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PE20050395A1 - PROCEDIMIENTOS DE PREPARACION DE DERIVADOS DE ACIDO PIRROLIDIN-1,2-DICARBOXILICO-1-(FENIL(-AMIDA))-2-(FENIL(-AMIDA)) Y ACIDO-1-(FENILCARBAMOIL)-PIRROLIDIN-2-CARBOXILICO COMO INHIBIDORES DEL FACTOR Xa - Google Patents

PROCEDIMIENTOS DE PREPARACION DE DERIVADOS DE ACIDO PIRROLIDIN-1,2-DICARBOXILICO-1-(FENIL(-AMIDA))-2-(FENIL(-AMIDA)) Y ACIDO-1-(FENILCARBAMOIL)-PIRROLIDIN-2-CARBOXILICO COMO INHIBIDORES DEL FACTOR Xa

Info

Publication number
PE20050395A1
PE20050395A1 PE2004000349A PE2004000349A PE20050395A1 PE 20050395 A1 PE20050395 A1 PE 20050395A1 PE 2004000349 A PE2004000349 A PE 2004000349A PE 2004000349 A PE2004000349 A PE 2004000349A PE 20050395 A1 PE20050395 A1 PE 20050395A1
Authority
PE
Peru
Prior art keywords
pyrrolidin
phenyl
amide
acid
oxo
Prior art date
Application number
PE2004000349A
Other languages
English (en)
Inventor
Werner Mederski
Christos Tsaklakidis
Dieter Dorsch
Johannes Gleitz
Bertram Cezanne
Original Assignee
Merck Patent Gmbh
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
Priority claimed from DE10315377A external-priority patent/DE10315377A1/de
Priority claimed from DE10327428A external-priority patent/DE10327428A1/de
Priority claimed from DE2003129295 external-priority patent/DE10329295A1/de
Priority claimed from DE2003134174 external-priority patent/DE10334174A1/de
Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh
Publication of PE20050395A1 publication Critical patent/PE20050395A1/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

SE REFIERE A UN PROCEDIMIENTO DE PREPARACION DE COMPUESTOS DERIVADOS DE PIRROLIDINA DE FORMULA (I), EN DONDE R ES HAL O CºCH; R1 ES H, =O, HAL, A, OH, A-COO-, ENTRE OTROS; R2 ES H, HAL O A; R3 ES 2-OXO-PIPERIDIN-1-ILO, 2-OXO-PIRROLIDIN-1-ILO, 2-OXO-1H-PIRIDIN-1-ILO, ENTRE OTROS; A ES ALQUILO LINEAL, RAMIFICADO O CICLICO(C1-C10), QUE COMPRENDE EN: a) TRANSFORMAR UN ACIDO R1-PIRROLIDIN-2-CARBOXILICO (CIS R1-D-PROLINA) CON UN 4-R-FENILISOCIANATO PARA DAR UN ACIDO -1-(4-R-FENILCARBAMIL-R1-PIRROLIDIN-2-CARBOXILICO b) TRANSFORMAR EL COMPUESTO OBTENIDO ANTERIORMENTE CON UN AMINOFENILR3R2, PARA DAR EL COMPUESTO DE FORMULA I, Y c) CONVERTIR EL MISMO, EN SUS DERIVADOS Y/O SOLVATOS DE USO FARMACEUTICO TRANSFORMANDO UNA BASE O UN ACIDO EN SUS SALES. SON COMPUESTOS PREFERIDOS: ACIDO (2R,4R)-4-HIDROXI-PIRROLIDIN-1,2-DICARBOXILICO-1-[(4-CLORO-FENIL)-AMIDO]-2-{[4-(3-OXO-MORFOLIN-4-IL)-FENIL]-AMIDA}, ACIDO (2R)-PIRROLIDIN-1,2-DICARBOXILICO-1-[(4-CLORO-FENIL)-AMIDO]-2-{[3-TRIFLUOROMETIL-4-(3-OXO-MORFOLIN-4-IL)-FENIL]-AMIDA}, ACIDO (2R,4S)-4-METOXI-PIRROLIDIN-1,2-DICARBOXILICO-1-[(4-CLORO-FENIL)-AMIDO]-2-{[4-(3-OXO-MORFOLIN-4-IL)-FENIL]-AMIDA}, ENTRE OTROS. ESTOS COMPUESTOS SON INHIBIDORES DEL FACTOR Xa Y SON UTILES PARA TRATAR Y/O PREVENIR ENFERMEDADES TROMBOEMBOLICAS COMO TROMBOSIS, INFARTO DEL MIOCARDIO, ARTERIOSCLEROSIS, INFLAMACIONES, APOPLEJIA, ANGINA DE PECHO, RESTONOSIS POSTERIORES A ANGIOPLASTIA Y CLAUDICACION INTERMITENTE
PE2004000349A 2003-04-03 2004-04-02 PROCEDIMIENTOS DE PREPARACION DE DERIVADOS DE ACIDO PIRROLIDIN-1,2-DICARBOXILICO-1-(FENIL(-AMIDA))-2-(FENIL(-AMIDA)) Y ACIDO-1-(FENILCARBAMOIL)-PIRROLIDIN-2-CARBOXILICO COMO INHIBIDORES DEL FACTOR Xa PE20050395A1 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE10315377A DE10315377A1 (de) 2003-04-03 2003-04-03 Carbonylverbindungen
DE10327428A DE10327428A1 (de) 2003-06-18 2003-06-18 Ethinylprolinderivate
DE2003129295 DE10329295A1 (de) 2003-06-30 2003-06-30 Carbonylverbindungen
DE10329457A DE10329457A1 (de) 2003-04-03 2003-07-01 Ethinylprolinderivate
DE2003134174 DE10334174A1 (de) 2003-07-26 2003-07-26 Pyrrolidinderivate und Verfahren zur Herstellung

