EA030003B1 - Полициклическое карбамоилпиридоновое соединение и его фармацевтическое применение для лечения вич-инфекции - Google Patents
Полициклическое карбамоилпиридоновое соединение и его фармацевтическое применение для лечения вич-инфекции Download PDFInfo
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- EA030003B1 EA030003B1 EA201591027A EA201591027A EA030003B1 EA 030003 B1 EA030003 B1 EA 030003B1 EA 201591027 A EA201591027 A EA 201591027A EA 201591027 A EA201591027 A EA 201591027A EA 030003 B1 EA030003 B1 EA 030003B1
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- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- hiv
- pharmaceutically acceptable
- inhibitors
- infection
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Classifications
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- 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
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- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- 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
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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
- C07D471/22—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 systems contains four or more hetero rings
-
- 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
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- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Public Health (AREA)
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- Pharmacology & Pharmacy (AREA)
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- General Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US201261745375P | 2012-12-21 | 2012-12-21 | |
| US201361788397P | 2013-03-15 | 2013-03-15 | |
| US201361845803P | 2013-07-12 | 2013-07-12 | |
| PCT/US2013/076367 WO2014100323A1 (en) | 2012-12-21 | 2013-12-19 | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
Publications (2)
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| EA201591027A1 EA201591027A1 (ru) | 2016-05-31 |
| EA030003B1 true EA030003B1 (ru) | 2018-06-29 |
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| EA201591027A EA030003B1 (ru) | 2012-12-21 | 2013-12-19 | Полициклическое карбамоилпиридоновое соединение и его фармацевтическое применение для лечения вич-инфекции |
| EA201890236A EA037633B1 (ru) | 2012-12-21 | 2013-12-19 | Полициклические карбамоилпиридоновые соединения, их фармацевтические композиции и применение |
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| EA201890236A EA037633B1 (ru) | 2012-12-21 | 2013-12-19 | Полициклические карбамоилпиридоновые соединения, их фармацевтические композиции и применение |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Families Citing this family (178)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013006738A1 (en) | 2011-07-06 | 2013-01-10 | Gilead Sciences, Inc. | Compounds for the treatment of hiv |
| RS56395B1 (sr) | 2012-04-26 | 2017-12-29 | Bristol Myers Squibb Co | Derivati imidazotiadiazola i imidazopirazina kao inhibitori proteazom aktiviranog receptora 4 (par4) za lečenje agregacije trombocita |
| 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 |
| AU2013361401C1 (en) * | 2012-12-21 | 2018-08-09 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| UA111305C2 (uk) | 2012-12-21 | 2016-04-11 | Пфайзер Інк. | Конденсовані лактами арилу та гетероарилу |
| WO2014110574A1 (en) | 2013-01-14 | 2014-07-17 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
| UA121098C2 (uk) | 2013-01-15 | 2020-04-10 | Інсайт Холдинґс Корпорейшн | Тіазолкарбоксаміди і піридинкарбоксаміди, які використовуються як інгібітори рім-кінази |
| NO2865735T3 (enExample) * | 2013-07-12 | 2018-07-21 | ||
| EP3019503B1 (en) | 2013-07-12 | 2017-09-06 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their use for the treatment of hiv infections |
| WO2015027124A1 (en) | 2013-08-23 | 2015-02-26 | Incyte Corporation | Furo- and thieno-pyridine carboxamide compounds useful as pim kinase inhibitors |
