EA019768B1 - СОЕДИНЕНИЯ, МОДУЛИРУЮЩИЕ АКТИВНОСТЬ Toll-ПОДОБНЫХ РЕЦЕПТОРОВ - Google Patents
СОЕДИНЕНИЯ, МОДУЛИРУЮЩИЕ АКТИВНОСТЬ Toll-ПОДОБНЫХ РЕЦЕПТОРОВ Download PDFInfo
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- EA019768B1 EA019768B1 EA201101165A EA201101165A EA019768B1 EA 019768 B1 EA019768 B1 EA 019768B1 EA 201101165 A EA201101165 A EA 201101165A EA 201101165 A EA201101165 A EA 201101165A EA 019768 B1 EA019768 B1 EA 019768B1
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- EA
- Eurasian Patent Office
- Prior art keywords
- alkyl
- substituted
- compound
- compound according
- alkoxy
- Prior art date
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Classifications
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- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
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- 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
- A61K31/52—Purines, e.g. adenine
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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
- C07D471/02—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 two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/24—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one nitrogen and one sulfur atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
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- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pretreatment Of Seeds And Plants (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15173709P | 2009-02-11 | 2009-02-11 | |
| PCT/US2010/000369 WO2010093436A2 (en) | 2009-02-11 | 2010-02-11 | Toll-like receptor modulators and treatment of diseases |
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| EA201101165A1 EA201101165A1 (ru) | 2012-04-30 |
| EA019768B1 true EA019768B1 (ru) | 2014-06-30 |
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| EP (2) | EP2607365A1 (OSRAM) |
| JP (1) | JP2012517428A (OSRAM) |
| KR (1) | KR20110117705A (OSRAM) |
| CN (1) | CN102439011B (OSRAM) |
| AU (1) | AU2010214112B2 (OSRAM) |
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| CA (1) | CA2752074A1 (OSRAM) |
| EA (1) | EA019768B1 (OSRAM) |
| IL (1) | IL214572A (OSRAM) |
| MX (1) | MX2011008500A (OSRAM) |
| SG (1) | SG173617A1 (OSRAM) |
| WO (1) | WO2010093436A2 (OSRAM) |
| ZA (1) | ZA201106268B (OSRAM) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US10947213B1 (en) | 2015-12-17 | 2021-03-16 | Merck Patent Gmbh | TLR7/8 antagonists and uses thereof |
| US11512069B2 (en) | 2016-08-08 | 2022-11-29 | Merck Patent Gmbh | TLR7/8 antagonists and uses thereof |
| US11697851B2 (en) | 2016-05-24 | 2023-07-11 | The Regents Of The University Of California | Early ovarian cancer detection diagnostic test based on mRNA isoforms |
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| CN101304748A (zh) | 2005-08-22 | 2008-11-12 | 加利福尼亚大学董事会 | Tlr激动剂 |
| AU2007257423B8 (en) | 2006-05-31 | 2012-02-16 | The Regents Of The University Of California | Purine analogs |
| CA2656427C (en) * | 2006-07-07 | 2014-12-09 | Gilead Sciences, Inc. | Modulators of toll-like receptor 7 |
| PL2125007T3 (pl) | 2007-02-07 | 2014-07-31 | Univ California | Koniugaty syntetycznych agonistów TLR i ich zastosowania |
