AR045895A1 - Derivados de bencimidazol inhibidores de quinasas y metodos de preparacion - Google Patents

Derivados de bencimidazol inhibidores de quinasas y metodos de preparacion

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Publication number
AR045895A1
AR045895A1 ARP040102409A ARP040102409A AR045895A1 AR 045895 A1 AR045895 A1 AR 045895A1 AR P040102409 A ARP040102409 A AR P040102409A AR P040102409 A ARP040102409 A AR P040102409A AR 045895 A1 AR045895 A1 AR 045895A1
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Argentina
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hal
group
independently selected
independently
conh2
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ARP040102409A
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English (en)
Inventor
Amendt Christiane Dr
Buchstaller Hans-Peter Dr
Finsinger Dirk Dr
Wiesner Matthias Dr
Burgdorf Lars Dr
Grell Matthias Dr
Sirrenberg Christian Dr
Zenke Frank Dr
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Merck Patent Gmbh
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Publication of AR045895A1 publication Critical patent/AR045895A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Communicable Diseases (AREA)
  • Hematology (AREA)
  • Vascular Medicine (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Derivados de bencimidazol de la fórmula (1), en donde: R6, R7 son, de modo independiente entre sí, H, A o SO2A, A está seleccionado, de modo independiente, del grupo integrado por alquilo, alquenilo, cicloalquilo, alquilencicloalquilo, alcoxi y alcoxialquilo; Ar2 está seleccionados, de modo independiente de hidrocarburos aromáticos C6-14 y residuos heterocíclicos insaturados o aromáticos etilénicos C3-10 y uno o dos heteroátomos, seleccionados de modo independiente de N, O y S; R8, R9 y R10 están seleccionados, de modo independiente, de un grupo integrado por H, A, cicloalquilo C3-7, Hal, CH2Hal, CH(Hal)2, C(Hal)3, NO2, (CH2)nCN, (CH2)nNR11R12, (CH2)nOR11, (CH2)nO(CH2)kNR11R12, (CH2)nCOOR12, (CH2)nCONR11R12, (CH2)nNR11COR13, (CH2)nNR11CONR11R12, (CH2)nNR11SO2A, (CH2)nSO2NR11R12, (CH2)nS(O)uR13, (CH2)nOC(O)R13, (CH2)nCOR13, (CH2)nSR11, CH=N-OA, CH2CH=N-OA, (CH2)nNHOA, (CH2)nCH=N-R11, (CH2)nOC(O)NR11R12, (CH2)nNR11COOR12, (CH2)nN(R11)CH2CH2OR13, (CH2)nN(R11)CH2CH2OCF3, (CH2)nN(R11)C(R13)HCOOR12, C(R13)HCOR12, (CH2)nN(R11)CH2CH2N(R12)CH2COOR12, (CH2)nN(R11)CH2CH2NR11R12, CH=CHCOOR11, CH=CHCH2NR11R12, CH=CHCH2NR11R12, CH=CHCH2OR13, (CH2)nN(COOR11)COOR12, (CH2)nN(CONH2)COOR11, (CH2)nN(CONH2)CONH2, (CH2)nN(CH2COOR11)COOR12, (CH2)nN(CH2CONH2)COOR11, (CH2)nN(CH2CONH2)CONH2, (CH2)nCHR13COR11, (CH2)nCHR13COOR11, (CH2)nCHR13CH2OR14, (CH2)nOCN y (CH2)nNCO, en donde R11, R12 están seleccionados, de modo independiente, de un grupo integrado por H, A, (CH2)mAr3 y (CH2)mHet, o en NR11R12; R11 y R12 forman, junto con el átomo de N al que están unidos, un heterociclo de 5, 6 ó 7 miembros que opcionalmente contiene 1 ó 2 heteroátomos adicionales seleccionado de N, O y S; R13, R14 están seleccionados, de modo independiente, de un grupo integrado por H, Hal, A, (CH2)mAr4 y (CH2)mHet; Ar3, Ar4 son, de modo independiente entre sí, residuos hidrocarbonados aromáticos que comprenden 5 a 12 y, con preferencia, C5-10 que están opcionalmente sustituidos con uno o varios sustituyentes, seleccionados de un grupo integrado por A, Hal, NO2, CN, OR15, NR15R16, COOR15, CONR15R16, NR15COR16, NR15CONR15R16, NR16SO2A, COR15, SO2R15R16, S(O)uA y OOCR15; Het