KR840004754A - 2환화합물의 제조방법 - Google Patents

2환화합물의 제조방법 Download PDF

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KR840004754A
KR840004754A KR1019830002033A KR830002033A KR840004754A KR 840004754 A KR840004754 A KR 840004754A KR 1019830002033 A KR1019830002033 A KR 1019830002033A KR 830002033 A KR830002033 A KR 830002033A KR 840004754 A KR840004754 A KR 840004754A
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리차드 애트우드 미카엘 (외 4)
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진-쟈께 오게이, 마이나드 슈미트
에프.호프만-라 롯슈 앤드 캄파니 아크티엔 게젤샤프트
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Abstract

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Description

2환화합물의 제조방법
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (26)

  1. (1) 다음 일반식(Ⅱ)의 화합물을 다음 일반식(Ⅲ)의 화합물과 반응시키거나, (2) 다음 일반식(Ⅳ)의 화합물을 다음 일반식(Ⅴ)의 화합물로 환원적 알킬화시키거나, (3) R2가 알콕시카보닐 또는 아르알콕시카보닐 그룹 또는 다음 일반식(ⅱ)의 그룹을 나타내고 R3가 알콕시카보닐 또는 아르알콕시카보닐 그룹을 나타내는 일반식(Ⅰ)의 화합물을 제조하기 위해서는, R3가 알콕시카보닐 또는 아르알콕시카보닐 그룹을 나타내는 다음 일반식(Ⅳ)의 화합물을 다음 일반식(Ⅵ)의 화합물과 반응시키거나, (4) R2가 다음 일반식 (ⅱ)의 그룹을 나타내고 R3가 카복실 그룹 또는 3급 부톡시카보닐 그룹을 나타내는 일반식(Ⅰ)의 화합물을 제조하기 위해서는, R2가 알콕시카보닐 그룹을 나타내고 R3가 카복실 그룹 또는 3급 부톡시카보닐 그룹을 나타내는 일반식(Ⅰ)의 화합물을 다음 일반식(Ⅶ)의 화합물과 반응시키거나, (5) B가 에틸렌 그룹을나타내는 일반식(Ⅰ)의 화합물을 제조하기 위해서는, 촉매를 사용하여 B가 비닐렌그룹을 나타내는일반식(Ⅰ)의 화합물을 수소화시키거나, (6) R2및/또는 R3가 알콕시카보닐 또는 아테알콕시카보닐 그룹을 나타내는 일반식(Ⅰ)의 화합물을 제조하기 위해서는, R2및/또는 R3가 카복실 그룹을 나타내는 일반식(Ⅰ)의 화합물을 적절히 에스테르화시키거나, (7) R2및/또는 R3가 카복실 그룹을 나타내는 일반식(Ⅰ)의 화합물을 제조하기 위해서는, R2및/또는 R3가 알콕시카보닐 그룹을 나타내는 일반식(Ⅰ)의 화합물을 산 또는 염기로써 처리하거나, (8) B가 메틸렌 또는 에틸렌 그룹을 나타내고 R2및/또는 R3가 카복실 그룹을 나타내는 일반식(Ⅰ)의 화합물을 제조하기 위해서는 R2및/또는 R3가 아르알콕시카보닐 그룹을 나타내는 일반식(Ⅰ)의 화합물을 가수소 분해시키거나, (9) R1이 아미노-알킬 그룹을 나타내는 일반식(Ⅰ)의 화합물을 제조하기 위해서는, R1이 알콕시카보닐아미노-알킬, 아릴옥시카보닐아미노-알킬 또는 아르알콕시카보닐아미노-알킬그룹을 나타내는 일반식(Ⅰ)의 화합물로부터 알콕시카보닐, 아릴옥시카보닐 또는 아르알콕시카보닐 그룹을 분해시키고, (10) 필요할 경우, 수득한 부분입체이성질체 혼합물을 부분 입체이성질체 라세미체 또는 광학적으로 순수한 부분입체이성질체로 분리시키고, 및/또는 (11) 필요한 경우, 수득한 라세미체를 두개의 대장체로 분할하고, (12) 필요할 경우, 일반식(Ⅰ)의 화합물을 약제학적으로 허용되는 염으로 전환시킴을 특징으로 하여 다음 일반식(Ⅰ)의 화합물 및 그의 약제학적으로 허용되는 염을 제조하는 방법.
