OA12264A - Tryasolyl tropane derivatives as CCR5 modulators. - Google Patents
Tryasolyl tropane derivatives as CCR5 modulators. Download PDFInfo
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- OA12264A OA12264A OA1200200343A OA1200200343A OA12264A OA 12264 A OA12264 A OA 12264A OA 1200200343 A OA1200200343 A OA 1200200343A OA 1200200343 A OA1200200343 A OA 1200200343A OA 12264 A OA12264 A OA 12264A
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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| EP1526134B1 (en) * | 2000-05-26 | 2008-09-03 | Pfizer Limited | Triazolyl tropane derivatives as ccr5 modulators |
| WO2002100848A1 (en) * | 2001-06-12 | 2002-12-19 | Sk Corporation | Novel phenylalkyl diamine and amide analogs |
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| ES2295924T3 (es) * | 2003-10-03 | 2008-04-16 | Pfizer, Inc. | Derivados de tropano imidazopirina sustituidos con actividad antagonista de los receptores ccr5 para el tratamiento de vih y de la inflamacion. |
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| EP1814549A2 (en) * | 2004-11-19 | 2007-08-08 | Boehringer Ingelheim International GmbH | Method for treating hiv infection through co-administration of tipranavir and uk-427, 857 |
| WO2006064340A2 (en) * | 2004-12-13 | 2006-06-22 | Pfizer Limited | Process for the preparation of n-acyl beta-aminoaldehydes |
| US7665658B2 (en) | 2005-06-07 | 2010-02-23 | First Data Corporation | Dynamic aggregation of payment transactions |
| EP1910573B1 (en) | 2005-07-22 | 2013-09-04 | CytoDyn, Inc. | Methods for reducing viral load in hiv-1-infected patients |
| EP1940781A1 (en) | 2005-10-19 | 2008-07-09 | F.Hoffmann-La Roche Ag | Phenyl-acetamide nnrt inhibitors |
| KR20090013827A (ko) * | 2006-06-12 | 2009-02-05 | 화이자 프로덕츠 인크. | Ｈｉｖ 환자에서 면역 재구성을 증진시키고 기회 감염을 치료하기 위한 ｃｃｒ５ 길항제 |
| DE602007013573D1 (de) | 2006-08-16 | 2011-05-12 | Hoffmann La Roche | Nicht-nukleosidische reverse-transkriptase-hemmer |
| WO2008063600A2 (en) * | 2006-11-17 | 2008-05-29 | Concert Pharmaceuticals Inc. | Triazolyl tropane derivatives |
| ES2550152T3 (es) | 2006-12-13 | 2015-11-04 | F. Hoffmann-La Roche Ag | Derivados de 2-(piperidin-4-il)-4-fenoxi-o fenilamino-pirimidina como inhibidores no nucleósidos de transcriptasa inversa |
| US20080146605A1 (en) * | 2006-12-19 | 2008-06-19 | Auspex Pharmaceuticals, Inc. | Preparation and utility of ccr5 inhibitors |
| EP1958947A1 (en) | 2007-02-15 | 2008-08-20 | Ranbaxy Laboratories Limited | Inhibitors of phosphodiesterase type 4 |
| WO2008132128A2 (en) * | 2007-04-27 | 2008-11-06 | Solvay (Société Anonyme) | Synthesis of a pharmaceutically active compound |
| RU2368613C1 (ru) * | 2008-02-19 | 2009-09-27 | Институт молекулярной генетики Российской Академии наук (ИМГ РАН) (Статус Государственного учреждения) | Равномерно меченный тритием 4,4-дифтор-n-{(1s)-3-[3-(3-изопропил-5-метил-4н-1,2,4-триазол-4-ил)-8-азабицикло[3.2.1]окт-8-ил]-1-фенилпропил}циклогексан карбодиимид |
| JP2011513317A (ja) * | 2008-02-29 | 2011-04-28 | シェーリング コーポレイション | Ｈｉｖ感染を防止するための予防薬としてのｃｃｒ５アンタゴニストおよびｈｉｖの伝播を抑制する方法 |
| CN101712679B (zh) * | 2008-10-08 | 2013-04-10 | 中国科学院上海药物研究所 | 一种酰胺类化合物、其药物组合物及其制备方法和用途 |
| JP5730871B2 (ja) * | 2009-07-24 | 2015-06-10 | グラクソスミスクライン エルエルシー | 治療化合物 |
| CN102140104B (zh) * | 2010-02-03 | 2014-11-12 | 中国科学院上海药物研究所 | 1-(3-(s)-氨基丙基)-哌啶-4-氨基酰胺类化合物、其药物组合物及其制备方法和用途 |
| MX2012011415A (es) | 2010-04-02 | 2013-02-26 | Phivco 1 Llc | Terapia de combinacion que comprende un antagonista de ccr5, un inhibidor de proteasa de vih-1, y un potenciador farmacocinetico. |
| CN103159754A (zh) * | 2011-12-19 | 2013-06-19 | 中国科学院上海药物研究所 | 一种氨基丙基取代托烷胺类化合物、其药物组合物及其制备方法和用途 |
