JP2005507932A - 肥満の処置のためのフェニル置換5−員窒素含有複素環 - Google Patents
肥満の処置のためのフェニル置換5−員窒素含有複素環 Download PDFInfo
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- JP2005507932A JP2005507932A JP2003539676A JP2003539676A JP2005507932A JP 2005507932 A JP2005507932 A JP 2005507932A JP 2003539676 A JP2003539676 A JP 2003539676A JP 2003539676 A JP2003539676 A JP 2003539676A JP 2005507932 A JP2005507932 A JP 2005507932A
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 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
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229940045860 white wax Drugs 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 235000016804 zinc Nutrition 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
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- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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
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- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
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- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/88—Nitrogen atoms, e.g. allantoin
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/90—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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- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
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- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
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- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
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- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
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- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- C07D471/10—Spiro-condensed systems
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32923601P | 2001-10-12 | 2001-10-12 | |
| PCT/US2002/032895 WO2003037332A1 (en) | 2001-10-12 | 2002-10-15 | Phenyl substituted 5-membered nitrogen containing heterocycles for the treatment of obesity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005507932A true JP2005507932A (ja) | 2005-03-24 |
| JP2005507932A5 JP2005507932A5 (enExample) | 2006-01-05 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003539676A Withdrawn JP2005507932A (ja) | 2001-10-12 | 2002-10-15 | 肥満の処置のためのフェニル置換5−員窒素含有複素環 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20050014805A1 (enExample) |
| EP (1) | EP1435951B1 (enExample) |
| JP (1) | JP2005507932A (enExample) |
| CA (1) | CA2463441A1 (enExample) |
| DE (1) | DE60208815T2 (enExample) |
| ES (1) | ES2256560T3 (enExample) |
| MX (1) | MXPA04002931A (enExample) |
| WO (1) | WO2003037332A1 (enExample) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007052843A1 (ja) * | 2005-11-04 | 2007-05-10 | Takeda Pharmaceutical Company Limited | 複素環アミド化合物およびその用途 |
| JP2016512209A (ja) * | 2013-03-13 | 2016-04-25 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ベンゾオキサゼピン化合物の作製方法 |
| JP2018500286A (ja) * | 2014-10-30 | 2018-01-11 | ヤンセン ファーマシューティカ エヌ.ベー. | RORγtのモジュレーターとしてのアミド置換チアゾール |
| JP2019506415A (ja) * | 2016-02-11 | 2019-03-07 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 有害生物防除剤としての置換2−(ヘタ)アリール−イミダゾリル−カルボキサミド類 |
| US10975037B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | Phenyl substituted pyrazoles as modulators of RORγt |
| US10975068B2 (en) | 2016-04-27 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl thiazoles as modulators of RORγT |
| US10975057B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl pyrazoles as modulators of RORgT |
| US11034658B2 (en) | 2018-06-18 | 2021-06-15 | Janssen Pharmaceutica Nv | Pyridinyl pyrazoles as modulators of RORγT |
| US11345666B2 (en) | 2018-06-18 | 2022-05-31 | Janssen Pharmaceutica Nv | Phenyl and pyridinyl substituted imidazoles as modulators of RORγT |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002319627A1 (en) | 2001-07-20 | 2003-03-03 | Merck And Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
| NZ534757A (en) | 2002-03-12 | 2006-07-28 | Merck & Co Inc | Substituted amides |