| US20090202626A1 (en) * | 2008-02-07 | 2009-08-13 | Carson Dennis A | Treatment of bladder diseases with a tlr7 activator |
| PE20120106A1 (es) | 2008-12-09 | 2012-02-20 | Gilead Sciences Inc | Moduladores de receptores tipo toll |
| WO2010088924A1 (en) | 2009-02-06 | 2010-08-12 | Telormedix Sa | Pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration |
| EP2607365A1 (en) | 2009-02-11 | 2013-06-26 | The Regents of The University of California | Toll-like receptor modulators and treatment of diseases |
| WO2010115229A1 (en) | 2009-04-09 | 2010-10-14 | The University Of Melbourne | Immunogenic composition and uses thereof |
| EA020488B1 (ru) | 2009-10-22 | 2014-11-28 | Джилид Сайэнс, Инк. | Производные пурина или деазапурина для применения при лечении вирусных инфекций и других заболеваний |
| CN103221067B (zh) | 2010-04-30 | 2016-01-06 | 泰勒麦迪克斯公司 | 磷脂药物类似物 |
| US9050319B2 (en) | 2010-04-30 | 2015-06-09 | Telormedix, Sa | Phospholipid drug analogs |
| CN103118682A (zh) * | 2010-04-30 | 2013-05-22 | 加利福尼亚大学校务委员会 | 合成tlr7激动剂的磷脂缀合物的用途 |
| US20120083473A1 (en) | 2010-09-21 | 2012-04-05 | Johanna Holldack | Treatment of conditions by toll-like receptor modulators |
| US9676819B2 (en) * | 2010-09-22 | 2017-06-13 | Innavac Pty Ltd | Immunostimulatory method |
| GB201022049D0 (en) * | 2010-12-29 | 2011-02-02 | Imp Innovations Ltd | Methods |
| HRP20170401T1 (hr) * | 2011-01-12 | 2017-05-19 | Ventirx Pharmaceuticals, Inc. | SUPSTITUIRANI BENZOAZEPINI KAO MODULATORI TOLL-u SLIČNIH RECEPTORA |
| TW201247706A (en) * | 2011-03-08 | 2012-12-01 | Baylor Res Inst | Novel vaccine adjuvants based on targeting adjuvants to antibodies directly to antigen-presenting cells |
| CA2837207A1 (en) | 2011-06-01 | 2012-12-06 | Janus Biotherapeutics, Inc. | Novel immune system modulators |
| GB201205360D0 (en) * | 2012-03-27 | 2012-05-09 | Univ Edinburgh | Biotinidase resistant biotinyl compounds |
| CN103254304A (zh) * | 2012-05-30 | 2013-08-21 | 深圳大学 | 免疫激动剂偶联体、其制备方法及免疫激动剂偶联体在抗肿瘤中的应用 |
| EP2674170B1 (en) | 2012-06-15 | 2014-11-19 | Invivogen | Novel compositions of TLR7 and/or TLR8 agonists conjugated to lipids |
| WO2014052828A1 (en) | 2012-09-27 | 2014-04-03 | The Regents Of The University Of California | Compositions and methods for modulating tlr4 |
| CN102993265B (zh) * | 2012-10-10 | 2015-05-13 | 深圳大学 | 免疫受体调节剂偶联体及其制备方法和应用、制备其的偶联前体以及合成偶联前体的化合物 |
| EP2732825B1 (en) | 2012-11-19 | 2015-07-01 | Invivogen | Conjugates of a TLR7 and/or TLR8 agonist and a TLR2 agonist |
| EP2769738B1 (en) | 2013-02-22 | 2016-07-20 | Invivogen | Conjugated TLR7 and/or TLR8 and TLR2 polycationic agonists |
| US9295732B2 (en) | 2013-02-22 | 2016-03-29 | Invivogen | Conjugated TLR7 and/or TLR8 and TLR2 polycationic agonists |
| CN103467590B (zh) * | 2013-09-02 | 2016-04-13 | 深圳大学 | 生物偶联体、制备其的嘌呤类化合物、合成方法、药用制剂以及其在免疫调节中的应用 |
| PL3134402T3 (pl) | 2014-04-22 | 2020-11-02 | F.Hoffmann-La Roche Ag | Związki 4-amino-imidazochinolinowe |
| KR20160144399A (ko) * | 2014-05-01 | 2016-12-16 | 노파르티스 아게 | 톨-유사 수용체 7 효능제로서의 화합물 및 조성물 |
| KR20190104438A (ko) | 2014-07-11 | 2019-09-09 | 길리애드 사이언시즈, 인코포레이티드 | Hiv의 치료를 위한 톨-유사 수용체의 조정제 |
| CN106715431A (zh) | 2014-09-16 | 2017-05-24 | 吉利德科学公司 | Toll样受体调节剂的固体形式 |
| RS58356B1 (sr) | 2015-03-06 | 2019-03-29 | Hoffmann La Roche | Jedinjenja benzazepin dikarboksamida |
