ES2437268T3 - Derivado de carbamoilpiridona policíclico que tiene actividad inhibidora de la integrasa del VIH - Google Patents
Derivado de carbamoilpiridona policíclico que tiene actividad inhibidora de la integrasa del VIH Download PDFInfo
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- ES2437268T3 ES2437268T3 ES06758843.4T ES06758843T ES2437268T3 ES 2437268 T3 ES2437268 T3 ES 2437268T3 ES 06758843 T ES06758843 T ES 06758843T ES 2437268 T3 ES2437268 T3 ES 2437268T3
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- -1 Polycyclic carbamoylpyridone derivative Chemical class 0.000 title description 9
- 230000002401 inhibitory effect Effects 0.000 title description 8
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- QDZZDVQGBKTLHV-UHFFFAOYSA-N (2,4-difluorophenyl)methanamine Chemical group NCC1=CC=C(F)C=C1F QDZZDVQGBKTLHV-UHFFFAOYSA-N 0.000 claims abstract description 4
- KVXRWTBFPVMIGC-SVRRBLITSA-N (4r,12as)-7-hydroxy-4-methyl-6,8-dioxo-3,4,12,12a-tetrahydro-2h-pyrido[5,6]pyrazino[2,6-b][1,3]oxazine-9-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)C(O)=C2C(=O)N3[C@H](C)CCO[C@H]3CN21 KVXRWTBFPVMIGC-SVRRBLITSA-N 0.000 claims abstract 2
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- 230000010534 mechanism of action Effects 0.000 description 6
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
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- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- 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
- A61K31/4985—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
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
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- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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Families Citing this family (152)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ551468A (en) | 2003-12-24 | 2010-05-28 | Biota Scient Management | Polycyclic agents for the treatment of respiratory syncytial virus infections |
| US7273859B2 (en) * | 2004-05-12 | 2007-09-25 | Bristol-Myers Squibb Company | HIV integrase inhibitors: cyclic pyrimidinone compounds |
| EP3187225B1 (en) * | 2005-04-28 | 2022-01-05 | VIIV Healthcare Company | Polycyclic carbamoylpyridone derivative having hiv integrase inhibitory activity |
| EP1881825B1 (en) | 2005-05-10 | 2013-07-24 | Merck Sharp & Dohme Corp. | Hiv integrase inhibitors |
| EP1937678B1 (en) | 2005-10-04 | 2011-07-27 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Hiv integrase inhibitors |
| KR20080064182A (ko) * | 2005-10-27 | 2008-07-08 | 시오노기세야쿠 가부시키가이샤 | Hiv 인테그라아제 억제활성을 가지는 다환성카르바모일피리돈 유도체 |
| TWI423972B (zh) | 2006-09-28 | 2014-01-21 | Biota Scient Management | 治療呼吸系融合細胞病毒感染之多環劑 |
| KR20100108337A (ko) * | 2007-11-15 | 2010-10-06 | 베링거 인겔하임 인터내셔날 게엠베하 | 사람 면역결핍 바이러스 복제의 억제제 |
| US8377960B2 (en) | 2007-11-15 | 2013-02-19 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| NZ585226A (en) | 2007-11-16 | 2012-08-31 | Gilead Sciences Inc | Inhibitors of human immunodeficiency virus replication |
| WO2010011816A1 (en) * | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| US8217034B2 (en) | 2008-07-25 | 2012-07-10 | Shionogi & Co., Ltd. | Chemical compounds |
| WO2010011815A1 (en) * | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| KR101700267B1 (ko) * | 2008-07-25 | 2017-01-26 | 비이브 헬쓰케어 컴퍼니 | 화합물 |
