP1297834A4 (en) | 2000-06-14 | 2007-05-09 | Shionogi & Co | ENZYME INHIBITOR HAVING TWO DIVALENT METAL IONS AS ACTIVE CENTERS |
| DE60128936T2 (de) * | 2000-10-12 | 2008-04-10 | Merck & Co, Inc. | Aza- und polyaza-naphthalenylcarbonsäureamide als hiv-integrase-hemmer |
| WO2003016275A1 (fr) | 2001-08-10 | 2003-02-27 | Shionogi & Co., Ltd. | Agent antiviral |
| MY169670A (en) | 2003-09-03 | 2019-05-08 | Tibotec Pharm Ltd | Combinations of a pyrimidine containing nnrti with rt inhibitors |
| CZ2004442A3 (cs) | 2001-10-03 | 2005-03-16 | Ucb, S.A. | Pyrrolidinonové deriváty |
| EP1441735B1 (en) | 2001-10-26 | 2006-02-22 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | N-substituted hydroxypyrimidinone carboxamide inhibitors of hiv integrase |
| WO2004004657A2 (en) | 2002-07-09 | 2004-01-15 | Bristol-Myers Squibb Company | Hiv integrase inhibitors |
| AU2003267098B2 (en) | 2002-09-11 | 2008-11-20 | Merck & Co., Inc. | Dihydroxypyridopyrazine-1,6-dione compounds useful as HIV integrase inhibitors |
| SI1564210T1 (sl) | 2002-11-20 | 2010-01-29 | Japan Tobacco Inc | 4-oksokinolinske spojine in njihova uporaba kot inhibitorji HIV integraze |
| JP4996241B2 (ja) | 2003-01-14 | 2012-08-08 | ギリアード サイエンシーズ, インコーポレイテッド | 組み合わせ抗ウイルス治療のための組成物および方法 |
| TW200510425A (en) | 2003-08-13 | 2005-03-16 | Japan Tobacco Inc | Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor |
| TW200528440A (en) | 2003-10-31 | 2005-09-01 | Fujisawa Pharmaceutical Co | 2-cyanopyrrolidinecarboxamide compound |
| CA2554120A1 (en) | 2004-01-30 | 2005-08-18 | Merck & Co., Inc. | N-benzyl-3,4-dihydroxypyridine-2-carboxamide and n-benzyl-2,3-dihydroxypyridine-4-carboxamide compounds useful as hiv integras inhibitors |
| AU2005211733A1 (en) | 2004-02-11 | 2005-08-25 | Shionogi & Co., Ltd | HIV integrase inhibitors |
| EP1725535A4 (en) | 2004-03-09 | 2009-11-25 | Merck & Co Inc | HIV integrase |
| WO2006028523A2 (en) | 2004-04-29 | 2006-03-16 | THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN DIEGO USDC Technology Transfer Office | Hydroxypyridinone, hydroxypyridinethione, pyrone, and thiopyrone metalloprotein inhibitors |
| WO2005110399A2 (en) | 2004-04-29 | 2005-11-24 | The Regents Of The University Of California | Zinc-binding groups for metalloprotein inhibitors |
| US7538112B2 (en) | 2004-05-07 | 2009-05-26 | Merck & Co., Inc. | HIV integrase inhibitors |
| US7273859B2 (en) | 2004-05-12 | 2007-09-25 | Bristol-Myers Squibb Company | HIV integrase inhibitors: cyclic pyrimidinone compounds |
| EA200602136A1 (ru) * | 2004-05-17 | 2007-04-27 | Тиботек Фармасьютикалз Лтд. | Комбинации замещенных 1-фенил-1,5-дигидропиридо[3,2-b] индол-2-онов и других ингибиторов вич |
| WO2005113509A1 (en) | 2004-05-20 | 2005-12-01 | Japan Tobacco Inc. | Novel 4-oxoquinoline compound and use thereof as hiv integrase inhibitor |
| MY134672A (en) | 2004-05-20 | 2007-12-31 | Japan Tobacco Inc | Stable crystal of 4-oxoquinoline compound |