| WO2015177537A1 (en) * | 2014-05-20 | 2015-11-26 | Cipla Limited | Process for preparing polycyclic carbamoyl pyridone derivatives and intermediates thereof |
| EA031892B1 (ru) | 2014-06-17 | 2019-03-29 | Пфайзер Инк. | Замещенные дигидроизохинолиноновые соединения для лечения аномального клеточного роста, ассоциированного с активностью ezh2 |
| 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 (enExample) | 2014-06-20 | 2018-06-23 | ||
| WO2016010897A1 (en) | 2014-07-14 | 2016-01-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors |
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| EP3196201B1 (en) * | 2014-08-22 | 2021-04-28 | Shionogi & Co., Ltd. | Polycyclic pyridone derivative having integrase-inhibiting activity |
| 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 |
| TWI695003B (zh) | 2014-12-23 | 2020-06-01 | 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 |
| CN107207498B (zh) | 2014-12-24 | 2020-03-24 | 吉利德科学公司 | 用于治疗hiv的稠合嘧啶化合物 |
| TWI770552B (zh) | 2014-12-24 | 2022-07-11 | 美商基利科學股份有限公司 | 喹唑啉化合物 |
| ES2705709T3 (es) | 2014-12-24 | 2019-03-26 | Gilead Sciences Inc | Compuestos de isoquinolina para el tratamiento del VIH |
| CN107427529A (zh) | 2014-12-26 | 2017-12-01 | 埃莫里大学 | N4‑羟基胞苷和衍生物及与其相关的抗病毒用途 |
| PH12021551982A1 (en) | 2015-03-04 | 2022-09-05 | Gilead Sciences Inc | Toll-like receptor modulating 4,6-diamino-pyrido[3,2-d]pyrimidine compounds |
| PT3466490T (pt) * | 2015-04-02 | 2020-12-24 | Gilead Sciences Inc | Compostos de carbamoilpiridona policíclicos e sua utilização farmacêutica |
| MX385402B (es) * | 2015-04-28 | 2025-03-18 | Shionogi & Co | Derivados de piridona policiclica sustituida y profarmaco de los mismos. |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
| US20210292327A1 (en) | 2015-08-26 | 2021-09-23 | Gilead Sciences, Inc. | Deuterated toll-like receptor modulators |
| TWI734699B (zh) | 2015-09-09 | 2021-08-01 | 美商英塞特公司 | Ｐｉｍ激酶抑制劑之鹽 |
| EP3356355B1 (en) | 2015-09-30 | 2020-05-13 | 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 |
| JP6621933B2 (ja) * | 2015-11-09 | 2019-12-18 | ギリアード サイエンシス インコーポレーテッド | ヒト免疫不全ウイルスを処置するための治療組成物 |
| 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 |
| WO2017197055A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| EP3455219A4 (en) | 2016-05-10 | 2019-12-18 | C4 Therapeutics, Inc. | AMINE-RELATED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN REDUCTION |
| WO2017197046A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | C3-carbon linked glutarimide degronimers for target protein degradation |
| EP3454862B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
| ES3035041T3 (en) * | 2016-06-23 | 2025-08-27 | Viiv Healthcare Co | Compositions and methods for the delivery of therapeutics |
| WO2018005328A1 (en) * | 2016-06-27 | 2018-01-04 | Concert Pharmaceuticals, Inc. | Deuterated bictegravir |
| PL3597646T3 (pl) | 2016-08-19 | 2023-12-11 | Gilead Sciences, Inc. | Związki terapeutyczne użyteczne do profilaktycznego lub terapeutycznego leczenia zakażenia wirusem HIV |
| 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 |
| US10370342B2 (en) | 2016-09-02 | 2019-08-06 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| 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 |
| US20180085387A1 (en) | 2016-09-27 | 2018-03-29 | Gilead Sciences, Inc. | Therapeutic compositions for treatment of human immunodeficiency virus |
| WO2018064080A1 (en) | 2016-09-28 | 2018-04-05 | Gilead Sciences, Inc. | Benzothiazol-6-yl acetic acid derivatives and their use for treating hiv infection |
| WO2018081292A1 (en) | 2016-10-27 | 2018-05-03 | Gilead Sciences, Inc. | Crystalline forms of darunavir free base, hydrate, solvates and salts |
| 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 |
| TWI784370B (zh) | 2017-01-31 | 2022-11-21 | 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 |