| WO2010011818A1 (en) * | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| CA2744019C (en) * | 2008-12-11 | 2017-03-14 | Shionogi & Co., Ltd. | Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates |
| KR101663222B1 (ko) * | 2008-12-11 | 2016-10-06 | 시오노기세야쿠 가부시키가이샤 | 말톨 에테르 방법 및 중간체 |
| AU2014277831C1 (en) * | 2008-12-11 | 2022-10-06 | Shionogi & Co. Ltd. | Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates |
| PT3617194T (pt) * | 2008-12-11 | 2023-11-27 | Shionogi & Co | Processos e intermediários para inibidores carbamoilpiridona da integrase do vih |
| 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 |
| PT2444400T (pt) | 2009-06-15 | 2018-06-06 | Shionogi & Co | Derivado de carbamoilpiridona policíclico substituído |
| WO2011011483A1 (en) * | 2009-07-22 | 2011-01-27 | Glaxosmithkline Llc | Chemical compounds |
| AU2010305805B2 (en) | 2009-10-13 | 2014-04-03 | Elanco Animal Health Ireland Limited | Macrocyclic integrase inhibitors |
| AU2014202404C1 (en) * | 2010-01-27 | 2022-06-23 | Viiv Healthcare Company | Antiviral therapy |
| PT3494972T (pt) * | 2010-01-27 | 2024-02-12 | Viiv Healthcare Co | Combinações de dolutegravir e lamivudina para o tratamento de infeção pelo hiv |
| AU2014202406C1 (en) * | 2010-01-27 | 2019-03-07 | Viiv Healthcare Company | Antiviral therapy |
| TWI508968B (zh) | 2010-02-08 | 2015-11-21 | Biota Scient Management | 用於治療呼吸道融合性病毒感染的化合物 |
| EP2540720B1 (en) * | 2010-02-26 | 2015-04-15 | 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 |
| JP5739517B2 (ja) | 2010-04-02 | 2015-06-24 | ヤンセン・アールアンドデイ・アイルランド | 大環状インテグラーゼ阻害剤 |
| JP5766690B2 (ja) * | 2010-04-12 | 2015-08-19 | 塩野義製薬株式会社 | インテグラーゼ阻害活性を有するピリドン誘導体 |
| WO2012006104A2 (en) | 2010-06-28 | 2012-01-12 | Academia Sinica, Taiwan | Compounds and methods for treating tuberculosis infection |
| WO2012018065A1 (ja) | 2010-08-05 | 2012-02-09 | 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化合物の製造方法 |
| TWI577377B (zh) * | 2010-09-16 | 2017-04-11 | Viiv醫療保健公司 | 醫藥組合物 |
| MX2013003139A (es) * | 2010-09-24 | 2013-06-18 | Shionogi & Co | Profarmaco de derivado de carbamoilpiridona policiclica substituida. |
| US8796303B2 (en) | 2010-11-26 | 2014-08-05 | Biota Scientific Management Pty Ltd. | Imidazo[2,1-G][1,7]naphthyridines for treating respiratory syncytial virus infections |
| WO2012151361A1 (en) | 2011-05-03 | 2012-11-08 | Concert Pharmaceuticals Inc. | Carbamoylpyridone derivatives |
| ES2613180T3 (es) | 2011-09-14 | 2017-05-23 | Mapi Pharma Limited | Forma amorfa de la sal sódica dolutegravir |
| EP2774928B1 (en) | 2011-10-12 | 2017-08-30 | Shionogi & Co., Ltd. | Polycyclic pyridone derivative having integrase-inhibiting activity |
| JP6242810B2 (ja) | 2011-12-28 | 2017-12-06 | グローバル・ブラッド・セラピューティクス・インコーポレイテッドGlobal Blood Therapeutics,Inc. | 置換ベンズアルデヒド化合物および組織酸素化の増加におけるそれらの使用方法 |
| WO2013102145A1 (en) | 2011-12-28 | 2013-07-04 | Global Blood Therapeutics, Inc. | Substituted heteroaryl aldehyde compounds and methods for their use in increasing tissue oxygenation |
| 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 |
| EP2940019B1 (en) | 2012-12-27 | 2018-03-28 | Japan Tobacco Inc. | SUBSTITUTED SPIROPYRIDO[1,2-a]PYRAZINE DERIVATIVE AND MEDICINAL USE THEREOF AS HIV INTEGRASE INHIBITOR |
| EP2956123A1 (en) | 2013-02-18 | 2015-12-23 | ratiopharm GmbH | Solid pharmaceutical dosage form of dolutegravir |
