KR20070043776A - 보릴옥시피리딜메타논을 사용하는 동물의 피부컨디션 또는 조직컨디션의 치료 또는 예방 - Google Patents
보릴옥시피리딜메타논을 사용하는 동물의 피부컨디션 또는 조직컨디션의 치료 또는 예방 Download PDFInfo
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- KR20070043776A KR20070043776A KR1020077000568A KR20077000568A KR20070043776A KR 20070043776 A KR20070043776 A KR 20070043776A KR 1020077000568 A KR1020077000568 A KR 1020077000568A KR 20077000568 A KR20077000568 A KR 20077000568A KR 20070043776 A KR20070043776 A KR 20070043776A
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- South Korea
- Prior art keywords
- alkyl
- substituted
- aryl
- compound
- optionally substituted
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
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- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
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Landscapes
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- Communicable Diseases (AREA)
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| US57942104P | 2004-06-14 | 2004-06-14 | |
| US60/579,421 | 2004-06-14 |
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| KR20070043776A true KR20070043776A (ko) | 2007-04-25 |
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| KR1020077000568A Ceased KR20070043776A (ko) | 2004-06-14 | 2005-06-14 | 보릴옥시피리딜메타논을 사용하는 동물의 피부컨디션 또는 조직컨디션의 치료 또는 예방 |
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| AU (1) | AU2005254095B2 (enExample) |
| BR (1) | BRPI0512054A (enExample) |
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| IL (1) | IL179616A0 (enExample) |
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| CA2597982C (en) | 2005-02-16 | 2014-07-08 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| AU2006226819A1 (en) * | 2005-03-24 | 2006-09-28 | Anacor Pharmaceuticals, Inc. | Topical formulations of boronic acid antibiotics and their methods of use |
| RU2008130902A (ru) * | 2005-12-28 | 2010-02-10 | Анакор Фармасьютикалз, Инк. (Us) | Способ получения пиколинатбориновых сложных эфиров |
| KR20080110984A (ko) | 2005-12-30 | 2008-12-22 | 아나코르 파마슈티칼스 인코포레이티드 | 보론함유 소분자 |
| RS54108B1 (sr) | 2006-02-16 | 2015-12-31 | Anacor Pharmaceuticals Inc. | Mali molekuli koji sadrže boron kao agensi protiv zapaljenja |
| WO2007146965A2 (en) * | 2006-06-12 | 2007-12-21 | Anacor Pharmaceuticals, Inc. | Compounds for the treatment of periodontal disease |
| EP2564857B1 (en) | 2008-03-06 | 2017-05-03 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-inflammatory agents |
| US8853424B2 (en) * | 2008-08-11 | 2014-10-07 | Japan Science And Technology Agency | Protein cross-linking inhibitor |
| WO2010028005A1 (en) | 2008-09-04 | 2010-03-11 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| EP2348863A4 (en) | 2008-09-04 | 2012-03-07 | Anacor Pharmaceuticals Inc | BORN SMALL MOLECULES |
| WO2010045503A1 (en) * | 2008-10-15 | 2010-04-22 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-protozoal agents |
| TW201110996A (en) | 2009-06-03 | 2011-04-01 | Colgate Palmolive Co | Borinic compositions |
| WO2011019618A1 (en) * | 2009-08-14 | 2011-02-17 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
| US9346834B2 (en) | 2009-10-20 | 2016-05-24 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
| WO2011060196A1 (en) | 2009-11-11 | 2011-05-19 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| US8716478B2 (en) | 2010-01-27 | 2014-05-06 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| AP2012006482A0 (en) | 2010-03-19 | 2012-10-31 | Anacor Pharmacueticals Inc | Boron-containing small molecules as anti-protozoalagent |
| KR102152901B1 (ko) | 2010-09-07 | 2020-09-07 | 아나코르 파마슈티칼스 인코포레이티드 | 세균 감염을 치료하기 위한 벤족사보롤 유도체 |
| US9585396B2 (en) | 2013-01-30 | 2017-03-07 | Agrofresh Inc. | Volatile applications against pathogens |
| MX356059B (es) | 2013-01-30 | 2018-05-11 | Dow Agrosciences Llc | Uso de benzoxaboroles como agentes antimicrobianos volatiles en carnes, plantas, o partes de plantas. |
