KR20180052755A - 항진균 화합물 및 이의 제조방법 - Google Patents
항진균 화합물 및 이의 제조방법 Download PDFInfo
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- KR20180052755A KR20180052755A KR1020187010879A KR20187010879A KR20180052755A KR 20180052755 A KR20180052755 A KR 20180052755A KR 1020187010879 A KR1020187010879 A KR 1020187010879A KR 20187010879 A KR20187010879 A KR 20187010879A KR 20180052755 A KR20180052755 A KR 20180052755A
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| US5088977A (en) | 1988-12-21 | 1992-02-18 | Drug Delivery Systems Inc. | Electrical transdermal drug applicator with counteractor and method of drug delivery |
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| EP0553769B1 (de) | 1992-01-29 | 1996-01-03 | FRANZ VÖLKL GmbH & CO. SKI UND TENNIS SPORTARTIKELFABRIK KG | Ballspielschläger, insbesondere Tennisschläger |
| JP2000344744A (ja) | 1999-06-04 | 2000-12-12 | Ss Pharmaceut Co Ltd | アセトフェノン誘導体およびその製法 |
| CN1565118A (zh) * | 2001-10-08 | 2005-01-12 | 皇家飞利浦电子股份有限公司 | 用于运动估计的装置和方法 |
| JP2004359646A (ja) | 2003-06-09 | 2004-12-24 | Ss Pharmaceut Co Ltd | 抗真菌活性を有する新規アゾール誘導体 |
| US7241800B2 (en) * | 2004-03-17 | 2007-07-10 | Mai De Ltd. | Anhydrous amorphous form of fluvastatin sodium |
| US8198448B2 (en) | 2006-07-14 | 2012-06-12 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| KR100889937B1 (ko) | 2007-08-06 | 2009-03-20 | 한미약품 주식회사 | 보리코나졸의 제조방법 |
| UA108596C2 (xx) | 2007-11-09 | 2015-05-25 | Інгібітори пептиддеформілази | |
| KR101109215B1 (ko) | 2009-06-17 | 2012-01-30 | 보령제약 주식회사 | 보리코나졸의 신규 중간체 및 이를 이용한 보리코나졸의 제조방법 |
| WO2010146113A1 (en) | 2009-06-18 | 2010-12-23 | Basf Se | Antifungal 1, 2, 4-triazolyl derivatives having a 5- sulfur substituent |
| BR112012027308B1 (pt) | 2010-04-24 | 2021-07-06 | Mycovia Pharmaceuticals, Inc. | compostos inibidores de metaloenzima e composições compreendendo os mesmos |
| IN2014DN00288A (enExample) | 2011-06-19 | 2015-06-05 | Viamet Pharmaceuticals Inc | |
| WO2012177608A1 (en) | 2011-06-19 | 2012-12-27 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| AU2012273007A1 (en) | 2011-06-23 | 2014-01-30 | Viamet Pharmaceuticals (NC), Inc. | Metalloenzyme inhibitor compounds |
| TW201329025A (zh) | 2011-11-01 | 2013-07-16 | Astex Therapeutics Ltd | 醫藥化合物 |
| US9309273B2 (en) * | 2011-12-11 | 2016-04-12 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| AU2013209516A1 (en) | 2012-01-20 | 2014-08-28 | Viamet Pharmaceuticals (NC), Inc. | Metalloenzyme inhibitor compounds |
| US9414596B2 (en) | 2012-01-20 | 2016-08-16 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| CA3218491A1 (en) | 2012-06-04 | 2013-12-12 | Pharmacyclics Llc | Crystalline forms of a bruton's tyrosine kinase inhibitor |
| KR20140012226A (ko) * | 2012-07-18 | 2014-02-03 | 엘지전자 주식회사 | 태양전지 모듈 |
| US20150246898A1 (en) | 2012-09-12 | 2015-09-03 | Dow Agrosciences Llc | Metalloenzyme inhibitor compounds |