| 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 |
| WO2018229798A1 (en) | 2017-06-13 | 2018-12-20 | Cipla Limited | Process for the preparation of bictegravir and intermediate thereof |
| 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 |
| AU2018290228B2 (en) | 2017-06-21 | 2021-07-01 | Gilead Sciences, Inc. | Multispecific antibodies that target HIV gp120 and CD3 |
| BR112019027915A2 (pt) | 2017-06-30 | 2020-07-14 | Viiv Healthcare Company | composição de carboidrato de baixo teor glicêmico disponível, composição nutricional líquida, e, uso de uma composição de carboidrato |
| PT3661937T (pt) | 2017-08-01 | 2021-09-24 | Gilead Sciences Inc | Formas cristalinas de ((s)-((((2r,5r)-5-(6-amino-9h-purin-9-il)-4-fluoro-2,5-dihidrofurano-2-il)oxi)metil)(fenoxi)fosforil)-l-alaninato de etil (gs-9131) para tratamento de infeções virais |
| WO2019030625A1 (en) | 2017-08-09 | 2019-02-14 | Viiv Healthcare Company | COMBINATIONS, USES AND CORRESPONDING TREATMENTS |
| JP2020530024A (ja) * | 2017-08-09 | 2020-10-15 | ヴィーブ ヘルスケア カンパニー | 組み合わせ並びにその使用及び治療 |
| AR112412A1 (es) | 2017-08-17 | 2019-10-23 | Gilead Sciences Inc | Formas de sal de colina de un inhibidor de la cápside del vih |
| TW202024061A (zh) | 2017-08-17 | 2020-07-01 | 美商基利科學股份有限公司 | Hiv蛋白質膜抑制劑之固體形式 |
| KR102714478B1 (ko) * | 2017-10-06 | 2024-10-10 | 시오노기세야쿠 가부시키가이샤 | 치환된 다환성 피리돈 유도체의 입체 선택적인 제조 방법 |
| JOP20180092A1 (ar) | 2017-10-13 | 2019-04-13 | Gilead Sciences Inc | مثبطات hiv بروتياز |
| WO2019084020A1 (en) | 2017-10-24 | 2019-05-02 | Gilead Sciences, Inc. | METHODS OF TREATING PATIENTS CO-INFECTED BY A VIRUS AND TUBERCULOSIS |
| ES2995458T3 (en) | 2017-12-07 | 2025-02-10 | Univ Emory | N4-hydroxycytidine derivative and anti-viral uses related thereto |
| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| JP7098748B2 (ja) | 2017-12-20 | 2022-07-11 | インスティチュート オブ オーガニック ケミストリー アンド バイオケミストリー エーエスシーアール，ヴイ．ヴイ．アイ． | Ｓｔｉｎｇアダプタータンパク質を活性化するホスホン酸結合を有する２’３’環状ジヌクレオチド |
| AU2018392213B2 (en) | 2017-12-20 | 2021-03-04 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3' cyclic dinucleotides with phosphonate bond activating the STING adaptor protein |
| EP3740209A1 (en) * | 2018-01-19 | 2020-11-25 | Gilead Sciences, Inc. | Metabolites of bictegravir |
| EP3749673B1 (en) | 2018-02-09 | 2022-03-16 | Sandoz AG | Crystalline form of bictegravir sodium |
| PL3752495T3 (pl) | 2018-02-15 | 2024-01-15 | Gilead Sciences, Inc. | Pochodne pirydynowe i ich zastosowanie do leczenia infekcji hiv |
| 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 |
| TWI823164B (zh) | 2018-02-16 | 2023-11-21 | 美商基利科學股份有限公司 | 用於製備有療效化合物之方法及中間物 |
| 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 |
| 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 |
| 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 |
| US20190359645A1 (en) | 2018-05-03 | 2019-11-28 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotides comprising carbocyclic 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 |
| KR102741390B1 (ko) | 2018-05-31 | 2024-12-10 | 시오노기 앤드 컴파니, 리미티드 | 다환성 카바모일피리돈 유도체 |
| BR112020024098A2 (pt) | 2018-05-31 | 2021-02-17 | Shionogi & Co., Ltd. | derivado de piridona policíclica |
| JP7307412B2 (ja) | 2018-06-27 | 2023-07-12 | 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 |
| US11623933B2 (en) | 2018-06-28 | 2023-04-11 | 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 |
| CN112368052B (zh) | 2018-07-03 | 2024-11-29 | 吉利德科学公司 | 靶向hiv gp120的抗体和使用方法 |
| US11634431B2 (en) | 2018-07-12 | 2023-04-25 | Laurus Labs Limited | Process for purification of protected polycyclic carbamoylpyridone derivatives |
| CN120053446A (zh) | 2018-07-16 | 2025-05-30 | 吉利德科学公司 | 用于治疗hiv的衣壳抑制剂 |
| 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 |
| AU2019344929B2 (en) | 2018-09-19 | 2023-03-30 | Gilead Sciences, Inc. | Integrase inhibitors for the prevention of HIV |
| US11179397B2 (en) | 2018-10-03 | 2021-11-23 | Gilead Sciences, Inc. | Imidazopyrimidine derivatives |