| EP2767272A1 (en) | 2013-02-18 | 2014-08-20 | Ratiopharm GmbH | Solid pharmaceutical dosage form of dolutegravir |
| US9573965B2 (en) | 2013-02-19 | 2017-02-21 | Aurobindo Pharma Ltd | Process for the preparation of Dolutegravir |
| US8952171B2 (en) | 2013-03-15 | 2015-02-10 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9604999B2 (en) | 2013-03-15 | 2017-03-28 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| SG11201507320QA (en) | 2013-03-15 | 2015-10-29 | Global Blood Therapeutics Inc | Compounds and uses thereof for the modulation of hemoglobin |
| US9458139B2 (en) | 2013-03-15 | 2016-10-04 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| ES2993155T3 (en) | 2013-03-15 | 2024-12-23 | Global Blood Therapeutics Inc | Compounds and uses thereof for the modulation of hemoglobin |
| SG11201507453VA (en) | 2013-03-15 | 2015-10-29 | Global Blood Therapeutics Inc | Compounds and uses thereof for the modulation of hemoglobin |
| US10100043B2 (en) | 2013-03-15 | 2018-10-16 | Global Blood Therapeutics, Inc. | Substituted aldehyde compounds and methods for their use in increasing tissue oxygenation |
| US9422279B2 (en) | 2013-03-15 | 2016-08-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US20140274961A1 (en) | 2013-03-15 | 2014-09-18 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9802900B2 (en) | 2013-03-15 | 2017-10-31 | Global Blood Therapeutics, Inc. | Bicyclic heteroaryl compounds and uses thereof for the modulation of hemoglobin |
| US10266551B2 (en) | 2013-03-15 | 2019-04-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| WO2014172188A2 (en) | 2013-04-16 | 2014-10-23 | Merck Sharp & Dohme Corp. | 4-pyridone derivative compounds and uses thereof as hiv integrase inhibitors |
| EP3008044B1 (en) * | 2013-06-13 | 2018-11-21 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
| EP3016935B1 (en) * | 2013-07-04 | 2018-09-05 | Hetero Research Foundation | Process for the preparation of intermediate of dolutegravir |
| NO2865735T3 (enExample) * | 2013-07-12 | 2018-07-21 | ||
| PL3019503T3 (pl) | 2013-07-12 | 2018-01-31 | Gilead Sciences Inc | Policykliczne związki karbamoilopirydonowe i ich zastosowanie do leczenia infekcji hiv |
| EP3022209B1 (en) | 2013-07-17 | 2018-03-07 | ratiopharm GmbH | Dolutegravir potassium salt |
| WO2015019310A1 (en) | 2013-08-07 | 2015-02-12 | Mylan Laboratories Ltd | Process for the preparation of dolute-gravir and intermediates thereof |
| 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 |
| EA201992707A1 (ru) | 2013-11-18 | 2020-06-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| WO2015089847A1 (en) * | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Spirocyclic heterocycle compounds useful as hiv integrase inhibitors |
| WO2015092752A1 (en) | 2013-12-20 | 2015-06-25 | Mylan Laboratories Ltd. | Novel crystalline form of dolutegravir sodium |
| WO2015108945A2 (en) | 2014-01-14 | 2015-07-23 | Board Of Regents Of The University Of Nebraska | Compositions and methods for the delivery of therapeutics |
| EP3096763B1 (en) | 2014-01-21 | 2019-12-25 | Laurus Labs Limited | Novel process for the preparation of dolutegravir and pharmaceutically acceptable salts thereof |
| PL3102208T5 (pl) | 2014-02-07 | 2024-10-14 | Global Blood Therapeutics, Inc. | Krystaliczny polimorf wolnej zasady 2-hydroksy-6-((2-(1-izopropylo-1h-pirazol-5-ilo)pirydyn-3-ylo)metoksy)benzaldehydu |
