AR040472A1 - Derivado de 2-(fenil)-2h-pirazol-3-carboxilico-n-4(tioxo-heterociclil)fenil-amida e imino-heterociclil derivados y compuestos relacionados, procedimiento, medicamentos, kit - Google Patents

Derivado de 2-(fenil)-2h-pirazol-3-carboxilico-n-4(tioxo-heterociclil)fenil-amida e imino-heterociclil derivados y compuestos relacionados, procedimiento, medicamentos, kit

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Publication number
AR040472A1
AR040472A1 AR20030102321A ARP030102321A AR040472A1 AR 040472 A1 AR040472 A1 AR 040472A1 AR 20030102321 A AR20030102321 A AR 20030102321A AR P030102321 A ARP030102321 A AR P030102321A AR 040472 A1 AR040472 A1 AR 040472A1
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AR
Argentina
Prior art keywords
atoms
mono
hal
con
coor2
Prior art date
Application number
AR20030102321A
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English (en)
Inventor
Cezanne Bertram Dr
Mederski Werner Dr
Tsaklakidis Christos Dr
Gleitz Johannes Dr
Dorsch Dieter Dr
Barnes Christopher Dr
Original Assignee
Merck Patent Gmbh
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Publication date
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Publication of AR040472A1 publication Critical patent/AR040472A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/12—Heterocyclic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/433—Thidiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Los compuestos son inhibidores del factor de coagulación Xa y pueden emplearse para la profilaxis y/o la terapia de enfermedades tromboembólicas y para el tratamiento de tumores. Reivindicación 1: Compuestos de la fórmula (1) donde: D está ausente o es una cadena de alquileno saturada, total o parcialmente no saturado de 3 a 4 miembros, en la cual 1 a 3 átomos de C pueden estar reemplazados por un átomo de N y/o 1 a 2 átomos de C pueden estar reemplazados por 1 a 2 átomos de O y/o 1 a 2 átomos de S, pero donde se reemplazan a lo sumo hasta 3 átomos de C y donde adicionalmente puede aparecer un mono, di o trisustitución de la cadena de alquileno y/o de un nitrógeno que se encuentra allí por Hal, A, -[C(R3)2]n-Ar, -[C(R3)2]n-Het, -[C(R3)2]n-cicloalquilo, OR2, N(R2)2, NO2, CN, COOR2, CON(R2)2, NR2COA, NR2SO2A, COR2, SO2NR2, y / o S(O)mA, y donde además un grupo CH2 de la cadena de alquileno puede estar reemplazado por un grupo C=O; M es un anillo de fenilo o un heterociclo aromático que puede contener 1-2 átomos de N, O y/o S; R1, R1' son en cada caso, independientemente entre sí, H, Hal, A, OR2, N(R2)2, NO2, CN, COOR2, CON(R2)2, C(=S)N(R2)2, -[C(R3)2]n-Ar, -[C(R3)2]n-Het o -[C(R3)2]n-cicloalquilo, -[C(R3)2]n-N(R3)2, CN, -C(=NH)-NH2 insustituido o monosustituido por C(=O)R3, COOR3, OR3, OCOR3, OCOOR3 o sustituido por un grupo de protección amino convencional, y de fórmula (2); R2 es H, A, -[C(R3)2]n-Ar, -[C(R3)2]n-Het, -[C(R3)2]n-cicloalquilo, -[C(R3)2]n-N(R3)2 o -[C(R3)2]n-OR3; R2' es H, A, -[C(R3)2]n-Ar', -[C(R3)2]n-Het', -[C(R3)2]n-cicloalquilo, -[C(R3)2]n-N(R3)2 o -[C(R3)2]n-OR3; R2'' es H, A, -[C(R3)2]n-Ar' o -[C(R3)2]n-cicloalquilo, -[C(R3)2]n-N(R3)2 o -[C(R3)2]n-OR3; R3 es H o A; W es un carbociclo o heterociclo mono o bicíclico saturado, no saturado o aromático con 1 a 4 átomos de N, O y/o S, que puede estar mono o disustituido por R2; X es CONR2, CONR2C(R3)2, -C(R3)2NR2 o -C(R3)2NR2C(R3)2, -C(R3)2O-, -C(R3)2OC(R3)2- o NR2CO; Y es alquileno, cicloalquileno, Het-diilo o Ar-diilo; T es un carbociclo o heterociclo mono o bicíclico saturado, no saturado o aromático con 1 a 4 átomos de N, O y/o S, que está mono o disustituido por =S, =NR2, =N-CN, =N-NO2, =NOR2, =NCOR2, =NCOOR2, =NOCOR2 y que además pueda estar mono, disustituido o trisustituido por Hal, A, -[C(R3)2]n-Ar, -[C(R3)2]n-Het -[C(R3)2]n-cicloalquilo, -OR3, N(R3)2, NO2, CN, COOR2, CON(R2)2, NR2COA, NR2CON(R2)2, NR2SO2A, COR2, SO2NR2 y/o S(O)mA; A es alquilo no ramificado o ramificado C1-10, donde uno o dos grupos CH2 pueden estar reemplazados por átomos de O o S y/o por grupos -CH=CH y/o también 1-7 átomos de H pueden estar reemplazados por F; Ar es fenilo, naftilo o bifenilo insustituido o mono, di o trisustituido por Hal, A, OR3, N(R3)2, NO2, CN, COOR3, CON(R3)2, NR3COA, NR3CON(R3)2, NR3SO2A, COR3, SO2N(R3)2, S(O)mA, -[C(R3)2]n-COOR2', u -O-[C(R3)2]o-COOR2'; Ar' es fenilo o bencilo insustituido o mono o disustituido por Hal; Het es un heterociclo mono o bicíclico saturado, no saturado o aromático con 1 a 4 átomos de N, O y/o S, que puede estar insustituido o mono, di o trisustituido por el oxígeno del carbonilo, =S, =N(R3)2, Hal, A, -[C(R3)2]n-Ar, -[C(R3)2]n-Het1, -[C(R3)2]n-cicloalquilo, -[C(R3)2]n-OR2', -[C(R3)2]n-N(R2')2, NO2, CN, -[C(R3)2]n-COOR2', -[C(R3)2]n-CON(R2')2, -[C(R3)2]n-NR2'COA, NR2'CON(R2')2, -[C(R3)2]n-NR2'SO2A, COR2', SO2NR2' y/o S(O)mA; Het1 es un heterociclo mono o bicíclico saturado, no saturado o aromático con 1 a 2 átomos de N, O y/o S, que puede estar insustituido o mono o disustituido por el oxígeno del carbonilo, =S, =N(R3)2, Hal, A, OR2'', N(R2'')2, NO2, CN, COOR2'', CON(R2'')2, NR2''COA, NR2''CON(R2'')2, NR2''SO2A, COR2'', SO2NR2'' y/o S(O)mA; Hal es F, Cl, Br o I; n es 0, 1 ó 2; m es 0, 1 ó 2; o es 1, 2 ó 3; así como los derivados, solvatos estereoisómeros de los mismos de uso farmacéutico, incluyendo las mezclas de los mismos en todas las proporciones.
AR20030102321A 2002-06-28 2003-06-27 Derivado de 2-(fenil)-2h-pirazol-3-carboxilico-n-4(tioxo-heterociclil)fenil-amida e imino-heterociclil derivados y compuestos relacionados, procedimiento, medicamentos, kit AR040472A1 (es)