| MX2021004679A (es) | 2018-10-22 | 2021-07-15 | Univ Nebraska | Profarmacos antivirales y nanoformulaciones de las mismas. |
| TWI721624B (zh) | 2018-10-31 | 2021-03-11 | 美商基利科學股份有限公司 | 經取代之6-氮雜苯并咪唑化合物 |
| ES2979163T3 (es) | 2018-10-31 | 2024-09-24 | Gilead Sciences Inc | Compuestos de 6-azabenzimidazol sustituidos como inhibidores de HPK1 |
| 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 |
| WO2020176510A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
| WO2020176505A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
| AU2020231201B2 (en) | 2019-03-07 | 2025-02-20 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotides and prodrugs thereof |
| WO2020178768A1 (en) | 2019-03-07 | 2020-09-10 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| AU2020231115B2 (en) | 2019-03-07 | 2025-02-20 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| CR20210486A (es) | 2019-03-22 | 2021-12-07 | Gilead Sciences Inc | Compuestos de carbamoyl piridona tricíclicos con puente y su uso farmacéutico |
| 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 |
| US20200347036A1 (en) | 2019-04-17 | 2020-11-05 | 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 |
| 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 |
| TWI762925B (zh) | 2019-05-21 | 2022-05-01 | 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 |
| US11453681B2 (en) | 2019-05-23 | 2022-09-27 | Gilead Sciences, Inc. | Substituted eneoxindoles and uses thereof |
| 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 |
| US20220305115A1 (en) | 2019-06-18 | 2022-09-29 | Janssen Sciences Ireland Unlimited Company | 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 |
| UA129329C2 (uk) | 2019-06-25 | 2025-03-19 | Гіліад Сайєнсіз, Інк. | ЗЛИТІ БІЛКИ FLT3L-Fc |
| US11248005B2 (en) | 2019-07-08 | 2022-02-15 | Lupin Limited | Process for preparation of intermediates used for the synthesis of HIV integrase inhibitor |
| CN120775062A (zh) | 2019-07-16 | 2025-10-14 | 吉利德科学公司 | Hiv疫苗及其制备和使用方法 |
| 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 |
| KR20220106165A (ko) | 2019-11-26 | 2022-07-28 | 길리애드 사이언시즈, 인코포레이티드 | Hiv의 예방을 위한 캡시드 억제제 |
| WO2021107066A1 (ja) | 2019-11-28 | 2021-06-03 | 塩野義製薬株式会社 | インテグラーゼ阻害剤及び抗ｈｉｖ薬を組み合わせることを特徴とするｈｉｖ感染症の予防及び治療用医薬 |
| WO2021107065A1 (ja) * | 2019-11-28 | 2021-06-03 | 塩野義製薬株式会社 | 多環性ピリドピラジン誘導体 |
| AU2020412875A1 (en) | 2019-12-24 | 2022-06-23 | Carna Biosciences, Inc. | Diacylglycerol kinase modulating compounds |
| IL295677A (en) | 2020-02-24 | 2022-10-01 | Gilead Sciences Inc | Tetracyclic compounds for treating hiv infection |
| AU2021237718B2 (en) | 2020-03-20 | 2023-09-21 | Gilead Sciences, Inc. | Prodrugs of 4'-C-substituted-2-halo-2'-deoxyadenosine nucleosides and methods of making and using the same |
| WO2021236944A1 (en) | 2020-05-21 | 2021-11-25 | 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 |
| CN116194144A (zh) | 2020-08-07 | 2023-05-30 | 吉利德科学公司 | 膦酰胺核苷酸类似物的前药及其药物用途 |
| WO2022072520A1 (en) * | 2020-09-30 | 2022-04-07 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| 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 |
| WO2022089562A1 (zh) * | 2020-10-30 | 2022-05-05 | 上海拓界生物医药科技有限公司 | 抑制基因缺陷的hiv病毒的用途 |
| EP4244396B1 (en) | 2020-11-11 | 2025-08-13 | Gilead Sciences, Inc. | Methods of identifying hiv patients sensitive to therapy with gp120 cd4 binding site-directed antibodies |
| JP7591155B2 (ja) | 2021-01-19 | 2024-11-27 | ギリアード サイエンシーズ， インコーポレイテッド | 置換ピリドトリアジン化合物及びその使用 |
| US20240309017A1 (en) * | 2021-01-22 | 2024-09-19 | 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 |
| US20220389394A1 (en) | 2021-05-18 | 2022-12-08 | Gilead Sciences, Inc. | METHODS OF USING FLT3L-Fc FUSION PROTEINS |
| CN117396478A (zh) | 2021-06-23 | 2024-01-12 | 吉利德科学公司 | 二酰基甘油激酶调节化合物 |
| KR20240023628A (ko) | 2021-06-23 | 2024-02-22 | 길리애드 사이언시즈, 인코포레이티드 | 디아실글리세롤 키나제 조절 화합물 |
| KR20240023629A (ko) | 2021-06-23 | 2024-02-22 | 길리애드 사이언시즈, 인코포레이티드 | 디아실글리세롤 키나제 조절 화합물 |