| WO2015138933A1 (en) | 2014-03-13 | 2015-09-17 | Assia Chemical Industries Ltd. | Solid state forms of dolutegravir sodium |
| CN107056813B (zh) * | 2014-03-19 | 2019-07-30 | 杭州普晒医药科技有限公司 | 德罗格韦钠盐的晶型及其制备方法 |
| IN2014MU00916A (enExample) | 2014-03-20 | 2015-09-25 | Cipla Ltd | |
| ZA201503540B (en) * | 2014-05-20 | 2016-10-26 | Cipla Ltd | Process for preparing polycyclic carbamoyl pyridone derivatives |
| TWI677489B (zh) * | 2014-06-20 | 2019-11-21 | 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 | ||
| EP3757105B1 (en) | 2014-08-22 | 2024-07-24 | Shionogi & Co., Ltd. | Polycyclic pyridone derivative having integrase inhibitory activity |
| WO2016057866A1 (en) | 2014-10-09 | 2016-04-14 | Board Of Regents Of The University Of Nebraska | Compositions and methods for the delivery of therapeutics |
| WO2016092527A1 (en) * | 2014-12-12 | 2016-06-16 | Sun Pharmaceutical Industries Limited | A process for the preparation of dolutegravir |
| 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 |
| EP3045461A1 (en) | 2015-01-16 | 2016-07-20 | LEK Pharmaceuticals d.d. | Processes for preparing dolutegravir and analogues thereof |
| WO2016125192A2 (en) | 2015-02-06 | 2016-08-11 | Mylan Laboratories Limited | Process for the preparation of dolutegravir |
| CZ201599A3 (cs) | 2015-02-13 | 2016-08-24 | Zentiva, K.S. | Pevné formy solí dolutegraviru a způsob jejich přípravy |
| WO2016154527A1 (en) * | 2015-03-26 | 2016-09-29 | Merck Sharp & Dohme Corp. | Phosphate-substituted quinolizine derivatives useful as hiv integrase inhibitors |
| MA41841A (fr) | 2015-03-30 | 2018-02-06 | Global Blood Therapeutics Inc | Composés aldéhyde pour le traitement de la fibrose pulmonaire, de l'hypoxie, et de maladies auto-immunes et des tissus conjonctifs |
| CN110790773A (zh) * | 2015-04-02 | 2020-02-14 | 吉利德科学公司 | 多环氨甲酰基吡啶酮化合物及其药物用途 |
| BR112017022550B1 (pt) * | 2015-04-28 | 2021-02-23 | Shionogi & Co., Ltd | derivados policíclicos de piridona substituída |
| WO2016187788A1 (en) | 2015-05-25 | 2016-12-01 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds useful for treating hiv infection |
| CZ2015537A3 (cs) | 2015-08-04 | 2017-02-15 | Zentiva, K.S. | Pevné formy amorfního dolutegraviru |
| EP3337479B1 (en) | 2015-08-19 | 2023-12-13 | Laurus Labs Limited | Novel polymorphs of dolutegravir and salts thereof |
| CA2948021C (en) | 2015-11-09 | 2024-06-18 | Gilead Sciences, Inc. | Pharmaceutical formulations of (2r,5s,13 ar)-8hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzy1)-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 |
| WO2017087257A1 (en) | 2015-11-17 | 2017-05-26 | Merck Sharp & Dohme Corp. | Amido-substituted pyridotriazine derivatives useful as hiv integrase inhibitors |
| ES3039236T3 (en) | 2015-12-04 | 2025-10-20 | Global Blood Therapeutics Inc | Dosing regimens for 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde |
| WO2017106071A1 (en) | 2015-12-15 | 2017-06-22 | Merck Sharp & Dohme Corp. | Spirocyclic quinolizine derivatives useful as hiv integrase inhibitors |
| US10696636B2 (en) | 2015-12-21 | 2020-06-30 | Lupin Limited | Process for the preparation of HIV integrase inhibitors |
| TWI752307B (zh) | 2016-05-12 | 2022-01-11 | 美商全球血液治療公司 | 新穎化合物及製造化合物之方法 |
| WO2017208105A1 (en) | 2016-05-30 | 2017-12-07 | Lupin Limited | Novel crystalline form of dolutegravir sodium |