| US8633219B2 (en) | 2004-05-21 | 2014-01-21 | Japan Tobacco Inc. | Combination therapy |
| WO2006030807A1 (ja) | 2004-09-15 | 2006-03-23 | Shionogi & Co., Ltd. | Hivインテグラーゼ阻害活性を有するカルバモイルピリドン誘導体 |
| JP2006118669A (ja) | 2004-10-25 | 2006-05-11 | Sanoh Industrial Co Ltd | 樹脂チューブ |
| WO2006066414A1 (en) | 2004-12-23 | 2006-06-29 | Virochem Pharma Inc. | Hydroxydihydropyridopy razine-1,8-diones and methods for inhibiting hiv integrase |
| JP5317257B2 (ja) | 2005-02-21 | 2013-10-16 | 塩野義製薬株式会社 | Hivインテグラーゼ阻害活性を有する2環性カルバモイルピリドン誘導体 |
| US8129385B2 (en) | 2005-04-28 | 2012-03-06 | Shionogi & Co., Ltd. | Substituted 5-hydroxy-3,4,6,9,9a, 10-hexanhydro-2h-1-oxa04a,8a-diaza-anthracene-6,10-dioness |
| TW200716632A (en) | 2005-05-16 | 2007-05-01 | Gilead Sciences Inc | Integrase inhibitor compounds |
| TWI471145B (zh) | 2005-06-13 | 2015-02-01 | Bristol Myers Squibb & Gilead Sciences Llc | 單一式藥學劑量型 |
| AU2006272521A1 (en) | 2005-07-27 | 2007-02-01 | Gilead Sciences, Inc. | Antiviral phosphonate conjugates for inhibition of HIV |
| AU2006307101A1 (en) | 2005-10-27 | 2007-05-03 | Shionogi & Co., Ltd. | Polycyclic carbamoylpyridone derivative having inhibitory activity on HIV integrase |
| EA018544B1 (ru) | 2005-12-30 | 2013-08-30 | Джилид Сайэнс, Инк. | Способ лечения ретровирусной инфекции |
| US7601844B2 (en) | 2006-01-27 | 2009-10-13 | Bristol-Myers Squibb Company | Piperidinyl derivatives as modulators of chemokine receptor activity |
| JP2009525261A (ja) | 2006-02-01 | 2009-07-09 | 日本たばこ産業株式会社 | レトロウイルス感染症の治療のための、6−(3−クロロ−2−フルオロベンジル)−1−[(2s)−1−ヒドロキシ−3−メチルブタン−2−イル]−7−メトキシ−4−オキソ−1,4−ジヒドロキノリン−3−カルボン酸またはその塩の使用 |
| MX2008011457A (es) | 2006-03-06 | 2008-09-24 | Japan Tobacco Inc | Metodo para producir un compuesto de 4-oxoquinolina. |
| CN101437801B (zh) | 2006-03-06 | 2013-02-06 | 日本烟草产业株式会社 | 制备4-氧代喹啉化合物的方法 |
| US7893055B2 (en) | 2006-06-28 | 2011-02-22 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| AU2007275805A1 (en) | 2006-07-19 | 2008-01-24 | University Of Georgia Research Foundation, Inc. | Pyridinone diketo acids: Inhibitors of HIV replication in combination therapy |
| CN105503721A (zh) | 2006-09-12 | 2016-04-20 | 吉里德科学公司 | 制备整合酶抑制剂的方法和中间体 |
| JP2010506913A (ja) | 2006-10-18 | 2010-03-04 | メルク エンド カムパニー インコーポレーテッド | Hivインテグラーゼ阻害剤 |
| EP2118082B1 (en) | 2007-02-23 | 2014-10-01 | Gilead Sciences, Inc. | Modulators of pharmacokinetic properties of therapeutics |
| US20080280945A1 (en) | 2007-05-09 | 2008-11-13 | Sachin Lohani | Crystalline forms of an HIV integrase inhibitor |
| AU2008270634B2 (en) | 2007-06-29 | 2014-01-16 | Gilead Sciences, Inc. | Therapeutic compositions and the use thereof |
| CA2692101A1 (en) | 2007-06-29 | 2009-01-08 | Gilead Sciences, Inc. | Combination of 6-(3-chloro-2-fluorobenzyl)-1-[(2s)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and a compound that inhibits a ugt pathway or ugt metabolism |
| US20090012103A1 (en) | 2007-07-05 | 2009-01-08 | Matthew Abelman | Substituted heterocyclic compounds |