es un residuo heterocíclico saturado, insaturado o aromático que está opcionalmente sustituido con uno o varios sustituyentes seleccionados de un grupo integrado por A, Hal, NO2, CN, OR15, NR15R16, COOR15, CONR15R16, NR15COR16, NR15CONR15R16, NR16SO2A, COR15, SO2R15R16, S(O)uA y OOCR15; R15, R16 están seleccionados, de modo independiente, de un grupo integrado por H, A y (CH2)mAr6, en donde: Ar6 es un hidrocarburo aromático de 5 ó 6 miembros que está opcionalmente sustituido con uno o varios sustituyentes seleccionados de un grupo integrado por metilo, etilo, propilo, 2-propilo, ter-butilo, Hal, CN, OH, NH2 y CF3; k, m y n son, de modo independiente entre sí, 0, 1, 2, 3, 4 ó 5; X representa un enlace o es (CR11R12)h o (CHR11)h-Q-(CHR12)i, en donde Q está seleccionado de un grupo integrado por O, S, N-R15, (CHal2)j, (O-CHR18)j, (CHR18-O)j, CR18=CR19, (O-CHR18CHR19)j, (CHR18CHR19-O)j, C=O, C=S, C=NR15, CH(OR15), C(OR15)(OR20), C(=O)O, OC(=O), OC(=O)O, C(=O)N(R15), N(R15)C(=O), OC(=O)N(R15), N(R15)C(=O)O, CH=N-O, CH=N-NR15, S=O, SO2, SO2NR15 y NR15SO2, en donde: R18, R19, R20 están seleccionado, de modo independiente, de los significados dados para R8, R9 y R10, con preferencia, seleccionados de modo independiente del grupo integrado por H, A, Hal, CH2Hal, CH(Hal)2, C(Hal)3, NO2, (CH2)nCN, (CH2)nOR11, (CH2)nNR11R12, (CH2)nO(CH2)kNR11R12, (CH2)nCOOR13, (CH2)nCONR11R12, (CH2)nNR11COR13, (CH2)nNR11CONR11R12, (CH2)nNR11SO2A, (CH2)nSO2NR11R12, (CH2)nS(O)uR13, (CH2)nCOR13, (CH2)nSR11, (CH2)nNHOA y (CH2)nNR11COOR13, h, i son, de modo independiente entre sí, 0, 1, 2, 3, 4, 5 ó 6, y j es 1, 2, 3, 4, 5 ó 6; Y está seleccionado de O, S, NR21, C(R22)-NO2, C(R22)-CN y (CN2), en donde: R21 está seleccionado, de modo independiente, de los significados dados para R13, R14; y R22 está seleccionado, de modo independiente, de los significados dados para R11, R12; p, r son, de modo independiente entre sí, 0, 1, 2, 3, 4 ó 5; q es 0, 1, 2, 3 ó 4, con preferencia, 0, 1 ó 2; u es 0, 1, 2 ó 3, con preferencia, 0, 1 ó 2; y Hal está seleccionado, de modo independiente, de un grupo integrado por F, Cl, Br e I; y sus derivados, sales y solvatos fisiológicamente aceptables. Al uso de los compuestos de la fórmula (1) como inhibidores de una o varias quinasas, al uso de los compuestos de la fórmula (1) para preparar una composición farmacéutica y a un método de tratamiento que comprende la administración de dicha composición farmacéutica a un paciente.
ARP040102409A 2003-07-11 2004-07-08 Derivados de bencimidazol inhibidores de quinasas y metodos de preparacion AR045895A1 (es)

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US (1) US7691886B2 (es)
EP (1) EP1653951B1 (es)
JP (1) JP4823903B2 (es)
AR (1) AR045895A1 (es)
AT (1) ATE538787T1 (es)
CA (1) CA2531859C (es)
ES (1) ES2380201T3 (es)
WO (1) WO2005004864A1 (es)

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WO2015041533A1 (en) 2013-09-20 2015-03-26 Stichting Het Nederlands Kanker Instituut Rock in combination with mapk-pathway
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ATE538787T1 (de) 2012-01-15
CA2531859A1 (en) 2005-01-20
JP2007513054A (ja) 2007-05-24
JP4823903B2 (ja) 2011-11-24
AU2004255403A1 (en) 2005-01-20
EP1653951B1 (en) 2011-12-28
WO2005004864A1 (en) 2005-01-20
EP1653951A1 (en) 2006-05-10
ES2380201T3 (es) 2012-05-09
CA2531859C (en) 2013-08-06
US7691886B2 (en) 2010-04-06
US20070010560A1 (en) 2007-01-11

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