CN103038245B - 作为hiv成熟抑制剂的c-3经修饰的桦木酸衍生物 - Google Patents
作为hiv成熟抑制剂的c-3经修饰的桦木酸衍生物 Download PDFInfo
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- CN103038245B CN103038245B CN201180038211.9A CN201180038211A CN103038245B CN 103038245 B CN103038245 B CN 103038245B CN 201180038211 A CN201180038211 A CN 201180038211A CN 103038245 B CN103038245 B CN 103038245B
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- acid
- pentamethyl
- alkene
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- 150000003839 salts Chemical class 0.000 claims description 20
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- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
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- 229910052796 boron Inorganic materials 0.000 description 18
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 229940094989 trimethylsilane Drugs 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35133810P | 2010-06-04 | 2010-06-04 | |
| US61/351,338 | 2010-06-04 | ||
| PCT/US2011/038879 WO2011153315A1 (en) | 2010-06-04 | 2011-06-02 | Modified c-3 betulinic acid derivatives as hiv maturation inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103038245A CN103038245A (zh) | 2013-04-10 |
| CN103038245B true CN103038245B (zh) | 2015-03-25 |
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Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8754068B2 (enExample) |
| EP (1) | EP2576585B8 (enExample) |
| JP (1) | JP5752789B2 (enExample) |
| CN (1) | CN103038245B (enExample) |
| AR (1) | AR081637A1 (enExample) |
| BR (1) | BR112012030818A2 (enExample) |
| CA (1) | CA2801487C (enExample) |
| EA (1) | EA022393B1 (enExample) |
| ES (1) | ES2612452T3 (enExample) |
| MX (1) | MX2012013703A (enExample) |
| TW (1) | TW201201793A (enExample) |
| WO (1) | WO2011153315A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11090313B2 (en) | 2010-05-20 | 2021-08-17 | University Of Iowa Research Foundation | Methods for inhibiting muscle atrophy |
| CN103037692B (zh) | 2010-05-20 | 2015-02-25 | 爱荷华大学研究基金会 | 用于抑制肌萎缩的方法 |
| ES2653847T3 (es) * | 2011-01-31 | 2018-02-09 | Viiv Healthcare Uk (No. 4) Limited | Triterpenoides C-17 y C-3 modificados con actividad inhibitoria contra maduración del VIH |
| CN103339141B (zh) * | 2011-01-31 | 2016-08-24 | 百时美施贵宝公司 | 作为hiv成熟抑制剂的c-3修饰的桦木酸衍生物的c-28胺 |
| US9295664B2 (en) | 2011-06-06 | 2016-03-29 | University Of Iowa Research Foundation | Methods for lowering blood glucose |
| ES2611727T3 (es) | 2011-09-21 | 2017-05-10 | VIIV Healthcare UK (No.5) Limited | Derivados de ácido betulínico novedosos con actividad antivírica |
| US8906889B2 (en) * | 2012-02-15 | 2014-12-09 | Bristol-Myers Squibb Company | C-3 cycloalkenyl triterpenoids with HIV maturation inhibitory activity |
| US8889854B2 (en) | 2012-05-07 | 2014-11-18 | Bristol-Myers Squibb Company | C-17 bicyclic amines of triterpenoids with HIV maturation inhibitory activity |
| WO2014105926A1 (en) | 2012-12-31 | 2014-07-03 | Hetero Research Foundation | Novel betulinic acid proline derivatives as hiv inhibitors |
| JP6186010B2 (ja) * | 2013-02-06 | 2017-08-23 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｈｉｖ成熟阻害活性を有するｃ−１９修飾トリテルペノイド類 |
| KR20150121712A (ko) * | 2013-02-25 | 2015-10-29 | 브리스톨-마이어스 스큅 컴퍼니 | Hiv의 치료에 유용한 c-3 알킬 및 알케닐 개질된 베툴린산 유도체 |
| MA39374A1 (fr) | 2014-04-11 | 2018-06-29 | Viiv Healthcare Uk No 4 Ltd | Triterpénoïdes présentant une activité d'inhibition de la maturation du vih, substitués en 3ème position par un cycle non aromatique portant un substituant halogénoalkyle |
| WO2015195776A1 (en) | 2014-06-19 | 2015-12-23 | Bristol-Myers Squibb Company | Betulinic acid derivatives with hiv maturation inhibitory activity |
