JP2014526533A - Ｐｄｅ１０ａ阻害剤としてのトリアゾロピリジン化合物 - Google Patents
Ｐｄｅ１０ａ阻害剤としてのトリアゾロピリジン化合物 Download PDFInfo
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- JP2014526533A JP2014526533A JP2014531187A JP2014531187A JP2014526533A JP 2014526533 A JP2014526533 A JP 2014526533A JP 2014531187 A JP2014531187 A JP 2014531187A JP 2014531187 A JP2014531187 A JP 2014531187A JP 2014526533 A JP2014526533 A JP 2014526533A
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- Prior art keywords
- methyl
- triazolo
- pyridin
- pyrazole
- disorder
- Prior art date
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- 150000008523 triazolopyridines Chemical class 0.000 title 1
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
- JOJAUJFFLWQSGY-UHFFFAOYSA-N 2-methylpyrazole-3,4-dicarboxylic acid Chemical compound CN1N=CC(C(O)=O)=C1C(O)=O JOJAUJFFLWQSGY-UHFFFAOYSA-N 0.000 claims description 27
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- 125000001424 substituent group Chemical group 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
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- 238000011282 treatment Methods 0.000 claims description 22
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- WESMGXSTLGHHBV-UHFFFAOYSA-N 4-(3-fluoroazetidine-1-carbonyl)-2-methylpyrazole-3-carboxylic acid;2-methyl-4-(morpholine-4-carbonyl)-n-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazole-3-carboxamide Chemical compound CN1N=CC(C(=O)N2CC(F)C2)=C1C(O)=O.C1=CC2=NC(C=3C=CC=CC=3)=NN2C=C1NC(=O)C=1N(C)N=CC=1C(=O)N1CCOCC1 WESMGXSTLGHHBV-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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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
- C07D471/04—Ortho-condensed systems
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Landscapes
- Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11181752.4 | 2011-09-19 | ||
| EP11181752 | 2011-09-19 | ||
| PCT/EP2012/068203 WO2013041472A1 (en) | 2011-09-19 | 2012-09-17 | Triazolopyridine compounds as pde10a inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2014526533A true JP2014526533A (ja) | 2014-10-06 |
| JP2014526533A5 JP2014526533A5 (enExample) | 2015-07-30 |
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| JP2014531187A Pending JP2014526533A (ja) | 2011-09-19 | 2012-09-17 | Ｐｄｅ１０ａ阻害剤としてのトリアゾロピリジン化合物 |
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| JP (1) | JP2014526533A (enExample) |
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| BR (1) | BR112014006248A2 (enExample) |
| CA (1) | CA2846758C (enExample) |
| CL (1) | CL2014000641A1 (enExample) |
| CO (1) | CO6900144A2 (enExample) |
| EA (1) | EA201490599A1 (enExample) |
| ES (1) | ES2626801T3 (enExample) |
| IL (1) | IL231403A0 (enExample) |
| MX (1) | MX2014003025A (enExample) |
| PE (1) | PE20141553A1 (enExample) |
| PH (1) | PH12014500499A1 (enExample) |
| SG (1) | SG11201400759RA (enExample) |
| UA (1) | UA108711C2 (enExample) |
| WO (1) | WO2013041472A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020531489A (ja) * | 2017-08-22 | 2020-11-05 | バイエル・アクチエンゲゼルシヤフト | 有害生物防除剤としてのヘテロサイクレン誘導体 |
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| EP2757882B1 (en) | 2011-09-22 | 2020-11-04 | Merck Sharp & Dohme Corp. | Imidazopyridyl compounds as aldosterone synthase inhibitors |
| EP2757883B1 (en) | 2011-09-22 | 2021-01-13 | Merck Sharp & Dohme Corp. | Triazolopyridyl compounds as aldosterone synthase inhibitors |
| CA2909477A1 (en) | 2013-04-30 | 2014-11-06 | F. Hoffmann-La Roche Ag | Pd-catalyzed coupling of pyrazole amides |
| TWI652014B (zh) | 2013-09-13 | 2019-03-01 | 美商艾佛艾姆希公司 | 雜環取代之雙環唑殺蟲劑 |
| EP3176168A4 (en) * | 2014-07-30 | 2018-05-02 | Mochida Pharmaceutical Co., Ltd. | Pyrazole derivative manufacturing method |
| EP3176167A4 (en) * | 2014-07-30 | 2018-03-28 | Mochida Pharmaceutical Co., Ltd. | Pyrazole derivative manufacturing method |
| WO2016144351A1 (en) | 2015-03-11 | 2016-09-15 | E. I. Du Pont De Nemours And Company | Heterocycle-substituted bicyclic azole pesticides |
| CN107743486B (zh) | 2015-03-12 | 2021-04-09 | Fmc公司 | 杂环取代的二环唑杀有害生物剂 |