| EP2182801A4 (en) | 2007-07-31 | 2011-04-13 | Limerick Biopharma Inc | COMPOSITIONS OF PYRONE ANALOGS AND METHODS |
| AR068403A1 (es) | 2007-09-11 | 2009-11-18 | Gilead Sciences Inc | Proceso e intermediarios para la preparacion de inhibidores de integrasa |
| KR20100097156A (ko) | 2007-11-16 | 2010-09-02 | 베링거 인겔하임 인터내셔날 게엠베하 | 사람 면역결핍 바이러스 복제의 억제제 |
| GB0803019D0 (en) | 2008-02-19 | 2008-03-26 | Btg Int Ltd | Fluorinated compounds |
| US8129398B2 (en) | 2008-03-19 | 2012-03-06 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| WO2010011813A1 (en) | 2008-07-23 | 2010-01-28 | Alkermes, Inc. | Complex of trospium and pharmaceutical compositions thereof |
| WO2010011815A1 (en) | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| US8183372B2 (en) * | 2008-07-25 | 2012-05-22 | Shionogi & Co., Ltd. | Substituted 9,11-dioxo-2,3,4a,5,9,11,13,13a-octahydor-1H-pyrido[1,2-a]pyrrolo[1′,2′:3,4]imidazo[1,2-d]pyrazines |
| SG192550A1 (en) | 2008-07-25 | 2013-08-30 | Viiv Healthcare Co | Chemical compounds |
| WO2010011818A1 (en) * | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| ES2448766T3 (es) | 2008-07-25 | 2014-03-17 | Viiv Healthcare Company | Profármacos de dolutegravir |
| WO2010011819A1 (en) | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| EP2376453B1 (en) | 2008-12-11 | 2019-11-20 | VIIV Healthcare Company | Intermediates for carbamoylpyridone hiv integrase inhibitors |
| EP2376080B1 (en) | 2008-12-11 | 2017-09-13 | Shionogi&Co., Ltd. | Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates |
| US9938268B2 (en) | 2008-12-17 | 2018-04-10 | Merck Patent Gmbh | C-ring modified tricyclic benzonaphthiridinone protein kinase inhibitors and use thereof |
| BRPI1008664A2 (pt) | 2009-02-06 | 2016-03-08 | Gilead Sciences Inc | comprimidos para a terapia de combinação |
| TWI518084B (zh) * | 2009-03-26 | 2016-01-21 | 鹽野義製藥股份有限公司 | 哌喃酮與吡啶酮衍生物之製造方法 |
| JP5697163B2 (ja) | 2009-03-26 | 2015-04-08 | 塩野義製薬株式会社 | 置換された3−ヒドロキシ−4−ピリドン誘導体 |
| RS57244B1 (sr) | 2009-06-15 | 2018-07-31 | Shionogi & Co | Supstituisani policiklički derivati karbamoilpiridona |
| WO2011011483A1 (en) * | 2009-07-22 | 2011-01-27 | Glaxosmithkline Llc | Chemical compounds |
| KR101280198B1 (ko) | 2009-09-02 | 2013-06-28 | 이화여자대학교 산학협력단 | 피라졸 유도체, 이의 제조방법 및 이를 포함하는 골다공증 예방 및 치료용 조성물 |
| EA032868B1 (ru) | 2010-01-27 | 2019-07-31 | Вайв Хелткер Компани | Комбинация для лечения вич-инфекции |
| PH12012501689A1 (en) | 2010-02-26 | 2012-11-05 | Japan Tobacco Inc | 1,3,4,8-tetrahydro-2h-pyrido[1,2-a]pyrazine derivative and use of same as hiv intergrase inhibitor |
| TWI582097B (zh) | 2010-03-23 | 2017-05-11 | Viiv醫療保健公司 | 製備胺甲醯吡啶酮衍生物及中間體之方法 |
| US20130165489A1 (en) | 2010-05-03 | 2013-06-27 | The Trustees Of The University Of Pennsylvania | Small Molecule Modulators of HIV-1 Capsid Stability and Methods Thereof |