    상기식에서, B는 메틸렌, 에틸렌 또는 비닐렌 그룹을 나타내며, R1은 수소원자 또 알킬, 아르알킬, 아미노-알킬, 모노알킬아미노, 알킬, 디알킬아미노-알킬, 아실아미노-알킬, 프탈이미도-알킬, 알콕시-카보닐아미노-알킬, 아릴옥시카보닐아미노-알킬, 아르알콕시카보닐아미노-알킬, 알킬아미노카보닐, 아미노-알킬, 아릴아미노카보닐아미노-알킬, 아르알킬아미노카보닐아미노-알킬, 알킬술포닐아미노-알킬 또는 아릴술포닐아미노-알킬그룹을 나타내며, R2는 카복실, 알콕시카부닐 또는 아르알콕시카보닐 그룹이거나 다음 일반식(ⅰ) 또는 (ⅱ)의 그룹을 나타내며,
    R3는 카복실, 알콕시카보닐 또는 아르알콕시카보닐 그룹을 나타니며, R4와 R5는 각각 수소원자를 나타내거나 R4및 R5가 함께 옥소그룹을 나타내며, R6와 R7은 각각 수소원자 또는 알킬 또는 아르알킬그룹을 나타내거나 또는 이들이 부착된 집소원자와 함께 또 하나의 질소원자 또는 산소 또는 황원자를 함유할 수 있는 5원 또는 6원헤테로모노사이클릭 환을 나타내며, n은 0,1 또는 2를 나타내며, Hal은 할로겐 원자를 나타내며, R20은 알콕시카보닐 또는 아르알콕시카보닐 그룹 또는 상기 일반식(ⅱ)의 그룹을 나타내며, 그리고 Q는 이탈원자 또는 그룹을 나타낸다.
  2. 제1항에 있어서, R1이 수소원자 또는 알킬, 아르알킬, 아미노-알킬, 모노알킬아미노-알킬, 디알킬아미노-알킬, 아실아미노-알킬, 알콕시카보닐-아미노-알킬, 아릴옥시카보닐아미노-알킬, 아르알콕시-카보닐아미노-알킬, 알킬아미노카보닐아미노-알킬, 아릴아미노카보닐아미노-알킬, 아르알킬아미노카보닐아미노-알킬, 알킬술포닐아미노-알킬 또는 아릴술포닐아미노-알킬 그룹을 나타내고, R2가 카복실 또는 알콕시카보닐 그룹 또는 상기 구조식(1)의 그룹을 나타내며 R3가 카복실 또는 알콕시카보닐 그룹을 나타내는 일반식(Ⅰ)의 화합물 또는 이의 약학적으로 허용되는 염을 상기의 태양(1),(2),(5),(6),(7),(9),(10),(11) 및/또는 (12)에 따라 제조하는 방법.
  3. 제1항에 있어서, B가 메틸렌 또는 에틸렌그룹인 방법.
  4. 제1항 또는 3항에 있어서, R1이 알킬, 아르알킬, 아실아미노-알킬, 프탈이미도-알킬, 아르알콕시 카보닐아미노-알킬 또는 아릴아미노카보닐-아미노-알킬그룹인 방법.
  5. 제1항 3항 또는 4항에 있어서, R2가 카복실, 알콕시카보닐 또는 아르알콕시카보닐 그룹이거나 상기 일반식(ⅱ)의 그룹인 방법.
  6. 제1항 또는 제3항 내지 5항중의 어느 하나에 있어서, R3가 카복실 그룹인 방법.
  7. 제1항 또는 제3항 내지 6항중의 어느 하나에 있어서, n이 2인 방법.
  8. 제1항 또는 제3항 내지 7항중의 어느 하나에 있어서, B가 메틸렌 또는 에틸렌 그룹이고, R1이 알킬, 아르알킬, 아실아미노-알킬, 프탈이미도-알킬, 아르알콕시카보닐 아미노-알킬 또는 아릴아미노카보닐-아미노알킬그룹이고, R2가 카보실, 알콕시카보닐 또는 아르알콕시카보닐그룹이거나 상기 일반식(ⅱ)의 그룹이고, R3가 카복실 그룹이며 n이 2인 방법.
  9. 제2항에 있어서, 9(1-카복시-3-페닐프로필-아미노)-옥타하이드로-6,10-디옥소-6H-피리드아조-[1,2-a][1,2] 디아제핀-1-카복실 산을 제조하는 방법.
