JP2006507329A - 新規アリールウレイド安息香酸誘導体及びその使用 - Google Patents
新規アリールウレイド安息香酸誘導体及びその使用 Download PDFInfo
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- JP2006507329A JP2006507329A JP2004552424A JP2004552424A JP2006507329A JP 2006507329 A JP2006507329 A JP 2006507329A JP 2004552424 A JP2004552424 A JP 2004552424A JP 2004552424 A JP2004552424 A JP 2004552424A JP 2006507329 A JP2006507329 A JP 2006507329A
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- alkyl
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008519761A (ja) * | 2004-11-09 | 2008-06-12 | スミスクライン ビーチャム コーポレーション | グリコーゲンホスホリラーゼ阻害化合物およびその医薬組成物 |
| JP2019520359A (ja) * | 2016-06-22 | 2019-07-18 | フーダン ユニヴァーシティFudan University | ビアリール尿素誘導体またはそれらの塩、およびそれらの調製方法および使用 |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102004005172A1 (de) | 2004-02-02 | 2005-08-18 | Aventis Pharma Deutschland Gmbh | Indazolderivate als Inhibitoren der Hormon Sensitiven Lipase |
| US7550499B2 (en) | 2004-05-12 | 2009-06-23 | Bristol-Myers Squibb Company | Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
| FR2878522B1 (fr) * | 2004-12-01 | 2008-04-18 | Merck Sante Soc Par Actions Si | Nouveaux inhibiteurs specifiques de la caspas-10 |
| CN101287456A (zh) * | 2004-12-17 | 2008-10-15 | 神经研究公司 | 用作钾通道激活剂的二苯基脲衍生物 |
| AU2006206611A1 (en) | 2005-01-19 | 2006-07-27 | Bristol-Myers Squibb Company | 2-phenoxy-N- (1, 3 , 4-thiadizol-2-yl) pyridin-3-amine derivatives and related compounds as P2Y1 receptor inhibitors for the treatment of thromboembolic disorders |
| EP1899299B1 (en) | 2005-06-27 | 2010-10-20 | Bristol-Myers Squibb Company | C-linked cyclic antagonists of p2y1 receptor useful in the treatment of thrombotic conditions |
| ES2360818T3 (es) | 2005-06-27 | 2011-06-09 | Bristol-Myers Squibb Company | Miméticos de urea lineal antagonistas del receptor p2y, útiles en el tratamiento de afecciones trombóticas. |
| US7714002B2 (en) | 2005-06-27 | 2010-05-11 | Bristol-Myers Squibb Company | Carbocycle and heterocycle antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
| MX2007016501A (es) | 2005-06-27 | 2008-03-06 | Squibb Bristol Myers Co | Antagonistas heterociclicos n-enlazados del receptor de p2y1, utiles en el tratamiento de condiciones tromboticas. |
| WO2007044724A2 (en) * | 2005-10-06 | 2007-04-19 | Exelixis, Inc. | Aminopyrimidine, aminopyridine and aniline derivatives inhibitors of pim-i and/or pim-3 |
| WO2007104719A1 (en) * | 2006-03-14 | 2007-09-20 | Neurosearch A/S | Diphenylurea derivatives and their use as chloride channel blockers or bkca channel modulators |
| US7960569B2 (en) | 2006-10-17 | 2011-06-14 | Bristol-Myers Squibb Company | Indole antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
| DE102007012908A1 (de) | 2007-03-19 | 2008-09-25 | Momentive Performance Materials Gmbh | Neue Polyamid-Polysiloxan-Verbindungen |
| AU2008309003A1 (en) * | 2007-09-28 | 2009-04-09 | Glaxosmithkline Llc | Glycogen phosphorylase inhibitor compound and pharmaceutical composition thereof |
| US20100292283A1 (en) * | 2007-11-28 | 2010-11-18 | Antonio Nardi | Novel phenyl-acetamide and phenyl-propionamide derivatives useful as potassium channel modulators |
| WO2011053468A1 (en) * | 2009-10-30 | 2011-05-05 | Sanofi-Aventis | Amino-benzoic acid derivatives for use in the treatment of dihydrogenase-related disorders |
| US10899702B2 (en) * | 2015-02-07 | 2021-01-26 | University of Pittsburgh—of the Commonwealth System of Higher Education | HTRPVI chemical agents |
| CN106008371A (zh) * | 2016-06-24 | 2016-10-12 | 谢阳 | 1-芳基脲基环烷基-1-甲酰胺类化合物及其药物组合物和应用 |
| CN106946786A (zh) * | 2017-04-11 | 2017-07-14 | 白银澐新生物科技有限公司 | 一种1‑苄基‑3‑羟基‑1h‑3‑吲唑钠盐的制备方法 |
| CN111116420B (zh) * | 2019-12-31 | 2022-01-14 | 浙江工业大学 | 一种对称脲类化合物的制备方法 |
| CN114539080A (zh) * | 2022-03-02 | 2022-05-27 | 八叶草健康产业研究院(厦门)有限公司 | 一种2-(2-氨基-6-氯苯基)-乙酸钠的制备方法 |
Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH220682A (de) * | 1940-02-05 | 1942-04-30 | Geigy Ag J R | Verfahren zum Schützen von Pelzen, Federn, Haaren, fibrösen Materialien und andern Waren gegen Schädlinge. |
| GB709455A (en) * | 1950-12-26 | 1954-05-26 | Variapat Ag | Water-soluble asymmetric ureas and thioureas and a process for their production |
| GB828231A (en) * | 1955-10-20 | 1960-02-17 | Geigy Ag J R | Improvements relating to insecticidal compounds and their use |
| GB1055786A (en) * | 1963-07-12 | 1967-01-18 | Ici Ltd | Urea derivatives |
| GB1210596A (en) * | 1967-04-06 | 1970-10-28 | Armour Grocery Products Compan | Antiseptic compositions |
| DE2315302A1 (de) * | 1973-03-27 | 1974-10-17 | Bayer Ag | Verfahren zur herstellung von nitrochinazolindionen |
| JPS49124042A (enExample) * | 1973-03-09 | 1974-11-27 | ||
| JPS61137880A (ja) * | 1984-11-24 | 1986-06-25 | シエーリング・アグロケミカルズ・リミテツド | 殺真菌および植物成長調整剤 |
| JPH02149502A (ja) * | 1988-08-24 | 1990-06-08 | Schering Agrochem Ltd | 殺有害生物組成物 |
| US5985872A (en) * | 1995-05-24 | 1999-11-16 | G.D. Searle & Co. | 2-amino-benzoxazinones for the treatment of viral infections |
| WO2001030749A1 (en) * | 1999-10-28 | 2001-05-03 | New Pharma Research Sweden Ab | Novel compounds |
| US6262113B1 (en) * | 1996-03-20 | 2001-07-17 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
| WO2002039987A2 (en) * | 2000-11-14 | 2002-05-23 | Neurosearch A/S | Use of malaria parasite anion channel blockers for treating malaria |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2722544A (en) | 1950-12-26 | 1955-11-01 | Variapat Ag | Trifluoromethyl halogenated diphenylcarbamide sulfonic acids and their preparation |
| US3332981A (en) * | 1964-09-14 | 1967-07-25 | Gen Aniline & Film Corp | Urea stilbene brighteners |
| DE2928485A1 (de) | 1979-07-14 | 1981-01-29 | Bayer Ag | Verwendung von harnstoffderivaten als arzneimittel bei der behandlung von fettstoffwechselstoerungen |
| DK41193D0 (da) | 1993-04-07 | 1993-04-07 | Neurosearch As | Ionkanalaabnere |
| US5547966A (en) | 1993-10-07 | 1996-08-20 | Bristol-Myers Squibb Company | Aryl urea and related compounds |
| CA2154323C (en) * | 1994-07-21 | 2001-03-27 | Tomoaki Nagai | Aminobenzenesulfonamide derivative and recording medium using the same |
| CA2161376C (en) * | 1994-10-27 | 2005-01-11 | Toshiaki Minami | Reversible multi-color thermal recording medium |
| EP0809492A4 (en) | 1995-02-17 | 2007-01-24 | Smithkline Beecham Corp | IL-8 RECEPTOR ANTAGONISTS |
| US5811369A (en) * | 1995-12-01 | 1998-09-22 | Nippon Paper Industries Co., Ltd. | Thermal recording medium |
| DE69612358T2 (de) * | 1995-12-08 | 2001-07-12 | Nippon Paper Industries Co. Ltd., Tokio/Tokyo | Wärmeempfindliches Aufzeichnungsmedium |
| EP0906273B1 (en) | 1996-05-24 | 2002-10-16 | Neurosearch A/S | Phenyl derivatives containing an acidic group, their preparation and their use as chloride channel blockers |
| JP2000510862A (ja) | 1996-05-24 | 2000-08-22 | ニューロサーチ・アクティーゼルスカブ | クロライドチャンネル遮断剤として有用なフエニル誘導体 |
| SK282818B6 (sk) | 1997-04-22 | 2002-12-03 | Neurosearch A/S | Substituované fenylderiváty, ich príprava, použitie a farmaceutický prípravok |
| US6093742A (en) * | 1997-06-27 | 2000-07-25 | Vertex Pharmaceuticals, Inc. | Inhibitors of p38 |
| WO1999038846A1 (en) | 1998-01-30 | 1999-08-05 | Procept, Inc. | Immunosuppressive agents |
| PL198852B1 (pl) * | 1998-10-22 | 2008-07-31 | Neurosearch As | Podstawione pochodne fenylu, kompozycja farmaceutyczna je zawierająca oraz ich zastosowanie |
| JP2004520396A (ja) | 2001-02-15 | 2004-07-08 | ニューロサーチ、アクティーゼルスカブ | 過剰な又は不十分な細胞死によって特徴づけられる疾患の治療 |
| WO2002070467A1 (en) | 2001-02-26 | 2002-09-12 | 4Sc Ag | Derivatives of diphenylurea, diphenyloxalic acid diamide and diphenylsulfuric acid diamide and their use as medicaments |