| WO2017046112A1 (en) | 2015-09-17 | 2017-03-23 | F. Hoffmann-La Roche Ag | Sulfinylphenyl or sulfonimidoylphenyl benzazepines |
| WO2017056494A1 (en) | 2015-09-29 | 2017-04-06 | Sumitomo Dainippon Pharma Co., Ltd. | Adenine conjugate compounds and their use as vaccine adjuvants |
| JP6769976B2 (ja) | 2015-10-07 | 2020-10-14 | 大日本住友製薬株式会社 | ピリミジン化合物 |
| CN109311854B (zh) | 2016-05-23 | 2021-08-10 | 豪夫迈·罗氏有限公司 | 具有仲酰胺官能团的苯并氮杂卓二甲酰胺化合物 |
| CN109153648B (zh) | 2016-05-23 | 2022-07-22 | 豪夫迈·罗氏有限公司 | 具有叔酰胺官能团的苯并氮杂卓二甲酰胺化合物 |
| CN109311851B (zh) | 2016-06-12 | 2021-08-10 | 豪夫迈·罗氏有限公司 | 二氢嘧啶基苯并氮杂䓬甲酰胺化合物 |
| CN106267188B (zh) * | 2016-08-15 | 2025-06-17 | 深圳大学 | 小分子免疫激动剂偶联pd-1抗体的新型抗体及其在抗肿瘤中的应用 |
| US10487084B2 (en) | 2017-08-16 | 2019-11-26 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a heterobiaryl moiety, conjugates thereof, and methods and uses therefor |
| US10472361B2 (en) | 2017-08-16 | 2019-11-12 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a benzotriazole moiety, conjugates thereof, and methods and uses therefor |
| US10494370B2 (en) * | 2017-08-16 | 2019-12-03 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor |
| US10457681B2 (en) * | 2017-08-16 | 2019-10-29 | Bristol_Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor |
| US10508115B2 (en) | 2017-08-16 | 2019-12-17 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor |
| CN111065636B (zh) * | 2017-09-22 | 2022-08-23 | 江苏恒瑞医药股份有限公司 | 稠合杂芳基衍生物、其制备方法及其在医药上的应用 |
| EP3707139B1 (en) * | 2017-11-06 | 2022-02-16 | Centre National de la Recherche Scientifique | Xanthine derivatives and uses thereof as inhibitors of bromodomains of bet proteins |
| AU2018391325B2 (en) | 2017-12-21 | 2024-07-11 | Axelia Oncology Pty Ltd | Optimised compounds |
| CN115192726A (zh) * | 2018-04-03 | 2022-10-18 | 深圳大学 | 免疫激动剂靶向化合物的合成及其应用 |
| WO2019209811A1 (en) | 2018-04-24 | 2019-10-31 | Bristol-Myers Squibb Company | Macrocyclic toll-like receptor 7 (tlr7) agonists |
| TW202011986A (zh) | 2018-07-23 | 2020-04-01 | 公益財團法人日本健康科學振興財團 | 包含流感疫苗之組合物 |
| US11554120B2 (en) | 2018-08-03 | 2023-01-17 | Bristol-Myers Squibb Company | 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists and methods and uses therefor |
| WO2020097398A1 (en) | 2018-11-07 | 2020-05-14 | Dana-Farber Cancer Institute, Inc. | Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof |
| KR102853071B1 (ko) * | 2019-02-07 | 2025-09-02 | 베이진 엘티디 | Tlr7 작용제로서의 이미다조[2,1-f][1,2,4]트리아진-4-아민 유도체 |
| CN113966326A (zh) * | 2019-04-05 | 2022-01-21 | 大日本住友制药株式会社 | 水溶性佐剂 |
| US20220241409A1 (en) | 2019-04-05 | 2022-08-04 | Sumitomo Dainippon Pharma Co., Ltd. | Water soluble adjuvant and composition containing same |
| WO2020237164A1 (en) | 2019-05-23 | 2020-11-26 | The University Of Montana | Vaccine adjuvants based on tlr receptor ligands |
| WO2020255038A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and pyridopyrimidine derivatives |
| EP3990428A4 (en) | 2019-06-26 | 2023-07-19 | ENA Respiratory Pty Ltd | NOVEL MOLECULES |
| JP7595643B2 (ja) * | 2019-08-02 | 2024-12-06 | ベイジーン リミテッド | Ｔｌｒ８アゴニストとしてのイミダゾ［２，１－ｆ］［１，２，４］トリアジン－４－アミン誘導体 |
| EP4013880A1 (en) | 2019-08-14 | 2022-06-22 | CureVac AG | Rna combinations and compositions with decreased immunostimulatory properties |