| EP4299133A3 (en) * | 2016-06-23 | 2024-03-13 | VIIV Healthcare Company | Compositions and methods for the delivery of therapeutics |
| ES2952878T3 (es) | 2016-08-08 | 2023-11-06 | Hetero Labs Ltd | Una composición antirretroviral multiclase |
| EP3496718A4 (en) | 2016-08-08 | 2020-01-22 | Hetero Labs Limited | ANTIRETROVIRAL COMPOSITIONS |
| EP3496724B8 (en) * | 2016-08-12 | 2021-11-17 | Madera Therapeutics, LLC | Protein kinase regulators |
| WO2018042332A1 (en) | 2016-08-31 | 2018-03-08 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations and uses and treatments thereof |
| US20190216725A1 (en) * | 2016-09-21 | 2019-07-18 | Merck Shapr & Dohme Corp. | Drug delivery system for the delivery of integrase inhibitors |
| TW202332423A (zh) | 2016-10-12 | 2023-08-16 | 美商全球血液治療公司 | 包含2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)吡啶-3-基)甲氧基)-苯甲醛之片劑 |
| AU2017367714B2 (en) | 2016-12-02 | 2020-11-12 | Merck Sharp & Dohme Corp. | Tricyclic heterocycle compounds useful as HIV integrase inhibitors |
| 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) |
| WO2018109786A1 (en) | 2016-12-16 | 2018-06-21 | Cipla Limited | Novel polymoprphs and salts of polycyclic carbamoyl pyridone derivatives |
| WO2018140368A1 (en) | 2017-01-26 | 2018-08-02 | Merck Sharp & Dohme Corp. | Substituted quinolizine derivatives useful as hiv integrase inhibitors |
| MX388699B (es) | 2017-02-16 | 2025-03-20 | Viiv Healthcare Uk No 3 Ltd | Formas cristalinas de cabotegravir de sodio |
| EP3363802B1 (en) | 2017-02-16 | 2019-11-20 | Sandoz AG | Crystalline form of cabotegravir sodium |
| US20200138845A1 (en) * | 2017-07-18 | 2020-05-07 | Viiv Healthcare Company | Combination Drug Therapy |
| KR20200031658A (ko) | 2017-07-21 | 2020-03-24 | 비이브 헬쓰케어 컴퍼니 | Hib 감염 및 aids를 치료하기 위한 요법 |
| EP3661940A1 (en) | 2017-09-07 | 2020-06-10 | Cipla Limited | New polymorphs of dolutegravir sodium |
| JP6924839B2 (ja) | 2017-10-06 | 2021-08-25 | 塩野義製薬株式会社 | 置換された多環性ピリドン誘導体の立体選択的な製造方法 |
| EP3737359A4 (en) | 2018-01-12 | 2021-11-03 | Board of Regents of the University of Nebraska | ANTIVIRAL MEDICINES AND FORMULATIONS OF THEM |
| 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 |
| CA3132832A1 (en) | 2018-04-09 | 2019-10-17 | Howard E. Gendelman | Antiviral prodrugs and formulations thereof |
| 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 |
| MX2020012176A (es) | 2018-05-31 | 2021-01-29 | Shionogi & Co | Derivado policiclico de carbamoilpiridona. |
| JP7353707B2 (ja) * | 2018-05-31 | 2023-10-02 | 塩野義製薬株式会社 | 多環性ピリドン誘導体 |
| TWI880373B (zh) * | 2018-05-31 | 2025-04-11 | 日商鹽野義製藥股份有限公司 | 多環性吡啶并三𠯤衍生物 |
| ES2975333T3 (es) | 2018-07-12 | 2024-07-04 | Laurus Labs Ltd | Un proceso para la purificación de derivados policíclicos de carbamoilpiridona protegidos |
| US11014884B2 (en) | 2018-10-01 | 2021-05-25 | Global Blood Therapeutics, Inc. | Modulators of hemoglobin |
| EP4234561A3 (en) | 2018-10-22 | 2023-09-13 | Board of Regents of the University of Nebraska | Antiviral prodrugs and nanoformulations thereof |
| US20220175936A1 (en) | 2018-11-29 | 2022-06-09 | Board Of Regents Of The University Of Nebraska | Antiviral prodrugs and nanoformulations thereof |
| PL3938047T3 (pl) | 2019-03-22 | 2022-11-07 | Gilead Sciences, Inc. | Zmostkowane tricykliczne związki karbamoilopirydonowe i ich zastosowanie farmaceutyczne |