| US11932634B2 (en) | 2021-06-23 | 2024-03-19 | Gilead Sciences, Inc. | Diacylglycerol 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 |
| KR20240113832A (ko) | 2021-12-03 | 2024-07-23 | 길리애드 사이언시즈, 인코포레이티드 | Hiv 바이러스 감염 치료용 화합물 |
| 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 |
| PL4445900T3 (pl) | 2021-12-03 | 2025-09-22 | Gilead Sciences, Inc. | Związki terapeutyczne przeciwko zakażeniu wirusem hiv |
| 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 |
| TWI843506B (zh) | 2022-04-06 | 2024-05-21 | 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 |
| US20240034724A1 (en) | 2022-07-01 | 2024-02-01 | 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 |
| JP2025527677A (ja) | 2022-08-26 | 2025-08-22 | ギリアード サイエンシーズ， インコーポレイテッド | 広域中和抗体のための投与及びスケジューリングレジメン |
| 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 |
| EP4598934A1 (en) | 2022-10-04 | 2025-08-13 | Gilead Sciences, Inc. | 4'-thionucleoside analogues and their pharmaceutical use |
| US20240390349A1 (en) | 2023-04-19 | 2024-11-28 | 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 |
| CN121219281A (zh) | 2023-05-31 | 2025-12-26 | 吉利德科学公司 | 用于治疗hiv的化合物的固体形式 |
| WO2025029247A1 (en) | 2023-07-28 | 2025-02-06 | Gilead Sciences, Inc. | Weekly regimen of lenacapavir for the treatment and prevention of hiv |
| EP4529922A1 (en) | 2023-09-29 | 2025-04-02 | Gilead Sciences, Inc. | Pharmaceutical formulations of bictegravir and lenacapavir |
| WO2025038715A1 (en) | 2023-08-15 | 2025-02-20 | 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 |
| TW202515549A (zh) | 2023-10-11 | 2025-04-16 | 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 |
| US20250122219A1 (en) | 2023-10-11 | 2025-04-17 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| US20250127801A1 (en) | 2023-10-11 | 2025-04-24 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| US20250230163A1 (en) | 2023-12-22 | 2025-07-17 | Gilead Sciences, Inc. | Solid forms of hiv integrase inhibitors |
| US20250296932A1 (en) | 2024-03-01 | 2025-09-25 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising hiv integrase inhibitors |
| WO2025184609A1 (en) | 2024-03-01 | 2025-09-04 | Gilead Sciences, Inc. | Antiviral compounds |
| US20250289822A1 (en) | 2024-03-01 | 2025-09-18 | Gilead Sciences, Inc. | Solid forms of hiv integrase inhibitors |
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006116764A1 (en) * | 2005-04-28 | 2006-11-02 | Smithkline Beecham Corporation | Polycyclic carbamoylpyridone derivative having hiv integrase inhibitory activity |
| EP2412709A1 (en) * | 2009-03-26 | 2012-02-01 | Shionogi & Co., Ltd. | Process for producing pyrone and pyridone derivatives |
Family Cites Families (133)
| 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 |
| DE3900736A1 (de) | 1989-01-12 | 1990-07-26 | Hoechst Ag | Positiv arbeitendes strahlungsempfindliches gemisch enthaltend einen mehrfunktionellen (alpha)-diazo-(beta)-ketoester, verfahren zu dessen herstellung und strahlungsempfindliches aufzeichnungsmaterial enthaltend dieses gemisch |
| US5204466A (en) | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| US6703396B1 (en) | 1990-02-01 | 2004-03-09 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nuclesoside enantiomers |
| US5914331A (en) | 1990-02-01 | 1999-06-22 | 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 |
| US6479531B1 (en) | 1998-11-09 | 2002-11-12 | 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 |
| HK1042701A1 (zh) | 1998-12-25 | 2002-08-23 | 盐野义制药株式会社 | 具有hiv整合酶抑制活性的芳族杂环化合物 |
| EP1297834A4 (en) | 2000-06-14 | 2007-05-09 | Shionogi & Co | ENZYME INHIBITOR HAVING TWO DIVALENT METAL IONS AS ACTIVE CENTERS |
| US6919351B2 (en) * | 2000-10-12 | 2005-07-19 | Merck & Co., Inc. | Aza-and polyaza-naphthalenyl-carboxamides useful as HIV integrase inhibitors |
| ES2572030T3 (es) | 2001-08-10 | 2017-07-19 | Shionogi & Co., Ltd. | Agente antiviral |