| EP4051387B1 (en) * | 2019-10-31 | 2025-02-19 | F. Hoffmann-La Roche AG | Hydropyrazino[1,2-d][1,4]diazepine compounds for the treatment of autoimmune disease |
| WO2021099284A1 (en) | 2019-11-19 | 2021-05-27 | F. Hoffmann-La Roche Ag | Hydro-1h-pyrrolo[1,2-a]pyrazine compounds for the treatment of autoimmune disease |
| JP7712942B2 (ja) | 2020-01-27 | 2025-07-24 | ブリストル－マイヤーズ スクイブ カンパニー | トール様受容体７（ＴＬＲ７）アゴニストとしての１Ｈ－ピラゾロ［４，３－ｄ］ピリミジン化合物 |
| KR20220132590A (ko) | 2020-01-27 | 2022-09-30 | 브리스톨-마이어스 스큅 컴퍼니 | 톨-유사 수용체 7 (TLR7) 효능제로서의 1H-피라졸로[4,3-d]피리미딘 화합물 |
| KR20220132593A (ko) | 2020-01-27 | 2022-09-30 | 브리스톨-마이어스 스큅 컴퍼니 | 톨-유사 수용체 7 (TLR7) 효능제로서의 1H-피라졸로[4,3-d]피리미딘 화합물 |
| US20230131192A1 (en) | 2020-01-27 | 2023-04-27 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| EP4097106A1 (en) | 2020-01-27 | 2022-12-07 | Bristol-Myers Squibb Company | 1h-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (tlr7) agonists |
| KR20220132602A (ko) | 2020-01-27 | 2022-09-30 | 브리스톨-마이어스 스큅 컴퍼니 | 톨-유사 수용체 7 (TLR7) 효능제로서의 1H-피라졸로[4,3-d]피리미딘 화합물 |
| JP7712941B2 (ja) | 2020-01-27 | 2025-07-24 | ブリストル－マイヤーズ スクイブ カンパニー | トール様受容体７（ＴＬＲ７）アゴニストとしての１Ｈ－ピラゾロ［４，３－ｄ］ピリミジン化合物 |
| CN115210235A (zh) | 2020-01-27 | 2022-10-18 | 百时美施贵宝公司 | 作为Toll样受体7(TLR7)激动剂的1H-吡唑并[4,3-d]嘧啶化合物 |
| CN115151546A (zh) | 2020-01-27 | 2022-10-04 | 百时美施贵宝公司 | 作为Toll样受体7(TLR7)激动剂的C3-取代的1H-吡唑并[4,3-d]嘧啶化合物 |
| WO2021168274A1 (en) | 2020-02-21 | 2021-08-26 | Silverback Therapeutics, Inc. | Nectin-4 antibody conjugates and uses thereof |
| CN111704614B (zh) | 2020-04-15 | 2021-10-22 | 深圳大学 | 一种系列免疫激动剂 |
| CA3181537A1 (en) | 2020-05-06 | 2021-11-11 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors |
| TW202216211A (zh) | 2020-07-01 | 2022-05-01 | 美商希沃爾拜克治療公司 | 抗asgr1抗體共軛物及其用途 |
| US20240124486A1 (en) * | 2020-09-27 | 2024-04-18 | Shanghai Visonpharma Co., Ltd. | Macrocyclic tlr7 agonist, preparation method therefor, pharmaceutical composition and use thereof |
| AU2021363606A1 (en) | 2020-10-21 | 2023-06-01 | Univerza V Ljubljani | Conjugated tlr7 and nod2 agonists |
| WO2022140527A1 (en) | 2020-12-23 | 2022-06-30 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors |
| JP7753397B2 (ja) | 2021-05-26 | 2025-10-14 | ノバルティス アーゲー | ウェルナー症候群ＲｅｃＱヘリカーゼ（ＷＲＮ）の阻害に関連する疾患を治療するためのトリアゾロ－ピリミジン類似体 |
| TW202334139A (zh) | 2021-11-09 | 2023-09-01 | 美商雅捷可斯治療公司 | 作為ｊａｋ２抑制劑之６－雜芳氧基苯并咪唑及氮雜苯并咪唑 |
| TW202325289A (zh) | 2021-11-09 | 2023-07-01 | 美商雅捷可斯治療公司 | Ｊａｋ２抑制劑之形式及組合物 |
| JP2025540756A (ja) * | 2022-12-05 | 2025-12-16 | 江蘇恒瑞医薬股▲ふん▼有限公司 | トリアゾール化合物、その製造方法と医薬的用途 |
| WO2024255765A1 (en) * | 2023-06-12 | 2024-12-19 | Nuphase Therapeutics (Hangzhou) Limited., Co. | Novel compounds, compositions comprising the same and uses thereof |
| WO2025040743A1 (en) | 2023-08-22 | 2025-02-27 | Univerza V Ljubljani | Conjugated tlr7 and rig-i agonists |
| WO2025093657A1 (en) | 2023-10-31 | 2025-05-08 | Univerza V Ljubljani | Conjugated tlr7 and tlr4 agonists |
| CN120424093A (zh) * | 2024-02-02 | 2025-08-05 | 中国科学院上海药物研究所 | 螺环类化合物、包含其的药物组合物及其用途 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007024707A2 (en) * | 2005-08-22 | 2007-03-01 | The Regents Of The University Of California | Tlr agonists |
| EP1939202A1 (en) * | 2005-09-22 | 2008-07-02 | Dainippon Sumitomo Pharma Co., Ltd. | Novel adenine compound |