| 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 |
| US20200398978A1 (en) | 2019-06-20 | 2020-12-24 | Bell Helicopter Textron Inc. | Low-drag rotor blade extension |
| US11248005B2 (en) | 2019-07-08 | 2022-02-15 | Lupin Limited | Process for preparation of intermediates used for the synthesis of HIV integrase inhibitor |
| EP4066839A4 (en) | 2019-11-28 | 2023-12-27 | Shionogi & Co., Ltd | PROPHYLACTIC AND THERAPEUTIC MEDICINAL PRODUCT FOR HIV INFECTIOUS DISEASES, CHARACTERIZED BY CONTAINING THE COMBINATION OF INTEGRAS INHIBITORS AND ANTI-HIV AGENTS |
| EP4072520B1 (en) | 2019-12-09 | 2025-09-24 | VIIV Healthcare Company | Pharmaceutical compositions comprising cabotegravir |
| CR20220418A (es) | 2020-02-24 | 2022-10-10 | Gilead Sciences Inc | Compuestos tetracíclicos para el tratamiento de infecciones por vih |
| WO2025068743A1 (en) | 2023-09-27 | 2025-04-03 | ViiV Healthcare UK (No.3) Limited | Pharmaceutical composition of cabotegravir |
| US20230218644A1 (en) | 2020-04-16 | 2023-07-13 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
| US20230321089A1 (en) | 2020-09-01 | 2023-10-12 | Viiv Healthcare Company | Combination of cabotegravir and levonorgestrel |
| US12421235B2 (en) | 2020-09-30 | 2025-09-23 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| WO2022079739A1 (en) | 2020-10-14 | 2022-04-21 | Cipla Limited | Fixed dose compositions of cabotegravir and rilpivirine |
| JP2024500322A (ja) | 2020-12-07 | 2024-01-09 | ヴィーブ、ヘルスケア、カンパニー | 併用療法 |
| PL4196479T3 (pl) | 2021-01-19 | 2024-03-18 | Gilead Sciences, Inc. | Podstawione związki pirydotriazynowe i ich zastosowania |
| WO2022253294A1 (zh) | 2021-06-03 | 2022-12-08 | 江苏恒瑞医药股份有限公司 | 具有整合酶抑制活性的吡啶酮化合物及其药用用途 |
| 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 |
| JP2024542776A (ja) | 2021-12-03 | 2024-11-15 | ヴィーブ、ヘルスケア、カンパニー | (r)-3-アミノブタン-1-オールの合成方法 |
| TW202446773A (zh) | 2022-04-06 | 2024-12-01 | 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 |
| AU2024209826A1 (en) * | 2023-01-18 | 2025-07-10 | Ascletis BioScience Co., Ltd | Integrase inhibitor and use thereof |
| WO2025068912A1 (en) | 2023-09-27 | 2025-04-03 | ViiV Healthcare UK (No.3) Limited | Pharmaceutical compositions |
| WO2025128498A1 (en) | 2023-12-12 | 2025-06-19 | Viiv Healthcare Company | Pharmaceutical compositions |
| WO2025128496A1 (en) | 2023-12-12 | 2025-06-19 | Viiv Healthcare Company | Crystalline form |
| WO2025181723A1 (en) | 2024-03-01 | 2025-09-04 | ViiV Healthcare UK (No.3) Limited | Dosing regimen |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3959316A (en) * | 1972-03-13 | 1976-05-25 | Snam Progetti S.P.A. | Procedure for propylene oxide synthesis |
| JPH0296506A (ja) | 1988-09-30 | 1990-04-09 | Daicel Chem Ind Ltd | 除草剤組成物 |
| JP2551472B2 (ja) | 1988-10-18 | 1996-11-06 | ダイセル化学工業株式会社 | 5−アルコキシ−γ−ピロン−3−カルボキサミド誘導体とその製造方法及び植物成長抑制剤 |
| JP2533796B2 (ja) | 1988-10-18 | 1996-09-11 | ダイセル化学工業株式会社 | 5−アルコキシピリジン−3−カルボキサミド誘導体とその製造方法及び植物成長抑制剤 |
| ATE303993T1 (de) | 1997-12-22 | 2005-09-15 | Pharmacia & Upjohn Co Llc | 4-hydroxychinolin-3-carboxamide und hydrazide als antivirale wirkstoffe |
| WO2001095905A1 (fr) † | 2000-06-14 | 2001-12-20 | Shionogi & Co., Ltd. | Inhibiteur d'enzymes possedant deux ions metal divalents en tant que centres actifs |
| US6580562B2 (en) | 2000-07-24 | 2003-06-17 | Yazaki Corporation | On-vehicle display unit |
