JP2011521940A - ピラゾロスピロケトンアセチルＣｏＡカルボキシラーゼ阻害剤 - Google Patents
ピラゾロスピロケトンアセチルＣｏＡカルボキシラーゼ阻害剤 Download PDFInfo
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- JP2011521940A JP2011521940A JP2011511102A JP2011511102A JP2011521940A JP 2011521940 A JP2011521940 A JP 2011521940A JP 2011511102 A JP2011511102 A JP 2011511102A JP 2011511102 A JP2011511102 A JP 2011511102A JP 2011521940 A JP2011521940 A JP 2011521940A
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- Diabetes (AREA)
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Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
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| US5665208P | 2008-05-28 | 2008-05-28 | |
| US61/056,652 | 2008-05-28 | ||
| US5868908P | 2008-06-04 | 2008-06-04 | |
| US61/058,689 | 2008-06-04 | ||
| US17111209P | 2009-04-21 | 2009-04-21 | |
| US61/171,112 | 2009-04-21 | ||
| PCT/IB2009/005659 WO2009144555A1 (en) | 2008-05-28 | 2009-05-18 | Pyrazolospiroketone acetyl-coa carboxylase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011521940A true JP2011521940A (ja) | 2011-07-28 |
| JP2011521940A5 JP2011521940A5 (cg-RX-API-DMAC7.html) | 2012-07-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2011511102A Withdrawn JP2011521940A (ja) | 2008-05-28 | 2009-05-18 | ピラゾロスピロケトンアセチルＣｏＡカルボキシラーゼ阻害剤 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20110009443A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2297164A1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2011521940A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2724603A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009144555A1 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017528485A (ja) * | 2014-09-17 | 2017-09-28 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 肥満症及び糖尿病の治療に有用なテトラヒドロイソキノリン誘導体及び医薬組成物 |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| EP2621493B1 (en) | 2010-09-30 | 2016-08-17 | Pfizer Inc | N1-PYRAZOLOSPIROKETONE ACETYL-CoA CARBOXYLASE INHIBITORS |
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| BR112017022340A2 (pt) | 2015-05-05 | 2018-07-10 | Pfizer | 2-tiopirimidinonas |
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| UA125334C2 (uk) | 2015-06-17 | 2022-02-23 | Пфайзер Інк. | Трициклічні сполуки та їх застосування як інгібіторів фосфодіестерази |
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| WO2020102575A1 (en) | 2018-11-16 | 2020-05-22 | Inception Ibd, Inc. | Heterocyclic aminothiazoles and uses thereof |
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| CN110922372A (zh) * | 2019-11-04 | 2020-03-27 | 天津大学 | 达格列净的氨基酸共晶物及其制备方法 |
| PH12022552056A1 (en) | 2020-02-07 | 2024-02-12 | Gasherbrum Bio Inc | Heterocyclic glp-1 agonists |
| AU2021275292A1 (en) * | 2020-05-21 | 2022-12-15 | Shionogi & Co., Ltd. | Pharmaceutical for treating fatty liver diseases |
| JP2025509281A (ja) | 2022-03-09 | 2025-04-11 | ガシャーブラム・バイオ・インコーポレイテッド | ヘテロ環式ｇｌｐ－１アゴニスト |
| WO2023198140A1 (en) | 2022-04-14 | 2023-10-19 | Gasherbrum Bio, Inc. | Heterocyclic glp-1 agonists |
| WO2024118524A1 (en) | 2022-11-28 | 2024-06-06 | Cerevel Therapeutics, Llc | Azaindole compounds and their use as phosphodiesterase inhibitors |
| WO2024125602A1 (en) | 2022-12-15 | 2024-06-20 | Gasherbrum Bio, Inc. | Salts and solid forms of a compound having glp-1 agonist activity |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2614963C (en) * | 2005-07-19 | 2014-10-07 | Merck & Co., Inc. | Spirochromanone derivatives as acetyl coenzyme a carboxylase (acc) inhibitors |
| ATE552262T1 (de) * | 2006-11-29 | 2012-04-15 | Pfizer Prod Inc | Spiroketone als inhibitoren von acetyl-coa- carboxylase |
-
2009
- 2009-05-18 CA CA2724603A patent/CA2724603A1/en not_active Abandoned
- 2009-05-18 US US12/934,396 patent/US20110009443A1/en not_active Abandoned
- 2009-05-18 JP JP2011511102A patent/JP2011521940A/ja not_active Withdrawn
- 2009-05-18 EP EP09754183A patent/EP2297164A1/en not_active Withdrawn
- 2009-05-18 WO PCT/IB2009/005659 patent/WO2009144555A1/en not_active Ceased
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017528485A (ja) * | 2014-09-17 | 2017-09-28 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 肥満症及び糖尿病の治療に有用なテトラヒドロイソキノリン誘導体及び医薬組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2297164A1 (en) | 2011-03-23 |
| WO2009144555A1 (en) | 2009-12-03 |
| US20110009443A1 (en) | 2011-01-13 |
| CA2724603A1 (en) | 2009-12-03 |
| WO2009144555A8 (en) | 2010-12-16 |
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