| WO2008115319A2 (en) * | 2007-02-07 | 2008-09-25 | Regents Of The University Of California | Conjugates of synthetic tlr agonists and uses therefor |
| WO2009005687A1 (en) * | 2007-06-29 | 2009-01-08 | Gilead Sciences, Inc. | Purine derivatives and their use as modulators of toll-like receptor 7 |
Family Cites Families (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2699908A (en) | 1955-01-18 | fletcher | ||
| CA1271477A (en) | 1983-11-18 | 1990-07-10 | John F. Gerster | 1h-imidazo[4,5-c]quinolin-4-amines |
| IL73534A (en) * | 1983-11-18 | 1990-12-23 | Riker Laboratories Inc | 1h-imidazo(4,5-c)quinoline-4-amines,their preparation and pharmaceutical compositions containing certain such compounds |
| US4938949A (en) | 1988-09-12 | 1990-07-03 | University Of New York | Treatment of damaged bone marrow and dosage units therefor |
| US5736553A (en) * | 1988-12-15 | 1998-04-07 | Riker Laboratories, Inc. | Topical formulations and transdermal delivery systems containing 1-isobutyl-1H-imidazo 4,5-C!quinolin-4-amine |
| US5238944A (en) * | 1988-12-15 | 1993-08-24 | Riker Laboratories, Inc. | Topical formulations and transdermal delivery systems containing 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine |
| US5037986A (en) * | 1989-03-23 | 1991-08-06 | Minnesota Mining And Manufacturing Company | Olefinic 1H-imidazo[4,5-c]quinolin-4-amines |
| US4929624A (en) * | 1989-03-23 | 1990-05-29 | Minnesota Mining And Manufacturing Company | Olefinic 1H-imidazo(4,5-c)quinolin-4-amines |
| NZ232740A (en) | 1989-04-20 | 1992-06-25 | Riker Laboratories Inc | Solution for parenteral administration comprising a 1h-imidazo(4,5-c) quinolin-4-amine derivative, an acid and a tonicity adjuster |
| DE69108920T2 (de) * | 1990-10-05 | 1995-11-30 | Minnesota Mining And Mfg. Co., Saint Paul, Minn. | Verfahren zur herstellung von imidazo[4,5-c]chinolin-4-aminen. |
| US5175296A (en) * | 1991-03-01 | 1992-12-29 | Minnesota Mining And Manufacturing Company | Imidazo[4,5-c]quinolin-4-amines and processes for their preparation |
| IL105325A (en) | 1992-04-16 | 1996-11-14 | Minnesota Mining & Mfg | Immunogen/vaccine adjuvant composition |
| US5395937A (en) | 1993-01-29 | 1995-03-07 | Minnesota Mining And Manufacturing Company | Process for preparing quinoline amines |
| US5352784A (en) * | 1993-07-15 | 1994-10-04 | Minnesota Mining And Manufacturing Company | Fused cycloalkylimidazopyridines |
| US5648516A (en) * | 1994-07-20 | 1997-07-15 | Minnesota Mining And Manufacturing Company | Fused cycloalkylimidazopyridines |
| US5525606A (en) * | 1994-08-01 | 1996-06-11 | The United States Of America As Represented By The Department Of Health And Human Services | Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines |
| DE19505168A1 (de) * | 1995-02-16 | 1996-08-22 | Boehringer Mannheim Gmbh | Spezifische Lipidkonjugate von Nucleosid-Diphosphonaten und deren Verwendung als Arzneimittel |
| US5624677A (en) | 1995-06-13 | 1997-04-29 | Pentech Pharmaceuticals, Inc. | Controlled release of drugs delivered by sublingual or buccal administration |
| US5741908A (en) | 1996-06-21 | 1998-04-21 | Minnesota Mining And Manufacturing Company | Process for reparing imidazoquinolinamines |
| US5693811A (en) * | 1996-06-21 | 1997-12-02 | Minnesota Mining And Manufacturing Company | Process for preparing tetrahdroimidazoquinolinamines |