| US10070649B2 (en) | 2013-01-30 | 2018-09-11 | Agrofresh Inc. | Volatile applications against pathogens |
| US11039617B2 (en) | 2013-01-30 | 2021-06-22 | Agrofresh Inc. | Large scale methods of uniformly coating packaging surfaces with a volatile antimicrobial to preserve food freshness |
| US8669207B1 (en) | 2013-01-30 | 2014-03-11 | Dow Agrosciences, Llc. | Compounds and compositions |
| KR101756785B1 (ko) * | 2015-03-10 | 2017-07-12 | 한국화학연구원 | 4배위 유기 붕소 화합물의 제조방법 |
| WO2016207411A1 (en) * | 2015-06-24 | 2016-12-29 | Oriel Seasalt Company Limited | A highly concentrated seawater mineral extract and uses thereof |
| EP3426029B1 (en) | 2016-03-07 | 2023-08-30 | AgroFresh Inc. | Synergistic methods of using benzoxaborole compounds and preservative gases as an antimicrobial for crops |
| EP3609504A4 (en) | 2017-03-01 | 2021-03-03 | Anacor Pharmaceuticals, Inc. | NEW OXABOROLE ANALOGUES AND USES OF THE LATEST |
| US20230340530A1 (en) | 2020-08-31 | 2023-10-26 | Pfizer Inc. | Methods of Protecting RNA |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE790627A (fr) * | 1971-10-27 | 1973-04-27 | Lilly Co Eli | L'antibiotique a477 et son procede de preparation |
| US5348947A (en) | 1993-05-07 | 1994-09-20 | American Cyanamid Company | Diarylboron ester and thioester fungicidal agents |
| US6123925A (en) * | 1998-07-27 | 2000-09-26 | Healthshield Technologies L.L.C. | Antibiotic toothpaste |
| US6350786B1 (en) * | 1998-09-22 | 2002-02-26 | Hoffmann-La Roche Inc. | Stable complexes of poorly soluble compounds in ionic polymers |
| JP2003514023A (ja) | 1999-11-19 | 2003-04-15 | トツプジーン・インコーポレイテツド | 抗炎症剤としてのホウ素化合物および複合体 |
| JP2006511613A (ja) * | 2002-12-18 | 2006-04-06 | アナコア ファーマシューティカルズ インコーポレイテッド | ボロン酸複合体を含む抗生物質および使用法 |
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2005
- 2005-06-13 AR ARP050102416A patent/AR049915A1/es unknown
- 2005-06-14 US US11/153,765 patent/US7652000B2/en not_active Expired - Fee Related
- 2005-06-14 JP JP2007516688A patent/JP2008502696A/ja not_active Withdrawn
- 2005-06-14 CA CA002570477A patent/CA2570477A1/en not_active Abandoned
- 2005-06-14 EP EP05786265A patent/EP1765358B1/en not_active Expired - Lifetime
- 2005-06-14 BR BRPI0512054-3A patent/BRPI0512054A/pt not_active IP Right Cessation
- 2005-06-14 AT AT05786265T patent/ATE499105T1/de not_active IP Right Cessation
- 2005-06-14 WO PCT/US2005/021165 patent/WO2005123094A2/en not_active Ceased
- 2005-06-14 MX MXPA06014416A patent/MXPA06014416A/es active IP Right Grant
- 2005-06-14 NZ NZ551726A patent/NZ551726A/en unknown
- 2005-06-14 TW TW094119690A patent/TW200612966A/zh unknown
- 2005-06-14 CN CNA2005800196020A patent/CN1972695A/zh active Pending
- 2005-06-14 DE DE602005026524T patent/DE602005026524D1/de not_active Expired - Lifetime
- 2005-06-14 RU RU2007101309/04A patent/RU2007101309A/ru not_active Application Discontinuation
- 2005-06-14 ZA ZA200610353A patent/ZA200610353B/xx unknown
- 2005-06-14 KR KR1020077000568A patent/KR20070043776A/ko not_active Ceased
- 2005-06-14 AU AU2005254095A patent/AU2005254095B2/en not_active Ceased
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| DE602005026524D1 (de) | 2011-04-07 |
| IL179616A0 (en) | 2007-05-15 |
| WO2005123094A2 (en) | 2005-12-29 |
| TW200612966A (en) | 2006-05-01 |
| CA2570477A1 (en) | 2005-12-29 |
| US7652000B2 (en) | 2010-01-26 |
| US20060009422A1 (en) | 2006-01-12 |
| MXPA06014416A (es) | 2007-03-08 |
| ZA200610353B (en) | 2010-07-28 |
| ATE499105T1 (de) | 2011-03-15 |
| CN1972695A (zh) | 2007-05-30 |
| JP2008502696A (ja) | 2008-01-31 |
| BRPI0512054A (pt) | 2008-02-06 |
| EP1765358A2 (en) | 2007-03-28 |
| NZ551726A (en) | 2010-09-30 |
| AR049915A1 (es) | 2006-09-13 |
| EP1765358B1 (en) | 2011-02-23 |
| AU2005254095B2 (en) | 2010-06-03 |
| AU2005254095A1 (en) | 2005-12-29 |
| WO2005123094A3 (en) | 2006-02-23 |
| RU2007101309A (ru) | 2008-07-20 |
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