| US6384263B1 (en) | 2000-08-04 | 2002-05-07 | E. I. Du Pont De Nemours And Company | Process for making 3-hydroxyalkanelnitriles and conversion of the 3-hydroxyalkanelnitrile to an hydroxyaminoalkane |
| EP1326611B1 (en) | 2000-10-12 | 2007-06-13 | Merck & Co., Inc. | Aza- and polyaza-naphthalenyl-carboxamides useful as hiv integrase inhibitors |
| JP2003032772A (ja) | 2001-07-12 | 2003-01-31 | Foster Electric Co Ltd | 耳掛け式イヤホン |
| CN101513402B (zh) | 2001-08-10 | 2012-03-21 | 盐野义制药株式会社 | 抗病毒药 |
| DK1441735T3 (da) | 2001-10-26 | 2006-06-12 | Angeletti P Ist Richerche Bio | N-substituerede hydroxypyrimidinon-carboxamid-inhibitorer af HIV-integrase |
| AU2002334205B2 (en) | 2001-10-26 | 2007-07-05 | Istituto Di Ricerche Di Biologia Molecolara P. Angeletti Spa | Dihydroxypyrimidine carboxamide inhibitors of HIV integrase |
| ATE370948T1 (de) | 2002-01-17 | 2007-09-15 | Merck & Co Inc | Hydroxynaphthyridinoncarbonsäureamide, die sich als inhibitoren der hiv-integrase eignen |
| US7109186B2 (en) | 2002-07-09 | 2006-09-19 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| EP2045242A1 (en) | 2002-08-13 | 2009-04-08 | Shionogi&Co., Ltd. | Heterocyclic compounds having inhibitory activity against HIV integrase |
| US7517532B2 (en) * | 2002-09-11 | 2009-04-14 | Merck & Co., Inc. | Dihydroxypyridopyrazine-1,6-dione compounds useful as HIV integrase inhibitors |
| KR20050087865A (ko) | 2002-12-27 | 2005-08-31 | 이스티투토 디 리세르쉐 디 비올로지아 몰레콜라레 피. 안젤레티에스.피.에이. | HIV 인테그라제 억제제로서 유용한테트라하이드로-4H-피리도[1,2-a]피리미딘 및 관련화합물 |
| US6960680B2 (en) | 2003-01-08 | 2005-11-01 | Rhodia Chirex, Inc. | Manufacture of water-soluble β-hydroxynitriles |
| JP2004244320A (ja) | 2003-02-10 | 2004-09-02 | Shionogi & Co Ltd | 含窒素複素環抗ウイルス剤 |
| US7812016B2 (en) | 2003-05-13 | 2010-10-12 | Smithkline Beecham Corporation | Naphthyridine integrase inhibitors |
| WO2005015927A1 (en) * | 2003-08-12 | 2005-02-17 | Rachel Beijer | Scheduled message service |
| TW200510425A (en) * | 2003-08-13 | 2005-03-16 | Japan Tobacco Inc | Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor |
| JP4530642B2 (ja) | 2003-10-31 | 2010-08-25 | オリンパス株式会社 | 内視鏡装置 |
| JP4859676B2 (ja) | 2004-02-11 | 2012-01-25 | スミスクライン ビーチャム コーポレーション | Hivインテグラーゼ阻害剤 |
| EP1725102A4 (en) | 2004-03-09 | 2009-04-29 | Merck & Co Inc | HIV integrase |
| US20070161639A1 (en) | 2004-03-09 | 2007-07-12 | Philip Jones | Hiv integrase inhibitors |
| CN1964975B (zh) | 2004-05-07 | 2011-11-30 | 默沙东公司 | Hiv整合酶抑制剂 |
| WO2006066414A1 (en) | 2004-12-23 | 2006-06-29 | Virochem Pharma Inc. | Hydroxydihydropyridopy razine-1,8-diones and methods for inhibiting hiv integrase |
| ATE516026T1 (de) * | 2005-02-21 | 2011-07-15 | Shionogi & Co | Bicyclisches carbamoylpyridonderivat mit hiv- integrase-hemmender wirkung |
| AU2006228278C1 (en) | 2005-03-31 | 2011-06-23 | Msd Italia S.R.L. | HIV integrase inhibitors |
| EP3187225B1 (en) * | 2005-04-28 | 2022-01-05 | VIIV Healthcare Company | Polycyclic carbamoylpyridone derivative having hiv integrase inhibitory activity |
| JP2005312076A (ja) | 2005-05-26 | 2005-11-04 | Olympus Corp | 電子撮像装置 |
| WO2007019098A2 (en) | 2005-08-04 | 2007-02-15 | Smithkline Beecham Corporation | Hiv integrase inhibitors |
| KR20080064182A (ko) | 2005-10-27 | 2008-07-08 | 시오노기세야쿠 가부시키가이샤 | Hiv 인테그라아제 억제활성을 가지는 다환성카르바모일피리돈 유도체 |
-
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