Applications Claiming Priority (1)

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DE10229070A DE10229070A1 (de) 2002-06-28 2002-06-28 Phenylderivate 5

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AR040472A1 true AR040472A1 (es) 2005-04-06

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US (1) US20050203127A1 (es)
EP (2) EP1517685A1 (es)
JP (1) JP2005535630A (es)
AR (1) AR040472A1 (es)
AU (1) AU2003238475A1 (es)
CA (1) CA2491271A1 (es)
DE (1) DE10229070A1 (es)
WO (1) WO2004002477A1 (es)

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DE102004051277A1 (de) * 2004-10-21 2006-04-27 Merck Patent Gmbh Heterocyclische Carbonylverbindungen
US7446210B2 (en) 2004-10-26 2008-11-04 Janssen Pharmaceutica N.V. Factor Xa compounds
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KR102113960B1 (ko) 2010-03-30 2020-05-21 베르선 코포레이션 트롬빈 억제제로서의 다중치환된 방향족 화합물
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EP1679073A1 (de) 2006-07-12
DE10229070A1 (de) 2004-01-15
WO2004002477A1 (de) 2004-01-08
CA2491271A1 (en) 2004-01-08
AU2003238475A1 (en) 2004-01-19
US20050203127A1 (en) 2005-09-15
WO2004002477A8 (de) 2004-04-15
JP2005535630A (ja) 2005-11-24
EP1517685A1 (de) 2005-03-30

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