| MY169670A (en) | 2003-09-03 | 2019-05-08 | Tibotec Pharm Ltd | Combinations of a pyrimidine containing nnrti with rt inhibitors |
| WO2003030897A1 (en) | 2001-10-03 | 2003-04-17 | Ucb, S.A. | Pyrrolidinone derivatives |
| DE122008000016I1 (de) | 2001-10-26 | 2011-12-01 | Angeletti P Ist Richerche Bio | N-substituierte hydroxypyrimidinoncarboxamidhemmerder HIV-integrase. |
| WO2004004657A2 (en) | 2002-07-09 | 2004-01-15 | Bristol-Myers Squibb Company | Hiv integrase inhibitors |
| EP1549315A4 (en) | 2002-09-11 | 2007-05-23 | Merck & Co Inc | DIHYDROXYPYRIDOPYRAZINE-1,6-DION COMPOUNDS 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 |
| DE602004014470D1 (de) | 2003-01-14 | 2008-07-31 | Gilead Sciences Inc | Zusammensetzungen und verfahren zur antiviralen kombinationstherapie |
| 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 |
| US20070155744A1 (en) | 2004-01-30 | 2007-07-05 | Istituto Di Ricerche Di Biologia Molecolare P, Angeletti S.P.A. | N-benzyl-3,4-dihyroxypyridine-2-carboxamide and n-benzyl-2,3-dihydroxypyridine-4- carboxamide compounds useful as hiv integrase inhibitors |
| WO2005077050A2 (en) | 2004-02-11 | 2005-08-25 | Smithkline Beecham Corporation | Hiv integrase inhibitors |
| WO2005086700A2 (en) | 2004-03-09 | 2005-09-22 | Merck & Co., Inc. | Hiv integrase inhibitors |
| WO2005110399A2 (en) | 2004-04-29 | 2005-11-24 | The Regents Of The University Of California | Zinc-binding groups for metalloprotein inhibitors |
| EP1755586A2 (en) | 2004-04-29 | 2007-02-28 | The Regents of the University of California | Hydroxypyridinone, hydroxypyridinethione, pyrone, and thiopyrone metalloprotein inhibitors |
| CN1964975B (zh) | 2004-05-07 | 2011-11-30 | 默沙东公司 | Hiv整合酶抑制剂 |
| US7273859B2 (en) | 2004-05-12 | 2007-09-25 | Bristol-Myers Squibb Company | HIV integrase inhibitors: cyclic pyrimidinone compounds |
| MXPA06013316A (es) * | 2004-05-17 | 2007-02-02 | Tibotec Pharm Ltd | Combinaciones de 1-fenil-1,5-dihidro-pirido-[3,2-b]indol-2-onas sustituidas y otros inhibidores de virus de inmunodeficiencia humana. |
| MY134672A (en) | 2004-05-20 | 2007-12-31 | Japan Tobacco Inc | Stable crystal of 4-oxoquinoline compound |
| US7531554B2 (en) | 2004-05-20 | 2009-05-12 | Japan Tobacco Inc. | 4-oxoquinoline compound and use thereof as HIV integrase inhibitor |
| US8633219B2 (en) | 2004-05-21 | 2014-01-21 | Japan Tobacco Inc. | Combination therapy |
| US7550463B2 (en) | 2004-09-15 | 2009-06-23 | Shionogi & Co., Ltd. | Carbamoylpyridone derivatives having inhibitory activity against HIV integrase |
| 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 |
| EP1888581A2 (en) | 2005-05-16 | 2008-02-20 | Gilead Sciences, Inc. | Hiv-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 |
| CA2847871C (en) | 2005-12-30 | 2016-07-26 | Gilead Sciences, Inc. | Methods for improving the pharmacokinetics of hiv integrase inhibitors |
| US7601844B2 (en) | 2006-01-27 | 2009-10-13 | Bristol-Myers Squibb Company | Piperidinyl derivatives as modulators of chemokine receptor activity |
| WO2007089030A1 (en) | 2006-02-01 | 2007-08-09 | Japan Tobacco Inc. | Use of 6-(3-chloro-2-fluorobenzyl)-1-[(2s)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or salt thereof for treating retrovirus infection |
| WO2007102499A1 (ja) | 2006-03-06 | 2007-09-13 | Japan Tobacco Inc. | ４－オキソキノリン化合物の製造方法 |
| AU2007223260C1 (en) | 2006-03-06 | 2011-02-03 | Japan Tobacco Inc. | Method for producing 4-oxoquinoline compound |
| US7893055B2 (en) | 2006-06-28 | 2011-02-22 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| US7888375B2 (en) | 2006-07-19 | 2011-02-15 | The University Of Georgia Research Foundation, Inc | Pyridinone diketo acids: inhibitors of HIV replication |
| HRP20090213B1 (hr) | 2006-09-12 | 2016-12-02 | Gilead Sciences, Inc. | Postupak i međuprodukti u pripravi inhibitora integraze |
| WO2008048538A1 (en) | 2006-10-18 | 2008-04-24 | Merck & Co., Inc. | Hiv integrase inhibitors |