| US9663488B2 (en) | 2013-01-28 | 2017-05-30 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| WO2014165861A1 (en) | 2013-04-05 | 2014-10-09 | The Regents Of The University Of California | Metal-catalyzed coupling of aryl and vinyl halides with alpha, alpha-difluorocarbonyl compounds |
| JP6387401B2 (ja) | 2013-05-28 | 2018-09-05 | ヴィアメット ファーマスーティカルズ(エヌシー),インコーポレイテッド | 殺真菌組成物 |
| CN105431418B (zh) | 2013-06-12 | 2019-02-05 | 北卡罗来纳维亚梅特制药公司 | 金属酶抑制剂化合物 |
| CA2942231A1 (en) | 2014-03-19 | 2015-09-24 | Viamet Pharmaceuticals, Inc. | Antifungal compound process |
| AU2015231226B2 (en) * | 2014-03-19 | 2019-04-04 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| WO2015143142A1 (en) * | 2014-03-19 | 2015-09-24 | Viamet Pharmaceuticals, Inc. | Antifungal compound process |
| AU2015231234B2 (en) | 2014-03-19 | 2019-04-04 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| WO2015143137A1 (en) * | 2014-03-19 | 2015-09-24 | Viamet Pharmaceuticals, Inc. | Antifungal compound process |
| EP3119756B9 (en) | 2014-03-19 | 2021-08-25 | Dow AgroSciences LLC | 2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-substituted-pyridin-2-yl)-3-(1h-tetrazol-1-yl)propan-2-ols and processes for their preparation |
| BR112016021257B1 (pt) | 2014-03-19 | 2021-03-02 | Viamet Pharmaceuticals (NC), Inc. | 2-(2,4- difluorofenil-1,1-diflúor-1-(5-substituído-piridin-2-il)-3- (1h-tetrazol-1-il)propan-2-óis e processos para preparação e uso dos mesmos |
| EP3119771B1 (en) | 2014-03-19 | 2020-05-06 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| CA2942932A1 (en) | 2014-03-19 | 2015-09-24 | Viamet Pharmaceuticals, Inc. | Antifungal compound process |
| US10399943B2 (en) | 2014-03-19 | 2019-09-03 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| LT3271347T (lt) | 2015-03-19 | 2022-10-10 | Mycovia Pharmaceuticals, Inc. | Priešgrybeliniai junginiai ir jų gamybos būdai |
| AU2016265932B2 (en) | 2015-05-18 | 2020-10-08 | Viamet Pharmaceuticals (NC), Inc. | Antifungal compounds |
| KR20180052755A (ko) | 2015-09-18 | 2018-05-18 | 브이피에스-3, 인크. | 항진균 화합물 및 이의 제조방법 |
| JP6987070B2 (ja) | 2015-11-17 | 2021-12-22 | コルテバ アグリサイエンス エルエルシー | 4−((6−(2−(2,4−ジフルオロフェニル)−1,1−ジフルオロ−2−オキソエチル)ピリジン−3−イル)オキシ)ベンゾニトリル及び製造方法 |
| WO2017087592A1 (en) | 2015-11-17 | 2017-05-26 | Viamet Pharmaceuticals, Inc. | 4-((6-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1h-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile and processes of preparation |
| TWI679198B (zh) | 2015-11-17 | 2019-12-11 | 美商陶氏益農有限責任公司 | 製備4-((6-(2-(2,4-二氟苯基)-1,1-二氟-2-羥基-3-(1h-1,2,4-三唑-1-基)丙基)吡啶-3-基)氧基)苄腈之方法 |
| KR20180101342A (ko) | 2015-11-17 | 2018-09-12 | 다우 아그로사이언시즈 엘엘씨 | 4-((6-(2-(2,4-디플루오로페닐)-1,1-디플루오로-2-히드록시-3-(1h-1,2,4-트리아졸-1-일)프로필)피리딘-3-일)옥시)벤조니트릴 및 제조방법 |
| JP6803923B2 (ja) | 2015-12-30 | 2020-12-23 | エヌキューピー 1598,リミテッド | 金属酵素阻害化合物 |
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