| BR112012033689A2 (pt) | 2010-07-02 | 2019-09-24 | Gilead Sciences Inc | derivados de ácido 2-quinolinil-acético como compostos de hiv antivirais |
| SG186820A1 (en) | 2010-07-02 | 2013-02-28 | Gilead Sciences Inc | Napht- 2 -ylacetic acid derivatives to treat aids |
| WO2012009009A2 (en) | 2010-07-14 | 2012-01-19 | Addex Pharma S.A. | Novel 2-amino-4-pyrazolyl-thiazole derivatives and their use as allosteric modulators of metabotropic glutamate receptors |
| ES2608377T3 (es) | 2010-08-05 | 2017-04-10 | Shionogi & Co., Ltd. | Procedimiento de preparación de un compuesto que tiene actividad inhibidora de la integrasa del HIV |
| CN103228653B (zh) | 2010-09-24 | 2016-03-16 | 盐野义制药株式会社 | 被取代的多环性氨基甲酰基吡啶酮衍生物的前药 |
| EA201691695A1 (ru) | 2010-11-19 | 2017-11-30 | Джилид Сайэнс, Инк. | Терапевтические композиции, содержащие рилпивирин hcl и тенофовира дизопроксилфумарат |
| WO2012106534A2 (en) | 2011-02-02 | 2012-08-09 | The Regents Of The University Of California | Hiv integrase inhibitors |
| ES2615734T3 (es) | 2011-04-21 | 2017-06-08 | Gilead Sciences, Inc. | Compuestos de benzotiazol y su uso farmacéutico |
| US20140213553A1 (en) | 2011-05-03 | 2014-07-31 | Concert Pharmaceuticals Inc. | Carbamoylpyridone derivatives |
| US9328075B2 (en) | 2011-05-05 | 2016-05-03 | St. Jude Children's Research Hospital | Pyrimidinone compounds and methods for treating influenza |
| US9121496B2 (en) | 2011-06-29 | 2015-09-01 | Arvinmeritor Technology, Llc | Drive axle system and a method of control |
| EP2729448B1 (en) | 2011-07-06 | 2015-09-09 | Gilead Sciences, Inc. | Compounds for the treatment of hiv |
| CN102863512B (zh) | 2011-07-07 | 2016-04-20 | 上海泓博智源医药技术有限公司 | 抗病毒化合物 |
| PL2729130T3 (pl) | 2011-07-07 | 2018-02-28 | Janssen Sciences Ireland Uc | Preparaty kombinowane darunawiru |
| EP2742051B1 (en) | 2011-09-14 | 2016-10-12 | Mapi Pharma Limited | Amorpous form of the dolutegravir sodium salt |
| BR112014008896A2 (pt) | 2011-10-12 | 2017-04-18 | Shionogi & Co | derivado de piridona policíclico tendo atividade inibidora de integrase |
| ES2650915T3 (es) | 2011-12-12 | 2018-01-23 | Bayer Intellectual Property Gmbh | Imidazopiridazinas amino-sustituidas |
| US9284323B2 (en) | 2012-01-04 | 2016-03-15 | Gilead Sciences, Inc. | Naphthalene acetic acid derivatives against HIV infection |
| WO2014008636A1 (en) | 2012-07-11 | 2014-01-16 | Merck Sharp & Dohme Corp. | Macrocyclic compounds as hiv integrase inhibitors |
| US20150166520A1 (en) | 2012-07-20 | 2015-06-18 | Merck Sharp & Dohme Corp. | Amido-substituted pyrimidinone derivatives useful for the treatment of hiv infection |
| US20150218164A1 (en) | 2012-07-25 | 2015-08-06 | Merck Sharp & Dohme Corp. | Substituted naphthyridinedione derivatives as hiv integrase inhibitors |
| US8877931B2 (en) | 2012-08-03 | 2014-11-04 | Gilead Sciences, Inc. | Process and intermediates for preparing integrase inhibitors |
| PE20150953A1 (es) | 2012-11-08 | 2015-06-20 | Bristol Myers Squibb Co | Compuestos de piridilo sustituidos con heteroarilo utiles como moduladores de cinasa |