  10. 제2항에 있어서, 9-(1-에톡시카보닐-3-페닐프로필아미노)-옥타하이드로-6,13-디옥소-6H-피리드아조 [1,2-a][1,2] 디아제핀-1-카복실 산을 제조하는 방법.
  11. 제2항에 있어서, 8-(1-카복시-3-페닐프로필-아미노)-2,3,6,7,8, 9-헥사하이드로-5,9-디옥소-1H,5H-피르아졸로 [1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  12. 제1항에 있어서, 9-(1-벤질옥시카보닐-3-페닐프로필아미노)-옥타하이드로-6,10-디옥소-6H-피리드아조 [1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  13. 제1항에 있어서, 9-(1-카바모일-3-페닐프로필-아미노)-옥타하이드로-6,10-디옥소-6H-피리드아조-[1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  14. 제1항에 있어서, 9-(1-에틸카바모일-3-페닐프로필아미노)-옥타하이드로-6,10-디옥소-6H-피리드아조 [1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  15. 제1항에 있어서, 9-(1-카복시-4-페닐부틸-아미노)-옥타하이드로-6,10-디옥소
    -6H-피리드아조-[1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  16. 제1항에 있어서, 9-(1-카복시-2-페닐에틸아미노)-옥타하이드로-6,10-디옥소-6H-피리드아조[1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  17. 제1항에 있어서, 9-(1-카복시-4-메틸펜틸아미노)-옥타하이드로-6,10-디옥소-6H-피리드아조 [1,2-a]-[1,2] 디아제핀-1-카복실산을 제조하는 방법.
  18. 제1항에 있어서, 9-(1에톡시카보닐-4-메틸펜틸아미노)-옥타하이드로-6,10-디옥소-6H-피리드아조 [1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  19. 제1항에 있어서, 9-[3-(4-클로로페닐)-1-에톡시카보닐프로필아미노]-옥타하이드로-6,10-디옥소-6H-피리드아조 [1,2-a]-[1,2] 디아제핀-1-카복실산을 제조하는 방법.
  20. 제1항에 있어서, 9-[1-에톡시카보닐-3-(4-메톡시페닐)프로필아미노]-옥타하이드로-6,10-디옥소-6H-피리드아조 [1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  21. 제1항에 있어서, 9-[3-(4-비페닐)-1-에톡시카보닐프로필아미노]-옥타하이드로-6,10-디옥소-6H-피리드아조 [1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  22. 제1항에 있어서, 9-(1-에톡시카보닐-5-프탈이미도펜틸아미노)-옥타하이드로-6,10-디옥소-6H-피리드아조 [1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  23. 제1항에 있어서, 8-(1-에톡시카보닐-3-페닐프로필아미노)-2,3,6,7, 8,9-헥사하이드로-5,9-디옥소-1H,5H-피르아졸로 [1,2-a][1,2]-디아제핀-1-카복실산을 제조하는 방법.
  24. 제1항에 있어서, 9-(1-에톡시카보닐페닐-3-프로필아미노)-옥타하이드로-10-옥소-6H-피리드아조-[1,2-a][1,2] 디아제핀-1-카복실산을 제조하는 방법.
  25. 제1항에 있어서, 9-(5-벤질옥시포름아미도-1-에톡시카보닐펜틸아미노)-옥타하이드로-6, 10-디옥소-6H-피리드아조 [1,2-a][1,2]-디아제핀-1-카복실산을 제조하는 방법.