| AU2003299791A1 (en) * | 2002-12-20 | 2004-07-22 | Bayer Pharmaceuticals Corporation | Substituted 3,5-dihydro-4h-imidazol-4-ones for the treatment of obesity |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| AU2004210711B2 (en) * | 2003-02-12 | 2010-07-08 | Transtech Pharma, Inc. | Substituted azole derivatives as therapeutic agents |
| WO2004099157A1 (en) * | 2003-05-07 | 2004-11-18 | Pfizer Products Inc. | Cannabinoid receptor ligands and uses thereof |
| NZ619746A (en) | 2003-08-06 | 2014-05-30 | Senomyx Inc | Novel flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof |
| JP4436369B2 (ja) | 2004-01-28 | 2010-03-24 | エフ.ホフマン−ラ ロシュ アーゲー | スピロ−ベンゾジオキソール類およびそれらのcb1アンタゴニストとしての使用 |
| AU2005214349B2 (en) * | 2004-02-12 | 2011-11-03 | Transtech Pharma, Inc. | Substituted azole derivatives, compositions, and methods of use |
| WO2005090340A1 (ja) * | 2004-03-22 | 2005-09-29 | Banyu Pharmaceutical Co., Ltd. | ピペリジン-1-カルボキサミド誘導体 |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| US7820704B2 (en) * | 2004-04-20 | 2010-10-26 | Transtech Pharma, Inc. | Substituted heteroaryl derivatives, compositions, and methods of use |
| ES2351348T3 (es) | 2004-11-09 | 2011-02-03 | F. Hoffmann-La Roche Ag | Derivados de la dibenzosuberona. |
| MY158077A (en) | 2005-02-04 | 2016-08-30 | Senomyx Inc | Compounds comprising linked heteroaryl moieties and their use as novel umami flavor modifiers tastants and taste enhancers for comestible compositions |
| US7728009B1 (en) | 2005-02-18 | 2010-06-01 | Neurogen Corporation | Thiazole amides, imidazole amides and related analogues |
| CA2607953A1 (en) | 2005-05-09 | 2006-11-16 | Tap Pharmaceutical Products, Inc. | Methods for treating nephrolithiasis |
| AR055329A1 (es) | 2005-06-15 | 2007-08-15 | Senomyx Inc | Amidas bis-aromaticas y sus usos como modificadores de sabor dulce, saborizantes, y realzadores de sabor |
| WO2007019153A2 (en) * | 2005-08-03 | 2007-02-15 | Tap Pharmaceutical Products, Inc. | Methods for treating hypertension |
| EA019385B1 (ru) | 2006-01-30 | 2014-03-31 | ТРАНСТЕК ФАРМА ЭлЭлСи | ЗАМЕЩЕННЫЕ ИМИДАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ, СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ РТРазы |
| US8148536B2 (en) | 2006-04-21 | 2012-04-03 | Senomyx, Inc. | Comestible compositions comprising high potency savory flavorants, and processes for producing them |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| US20100120694A1 (en) | 2008-06-04 | 2010-05-13 | Synergy Pharmaceuticals, Inc. | Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders |
| JP5546451B2 (ja) | 2007-06-04 | 2014-07-09 | シナジー ファーマシューティカルズ インコーポレイテッド | 胃腸の障害、炎症、癌および他の障害の処置に有用なグアニル酸シクラーゼのアゴニスト |
| CN101687844B (zh) * | 2007-07-02 | 2013-11-13 | 弗·哈夫曼-拉罗切有限公司 | 用作ccr2受体拮抗剂的咪唑衍生物 |
| WO2009018065A2 (en) | 2007-07-27 | 2009-02-05 | Bristol-Myers Squibb Company | Novel glucokinase activators and methods of using same |
| US8822513B2 (en) | 2010-03-01 | 2014-09-02 | Gtx, Inc. | Compounds for treatment of cancer |
| US9447049B2 (en) | 2010-03-01 | 2016-09-20 | University Of Tennessee Research Foundation | Compounds for treatment of cancer |
| US9029408B2 (en) | 2008-06-16 | 2015-05-12 | Gtx, Inc. | Compounds for treatment of cancer |
| HUE060249T2 (hu) | 2008-06-16 | 2023-02-28 | Univ Tennessee Res Found | Vegyületek rák kezelésére |
| EP3241839B1 (en) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| JP2012501334A (ja) * | 2008-08-29 | 2012-01-19 | トランス テック ファーマ,インコーポレイテッド | 置換アミノチアゾール誘導体、医薬組成物、および使用の方法 |
| EP2348857B1 (en) | 2008-10-22 | 2016-02-24 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| AU2009309037A1 (en) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| US8895596B2 (en) | 2010-02-25 | 2014-11-25 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| AU2010347233B2 (en) | 2010-03-01 | 2015-06-18 | Oncternal Therapeutics, Inc. | Compounds for treatment of cancer |
| CN103168032A (zh) | 2010-08-05 | 2013-06-19 | 安美基公司 | 抑制间变性淋巴瘤激酶的苯并咪唑和氮杂苯并咪唑化合物 |