| EA019893B1 (ru) | 2007-02-23 | 2014-07-30 | Джилид Сайэнс, Инк. | Фармацевтическая композиция и способ лечения вич-инфекции |
| US20080280945A1 (en) | 2007-05-09 | 2008-11-13 | Sachin Lohani | Crystalline forms of an HIV integrase inhibitor |
| JP5547067B2 (ja) | 2007-06-29 | 2014-07-09 | ギリアード サイエンシーズ， インコーポレイテッド | 治療組成物およびその使用 |
| JP5547066B2 (ja) | 2007-06-29 | 2014-07-09 | ギリアード サイエンシーズ， インコーポレイテッド | 治療用組成物およびその使用 |
| US20090012103A1 (en) | 2007-07-05 | 2009-01-08 | Matthew Abelman | Substituted heterocyclic compounds |
| WO2009018350A1 (en) | 2007-07-31 | 2009-02-05 | Limerick Biopharma, Inc. | Pyrone analog compositions 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 |
| PL2320908T3 (pl) | 2008-07-25 | 2014-06-30 | Viiv Healthcare Co | Proleki dolutegrawiru |
| WO2010011819A1 (en) | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| EP2330902B1 (en) * | 2008-07-25 | 2012-11-14 | GlaxoSmithKline LLC | Chemical compounds |
| WO2010011818A1 (en) * | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| KR101772610B1 (ko) | 2008-07-25 | 2017-09-12 | 비이브 헬쓰케어 컴퍼니 | 화합물 |
| MX383683B (es) * | 2008-12-11 | 2025-03-11 | Shionogi & Co | Sintesis de inhibidores de integrasa de vih de carbamoil-piridona e intermediarios. |
| KR101682058B1 (ko) | 2008-12-11 | 2016-12-02 | 비이브 헬쓰케어 컴퍼니 | 카르바모일피리돈 ｈｉｖ 인테그라제 억제제를 위한 제조방법 및 중간체 |
| US9938268B2 (en) | 2008-12-17 | 2018-04-10 | Merck Patent Gmbh | C-ring modified tricyclic benzonaphthiridinone protein kinase inhibitors and use thereof |
| ES2548886T3 (es) | 2009-02-06 | 2015-10-21 | Gilead Sciences, Inc. | Comprimidos bicapa que comprenden elvitegravir, cobicistat, emtricitabina y tenofovir |
| 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 |
| JP5737691B2 (ja) | 2009-06-15 | 2015-06-17 | 塩野義製薬株式会社 | 置換された多環性カルバモイルピリドン誘導体 |
| WO2011011483A1 (en) * | 2009-07-22 | 2011-01-27 | Glaxosmithkline Llc | Chemical compounds |
| WO2011028044A2 (ko) | 2009-09-02 | 2011-03-10 | 이화여자대학교 산학협력단 | 피라졸 유도체, 이의 제조방법 및 이를 포함하는 골다공증 예방 및 치료용 조성물 |
| ES2670811T3 (es) | 2010-01-27 | 2018-06-01 | Viiv Healthcare Company | Terapia antivírica |
| NZ601847A (en) | 2010-02-26 | 2014-03-28 | Japan Tobacco Inc | 1,3,4,8-tetrahydro-2h-pyrido[1,2-a]pyrazine derivative and use of same as hiv integrase 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 |
| WO2011139637A1 (en) | 2010-05-03 | 2011-11-10 | Philadelphia Health & Education Corporation | Small-molecule modulators of hiv-1 capsid stability and methods thereof |
| MA34397B1 (fr) | 2010-07-02 | 2013-07-03 | Gilead Sciences Inc | Dérivés d'acide napht-2-ylacétique dans le traitement du sida |
| NZ604716A (en) | 2010-07-02 | 2014-12-24 | Gilead Sciences Inc | 2-quinolinyl-acetic acid derivatives as hiv antiviral compounds |
| 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 |
| PT3127908T (pt) | 2010-08-05 | 2019-02-04 | Shionogi & Co | Processo para preparar composto possuindo atividade inibidora de integrase do vih |
| WO2012039414A1 (ja) | 2010-09-24 | 2012-03-29 | 塩野義製薬株式会社 | 置換された多環性カルバモイルピリドン誘導体のプロドラッグ |
| TWI556840B (zh) | 2010-11-19 | 2016-11-11 | 吉李德科學股份有限公司 | 治療用組成物 |
| WO2012106534A2 (en) | 2011-02-02 | 2012-08-09 | The Regents Of The University Of California | Hiv integrase inhibitors |
| AP2013007249A0 (en) | 2011-04-21 | 2013-11-30 | Gilead Sciences Inc | Benzothiazole compounds and their pharmaceutical use |
| WO2012151361A1 (en) | 2011-05-03 | 2012-11-08 | Concert Pharmaceuticals Inc. | Carbamoylpyridone derivatives |
| WO2012151567A1 (en) | 2011-05-05 | 2012-11-08 | St. Jude Children's Research Hospital | Pyrimidinone compounds and methods for preventing and treating influenza |
| US9121496B2 (en) | 2011-06-29 | 2015-09-01 | Arvinmeritor Technology, Llc | Drive axle system and a method of control |
| WO2013006738A1 (en) | 2011-07-06 | 2013-01-10 | 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 |
| WO2013004818A1 (en) | 2011-07-07 | 2013-01-10 | Janssen R&D Ireland | Darunavir combination formulations |