| US9227990B2 (en) | 2012-10-29 | 2016-01-05 | Cipla Limited | Antiviral phosphonate analogues and process for preparation thereof |
| CZ306455B6 (cs) | 2013-04-26 | 2017-02-01 | Zentiva, K.S. | Nový způsob syntézy Maravirocu |
| CN103497164B (zh) * | 2013-09-23 | 2015-12-23 | 西安近代化学研究所 | 一种蒽衍生物及其制备方法 |
| CN104304248B (zh) * | 2014-10-23 | 2016-08-10 | 西北农林科技大学 | 3-芳基丙酸酯类化合物作为制备杀螨药物的应用 |
| CN104402883B (zh) * | 2014-10-24 | 2016-04-27 | 艾琪康医药科技（上海）有限公司 | 4，4-二氟金刚烷甲酰胺衍生物、药物组合物及其制备方法和用途 |
| CN104387379B (zh) * | 2014-11-26 | 2017-01-11 | 扬州氟药科技有限公司 | 一种二氟亚甲基哌啶甲酰胺衍生物及其制备方法和用途 |
| CN104860946A (zh) * | 2015-05-14 | 2015-08-26 | 湖北生物医药产业技术研究院有限公司 | Ccr5拮抗剂的制备方法 |
| CN107879963A (zh) * | 2016-09-29 | 2018-04-06 | 中国科学院上海药物研究所 | 新型手性配体、金属螯合物、多种非天然氨基酸、马拉维诺及其关键中间体的合成方法 |
| US11629196B2 (en) | 2020-04-27 | 2023-04-18 | Incelldx, Inc. | Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
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| FR2676444B1 (fr) * | 1991-05-16 | 1995-03-10 | Sanofi Elf | Nouveaux derives d'amino-3 pyridazines actifs sur le systeme nerveux central, procede de preparation et compositions pharmaceutiques en contenant. |
| GB9310713D0 (en) * | 1993-05-24 | 1993-07-07 | Zeneca Ltd | Aryl substituted heterocycles |
| CN1043763C (zh) * | 1994-04-19 | 1999-06-23 | 纽罗研究公司 | 莨菪烷衍生物及其制备方法和应用 |
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| DE19546462A1 (de) * | 1995-12-13 | 1997-06-19 | Bayer Ag | Diarylacetylenketone |
| WO1997024325A1 (en) * | 1995-12-28 | 1997-07-10 | Takeda Chemical Industries, Ltd. | DIPHENYLMETHANE DERIVATIVES AS MIP-1α/RANTES RECEPTOR ANTAGONISTS |
| US6323206B1 (en) * | 1996-07-12 | 2001-11-27 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| JP2000516210A (ja) * | 1996-07-12 | 2000-12-05 | ロイコサイト，インコーポレーテッド | ケモカインレセプターアンタゴニストとその使用方法 |
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| WO1998025604A1 (en) * | 1996-12-13 | 1998-06-18 | Merck & Co., Inc. | Spiro-substituted azacycles as modulators of chemokine receptor activity |
| GB9711643D0 (en) | 1997-06-05 | 1997-07-30 | Janssen Pharmaceutica Nv | Glass thermoplastic systems |
| EP1003514A4 (en) * | 1997-07-25 | 2000-10-11 | Merck & Co Inc | CYCLIC AMINE MODULATORS OF CHEMOKIN RECEPTORS |
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| AR013669A1 (es) * | 1997-10-07 | 2001-01-10 | Smithkline Beecham Corp | Compuestos y metodos |
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| US7217714B1 (en) * | 1998-12-23 | 2007-05-15 | Agouron Pharmaceuticals, Inc. | CCR5 modulators |
| EP1013276A1 (en) | 1998-12-23 | 2000-06-28 | Pfizer Inc. | Aminoazacycloalkanes as CCR5 modulators |
| PE20001420A1 (es) * | 1998-12-23 | 2000-12-18 | Pfizer | Moduladores de ccr5 |
| EP1526134B1 (en) * | 2000-05-26 | 2008-09-03 | Pfizer Limited | Triazolyl tropane derivatives as ccr5 modulators |
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2008
- 2008-02-22 NL NL300338C patent/NL300338I2/nl unknown
- 2008-02-22 LU LU91417C patent/LU91417I2/fr unknown
- 2008-02-25 LT LTPA2008004C patent/LTC1284974I2/lt unknown
- 2008-03-04 FR FR08C0007C patent/FR08C0007I2/fr active Active
- 2008-03-17 CY CY200800006C patent/CY2008006I1/el unknown
- 2008-07-16 CR CR10145A patent/CR10145A/es unknown
- 2008-10-24 CY CY081101203T patent/CY1108451T1/el unknown
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2010
- 2010-04-08 NO NO2010007C patent/NO2010007I2/no unknown
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2020
- 2020-06-30 NO NO2020019C patent/NO2020019I1/no not_active IP Right Cessation
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2022
- 2022-04-19 CY CY2022009C patent/CY2022009I1/el unknown
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