  26. 제1항 내지 25항중의 어느 하나에 있어서, 각 부재탄소원자에 있어서의 배향구조가 (S)인 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019830002033A 1982-05-12 1983-05-11 2환 화합물의 제조방법 KR890002106B1 (ko)

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Families Citing this family (102)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2128984B (en) * 1982-05-12 1985-05-22 Hoffmann La Roche Diaza-bicyclic compounds
NZ204130A (en) * 1982-05-12 1986-03-14 Hoffmann La Roche Bicyclic heterocyclic compounds and pharmaceutical compositions
DE3315464A1 (de) * 1983-04-28 1984-10-31 Hoechst Ag, 6230 Frankfurt Verfahren zur herstellung von n-alkylierten dipeptiden und deren estern
US4801721A (en) * 1984-08-16 1989-01-31 Ryan James W Stereospecific synthesis of carboxyalkyl peptides
US4692438A (en) * 1984-08-24 1987-09-08 Hoffmann-La Roche Inc. Pyridazo-diazepines, diazocines, and -triazepines having anti-hypertensive activity
IL78634A0 (en) * 1985-04-30 1986-08-31 Lilly Co Eli 7-substituted bicyclic pyrazolidinones
US4902707A (en) * 1985-04-30 1990-02-20 Eli Lilly And Company Bicyclic pyrazolidinones, compositions and use
US4940718A (en) * 1985-04-30 1990-07-10 Eli Lilly And Company 7-substituted bicyclic pyrazolidinones, pharmaceutical compositions and use
US4826992A (en) * 1985-04-30 1989-05-02 Eli Lilly And Company 2,3-(Dihydro) bicyclic pyrazolidinones
ZW11586A1 (en) * 1985-07-01 1987-12-30 Hoffmann La Roche Bicyclic compounds
US4832763A (en) * 1985-10-15 1989-05-23 Westinghouse Electric Corp. Method of stress-relief annealing a magnetic core containing amorphous material
DE3542794A1 (de) * 1985-12-04 1987-06-11 Bayer Ag Antihypertensives kombinationspraeparat
EP0254032A3 (en) * 1986-06-20 1990-09-05 Schering Corporation Neutral metalloendopeptidase inhibitors in the treatment of hypertension
EP0566157A1 (en) 1986-06-20 1993-10-20 Schering Corporation Neutral metalloendopeptidase inhibitors in the treatment of hypertension
GB8629875D0 (en) * 1986-12-15 1987-01-28 Hoffmann La Roche Pyridazodiazepine derivatives
US5262436A (en) * 1987-03-27 1993-11-16 Schering Corporation Acylamino acid antihypertensives in the treatment of congestive heart failure
US4956490A (en) * 1989-03-09 1990-09-11 Merck & Co., Inc. Process for preparing benzylpyruvic acids and esters
ZA902661B (en) * 1989-04-10 1991-01-30 Schering Corp Mercapto-acyl amino acids
DE3917255A1 (de) * 1989-05-26 1990-11-29 Schopf Masch Verfahren und vorrichtung zum aufnehmen eines flugzeugbugfahrwerks durch einen flugzeugschlepper
US5011938A (en) * 1989-10-02 1991-04-30 Eli Lilly And Company 7-substituted bicyclic pyrazolidinones
CA2069112A1 (en) * 1989-11-21 1991-05-22 Bernard R. Neustadt Carboxyalkylcarbonyl aminoacid endopeptidase inhibitors
WO1991009840A1 (en) * 1989-12-22 1991-07-11 Schering Corporation Mercaptocycloacyl aminoacid endopeptidase inhibitors
US5075302A (en) * 1990-03-09 1991-12-24 Schering Corporation Mercaptoacyl aminolactam endopeptidase inhibitors
US5173506A (en) * 1990-08-16 1992-12-22 Schering Corporation N-(mercaptoalkyl)ureas and carbamates
DE59107840D1 (de) * 1990-11-21 1996-06-27 Ciba Geigy Ag Silylierte Acylphosphinoxide
US5208230A (en) * 1990-12-21 1993-05-04 Merrell Dow Pharmaceuticals Amino and nitro containing tricyclic compounds useful as inhibitors of ACE