Publications (1)

Publication Number Publication Date
PE20050395A1 true PE20050395A1 (es) 2005-06-04

Family

ID=33136213

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2004000349A PE20050395A1 (es) 2003-04-03 2004-04-02 PROCEDIMIENTOS DE PREPARACION DE DERIVADOS DE ACIDO PIRROLIDIN-1,2-DICARBOXILICO-1-(FENIL(-AMIDA))-2-(FENIL(-AMIDA)) Y ACIDO-1-(FENILCARBAMOIL)-PIRROLIDIN-2-CARBOXILICO COMO INHIBIDORES DEL FACTOR Xa

Country Status (16)

Country Link
US (1) US7504500B2 (es)
EP (1) EP1608646B1 (es)
JP (1) JP4634369B2 (es)
KR (1) KR20050118709A (es)
AR (1) AR043831A1 (es)
AT (1) ATE366732T1 (es)
AU (1) AU2004226280B2 (es)
BR (1) BRPI0408888A (es)
CA (1) CA2520893C (es)
DE (2) DE10329457A1 (es)
ES (1) ES2287708T3 (es)
MX (1) MXPA05010433A (es)
PE (1) PE20050395A1 (es)
PL (1) PL377138A1 (es)
TW (1) TW200500339A (es)
WO (1) WO2004087695A1 (es)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050119266A1 (en) * 2003-10-01 2005-06-02 Yan Shi Pyrrolidine and piperidine derivatives as factor Xa inhibitors
DE102004004731A1 (de) * 2004-01-30 2005-08-18 Merck Patent Gmbh Harnstoffderivate
DE102004045796A1 (de) * 2004-09-22 2006-03-23 Merck Patent Gmbh Arzneimittel enthaltend Carbonylverbindungen sowie deren Verwendung
DE102004047254A1 (de) * 2004-09-29 2006-04-13 Merck Patent Gmbh Carbonylverbindungen
DE102004050283A1 (de) * 2004-10-15 2006-04-27 Lanxess Deutschland Gmbh 4-Aminophenyl-morpholinon-Derivate und deren Herstellung
US7301817B2 (en) * 2005-10-27 2007-11-27 Sandisk Corporation Method for programming of multi-state non-volatile memory using smart verify
AU2006314637A1 (en) * 2005-11-16 2007-05-24 F. Hoffmann-La Roche Ag Novel pyrrolidine derivatives as inhibitors of coagulation factor Xa
EP1818330A1 (de) * 2006-02-14 2007-08-15 Boehringer Ingelheim Pharma GmbH & Co.KG Substituierte Prolinamide, deren Herstellung und deren Verwendung als Arzneimittel
EA200802210A1 (ru) 2006-05-16 2009-06-30 Бёрингер Ингельхайм Интернациональ Гмбх Замещенные пролинамиды, их получение и их применение в качестве лекарственных средств
US8673920B2 (en) 2009-05-06 2014-03-18 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
EP2632465B1 (en) 2010-10-27 2015-12-30 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
US9056859B2 (en) 2010-10-29 2015-06-16 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
EP2744499B1 (en) 2011-08-19 2016-09-28 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
US9527830B2 (en) 2011-09-16 2016-12-27 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