| US20170129916A1 (en) | 2014-06-26 | 2017-05-11 | Hetero Research Foundation | Novel betulinic proline imidazole derivatives as hiv inhibitors |
| BR112017009850A2 (pt) * | 2014-11-14 | 2018-01-16 | Viiv Healthcare Uk No 5 Ltd | composto, composição, e, uso de uma quantidade melhoradora de hiv de um composto |
| WO2016077572A1 (en) * | 2014-11-14 | 2016-05-19 | Bristol-Myers Squibb Company | Extended betulinic acid analogs |
| RU2017118576A (ru) | 2014-11-14 | 2018-12-14 | ВАЙВ ХЕЛТКЕР ЮКей (N5) ЛИМИТЕД | C-17-арил-замещённые аналоги бетулиновой кислоты |
| MA40886B1 (fr) | 2015-02-09 | 2020-03-31 | Hetero Research Foundation | Nouveau triterpénone en c-3 avec des dérivés d'amide inverse en c-28 en tant qu'inhibiteurs du vih |
| WO2016147099A2 (en) | 2015-03-16 | 2016-09-22 | Hetero Research Foundation | C-3 novel triterpenone with c-28 amide derivatives as hiv inhibitors |
| KR20180028534A (ko) | 2015-07-28 | 2018-03-16 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | Hiv 감염을 예방하거나 치료하기 위한 베투인 유도체 |
| RU2018105352A (ru) | 2015-07-28 | 2019-08-29 | ГлаксоСмитКлайн Интеллекчуал Проперти (N2) Лимитед | Производные бетулина для предупреждения или лечения ВИЧ-инфекций |
| CN108368071A (zh) | 2015-09-24 | 2018-08-03 | 葛兰素史克知识产权第二有限公司 | 具有hiv成熟抑制活性的化合物 |
| CN108699103A (zh) | 2016-01-20 | 2018-10-23 | 葛兰素史克知识产权第二有限公司 | 具有hiv成熟抑制活性的羽扇烷类的胺衍生物 |
| AR107512A1 (es) | 2016-02-04 | 2018-05-09 | VIIV HEALTHCARE UK Nº 5 LTD | Triterpenoides modificados en c-3 y c-17 como inhibidores del vih-1 |
| EP3478661A1 (en) * | 2016-06-30 | 2019-05-08 | ViiV Healthcare UK (No.5) Limited | Aza-substituted inhibitors of human immunodeficiency virus replication |
| EP3478703A1 (en) * | 2016-06-30 | 2019-05-08 | ViiV Healthcare UK (No.5) Limited | Triterpenoid inhibitors of human immunodeficiency virus replication |
| US10493070B2 (en) | 2016-06-30 | 2019-12-03 | Viiv Healthcare Uk (No. 5) Limited | Azadecalin derivatives as inhibitors of human immunodeficiency virus replication |
| WO2019207460A1 (en) | 2018-04-24 | 2019-10-31 | VIIV Healthcare UK (No.5) Limited | Compounds with hiv maturation inhibitory activity |
| PL237998B1 (pl) | 2018-05-28 | 2021-06-28 | Narodowy Inst Lekow | Fosfonowe pochodne kwasu 3-karboksyacylobetulinowego, sposób ich otrzymywania oraz ich zastosowanie |
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| WO1999045025A1 (en) * | 1998-03-02 | 1999-09-10 | The University Of North Carolina At Chapel Hill | Acylated betulin and dihydrobetulin derivatives, preparation thereof and use thereof |
| WO2005112929A2 (en) * | 2004-05-20 | 2005-12-01 | Cornell Research Foundation, Inc. | Anti-hiv-1 activity of betulinol derivatives |
| CN1747964A (zh) * | 2003-02-11 | 2006-03-15 | 诺瓦利克斯制药公司 | 抑制肿瘤生长的药物 |
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| US5413999A (en) | 1991-11-08 | 1995-05-09 | Merck & Co., Inc. | HIV protease inhibitors useful for the treatment of AIDS |
| US5962527A (en) | 1995-03-21 | 1999-10-05 | The Board Of Trustees Of The University Of Illinois | Method and composition for treating cancers |
| US5869535A (en) | 1995-03-21 | 1999-02-09 | The Board Of Trustees Of The University Of Illinois | Method and composition for selectively inhibiting melanoma |
| US5679828A (en) * | 1995-06-05 | 1997-10-21 | Biotech Research Labs, Inc. | Betulinic acid and dihydrobetulinic acid derivatives and uses therefor |
| US20040110785A1 (en) | 2001-02-02 | 2004-06-10 | Tao Wang | Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives |
| US7365221B2 (en) | 2002-09-26 | 2008-04-29 | Panacos Pharmaceuticals, Inc. | Monoacylated betulin and dihydrobetulin derivatives, preparation thereof and use thereof |
| NZ538896A (en) * | 2002-09-26 | 2007-10-26 | Niigata University Of Pharmacy | Monoacylated betulin and dihydrobetulin derivatives, preparation thereof and use thereof |