WO1992016510A1 (en) * 1991-03-19 1992-10-01 Ciba-Geigy Ag Novel herbicidally, acaricidally and insecticidally active compounds
TW216770B (ko) * 1991-07-23 1993-12-01 Hoffmann La Roche
CA2078759C (en) * 1991-09-27 2003-09-16 Alan M. Warshawsky Novel carboxyalkyl derivatives useful as inhibitors of enkephalinase and ace
US5455242A (en) * 1991-09-27 1995-10-03 Merrell Dow Pharmaceuticals Inc. Carboxyalkyl tricyclic derivatives useful as inhibitors of enkephalinase and ace
US5457196A (en) * 1991-09-27 1995-10-10 Merrell Dow Pharmaceuticals Inc. 2-substituted indane-2-carboxyalkyl derivatives useful as inhibitors of enkephalinase and ACE
JPH06107661A (ja) * 1991-10-24 1994-04-19 Upjohn Co:The イミダゾール誘導体およびこれを有効成分とする医薬組成物
US5442062A (en) * 1991-10-24 1995-08-15 The Upjohn Company Imidazole derivatives and pharmaceutical compositions containing the same
US5977160A (en) * 1992-04-10 1999-11-02 Brigham And Women's Hospital, Inc. Methods for reducing risk of repeat myocardial infarction and increasing survival in heart attack victims
US5972990A (en) * 1992-04-10 1999-10-26 Brigham And Women's Hospital, Inc. Methods for reducing risk of repeat myocardial infarction and increasing survival in heart attack victims
US5552397A (en) * 1992-05-18 1996-09-03 E. R. Squibb & Sons, Inc. Substituted azepinone dual inhibitors of angiotensin converting enzyme and neutral exdopeptidase
KR100281450B1 (ko) * 1992-05-15 2001-02-01 슈테펜 엘. 네스비트 엔케팔리나제 및 안지오텐신 전환 효소의 억제제로서 유용한 신규 메르캅토아세틸아미도 피리다조[1,2]피리다진, 피라졸로[1,2]피리다진, 피리다조[1,2-a][1,2]디아제핀 및 피라졸로[1,2-a][1,2]디아제핀 유도체
ATE203242T1 (de) * 1992-05-18 2001-08-15 Hoffmann La Roche Asymmetrische hydrierung
US5238932A (en) * 1992-05-20 1993-08-24 Merrell Dow Pharmaceuticals Inc. Mercaptoacetylamide tricyclic derivatives useful as inhibitors of enkephalinase
DK0669936T3 (da) * 1992-10-30 2001-02-05 Merrell Pharma Inc Mercaptoacetylamidsubstitueret bicyklisk lactam til anvendelse som enkephalinase- og ACE-inhibitorer
JPH072859A (ja) * 1993-01-28 1995-01-06 Upjohn Co:The ピラゾール誘導体およびこれを有効成分とする医薬組成物
US5476395A (en) * 1993-03-01 1995-12-19 Methode Electronics, Inc. Planar fuse panel
US5654294A (en) * 1993-05-13 1997-08-05 Bristol-Myers Squibb Spiro lactam dual action inhibitors
ATE198551T1 (de) * 1993-07-15 2001-01-15 Hoffmann La Roche Pharmazeutische kombination, die einen hemmer des renin-angiotensin-systems und einen endothelin- antagonisten enthält
HUT74385A (en) * 1994-02-14 1996-12-30 Merrell Pharma Inc Novel mercaptoacetylamido 1,3,4,5-tetrahydro-benzo[c]azepin-3-one disulfide derivatives useful as inhibitors of enkephalinase and ace
WO1995021839A1 (en) * 1994-02-14 1995-08-17 Merrell Pharmaceuticals Inc. Novel mercaptoacetylamide disulfide derivatives useful as inhibitors of enkephalinase and ace
US5530013A (en) * 1994-02-14 1996-06-25 American Home Products Corporation Venlafaxine in the inducement of cognition enhancement
DE69524064T2 (de) * 1994-02-14 2002-07-11 Merrell Pharma Inc Indan-2-mercaptoacetylamid disulfidderivate als enkephalinase inhibitoren
JP3561753B2 (ja) * 1994-02-14 2004-09-02 メレル ファーマスーティカルズ インコーポレーテッド エンケファリナーゼ及びａｃｅの阻害剤として有用な、新規な２−置換インダン−２−メルカプトアセチルアミドジスルフィド誘導体類
US5484783A (en) * 1994-03-24 1996-01-16 Merrell Dow Pharmaceuticals Inc. Hypocholesterolemic, antiatherosclerotic and hypotriglyceridemic mercaptoacetylamide and benzazapine derivatives
