CL2014002326A1 - Combinacion que comprende benzodioxanos y uno o mas agentes activos y su uso en el tratamiento de enfermedades tales como ateroesclerosis e infarto al miocardio. - Google Patents

Combinacion que comprende benzodioxanos y uno o mas agentes activos y su uso en el tratamiento de enfermedades tales como ateroesclerosis e infarto al miocardio.

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Publication number
CL2014002326A1
CL2014002326A1 CL2014002326A CL2014002326A CL2014002326A1 CL 2014002326 A1 CL2014002326 A1 CL 2014002326A1 CL 2014002326 A CL2014002326 A CL 2014002326A CL 2014002326 A CL2014002326 A CL 2014002326A CL 2014002326 A1 CL2014002326 A1 CL 2014002326A1
Authority
CL
Chile
Prior art keywords
benzodioxanes
atherosclerosis
diseases
treatment
combination
Prior art date
Application number
CL2014002326A
Other languages
English (en)
Spanish (es)
Inventor
Lars Anders Bylock
Original Assignee
Boehringer Ingelheim Int
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int
Publication of CL2014002326A1 publication Critical patent/CL2014002326A1/es

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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
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Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103415513B (zh) 2011-03-14 2016-01-20 勃林格殷格翰国际有限公司 白三烯产物的苯并二氧杂环己烷抑制剂
EP2734516B1 (en) 2011-07-19 2015-06-17 Boehringer Ingelheim International GmbH Arylpyrazole ethers as inhibitors of leukotriene a4 hydrolase
JP6080226B2 (ja) 2012-03-06 2017-02-15 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 他の活性物質と組み合わせたロイコトリエン産生阻害用ベンゾジオキサン
WO2013134226A1 (en) * 2012-03-06 2013-09-12 Boehringer Ingelheim International Gmbh Benzodioxanes for inhibiting leukotriene production
US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
WO2014014874A1 (en) 2012-07-17 2014-01-23 Boehringer Ingelheim International Gmbh Pyrazole derivatives which inhibit leukotriene production
PL2978859T3 (pl) 2013-03-27 2018-10-31 F.Hoffmann-La Roche Ag Markery genetyczne do przewidywania reakcji na terapię
JP2016523982A (ja) 2013-07-15 2016-08-12 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 ロイコトリエン生成の阻害剤
EP3022193B1 (en) 2013-07-15 2017-04-26 Boehringer Ingelheim International GmbH Inhibitors of leukotriene production
EP3795695A1 (en) 2014-07-30 2021-03-24 F. Hoffmann-La Roche AG Genetic markers for predicting responsiveness to therapy
US10968193B2 (en) * 2014-08-08 2021-04-06 Merck Sharp & Dohme Corp. Antidiabetic bicyclic compounds
CN104181252B (zh) * 2014-09-01 2015-12-02 广东东阳光药业有限公司 一种分离检测安塞曲匹及其异构体的方法
CN105748469B (zh) * 2016-02-24 2019-07-23 长沙佰顺生物科技有限公司 一种安塞曲匹辛伐他汀药物组合物
WO2017170830A1 (ja) * 2016-03-31 2017-10-05 武田薬品工業株式会社 複素環化合物
KR20230051227A (ko) 2020-08-14 2023-04-17 노파르티스 아게 헤테로아릴 치환된 스피로피페리디닐 유도체 및 이의 제약 용도
CN112076189B (zh) * 2020-09-23 2021-11-12 唐怡庭 一种酰胺化合物在制备治疗脓毒症药物中的应用
US11957671B2 (en) 2021-11-01 2024-04-16 Alkahest, Inc. Benzodioxane modulators of leukotriene A4 hydrolase (LTA4H) for prevention and treatment of aging-associated diseases