| US9206197B2 (en) | 2011-09-14 | 2015-12-08 | Mapi Pharma Ltd. | Amorphous form of dolutegravir |
| BR112014008896A2 (pt) | 2011-10-12 | 2017-04-18 | Shionogi & Co | derivado de piridona policíclico tendo atividade inibidora de integrase |
| CN104114559B (zh) | 2011-12-12 | 2016-08-24 | 拜耳知识产权有限责任公司 | 氨基取代的咪唑并哒嗪 |
| WO2013103738A1 (en) | 2012-01-04 | 2013-07-11 | Gilead Sciences, Inc. | Napthalene acetic acid derivatives against hiv infection |
| WO2014008636A1 (en) | 2012-07-11 | 2014-01-16 | Merck Sharp & Dohme Corp. | Macrocyclic compounds as hiv integrase inhibitors |
| EP2875024A4 (en) | 2012-07-20 | 2015-12-23 | Merck Sharp & Dohme | HIV TREATMENT WITH AMIDOSUBSTITUTED PYRIMIDINONE DERIVATIVES |
| WO2014018449A1 (en) | 2012-07-25 | 2014-01-30 | Merck Sharp & Dohme Corp. | Substituted naphthyridinedione derivatives as hiv integrase inhibitors |
| AU2013296289B2 (en) | 2012-08-03 | 2017-10-05 | Gilead Sciences, Inc. | Process and intermediates for preparing integrase inhibitors |
| CA2890983A1 (en) | 2012-11-08 | 2014-05-15 | Bristol-Myers Squibb Company | Heteroaryl substituted pyridyl compounds useful as kinase modulators |
| US9795619B2 (en) | 2012-12-14 | 2017-10-24 | Glaxosmithkline Llc | Pharmaceutical compositions |
| WO2014099586A1 (en) | 2012-12-17 | 2014-06-26 | Merck Sharp & Dohme Corp. | 4-pyridinonetriazine derivatives as hiv integrase inhibitors |
| AU2013361401C1 (en) | 2012-12-21 | 2018-08-09 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| WO2014100077A1 (en) | 2012-12-21 | 2014-06-26 | Merck Sharp & Dohme Corp. | Gastro-retentive formulations |
| US20140221355A1 (en) | 2012-12-21 | 2014-08-07 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| AR094311A1 (es) | 2012-12-27 | 2015-07-22 | Japan Tobacco Inc | Derivados de tetrahidroespiro-ciclopropil-pirido[1,2-a]pirazina inhibidores de la integrasa del hiv |
| US9493479B2 (en) | 2013-04-16 | 2016-11-15 | Merck Sharp & Dohme Corp. | Substituted pyrido[1,2-a]pyrazines as HIV integrase inhibitors |
| US9951079B2 (en) | 2013-06-13 | 2018-04-24 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as HIV integrase inhibitors |
| EP3019503B1 (en) * | 2013-07-12 | 2017-09-06 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their use for the treatment of hiv infections |
| NO2865735T3 (enExample) | 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 |
| UA117499C2 (uk) | 2013-09-27 | 2018-08-10 | Мерк Шарп Енд Доум Корп. | Заміщені похідні хінолізину, які можна використовувати як інгібітори інтегрази віл |
| WO2015089847A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Spirocyclic heterocycle compounds useful as hiv integrase inhibitors |
| EP3096763B1 (en) | 2014-01-21 | 2019-12-25 | Laurus Labs 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 (enExample) | 2014-06-20 | 2018-06-23 | ||
| JP6522732B2 (ja) * | 2014-07-11 | 2019-05-29 | ギリアード サイエンシーズ， インコーポレイテッド | Ｈｉｖを治療するためのトール様受容体の調節因子 |
| TWI695003B (zh) | 2014-12-23 | 2020-06-01 | 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 |
| PT3466490T (pt) | 2015-04-02 | 2020-12-24 | Gilead Sciences Inc | Compostos de carbamoilpiridona policíclicos e sua utilização farmacêutica |
| US20170000807A1 (en) | 2015-06-30 | 2017-01-05 | Gilead Sciences, Inc. | Pharmaceutical formulations |
| CA2921336A1 (en) | 2015-06-30 | 2016-12-30 | Gilead Sciences, Inc. | Pharmaceutical formulations |
| JP6621933B2 (ja) | 2015-11-09 | 2019-12-18 | ギリアード サイエンシス インコーポレーテッド | ヒト免疫不全ウイルスを処置するための治療組成物 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006116764A1 (en) * | 2005-04-28 | 2006-11-02 | Smithkline Beecham Corporation | Polycyclic carbamoylpyridone derivative having hiv integrase inhibitory activity |
| EP2412709A1 (en) * | 2009-03-26 | 2012-02-01 | Shionogi & Co., Ltd. | Process for producing pyrone and pyridone derivatives |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
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