DK0751783T3 (da) * 1994-03-24 2000-06-26 Merrell Pharma Inc Hypokolesterolæmisk, antiatherosklerotisk og hypotriglyceridæmisk anvendelse af aminoacetylmercaptoderivater
NZ282565A (en) * 1994-03-24 1999-11-29 Merrell Pharma Inc Condensed mercaptoacetylamidedisulphidebenzazepines used in treating elevated cholesterol levels, atherosclerosis, and hypotriglyceridemia
US5756466A (en) 1994-06-17 1998-05-26 Vertex Pharmaceuticals, Inc. Inhibitors of interleukin-1β converting enzyme
US5587375A (en) * 1995-02-17 1996-12-24 Bristol-Myers Squibb Company Azepinone compounds useful in the inhibition of ACE and NEP
US5877313A (en) 1995-05-17 1999-03-02 Bristol-Myers Squibb Benzo-fused azepinone and piperidinone compounds useful in the inhibition of ACE and NEP
US5650408A (en) * 1995-06-07 1997-07-22 Karanewsky; Donald S. Thiazolo benzazepine containing dual action inhibitors
US5635504A (en) * 1995-06-07 1997-06-03 Bristol-Myers Squibb Co. Diazepine containing dual action inhibitors
AU2003200034B2 (en) * 1998-04-27 2006-07-20 Aventis Pharma S.A. New derivatives of octahydro-6, 10-dioxo-6H-pyridazino [1,2-A][1,2]diazepine-1-carboxylic acid, their preparation process and their use in the preparation of therapeutically active compounds
FR2777888B1 (fr) 1998-04-27 2004-07-16 Hoechst Marion Roussel Inc Nouveaux derives de l'acide (3,4,7,8,9,10-hexahydro-6,10- dioxo-6h-pyridazino[1,2-a][1,2]diazepine-1-carboxylique, leur procede de preparation et leur application a la preparation de medicaments
FR2777889B1 (fr) * 1998-04-27 2004-07-09 Hoechst Marion Roussel Inc Nouveaux derives de l'acide octahydro-6,10-dioxo-6h- pyridazino[1,2-a][1,2]diazepine-1-carboxylique, leur procede de preparation et leur application a la preparation de composes therapeutiquement actifs
US6703500B2 (en) 1998-08-19 2004-03-09 Vertex Pharmaceuticals, Incorporated Method of preparing bicyclic intermediates from piperazic acid or an ester thereof useful in the manufacture of caspase inhibitors
US6177565B1 (en) * 1998-08-19 2001-01-23 Vertex Pharmaceuticals Inc. Process for synthesizing piperazic acid
US6559304B1 (en) * 1998-08-19 2003-05-06 Vertex Pharmaceuticals Incorporated Method for synthesizing caspase inhibitors
FR2788276B1 (fr) * 1999-01-12 2001-02-16 Hoechst Marion Roussel Inc NOUVEAU PROCEDE DE PREPARATION DE COMPOSES BICYCLIQUES ET L'APPLICATION DE CE PROCEDE COMME ETAPE INTERMEDIAIRE POUR LA PREPARATION D'UN COMPOSE INHIBITEUR DE L'ENZYME DE CONVERSION DE L'INTERLEUKINE 1-BETA (ice)
AU3885901A (en) * 1999-09-21 2001-04-24 Emory University Methods and compositions for treating platelet-related disorders
US20030113330A1 (en) * 1999-11-08 2003-06-19 Uhal Bruce D. Methods for treating pulmonary fibrosis
AU3084802A (en) 2000-12-14 2002-06-24 Brigham & Womens Hospital Inflammatory markers as tools in the detection and prevention of diabetes mellitus and as tools to aid in the selection of agents to be used for the prevention and treatment of diabetes
GB0119305D0 (en) 2001-04-12 2001-10-03 Aventis Pharma Gmbh Mercaptoacetylamide derivatives,a process for their preparation and their use
ES2375181T3 (es) 2002-05-09 2012-02-27 The Brigham And Women's Hospital, Inc. 1l 1rl-1 como un marcador de enfermedades cardiovasculares.