| DE19637209B4 (de) * | 1996-09-12 | 2006-12-14 | Siemens Ag | Verfahren zum Steuern des Antriebsstrangs eines Kraftfahrzeugs und integrierte Antriebsstrangsteuerung |
| IL129319A0 (en) | 1996-10-25 | 2000-02-17 | Minnesota Mining & Mfg | Immune response modifier compounds for treatment of TH2 mediated and related diseases |
| WO1999024432A1 (fr) * | 1997-11-12 | 1999-05-20 | Mitsubishi Chemical Corporation | Derives de purine et medicament les renfermant en tant qu'ingredient actif |
| KR100613634B1 (ko) | 1997-11-28 | 2006-08-18 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 신규한 복소환 화합물 |
| US7001609B1 (en) * | 1998-10-02 | 2006-02-21 | Regents Of The University Of Minnesota | Mucosal originated drug delivery systems and animal applications |
| SK287112B6 (sk) * | 1999-01-08 | 2009-12-07 | 3M Innovative Properties Company | Použitie zlúčeniny modifikujúcej imunitnú odpoveď pri liečení cervikálnej dysplázie |
| US20020058674A1 (en) * | 1999-01-08 | 2002-05-16 | Hedenstrom John C. | Systems and methods for treating a mucosal surface |
| US6486168B1 (en) * | 1999-01-08 | 2002-11-26 | 3M Innovative Properties Company | Formulations and methods for treatment of mucosal associated conditions with an immune response modifier |
| CZ27399A3 (cs) * | 1999-01-26 | 2000-08-16 | Ústav Experimentální Botaniky Av Čr | Substituované dusíkaté heterocyklické deriváty, způsob jejich přípravy, tyto deriváty pro použití jako léčiva, farmaceutická kompozice a kombinovaný farmaceutický přípravek tyto deriváty obsahující a použití těchto derivátů pro výrobu léčiv |
| EP1244668B1 (en) * | 2000-01-07 | 2006-04-05 | Universitaire Instelling Antwerpen | Purine derivatives, process for their preparation and use thereof |
| US6733764B2 (en) * | 2000-06-14 | 2004-05-11 | Alain Martin | Immunostimulator anti-cancer compounds and methods for their use in the treatment of cancer |
| WO2002023186A2 (en) * | 2000-09-15 | 2002-03-21 | Virco Bvba | System and method for optimizing drug therapy for the treatment of diseases |
| US20020127224A1 (en) * | 2001-03-02 | 2002-09-12 | James Chen | Use of photoluminescent nanoparticles for photodynamic therapy |
| PT1385823E (pt) * | 2001-04-09 | 2007-01-31 | Novartis Vaccines & Diagnostic | Compostos de guanidino como agonistas do receptor de melanocortina-4 (r-mc4) |
| JP4331944B2 (ja) * | 2001-04-17 | 2009-09-16 | 大日本住友製薬株式会社 | 新規アデニン誘導体 |
| KR100883292B1 (ko) * | 2001-06-29 | 2009-02-11 | 씨브이 쎄러퓨틱스, 인코포레이티드 | Ａ２ｂ 아데노신 수용체 길항제로서의 퓨린 유도체 |
| WO2003037860A2 (en) * | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
| TWI349671B (en) * | 2002-09-27 | 2011-10-01 | Dainippon Sumitomo Pharma Co | Novel adenine derivative and its use |
| WO2004066947A2 (en) | 2003-01-28 | 2004-08-12 | Shanghai Sunway Biotech Co., Ltd. | Hyperthermia oncolysis co-therapy |
| US20040265351A1 (en) * | 2003-04-10 | 2004-12-30 | Miller Richard L. | Methods and compositions for enhancing immune response |
| WO2005016235A2 (en) * | 2003-04-14 | 2005-02-24 | The Regents Of The University Of California | Combined use of impdh inhibitors with toll-like receptor agonists |
| US20050059613A1 (en) * | 2003-07-08 | 2005-03-17 | Bahram Memarzadeh | Compositions and methods for the enhanced uptake of therapeutic agents through the bladder epithelium |