| WO2004089357A2 (en) | 2003-04-02 | 2004-10-21 | Regents Of The University Of Minnesota | Anti-fungal formulation of triterpene and essential oil |
| US7745625B2 (en) | 2004-03-15 | 2010-06-29 | Bristol-Myers Squibb Company | Prodrugs of piperazine and substituted piperidine antiviral agents |
| JP2007529544A (ja) * | 2004-03-17 | 2007-10-25 | パナコス ファーマシューティカルズ， インコーポレイテッド | ３−ｏ−（３’，３’−ジメチルスクシニル）ベツリン酸の製薬的な塩 |
| TW200628161A (en) * | 2004-11-12 | 2006-08-16 | Panacos Pharmaceuticals Inc | Novel betulin derivatives, preparation thereof and use thereof |
| EP1986654A2 (en) * | 2006-02-21 | 2008-11-05 | Achillion Pharmaceuticals, Inc. | Substituted taraxastanes useful for treating viral infections |
| WO2008127364A2 (en) | 2006-10-13 | 2008-10-23 | Myriad Genetics, Inc. | Antiviral compounds and use thereof |
| US20110144069A1 (en) | 2006-10-16 | 2011-06-16 | Myriad Genetics, Incorporated | Compounds for treating viral infections |
| US20090062243A1 (en) * | 2007-08-03 | 2009-03-05 | Advanced Life Sciences, Inc. | Lupane-Type Triterpenoids Modified at 30-Position and Analogues Thereof |
| WO2009042166A1 (en) | 2007-09-25 | 2009-04-02 | Panacos Pharmaceuticals, Inc. | Liquid bevirimat dosage forms for oral administration |
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| KR20120138761A (ko) * | 2010-02-11 | 2012-12-26 | 글락소스미스클라인 엘엘씨 | 베툴린의 유도체 |
-
2011
- 2011-06-02 ES ES11726563.7T patent/ES2612452T3/es active Active
- 2011-06-02 CN CN201180038211.9A patent/CN103038245B/zh not_active Expired - Fee Related
- 2011-06-02 MX MX2012013703A patent/MX2012013703A/es active IP Right Grant
- 2011-06-02 JP JP2013513339A patent/JP5752789B2/ja not_active Expired - Fee Related
- 2011-06-02 EP EP11726563.7A patent/EP2576585B8/en not_active Not-in-force
- 2011-06-02 US US13/151,706 patent/US8754068B2/en not_active Expired - Fee Related
- 2011-06-02 CA CA2801487A patent/CA2801487C/en not_active Expired - Fee Related
- 2011-06-02 EA EA201270780A patent/EA022393B1/ru not_active IP Right Cessation
- 2011-06-02 BR BR112012030818A patent/BR112012030818A2/pt not_active IP Right Cessation
- 2011-06-02 WO PCT/US2011/038879 patent/WO2011153315A1/en not_active Ceased
- 2011-06-03 TW TW100119644A patent/TW201201793A/zh unknown
- 2011-06-03 AR ARP110101944A patent/AR081637A1/es not_active Application Discontinuation
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| WO1999045025A1 (en) * | 1998-03-02 | 1999-09-10 | The University Of North Carolina At Chapel Hill | Acylated betulin and dihydrobetulin derivatives, preparation thereof and use thereof |
| CN1747964A (zh) * | 2003-02-11 | 2006-03-15 | 诺瓦利克斯制药公司 | 抑制肿瘤生长的药物 |
| WO2005112929A2 (en) * | 2004-05-20 | 2005-12-01 | Cornell Research Foundation, Inc. | Anti-hiv-1 activity of betulinol derivatives |
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| Synthesis and Anti-HIV Activity of Oleanolic Acid Derivatives;Yong-Ming Zhu,et al.;《Bioorganic & Medicinal Chemistry Letters》;20011231;第11卷;3115–3118 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013527242A (ja) | 2013-06-27 |
| EP2576585A1 (en) | 2013-04-10 |
| EA201270780A1 (ru) | 2013-04-30 |
| WO2011153315A1 (en) | 2011-12-08 |
| EA022393B1 (ru) | 2015-12-30 |
| CA2801487C (en) | 2017-12-05 |
| US20120142707A1 (en) | 2012-06-07 |
| AR081637A1 (es) | 2012-10-10 |
| US8754068B2 (en) | 2014-06-17 |
| JP5752789B2 (ja) | 2015-07-22 |
| TW201201793A (en) | 2012-01-16 |
| EP2576585B8 (en) | 2016-12-21 |
| ES2612452T3 (es) | 2017-05-17 |
| EP2576585B1 (en) | 2016-10-12 |
| MX2012013703A (es) | 2012-12-17 |
| CN103038245A (zh) | 2013-04-10 |
| BR112012030818A2 (pt) | 2019-09-24 |
| CA2801487A1 (en) | 2011-12-08 |
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