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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- 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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| US57942104P | 2004-06-14 | 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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| US7767657B2 (en) | 2005-02-16 | 2010-08-03 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| ES2872962T3 (es) | 2005-02-16 | 2021-11-03 | Anacor Pharmaceuticals Inc | Boronoftalidas para uso terapéutico |
| MX2007011486A (es) * | 2005-03-24 | 2007-11-20 | Anacor Pharmaceuticals Inc | Formulaciones topicas de antibioticos de acido borinico y sus metodos de uso. |
| EP1965647A2 (en) * | 2005-12-28 | 2008-09-10 | Anacor Pharmaceuticals, Inc. | Process for manufacturing picolinate borinic esters |
| RU2642628C2 (ru) | 2006-02-16 | 2018-01-25 | Анакор Фармасьютикалз, Инк. | Бор-содержащие малые молекулы в качестве противовоспалительных средств |
| BRPI0713010A2 (pt) * | 2006-06-12 | 2012-10-09 | Anacor Pharmaceuticals Inc | compostos para o tratamento de doença periodontal |
| EP3246034A1 (en) | 2008-03-06 | 2017-11-22 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-inflammatory agents |
| WO2010018836A2 (ja) * | 2008-08-11 | 2010-02-18 | 独立行政法人科学技術振興機構 | ポリグルタミン凝集阻害剤 |
| WO2010027975A1 (en) | 2008-09-04 | 2010-03-11 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| US8461336B2 (en) | 2008-09-04 | 2013-06-11 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| US9493489B2 (en) * | 2008-10-15 | 2016-11-15 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-protozoal agents |
| TW201110996A (en) | 2009-06-03 | 2011-04-01 | Colgate Palmolive Co | Borinic compositions |
| AP4039A (en) * | 2009-08-14 | 2017-02-28 | Daitao Chen | Boron-containing small molecules as antiprotozoal agents |
| WO2011049971A1 (en) | 2009-10-20 | 2011-04-28 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
| US8461134B2 (en) | 2009-11-11 | 2013-06-11 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| US8716478B2 (en) | 2010-01-27 | 2014-05-06 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
| WO2011116348A1 (en) | 2010-03-19 | 2011-09-22 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-protozoal agent |
| DK2613788T3 (en) | 2010-09-07 | 2017-08-07 | Anacor Pharmaceuticals Inc | BENZOXABOROLD DERIVATIVES FOR TREATMENT OF BACTERIA INFECTIONS |
| US9585396B2 (en) | 2013-01-30 | 2017-03-07 | Agrofresh Inc. | Volatile applications against pathogens |
| US10070649B2 (en) | 2013-01-30 | 2018-09-11 | Agrofresh Inc. | Volatile applications against pathogens |
| US8669207B1 (en) | 2013-01-30 | 2014-03-11 | Dow Agrosciences, Llc. | Compounds and compositions |
| AR094666A1 (es) | 2013-01-30 | 2015-08-19 | Dow Agrosciences Llc | Uso de benzoxaborolas como agentes antimicrobianos volátiles en carnes, plantas o partes de plantas |
| 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 |
| KR101756785B1 (ko) * | 2015-03-10 | 2017-07-12 | 한국화학연구원 | 4배위 유기 붕소 화합물의 제조방법 |
| IES86830B2 (en) * | 2015-06-24 | 2017-10-04 | Oriel Seasalt Company Ltd | A super-concentrated seawater mineral extract and uses thereof |
| WO2017155879A1 (en) | 2016-03-07 | 2017-09-14 | Agrofresh Inc. | Synergistic methods of using benzoxaborole compounds and preservative gases as an antimicrobial for crops |
| US10961261B2 (en) | 2017-03-01 | 2021-03-30 | Anacor Pharmaceuticals, Inc. | Oxaborole analogs and uses thereof |
| WO2022043936A1 (en) | 2020-08-31 | 2022-03-03 | 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 |
| EP1233772A4 (en) | 1999-11-19 | 2004-06-16 | Topgene Inc | Boron compounds and complexes as anti-inflammatories |
| MXPA05006685A (es) * | 2002-12-18 | 2005-12-14 | Anacor Pharmaceuticals Inc | Antibioticos que contienen complejos de acido borinico y metodos de uso. |
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2005
- 2005-06-13 AR ARP050102416A patent/AR049915A1/es unknown
- 2005-06-14 CA CA002570477A patent/CA2570477A1/en not_active Abandoned
- 2005-06-14 CN CNA2005800196020A patent/CN1972695A/zh active Pending
- 2005-06-14 ZA ZA200610353A patent/ZA200610353B/xx unknown
- 2005-06-14 NZ NZ551726A patent/NZ551726A/en unknown
- 2005-06-14 RU RU2007101309/04A patent/RU2007101309A/ru not_active Application Discontinuation
- 2005-06-14 MX MXPA06014416A patent/MXPA06014416A/es active IP Right Grant
- 2005-06-14 KR KR1020077000568A patent/KR20070043776A/ko not_active Ceased
- 2005-06-14 DE DE602005026524T patent/DE602005026524D1/de not_active Expired - Lifetime
- 2005-06-14 BR BRPI0512054-3A patent/BRPI0512054A/pt not_active IP Right Cessation
- 2005-06-14 EP EP05786265A patent/EP1765358B1/en not_active Expired - Lifetime
- 2005-06-14 WO PCT/US2005/021165 patent/WO2005123094A2/en not_active Ceased
- 2005-06-14 AU AU2005254095A patent/AU2005254095B2/en not_active Ceased
- 2005-06-14 JP JP2007516688A patent/JP2008502696A/ja not_active Withdrawn
- 2005-06-14 US US11/153,765 patent/US7652000B2/en not_active Expired - Fee Related
- 2005-06-14 AT AT05786265T patent/ATE499105T1/de not_active IP Right Cessation
- 2005-06-14 TW TW094119690A patent/TW200612966A/zh unknown
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| JP2008502696A (ja) | 2008-01-31 |
| EP1765358A2 (en) | 2007-03-28 |
| BRPI0512054A (pt) | 2008-02-06 |
| EP1765358B1 (en) | 2011-02-23 |
| NZ551726A (en) | 2010-09-30 |
| IL179616A0 (en) | 2007-05-15 |
| AR049915A1 (es) | 2006-09-13 |
| US20060009422A1 (en) | 2006-01-12 |
| AU2005254095B2 (en) | 2010-06-03 |
| RU2007101309A (ru) | 2008-07-20 |
| TW200612966A (en) | 2006-05-01 |
| DE602005026524D1 (de) | 2011-04-07 |
| MXPA06014416A (es) | 2007-03-08 |
| WO2005123094A3 (en) | 2006-02-23 |
| CA2570477A1 (en) | 2005-12-29 |
| US7652000B2 (en) | 2010-01-26 |
| ATE499105T1 (de) | 2011-03-15 |
| WO2005123094A2 (en) | 2005-12-29 |
| ZA200610353B (en) | 2010-07-28 |
| AU2005254095A1 (en) | 2005-12-29 |
| CN1972695A (zh) | 2007-05-30 |
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