US20040110241A1 (en) * 2002-12-06 2004-06-10 Segal Mark S. Materials and methods for monitoring vascular endothelial function
CA2510319A1 (en) 2002-12-20 2004-07-15 Thomas J. Smith High pressure compaction for pharmaceutical formulations
WO2004078761A1 (en) * 2003-03-06 2004-09-16 Ranbaxy Laboratories Limited Enantiomerically pure cilazapril,process for preparation
WO2005003134A1 (en) * 2003-07-07 2005-01-13 Hetero Drugs Limited A novel process for the preparation of cilazapril
EP3081214A3 (en) 2003-08-29 2016-11-16 The Brigham And Women's Hospital, Inc. Inhibitors of cellular necrosis
ATE546734T1 (de) 2003-12-05 2012-03-15 Cleveland Clinic Foundation Risikomarker für eine herzkreislaufkrankheit
US7803838B2 (en) * 2004-06-04 2010-09-28 Forest Laboratories Holdings Limited Compositions comprising nebivolol
WO2005122682A2 (en) 2004-06-18 2005-12-29 Ranbaxy Laboratories Limited Process for the preparation of esters of piperazic acid
WO2006042192A2 (en) 2004-10-06 2006-04-20 The Brigham And Womens's Hospital, Inc. Relevance of achieved levels of markers of systemic inflammation following treatment
EP1846380A4 (en) * 2005-01-21 2010-02-17 Nicox Sa HETEROCYCLIC NITROGEN MONOXIDE DONOR COMPOSITIONS CONTAINING CARDIOVASCULAR COMPOUNDS, AND METHODS OF USING THE SAME
EP1848424B1 (en) * 2005-01-31 2017-04-05 Mylan Laboratories, Inc Pharmaceutical composition comprising hydroxylated nebivolol
AP2896A (en) 2005-05-31 2014-05-31 Mylan Lab Inc Compositions comprising nebivolol
US8119358B2 (en) * 2005-10-11 2012-02-21 Tethys Bioscience, Inc. Diabetes-related biomarkers and methods of use thereof
DE602006000402T8 (de) 2006-06-02 2009-04-09 Teva Pharmaceutical Industries Ltd. Stabile Zubereitung enthaltend eine feuchtigkeitsempfindliche aktive Substanz und Verfahren zur Herstellung der Zubereitung.
US20070281000A1 (en) * 2006-06-02 2007-12-06 Michael Fox Stable formulation comprising moisture sensitive drug/s and manufacturing procedure thereof
EP2030025A2 (en) 2006-06-07 2009-03-04 Tethys Bioscience, Inc. Markers associated with arteriovascular events and methods of use thereof
US20080008751A1 (en) * 2006-07-10 2008-01-10 Michael Fox Stable formulation comprising a combination of a moisture sensitive drug and a second drug and manufacturing procedure thereof
ES2434215T3 (es) 2007-04-18 2013-12-16 Tethys Bioscience, Inc. Biomarcadores relacionados con la diabetes y métodos de uso de los mismos
US7828840B2 (en) * 2007-11-15 2010-11-09 Med Institute, Inc. Medical devices and methods for local delivery of angiotensin II type 2 receptor antagonists
GB2462022B (en) 2008-06-16 2011-05-25 Biovascular Inc Controlled release compositions of agents that reduce circulating levels of platelets and methods thereof
EP2221299A3 (en) 2009-02-11 2010-11-03 Dr. Reddy's Laboratories Ltd. Preparation of cilazapril intermediates
CN103037829A (zh) 2010-02-01 2013-04-10 儿童医院 用于治疗和预防再狭窄的远程缺血调节
CA2795053A1 (en) 2010-03-31 2011-10-06 The Hospital For Sick Children Use of remote ischemic conditioning to improve outcome after myocardial infarction
CA2800520A1 (en) 2010-04-08 2011-10-13 The Hospital For Sick Children Use of remote ischemic conditioning for traumatic injury
WO2012049646A1 (en) 2010-10-12 2012-04-19 Ranbaxy Laboratories Limited Process for the preparation of an intermediate of cilazapril
EP2537534B1 (en) 2011-06-22 2014-12-17 Hexal AG Esters of (1S,9S)-9-[[(1S)-1-carboxy-3-phenylpropyl]amino]octahydro-10-oxo-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid and their therapeutic use.