| US20070161582A1 (en) * | 2003-08-08 | 2007-07-12 | Dusan Mijikovic | Pharmaceutical compositions and methods for metabolic modulation |
| WO2005025583A2 (en) * | 2003-09-05 | 2005-03-24 | Anadys Pharmaceuticals, Inc. | Tlr7 ligands for the treatment of hepatitis c |
| JP2005089334A (ja) | 2003-09-12 | 2005-04-07 | Sumitomo Pharmaceut Co Ltd | ８−ヒドロキシアデニン化合物 |
| US7138401B2 (en) * | 2003-09-18 | 2006-11-21 | Conforma Therapeutics Corporation | 2-aminopurine analogs having HSP90-inhibiting activity |
| FR2863890B1 (fr) * | 2003-12-19 | 2006-03-24 | Aventis Pasteur | Composition immunostimulante |
| EP1722762A2 (en) * | 2004-03-02 | 2006-11-22 | Massachusetts Institute of Technology | Nanocell drug delivery system |
| WO2005092893A1 (ja) * | 2004-03-26 | 2005-10-06 | Dainippon Sumitomo Pharma Co., Ltd. | ９置換−８−オキソアデニン化合物 |
| WO2006054129A1 (en) * | 2004-11-19 | 2006-05-26 | Institut Gustave Roussy | Improved treatment of cancer by double-stranded rna |
| WO2006100226A1 (en) | 2005-03-21 | 2006-09-28 | Ferrer Internacional, S. A. | Method for making 1-substituted 1h-imidazo[4,5-c]quinolin-4-amine compounds and intermediates therefor |
| US20070292418A1 (en) * | 2005-04-26 | 2007-12-20 | Eisai Co., Ltd. | Compositions and methods for immunotherapy |
| EP1939201A4 (en) | 2005-09-22 | 2010-06-16 | Dainippon Sumitomo Pharma Co | NEW ADENINE CONNECTION |
| EA200800943A1 (ru) | 2005-09-27 | 2008-12-30 | Коли Фармасьютикал Гмбх | Модуляция tlr-опосредуемых иммунных ответов с использованием олигонуклеотидов-адаптеров |
| US20070100146A1 (en) * | 2005-11-03 | 2007-05-03 | Trevor Dzwiniel | Process for the preparation of imidazo[4,5-c]-quinolin-4-amines |
| AU2007257423B8 (en) | 2006-05-31 | 2012-02-16 | The Regents Of The University Of California | Purine analogs |
| CA2656427C (en) * | 2006-07-07 | 2014-12-09 | Gilead Sciences, Inc. | Modulators of toll-like receptor 7 |
| CL2007002866A1 (es) * | 2006-10-04 | 2008-07-04 | Pharmacopeia Inc | Compuestos derivados de 6-sustituidos-2-(bencimidazolil) purina y purinona; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto en el tratamiento de enfermedades autoinmunes, enfermedad inflamatoria, enfermedad mediada por m |
| US7902187B2 (en) * | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| US20090099212A1 (en) * | 2007-10-16 | 2009-04-16 | Jeff Zablocki | A3 adenosine receptor antagonists |
| US20090202626A1 (en) | 2008-02-07 | 2009-08-13 | Carson Dennis A | Treatment of bladder diseases with a tlr7 activator |
| WO2010088924A1 (en) * | 2009-02-06 | 2010-08-12 | Telormedix Sa | Pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration |
| EP2607365A1 (en) | 2009-02-11 | 2013-06-26 | The Regents of The University of California | Toll-like receptor modulators and treatment of diseases |
| EA020488B1 (ru) * | 2009-10-22 | 2014-11-28 | Джилид Сайэнс, Инк. | Производные пурина или деазапурина для применения при лечении вирусных инфекций и других заболеваний |
| CN103118682A (zh) * | 2010-04-30 | 2013-05-22 | 加利福尼亚大学校务委员会 | 合成tlr7激动剂的磷脂缀合物的用途 |
| US20120003298A1 (en) * | 2010-04-30 | 2012-01-05 | Alcide Barberis | Methods for inducing an immune response |
| CN103221067B (zh) * | 2010-04-30 | 2016-01-06 | 泰勒麦迪克斯公司 | 磷脂药物类似物 |
