JP2006512339A - Ｃｃｒ５アンタゴニストとしてのインダン化合物 - Google Patents
Ｃｃｒ５アンタゴニストとしてのインダン化合物 Download PDFInfo
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- JP2006512339A JP2006512339A JP2004560887A JP2004560887A JP2006512339A JP 2006512339 A JP2006512339 A JP 2006512339A JP 2004560887 A JP2004560887 A JP 2004560887A JP 2004560887 A JP2004560887 A JP 2004560887A JP 2006512339 A JP2006512339 A JP 2006512339A
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/28—Radicals substituted by nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D471/10—Spiro-condensed systems
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| US43337802P | 2002-12-13 | 2002-12-13 | |
| PCT/US2003/039975 WO2004055012A1 (en) | 2002-12-13 | 2003-12-12 | Indane compounds as ccr5 antagonists |
Publications (2)
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| JP2006512339A true JP2006512339A (ja) | 2006-04-13 |
| JP2006512339A5 JP2006512339A5 (enExample) | 2007-01-11 |
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| EP (1) | EP1581530A1 (enExample) |
| JP (1) | JP2006512339A (enExample) |
| AU (1) | AU2003300952A1 (enExample) |
| WO (1) | WO2004055012A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE484509T1 (de) | 2004-08-02 | 2010-10-15 | Glaxo Group Ltd | Antibakterielle mittel |
| WO2008030853A2 (en) * | 2006-09-06 | 2008-03-13 | Incyte Corporation | Combination therapy for human immunodeficiency virus infection |
| CN102176911B (zh) | 2008-08-11 | 2014-12-10 | 葛兰素史密丝克莱恩有限责任公司 | 新的腺嘌呤衍生物 |
| KR20110042116A (ko) | 2008-08-11 | 2011-04-22 | 글락소스미스클라인 엘엘씨 | 알레르기성, 염증성 및 감염성 질환의 치료에서 사용하기 위한 푸린 유도체 |
| UA103195C2 (uk) | 2008-08-11 | 2013-09-25 | Глаксосмитклайн Ллк | Похідні пурину для застосування у лікуванні алергій, запальних та інфекційних захворювань |
| WO2011098451A1 (en) | 2010-02-10 | 2011-08-18 | Glaxosmithkline Llc | Purine derivatives and their pharmaceutical uses |
| BR112012018904A2 (pt) | 2010-02-10 | 2020-09-01 | Glaxosmithkline Llc | composto, adjuvante de vacina, composições imunogênica, de vacina e farmacêutica, e uso de um composto" |
| JO3387B1 (ar) | 2011-12-16 | 2019-03-13 | Glaxosmithkline Llc | مشتقات بيتولين |
| CN104812246B (zh) | 2012-09-28 | 2020-06-23 | 美国陶氏益农公司 | 来自施用环丙嘧啶酸和氯氨吡啶酸的协同杂草控制 |
| CA2895041C (en) | 2012-12-14 | 2021-02-02 | Dow Agrosciences Llc | Synergistic weed control from applications of aminopyralid and clopyralid |
| US10412964B2 (en) | 2012-12-14 | 2019-09-17 | Dow Agrosciences Llc | Synergistic weed control from applications of aminopyralid and clopyralid |
| WO2015124591A1 (en) | 2014-02-20 | 2015-08-27 | Glaxosmithkline Intellectual Property (No.2) Limited | Pyrrolo[3,2] pyrimidine derivatives as inducers of human interferon |
| US10584125B2 (en) | 2014-11-13 | 2020-03-10 | Glaxosmithkline Biologicals Sa | Adenine derivatives which are useful in the treatment of allergic diseases or other inflammatory conditions |
| RU2020113165A (ru) | 2015-12-03 | 2020-06-09 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Циклические пуриновые динуклеотиды в качестве модуляторов sting |