US8748110B2 (en) 2011-07-18 2014-06-10 Critical Care Diagnostics, Inc. Methods of treating cardiovascular diseases and predicting the efficacy of exercise therapy
CA2873214C (en) 2012-05-11 2021-02-16 Reset Therapeutics, Inc. Carbazole-containing sulfonamides as cryptochrome modulators
AU2013296803B2 (en) 2012-08-01 2018-03-08 Eric Ostertag Free flowing, frozen compositions comprising a therapeutic agent
US9725452B2 (en) 2013-03-15 2017-08-08 Presidents And Fellows Of Harvard College Substituted indoles and pyrroles as RIP kinase inhibitors
CN110575445B (zh) 2013-03-21 2023-08-18 优普顺药物公司美国分部 可注射的持续释放组合物及其用于治疗关节炎症及相关疼痛的方法
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ES2672993T3 (es) 2015-10-27 2018-06-19 Eupraxia Pharmaceuticals Inc. Formulaciones de liberación sostenida de anestésicos locales

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL58849A (en) * 1978-12-11 1983-03-31 Merck & Co Inc Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them
IL60617A0 (en) * 1979-07-23 1980-09-16 Sparamedica Ag Triazolopyridazine derivative,their preparation and pharmaceutical compositions containing them
EP0025941B1 (de) * 1979-09-19 1983-05-04 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Pyridazopyridazinderivate, Verfahren zu deren Herstellung und Arzneimittel enthaltend solche Pyridazopyridazinderivate
EP0042100A1 (de) * 1980-06-13 1981-12-23 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Pyrazolopyridazin-Derivate, Zwischenprodukte und Verfahren zu deren Herstellung, sowie diese enthaltende Arzneimittel
DE3169261D1 (en) * 1980-09-10 1985-04-18 Beecham Group Plc Aryl diazabicyclyl amides, a process for their preparation and use
GB2128984B (en) * 1982-05-12 1985-05-22 Hoffmann La Roche Diaza-bicyclic compounds

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DZ540A1 (fr) 2004-09-13
DE3381884D1 (de) 1990-10-25
DE3317290A1 (de) 1983-11-17
US4658024A (en) 1987-04-14
ES8601994A1 (es) 1985-11-16
FR2531956B1 (fr) 1987-02-20
KR890002106B1 (ko) 1989-06-19
DOP1983004163A (es) 1988-09-20
LU84803A1 (fr) 1985-03-21
FI77244B (fi) 1988-10-31
ES8607970A1 (es) 1986-06-16
SE8302716L (sv) 1983-11-13
DK194783D0 (da) 1983-05-02
US4772701A (en) 1988-09-20
DK194783A (da) 1983-11-13
AR240940A2 (es) 1991-03-27
HK91692A (en) 1992-11-27
EP0094095B1 (de) 1990-09-19
ES528630A0 (es) 1986-06-16
DK160612B (da) 1991-04-02
HU199842B (en) 1990-03-28
MY102889A (en) 1993-03-31
ES528625A0 (es) 1985-05-16
SG81192G (en) 1993-01-29
DK160612C (da) 1991-09-23
NO160368C (no) 1989-04-12
SE8302716D0 (sv) 1983-05-11
AU1436483A (en) 1983-11-17
FI831661L (fi) 1983-11-13
ES8407049A1 (es) 1984-08-16
LU88299I2 (fr) 1994-09-09
MC1515A1 (fr) 1984-02-10
CS249128B2 (en) 1987-03-12
GB2128984B (en) 1985-05-22
GB8305505D0 (en) 1983-03-30
BG61123B2 (bg) 1996-11-29
CU21532A3 (en) 1987-06-09
IE56480B1 (en) 1991-08-14
FI831661A0 (fi) 1983-05-12
ES8800170A1 (es) 1987-11-01
IE831084L (en) 1983-11-12
ES528627A0 (es) 1985-11-16
ES8505173A1 (es) 1985-05-16
NL930055I1 (nl) 1993-09-01
ES8706672A1 (es) 1987-07-16
IT1212738B (it) 1989-11-30
AR240940A1 (es) 1991-03-27
NL8301640A (nl) 1983-12-01
HU198935B (en) 1989-12-28
FI77244C (fi) 1989-02-10
FR2531956A1 (fr) 1984-02-24
IL68620A (en) 1987-11-30
NO831675L (no) 1983-11-14
ZW9883A1 (en) 1984-11-21
CS402191A3 (en) 1992-10-14
GR77462B (ko) 1984-09-24
EP0094095A3 (en) 1984-11-21
ES554935A0 (es) 1987-11-01
US4512924A (en) 1985-04-23
IT8321000A0 (it) 1983-05-09
AU567873B2 (en) 1987-12-10
HU195965B (en) 1988-08-29
NO160368B (no) 1989-01-02
SE461792B (sv) 1990-03-26
NL930055I2 (nl) 1993-10-01
GB2128984A (en) 1984-05-10
PT76681A (en) 1983-06-01
ES528628A0 (es) 1987-07-16
IL68620A0 (en) 1983-09-30
PT76681B (en) 1986-05-20
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CA1234568A (en) 1988-03-29
EP0094095A2 (de) 1983-11-16

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