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US498770A (en) * 1893-06-06 Electrolytic apparatus
US4918092A (en) * 1983-12-21 1990-04-17 Merck Frosst Canada, Inc. Leukotriene antagonists
US5120758A (en) 1991-02-08 1992-06-09 Ciba-Geigy Corporation Certain benzodioxole, benzodioxane and benzodioxepin derivatives useful as 5-lipoxygenase inhibitors
DE4127849A1 (de) 1991-08-22 1993-02-25 Merck Patent Gmbh Benzodioxanderivate
US6506876B1 (en) 1994-10-11 2003-01-14 G.D. Searle & Co. LTA4 hydrolase inhibitor pharmaceutical compositions and methods of use
US5585492A (en) 1994-10-11 1996-12-17 G. D. Searle & Co. LTA4 Hydrolase inhibitors
DE19705450A1 (de) 1997-02-13 1998-08-20 Merck Patent Gmbh Bicyclische aromatische Aminosäuren
DE19821003A1 (de) 1998-05-11 1999-11-18 Dresden Arzneimittel Neue 1,2,5-trisubstituierte 1,2-dihydro-indazol-3-one mit antiasthmatischer, antiallergischer, entzündungshemmender, immunmodulierender und neuroprotektiver Wirkung, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
KR20030061825A (ko) 2000-10-26 2003-07-22 화이자 프로덕츠 인크. 피리미딘-2,4,6-트리온 메탈로프로테이나제 억제제
US20060019269A1 (en) * 2002-10-17 2006-01-26 Decode Genetics, Inc. Susceptibility gene for myocardial infarction, stroke, and PAOD, methods of treatment
NZ540148A (en) 2002-12-20 2007-11-30 Glaxo Group Ltd Benzazepine derivatives for the treatment of neurological disorders
US7098222B2 (en) 2004-05-12 2006-08-29 Abbott Laboratories Bicyclic-substituted amines having cyclic-substituted monocyclic substituents
CN101098866A (zh) 2005-01-07 2008-01-02 辉瑞产品公司 杂芳族喹啉化合物及其作为pde10抑制剂的用途
CN101189012A (zh) 2005-03-31 2008-05-28 詹森药业有限公司 苯基和吡啶基lta4h调节剂
UA101943C2 (ru) 2005-09-21 2013-05-27 Декод Дженетикс Ехф Биарилзамещенные гетероциклические ингибиторы lta4h для лечения воспаления
WO2007073405A1 (en) 2005-12-21 2007-06-28 Decode Genetics Ehf N-linked aryl heteroaryl inhibitors of lta4h for treating inflammation
AU2006333522A1 (en) 2005-12-21 2007-07-12 Decode Genetics, Ehf. Biaryl nitrogen heterocycle inhibitors of LTA4H for treating inflammation
CL2007003065A1 (es) 2006-10-24 2008-01-25 Wyeth Corp Compuestos derivados de benzodioxano, agonista 5ht2c, composicion farmaceutica que lois comprende; y sus uso en el tratamiento de un trastorno psicotico, ansiedad, depresion, trastorno bipolar, sindrome premenstrual, entre otros
MX2010011154A (es) 2008-04-11 2010-12-21 Janssen Pharmaceutica Nv Tiazolopiridin-2-iloxi-fenilo y tiazolopirazin-2-iloxifenilaminas como moduladores de la leucotrieno a4 hidrolasa.
ES2567311T3 (es) 2009-04-08 2016-04-21 Actelion Pharmaceuticals Ltd. 6-(3-Aza-biciclo[3.1.0]hex-3-il)-2-fenil-pirimidinas como antagonistas del receptor de ADP
WO2011032050A2 (en) 2009-09-11 2011-03-17 Trius Therapeutics, Inc. Gyrase inhibitors
CN102946877B (zh) 2010-03-18 2019-07-05 香港科技大学 乳突果及其分离的化合物在制备用于治疗神经疾病的药物中的用途
CN103415513B (zh) * 2011-03-14 2016-01-20 勃林格殷格翰国际有限公司 白三烯产物的苯并二氧杂环己烷抑制剂
EP2734516B1 (en) 2011-07-19 2015-06-17 Boehringer Ingelheim International GmbH Arylpyrazole ethers as inhibitors of leukotriene a4 hydrolase
WO2013134226A1 (en) 2012-03-06 2013-09-12 Boehringer Ingelheim International Gmbh Benzodioxanes for inhibiting leukotriene production
JP6080226B2 (ja) 2012-03-06 2017-02-15 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 他の活性物質と組み合わせたロイコトリエン産生阻害用ベンゾジオキサン
WO2014014874A1 (en) 2012-07-17 2014-01-23 Boehringer Ingelheim International Gmbh Pyrazole derivatives which inhibit leukotriene production

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