| CN105999275A (zh) * | 2010-09-01 | 2016-10-12 | 诺华有限公司 | 免疫增强剂吸附不溶性金属离子 |
| US20120083473A1 (en) * | 2010-09-21 | 2012-04-05 | Johanna Holldack | Treatment of conditions by toll-like receptor modulators |
-
2010
- 2010-02-11 EP EP13001458.2A patent/EP2607365A1/en not_active Withdrawn
- 2010-02-11 EP EP10706399A patent/EP2396328A2/en not_active Withdrawn
- 2010-02-11 CA CA2752074A patent/CA2752074A1/en not_active Abandoned
- 2010-02-11 JP JP2011549168A patent/JP2012517428A/ja active Pending
- 2010-02-11 AU AU2010214112A patent/AU2010214112B2/en not_active Ceased
- 2010-02-11 SG SG2011057429A patent/SG173617A1/en unknown
- 2010-02-11 MX MX2011008500A patent/MX2011008500A/es active IP Right Grant
- 2010-02-11 BR BRPI1008383A patent/BRPI1008383A2/pt not_active IP Right Cessation
- 2010-02-11 KR KR1020117021190A patent/KR20110117705A/ko not_active Ceased
- 2010-02-11 US US12/704,343 patent/US8729088B2/en active Active
- 2010-02-11 WO PCT/US2010/000369 patent/WO2010093436A2/en not_active Ceased
- 2010-02-11 EA EA201101165A patent/EA019768B1/ru not_active IP Right Cessation
- 2010-02-11 CN CN201080016320.6A patent/CN102439011B/zh not_active Expired - Fee Related
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2011
- 2011-08-09 IL IL214572A patent/IL214572A/en not_active IP Right Cessation
- 2011-08-25 ZA ZA2011/06268A patent/ZA201106268B/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007024707A2 (en) * | 2005-08-22 | 2007-03-01 | The Regents Of The University Of California | Tlr agonists |
| EP1939202A1 (en) * | 2005-09-22 | 2008-07-02 | Dainippon Sumitomo Pharma Co., Ltd. | Novel adenine compound |
| WO2008115319A2 (en) * | 2007-02-07 | 2008-09-25 | Regents Of The University Of California | Conjugates of synthetic tlr agonists and uses therefor |
| WO2009005687A1 (en) * | 2007-06-29 | 2009-01-08 | Gilead Sciences, Inc. | Purine derivatives and their use as modulators of toll-like receptor 7 |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10947213B1 (en) | 2015-12-17 | 2021-03-16 | Merck Patent Gmbh | TLR7/8 antagonists and uses thereof |
| US11629134B2 (en) | 2015-12-17 | 2023-04-18 | Merck Patent Gmbh | TLR7/8 antagonists and uses thereof |
| US11697851B2 (en) | 2016-05-24 | 2023-07-11 | The Regents Of The University Of California | Early ovarian cancer detection diagnostic test based on mRNA isoforms |
| US11512069B2 (en) | 2016-08-08 | 2022-11-29 | Merck Patent Gmbh | TLR7/8 antagonists and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| IL214572A (en) | 2015-04-30 |
| CN102439011A (zh) | 2012-05-02 |
| EA201101165A1 (ru) | 2012-04-30 |
| US20100210598A1 (en) | 2010-08-19 |
| CN102439011B (zh) | 2016-05-04 |
| KR20110117705A (ko) | 2011-10-27 |
| ZA201106268B (en) | 2013-02-27 |
| CA2752074A1 (en) | 2010-08-19 |
| MX2011008500A (es) | 2011-09-26 |
| US8729088B2 (en) | 2014-05-20 |
| AU2010214112A1 (en) | 2011-09-01 |
| IL214572A0 (en) | 2011-09-27 |
| JP2012517428A (ja) | 2012-08-02 |
| BRPI1008383A2 (pt) | 2016-02-23 |
| EP2396328A2 (en) | 2011-12-21 |
| EP2607365A1 (en) | 2013-06-26 |
| WO2010093436A3 (en) | 2010-11-11 |
| AU2010214112B2 (en) | 2015-04-09 |
| WO2010093436A2 (en) | 2010-08-19 |
| SG173617A1 (en) | 2011-09-29 |
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