| BR112018007034B1 (pt) | 2015-10-08 | 2022-10-11 | Fmc Corporation | Composto, composição, método para controlar uma praga de invertebrados e semente revestida |
| CN113906024B (zh) | 2019-05-27 | 2023-10-20 | 日本农药株式会社 | 交联部有氮原子的缩合杂环化合物或其盐类及含该化合物的农业园艺用杀虫剂及其使用方法 |
| AR119140A1 (es) | 2019-06-13 | 2021-11-24 | Pi Industries Ltd | Compuestos heterocíclicos fusionados y su uso como agentes de control de plagas |
| CN110396157B (zh) * | 2019-08-07 | 2021-07-30 | 广州市建筑科学研究院有限公司 | 缓释型聚羧酸纳米减水剂及其制备方法和应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010035745A1 (ja) * | 2008-09-25 | 2010-04-01 | 杏林製薬株式会社 | ヘテロ環ビアリール誘導体及びそれらを有効成分とするｐｄｅ阻害剤 |
| WO2011036127A1 (en) * | 2009-09-24 | 2011-03-31 | F. Hoffmann-La Roche Ag | Imidazopyridine or imidazopyrimidine derivatives as phosphodiesterase 10a inhibitors |
| WO2011072695A1 (en) * | 2009-12-17 | 2011-06-23 | H. Lundbeck A/S | Phenylimidazole derivatives comprising an ethynylene linker as pde10a enzyme inhibitors |
| WO2011072697A1 (en) * | 2009-12-17 | 2011-06-23 | H. Lundbeck A/S | Heteroaromatic aryl triazole derivatives as pde10a enzyme inhibitors |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6355653B1 (en) * | 1999-09-06 | 2002-03-12 | Hoffmann-La Roche Inc. | Amino-triazolopyridine derivatives |
| JP2007508241A (ja) | 2003-07-31 | 2007-04-05 | バイエル・フアーマシユーチカルズ・コーポレーシヨン | Ｐｄｅ１０ａ阻害剤を用いる糖尿病および関連障害の処置方法 |
| NL2000397C2 (nl) * | 2006-01-05 | 2007-10-30 | Pfizer Prod Inc | Bicyclische heteroarylverbindingen als PDE10 inhibitoren. |
| WO2010059836A1 (en) * | 2008-11-20 | 2010-05-27 | Decode Genetics Ehf | Substituted aza-bridged bicyclics for cardiovascular and cns disease |
| US8685967B2 (en) * | 2009-04-07 | 2014-04-01 | Merck Sharp & Dohme Corp. | Substituted triazolopyridines and analogs thereof |
| CN102696239B (zh) | 2009-11-24 | 2020-08-25 | 诺基亚技术有限公司 | 一种设备 |
| TWI485151B (zh) * | 2009-12-17 | 2015-05-21 | Lundbeck & Co As H | 作為ｐｄｅ１０ａ酵素抑制劑之雜芳香族苯基咪唑衍生物 |
-
2012
- 2012-09-17 EA EA201490599A patent/EA201490599A1/ru unknown
- 2012-09-17 CA CA2846758A patent/CA2846758C/en not_active Expired - Fee Related
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-
2014
- 2014-03-05 CO CO14047250A patent/CO6900144A2/es unknown
- 2014-03-06 IL IL231403A patent/IL231403A0/en unknown
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010035745A1 (ja) * | 2008-09-25 | 2010-04-01 | 杏林製薬株式会社 | ヘテロ環ビアリール誘導体及びそれらを有効成分とするｐｄｅ阻害剤 |
| WO2011036127A1 (en) * | 2009-09-24 | 2011-03-31 | F. Hoffmann-La Roche Ag | Imidazopyridine or imidazopyrimidine derivatives as phosphodiesterase 10a inhibitors |
| WO2011072695A1 (en) * | 2009-12-17 | 2011-06-23 | H. Lundbeck A/S | Phenylimidazole derivatives comprising an ethynylene linker as pde10a enzyme inhibitors |
| WO2011072697A1 (en) * | 2009-12-17 | 2011-06-23 | H. Lundbeck A/S | Heteroaromatic aryl triazole derivatives as pde10a enzyme inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| JPN6015008744; Ｐａｔｒｉｃｋ Ｒ． Ｖｅｒｈｏｅｓｔ， ｅｔ ａｌ．: Ｊ． Ｍｅｄ． Ｃｈｅｍ． Ｖｏｌ．５２, 2009, ｐｐ．５１８８-５１９６ * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020531489A (ja) * | 2017-08-22 | 2020-11-05 | バイエル・アクチエンゲゼルシヤフト | 有害生物防除剤としてのヘテロサイクレン誘導体 |
| JP7202360B2 (ja) | 2017-08-22 | 2023-01-11 | バイエル・アクチエンゲゼルシヤフト | 有害生物防除剤としてのヘテロサイクレン誘導体 |
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| CA2846758C (en) | 2017-09-12 |
| CN103827114A (zh) | 2014-05-28 |
| US8946427B2 (en) | 2015-02-03 |
| UA108711C2 (uk) | 2015-05-25 |
| US9227970B2 (en) | 2016-01-05 |
| AU2012311713A1 (en) | 2014-03-13 |
| KR20140075716A (ko) | 2014-06-19 |
| US20140303141A1 (en) | 2014-10-09 |
| MX2014003025A (es) | 2014-05-28 |
| CO6900144A2 (es) | 2014-03-20 |
| PH12014500499A1 (en) | 2014-04-14 |
| KR101584925B1 (ko) | 2016-01-12 |
| EP2758396A1 (en) | 2014-07-30 |
| PE20141553A1 (es) | 2014-10-30 |
| IL231403A0 (en) | 2014-04-30 |
| ES2626801T3 (es) | 2017-07-26 |
| SG11201400759RA (en) | 2014-07-30 |
| US20150099735A1 (en) | 2015-04-09 |
| EA201490599A1 (ru) | 2014-07-30 |
| NZ621597A (en) | 2015-04-24 |
| CA2846758A1 (en) | 2013-03-28 |
| CN103827114B (zh) | 2016-08-24 |
| CL2014000641A1 (es) | 2014-11-14 |
| WO2013041472A1 (en) | 2013-03-28 |
| EP2758396B1 (en) | 2017-03-29 |
| BR112014006248A2 (pt) | 2017-04-11 |
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