| WO2003000245A1 (en) | 2001-06-22 | 2003-01-03 | Poseidon Pharmaceuticals A/S | Compounds for use in disorders associated with mast cell or basophil activity |
| DE10131133A1 (de) | 2001-06-28 | 2003-01-16 | Bayer Ag | Pyridazinone |
| US7211575B2 (en) | 2001-09-13 | 2007-05-01 | Boehringer Ingelheim Pharmaceuticals, Inc. | Methods of treating cytokine mediated diseases |
-
2003
- 2003-11-10 DE DE60327652T patent/DE60327652D1/de not_active Expired - Lifetime
- 2003-11-10 JP JP2004552424A patent/JP2006507329A/ja active Pending
- 2003-11-10 PT PT03770917T patent/PT1565429E/pt unknown
- 2003-11-10 CA CA002502705A patent/CA2502705A1/en not_active Abandoned
- 2003-11-10 ES ES03770917T patent/ES2327834T3/es not_active Expired - Lifetime
- 2003-11-10 WO PCT/DK2003/000768 patent/WO2004046090A2/en not_active Ceased
- 2003-11-10 CN CNA200380103761XA patent/CN1714076A/zh active Pending
- 2003-11-10 US US10/535,683 patent/US7521480B2/en not_active Expired - Fee Related
- 2003-11-10 EP EP03770917A patent/EP1565429B1/en not_active Expired - Lifetime
- 2003-11-10 AT AT03770917T patent/ATE431335T1/de not_active IP Right Cessation
- 2003-11-10 AU AU2003280308A patent/AU2003280308A1/en not_active Abandoned
- 2003-11-10 MX MXPA05005409A patent/MXPA05005409A/es unknown
- 2003-11-10 NZ NZ539499A patent/NZ539499A/en unknown
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH220682A (de) * | 1940-02-05 | 1942-04-30 | Geigy Ag J R | Verfahren zum Schützen von Pelzen, Federn, Haaren, fibrösen Materialien und andern Waren gegen Schädlinge. |
| GB709455A (en) * | 1950-12-26 | 1954-05-26 | Variapat Ag | Water-soluble asymmetric ureas and thioureas and a process for their production |
| GB828231A (en) * | 1955-10-20 | 1960-02-17 | Geigy Ag J R | Improvements relating to insecticidal compounds and their use |
| GB1055786A (en) * | 1963-07-12 | 1967-01-18 | Ici Ltd | Urea derivatives |
| GB1210596A (en) * | 1967-04-06 | 1970-10-28 | Armour Grocery Products Compan | Antiseptic compositions |
| JPS49124042A (enExample) * | 1973-03-09 | 1974-11-27 | ||
| DE2315302A1 (de) * | 1973-03-27 | 1974-10-17 | Bayer Ag | Verfahren zur herstellung von nitrochinazolindionen |
| JPS61137880A (ja) * | 1984-11-24 | 1986-06-25 | シエーリング・アグロケミカルズ・リミテツド | 殺真菌および植物成長調整剤 |
| JPH02149502A (ja) * | 1988-08-24 | 1990-06-08 | Schering Agrochem Ltd | 殺有害生物組成物 |
| US5985872A (en) * | 1995-05-24 | 1999-11-16 | G.D. Searle & Co. | 2-amino-benzoxazinones for the treatment of viral infections |
| US6262113B1 (en) * | 1996-03-20 | 2001-07-17 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
| WO2001030749A1 (en) * | 1999-10-28 | 2001-05-03 | New Pharma Research Sweden Ab | Novel compounds |
| WO2002039987A2 (en) * | 2000-11-14 | 2002-05-23 | Neurosearch A/S | Use of malaria parasite anion channel blockers for treating malaria |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008519761A (ja) * | 2004-11-09 | 2008-06-12 | スミスクライン ビーチャム コーポレーション | グリコーゲンホスホリラーゼ阻害化合物およびその医薬組成物 |
| JP2019520359A (ja) * | 2016-06-22 | 2019-07-18 | フーダン ユニヴァーシティFudan University | ビアリール尿素誘導体またはそれらの塩、およびそれらの調製方法および使用 |
| JP7092356B2 (ja) | 2016-06-22 | 2022-06-28 | フーダン ユニヴァーシティ | ビアリール尿素誘導体またはそれらの塩、およびそれらの調製方法および使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ539499A (en) | 2007-09-28 |
| CN1714076A (zh) | 2005-12-28 |
| US20060069255A1 (en) | 2006-03-30 |
| EP1565429B1 (en) | 2009-05-13 |
| CA2502705A1 (en) | 2004-06-03 |
| AU2003280308A1 (en) | 2004-06-15 |
| PT1565429E (pt) | 2009-07-23 |
| WO2004046090A3 (en) | 2004-08-19 |
| EP1565429A2 (en) | 2005-08-24 |
| WO2004046090A2 (en) | 2004-06-03 |
| US7521480B2 (en) | 2009-04-21 |
| ATE431335T1 (de) | 2009-05-15 |
| DE60327652D1 (de) | 2009-06-25 |
| MXPA05005409A (es) | 2005-08-03 |
| ES2327834T3 (es) | 2009-11-04 |
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