| SG11201503807TA (en) | 2012-12-14 | 2015-06-29 | Glaxosmithkline Llc | Pharmaceutical compositions |
| WO2014099586A1 (en) | 2012-12-17 | 2014-06-26 | Merck Sharp & Dohme Corp. | 4-pyridinonetriazine derivatives as hiv integrase inhibitors |
| US20160000721A1 (en) | 2012-12-21 | 2016-01-07 | Merck Sharp & Dohme Corp. | Gastro-retentive formulations |
| MX344879B (es) * | 2012-12-21 | 2017-01-11 | Gilead Sciences Inc | Compuestos de carbamoilpiridona policiclicos y su uso farmaceutico. |
| US20140221355A1 (en) | 2012-12-21 | 2014-08-07 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| RU2015131006A (ru) | 2012-12-27 | 2017-01-30 | Джапан Тобакко Инк. | ЗАМЕЩЕННОЕ ПРОИЗВОДНОЕ СПИРОПИРИДО[1,2-a]ПИРАЗИНА И ЕГО ПРИМЕНЕНИЕ В МЕДИЦИНЕ В КАЧЕСТВЕ ИНГИБИТОРА ИНТЕГРАЗЫ ВИРУСА ИММУНОДЕФИЦИТА ЧЕЛОВЕКА (ВИЧ) |
| EP2986291B1 (en) | 2013-04-16 | 2020-05-27 | Merck Sharp & Dohme Corp. | 4-pyridone derivative compounds and uses thereof as hiv integrase inhibitors |
| US9951079B2 (en) | 2013-06-13 | 2018-04-24 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as HIV integrase inhibitors |
| LT3019503T (lt) * | 2013-07-12 | 2017-11-27 | Gilead Sciences, Inc. | Policikliniai karbamoilpiridono junginiai ir jų panaudojimas živ infekcijų gydymui |
| NO2865735T3 (OSRAM) | 2013-07-12 | 2018-07-21 | ||
| WO2015039348A1 (en) | 2013-09-23 | 2015-03-26 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds useful as hiv integrase inhibitors |
| MX367057B (es) | 2013-09-27 | 2019-08-02 | Merck Sharp & Dohme | Derivados de quinolizina sustituidos utiles como inhibidores de integrasa del vih. |
| WO2015089847A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Spirocyclic heterocycle compounds useful as hiv integrase inhibitors |
| WO2015110897A2 (en) | 2014-01-21 | 2015-07-30 | Laurus Labs Private Limited | Novel process for the preparation of dolutegravir and pharmaceutically acceptable salts thereof |
| TWI744723B (zh) | 2014-06-20 | 2021-11-01 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
| TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
| NO2717902T3 (OSRAM) | 2014-06-20 | 2018-06-23 | ||
| EP4140485A1 (en) * | 2014-07-11 | 2023-03-01 | Gilead Sciences, Inc. | Modulators of toll-like receptors for the treatment of hiv |
| TWI738321B (zh) | 2014-12-23 | 2021-09-01 | 美商基利科學股份有限公司 | 多環胺甲醯基吡啶酮化合物及其醫藥用途 |
| WO2016102078A1 (en) | 2014-12-24 | 2016-06-30 | Ratiopharm Gmbh | Solid state forms of dolutegravir sodium |
| CA2980362C (en) | 2015-04-02 | 2020-02-25 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| CA2921336A1 (en) | 2015-06-30 | 2016-12-30 | Gilead Sciences, Inc. | Pharmaceutical formulations |
| EP4070787B1 (en) | 2015-06-30 | 2023-03-01 | Gilead Sciences, Inc. | Pharmaceutical formulations |
| KR102606625B1 (ko) | 2015-11-09 | 2023-11-27 | 길리애드 사이언시즈, 인코포레이티드 | 인간 면역결핍 바이러스의 치료를 위한 치료 조성물 |
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