WO2013062892A1 (en) 2011-10-25 2013-05-02 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
WO2013062900A1 (en) 2011-10-25 2013-05-02 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
EP2773351B1 (en) 2011-10-31 2017-08-23 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
EP2773199B1 (en) 2011-10-31 2019-04-10 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
EP2773206B1 (en) 2011-10-31 2018-02-21 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
EP2790511B1 (en) 2011-12-16 2016-09-14 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
AR092031A1 (es) 2012-07-26 2015-03-18 Merck Sharp & Dohme Inhibidores del canal de potasio medular externo renal
US9777002B2 (en) 2012-11-29 2017-10-03 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
US9573961B2 (en) 2012-12-19 2017-02-21 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
EP2956142B1 (en) 2013-02-18 2017-09-20 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
US9765074B2 (en) 2013-03-15 2017-09-19 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
US9751881B2 (en) 2013-07-31 2017-09-05 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel
WO2015065866A1 (en) 2013-10-31 2015-05-07 Merck Sharp & Dohme Corp. Inhibitors of the renal outer medullary potassium channel

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5822111B2 (ja) * 1977-10-29 1983-05-06 協和醗酵工業株式会社 柑橘類果実の改質剤
JPS63232846A (ja) * 1987-03-20 1988-09-28 Haruo Ogura 新規な固定相担体
AU4966497A (en) * 1996-11-18 1998-06-10 Yamanouchi Pharmaceutical Co., Ltd. Novel acylamino-substituted acylanilide derivatives or pharmaceutical composition comprising the same
US7030141B2 (en) * 2001-11-29 2006-04-18 Christopher Franklin Bigge Inhibitors of factor Xa and other serine proteases involved in the coagulation cascade

Also Published As

Publication number Publication date
ATE366732T1 (de) 2007-08-15
US20060211692A1 (en) 2006-09-21
MXPA05010433A (es) 2005-11-04
US7504500B2 (en) 2009-03-17
CA2520893C (en) 2012-07-10
AU2004226280B2 (en) 2010-06-17
PL377138A1 (pl) 2006-01-23
TW200500339A (en) 2005-01-01
ES2287708T3 (es) 2007-12-16
JP4634369B2 (ja) 2011-02-16
DE10329457A1 (de) 2005-01-20
AR043831A1 (es) 2005-08-17
AU2004226280A1 (en) 2004-10-14
EP1608646A1 (de) 2005-12-28
DE502004004294D1 (de) 2007-08-23
KR20050118709A (ko) 2005-12-19
JP2006522037A (ja) 2006-09-28
WO2004087695A1 (de) 2004-10-14
BRPI0408888A (pt) 2006-04-11
CA2520893A1 (en) 2004-10-14
EP1608646B1 (de) 2007-07-11

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