| CN113549110B (zh) | 2016-04-07 | 2024-08-16 | 葛兰素史密斯克莱知识产权发展有限公司 | 用作蛋白质调节剂的杂环酰胺 |
| JP2019510802A (ja) | 2016-04-07 | 2019-04-18 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | タンパク質調節物質として有用な複素環アミド |
| JP2020536106A (ja) | 2017-10-05 | 2020-12-10 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | Ｈｉｖの処置に有用なインターフェロン遺伝子の刺激物質（ｓｔｉｎｇ）の調節物質 |
| BR112020006780A2 (pt) | 2017-10-05 | 2020-10-06 | Glaxosmithkline Intellectual Property Development Limited | moduladores do estimulador de genes do interferon (sting) |
| GB201807924D0 (en) | 2018-05-16 | 2018-06-27 | Ctxt Pty Ltd | Compounds |
| CN109593089B (zh) * | 2019-01-24 | 2022-01-28 | 西南大学 | 二氮杂螺癸烷哌啶甲酰胺类化合物制备和应用 |
| EP3969452A1 (en) | 2019-05-16 | 2022-03-23 | Stingthera, Inc. | Benzo[b][1,8]naphthyridine acetic acid derivatives and methods of use |
| JP2022533390A (ja) | 2019-05-16 | 2022-07-22 | スティングセラ インコーポレイテッド | オキソアクリジニル酢酸誘導体および使用方法 |
| GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| CN114981265B (zh) | 2019-12-18 | 2025-01-03 | Ctxt私人有限公司 | 化合物 |
| US11116737B1 (en) | 2020-04-10 | 2021-09-14 | University Of Georgia Research Foundation, Inc. | Methods of using probenecid for treatment of coronavirus infections |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001058992A (ja) * | 1999-06-16 | 2001-03-06 | Takeda Chem Ind Ltd | ベンゾアゼピン誘導体、その製造法および用途 |
| JP2001058988A (ja) * | 1998-12-21 | 2001-03-06 | Takeda Chem Ind Ltd | アニリド誘導体、その製造法および用途 |
| WO2001042208A1 (en) * | 1999-12-08 | 2001-06-14 | Teijin Limited | Cycloamine ccr5 receptor antagonists |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5301599A (en) | 1998-08-20 | 2000-03-14 | Takeda Chemical Industries Ltd. | Quaternary ammonium salts and their use |
| KR100503161B1 (ko) | 2002-07-18 | 2005-07-25 | 한미약품 주식회사 | 신규한 ｐ-당단백질 저해제, 그의 제조방법 및 이를유효성분으로 하는 경구투여용 조성물 |
-
2003
- 2003-12-12 AU AU2003300952A patent/AU2003300952A1/en not_active Abandoned
- 2003-12-12 JP JP2004560887A patent/JP2006512339A/ja active Pending
- 2003-12-12 WO PCT/US2003/039975 patent/WO2004055012A1/en not_active Ceased
- 2003-12-12 US US10/538,183 patent/US7531661B2/en not_active Expired - Fee Related
- 2003-12-12 EP EP03813460A patent/EP1581530A1/en not_active Withdrawn
-
2009
- 2009-04-01 US US12/416,178 patent/US7589204B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001058988A (ja) * | 1998-12-21 | 2001-03-06 | Takeda Chem Ind Ltd | アニリド誘導体、その製造法および用途 |
| JP2001058992A (ja) * | 1999-06-16 | 2001-03-06 | Takeda Chem Ind Ltd | ベンゾアゼピン誘導体、その製造法および用途 |
| WO2001042208A1 (en) * | 1999-12-08 | 2001-06-14 | Teijin Limited | Cycloamine ccr5 receptor antagonists |
Non-Patent Citations (1)
| Title |
|---|
| JPN6010036229, Ｔｏｘｉｃｏｌｏｇｉｃａｌ Ｓｃｉｅｎｃｅ, 2001, ６４, １６２−１６８ * |
Also Published As
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| AU2003300952A1 (en) | 2004-07-09 |
| US7589204B2 (en) | 2009-09-15 |
| US20090187021A1 (en) | 2009-07-23 |
| EP1581530A1 (en) | 2005-10-05 |
| US7531661B2 (en) | 2009-05-12 |
| WO2004055012A1 (en) | 2004-07-01 |
| US20060047116A1 (en) | 2006-03-02 |
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