| CN103298466B (zh) | 2010-09-10 | 2015-11-25 | 武田制药美国有限公司 | 茶碱和非布索坦的联合治疗方法 |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| MY159058A (en) | 2011-02-25 | 2016-12-15 | Merck Sharp & Dohme | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agent |
| EP2880028B1 (en) | 2012-08-02 | 2020-09-30 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| JP2016516004A (ja) | 2013-02-22 | 2016-06-02 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | 抗糖尿病二環式化合物 |
| WO2014139388A1 (en) | 2013-03-14 | 2014-09-18 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
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Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US69849A (en) * | 1867-10-15 | sheppaed | ||
| WO1998027065A1 (en) * | 1996-12-16 | 1998-06-25 | Ontogen Corporation | Modulators of proteins with phosphotyrosine recognition units |
| AU726311B2 (en) * | 1996-11-20 | 2000-11-02 | Merck & Co., Inc. | Triaryl substituted imidazoles and methods of use |
| BR9807096A (pt) * | 1997-01-28 | 2000-04-18 | Merck & Co Inc | Composto, processos para o tratamento do diabetes, da obesidade em um mamìfero, para reduzir nìveis de triglicerìdeos e nìveis de colesterol ou elevar nìveis de lipoproteìnas de alta densidade, para diminuir a motilidade do intestino, para reduzir inflamação neurogênica das vias aéreas e a depressão e para tratar distúrbios gastrintestinais, e, composições para o tratamento dos distúrbios acima e farmacêutica |
| FR2763337B1 (fr) * | 1997-05-13 | 1999-08-20 | Sanofi Sa | Nouveaux derives du triazole, un procede pour leur preparation et compositions pharmaceutiques les contenant |
| EP1177188B1 (en) * | 1999-05-12 | 2005-10-12 | Ortho-McNeil Pharmaceutical, Inc. | Pyrazole carboxamides useful for the treatment of obesity and other disorders |
| PE20011010A1 (es) * | 1999-12-02 | 2001-10-18 | Glaxo Group Ltd | Oxazoles y tiazoles sustituidos como agonista del receptor activado por el proliferador de peroxisomas humano |
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2002
- 2002-10-15 DE DE60208815T patent/DE60208815T2/de not_active Expired - Fee Related
- 2002-10-15 EP EP02782159A patent/EP1435951B1/en not_active Expired - Lifetime
- 2002-10-15 ES ES02782159T patent/ES2256560T3/es not_active Expired - Lifetime
- 2002-10-15 WO PCT/US2002/032895 patent/WO2003037332A1/en not_active Ceased
- 2002-10-15 JP JP2003539676A patent/JP2005507932A/ja not_active Withdrawn
- 2002-10-15 CA CA002463441A patent/CA2463441A1/en not_active Abandoned
- 2002-10-15 US US10/490,826 patent/US20050014805A1/en not_active Abandoned
- 2002-10-15 MX MXPA04002931A patent/MXPA04002931A/es active IP Right Grant
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007052843A1 (ja) * | 2005-11-04 | 2007-05-10 | Takeda Pharmaceutical Company Limited | 複素環アミド化合物およびその用途 |
| JP2016512209A (ja) * | 2013-03-13 | 2016-04-25 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ベンゾオキサゼピン化合物の作製方法 |
| JP2018500286A (ja) * | 2014-10-30 | 2018-01-11 | ヤンセン ファーマシューティカ エヌ.ベー. | RORγtのモジュレーターとしてのアミド置換チアゾール |
| JP2019506415A (ja) * | 2016-02-11 | 2019-03-07 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 有害生物防除剤としての置換2−(ヘタ)アリール−イミダゾリル−カルボキサミド類 |
| US10975068B2 (en) | 2016-04-27 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl thiazoles as modulators of RORγT |
| US10975037B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | Phenyl substituted pyrazoles as modulators of RORγt |
| US10975057B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl pyrazoles as modulators of RORgT |
| US11034658B2 (en) | 2018-06-18 | 2021-06-15 | Janssen Pharmaceutica Nv | Pyridinyl pyrazoles as modulators of RORγT |
| US11345666B2 (en) | 2018-06-18 | 2022-05-31 | Janssen Pharmaceutica Nv | Phenyl and pyridinyl substituted imidazoles as modulators of RORγT |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA04002931A (es) | 2005-04-11 |
| DE60208815T2 (de) | 2006-07-20 |
| DE60208815D1 (de) | 2006-04-06 |
| WO2003037332A1 (en) | 2003-05-08 |
| CA2463441A1 (en) | 2003-05-08 |
| ES2256560T3 (es) | 2006-07-16 |
| EP1435951B1 (en) | 2006-01-18 |
| US20050014805A1 (en) | 2005-01-20 |
| EP1435951A1 (en) | 2004-07-14 |
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