JP2007504285A - Ｎ−シクロヘキシルアミノカルボニルベンゼンスルホンアミド誘導体 - Google Patents
Ｎ−シクロヘキシルアミノカルボニルベンゼンスルホンアミド誘導体 Download PDFInfo
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- JP2007504285A JP2007504285A JP2006536529A JP2006536529A JP2007504285A JP 2007504285 A JP2007504285 A JP 2007504285A JP 2006536529 A JP2006536529 A JP 2006536529A JP 2006536529 A JP2006536529 A JP 2006536529A JP 2007504285 A JP2007504285 A JP 2007504285A
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- DNIIWANRGRGVRG-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-cyclohexylurea Chemical class C=1C=CC=CC=1S(=O)(=O)NC(=O)NC1CCCCC1 DNIIWANRGRGVRG-UHFFFAOYSA-N 0.000 title claims abstract description 6
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- C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
- C07C311/57—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings
- C07C311/59—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings having nitrogen atoms of the sulfonylurea groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44076103P | 2003-01-17 | 2003-01-17 | |
| PCT/US2004/000689 WO2004066963A2 (en) | 2003-01-17 | 2004-01-13 | N-cyclohexylaminocarbonyl benzenesulfonamide derivatives |
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| Publication Number | Publication Date |
|---|---|
| JP2007504285A true JP2007504285A (ja) | 2007-03-01 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006536529A Pending JP2007504285A (ja) | 2003-01-17 | 2004-01-13 | Ｎ−シクロヘキシルアミノカルボニルベンゼンスルホンアミド誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7319170B2 (en:Method) |
| EP (1) | EP1587535A4 (en:Method) |
| JP (1) | JP2007504285A (en:Method) |
| AU (1) | AU2004207444B2 (en:Method) |
| CA (1) | CA2512879A1 (en:Method) |
| WO (1) | WO2004066963A2 (en:Method) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015108010A (ja) * | 2011-12-07 | 2015-06-11 | カルピス株式会社 | 乳酸菌又はその処理物を含む脂質代謝及び／又は糖代謝改善剤 |
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| KR20060058632A (ko) * | 2004-11-25 | 2006-05-30 | 주식회사 엘지생명과학 | ＰＰＡＲ ｇａｍｍａ와 ＰＰＡＲ ａｌｐｈａ의 활성을항진시키는 신규 화합물, 그것의 제조방법, 및 그것을함유한 약제 조성물 |
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Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5254589A (en) * | 1991-10-15 | 1993-10-19 | Warner-Lambert Company | Sulfonyl urea and carbamate ACAT inhibitors |
| US6008237A (en) * | 1997-12-19 | 1999-12-28 | Merck & Co., Inc. | Arylthiazolidinedione derivatives |
| PT1206457E (pt) * | 1999-08-27 | 2004-03-31 | Lilly Co Eli | Derivados de diaril-oxa(tia)zol e seu uso como moduladores dos ppars |
| AU7115300A (en) * | 1999-09-08 | 2001-04-10 | Glaxo Group Limited | Oxazole ppar antagonists |
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2004
- 2004-01-13 US US10/542,287 patent/US7319170B2/en not_active Expired - Fee Related
- 2004-01-13 WO PCT/US2004/000689 patent/WO2004066963A2/en active Application Filing
- 2004-01-13 CA CA002512879A patent/CA2512879A1/en not_active Abandoned
- 2004-01-13 AU AU2004207444A patent/AU2004207444B2/en not_active Ceased
- 2004-01-13 EP EP04701735A patent/EP1587535A4/en not_active Withdrawn
- 2004-01-13 JP JP2006536529A patent/JP2007504285A/ja active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015108010A (ja) * | 2011-12-07 | 2015-06-11 | カルピス株式会社 | 乳酸菌又はその処理物を含む脂質代謝及び／又は糖代謝改善剤 |
| US10245291B2 (en) | 2011-12-07 | 2019-04-02 | Asahi Group Holdings, Ltd. | Lipid metabolism and/or sugar metabolism improver containing lactic acid bacterium or treatment product thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1587535A2 (en) | 2005-10-26 |
| WO2004066963A3 (en) | 2004-11-11 |
| EP1587535A4 (en) | 2010-02-24 |
| CA2512879A1 (en) | 2004-08-12 |
| US20060111585A1 (en) | 2006-05-25 |
| US7319170B2 (en) | 2008-01-15 |
| AU2004207444A1 (en) | 2004-08-12 |
| WO2004066963A2 (en) | 2004-08-12 |
| AU2004207444B2 (en) | 2008-07-31 |
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