AR063625A1 - COMPUESTOS HETEROCICLICOS eTILES COMO AGENTES ANTICANCEROSOS - Google Patents

COMPUESTOS HETEROCICLICOS eTILES COMO AGENTES ANTICANCEROSOS

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Publication number
AR063625A1
AR063625A1 ARP070104984A ARP070104984A AR063625A1 AR 063625 A1 AR063625 A1 AR 063625A1 AR P070104984 A ARP070104984 A AR P070104984A AR P070104984 A ARP070104984 A AR P070104984A AR 063625 A1 AR063625 A1 AR 063625A1
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AR
Argentina
Prior art keywords
alkyl
heterocyclyl
carbamoyl
optionally substituted
carbon
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ARP070104984A
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English (en)
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Vibha Oza
Gurmit Grewal
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Astrazeneca Ab
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Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Publication of AR063625A1 publication Critical patent/AR063625A1/es

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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/14Radicals substituted by nitrogen atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
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    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
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    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/06Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
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    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
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    • 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
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D407/00Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
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    • C07DHETEROCYCLIC COMPOUNDS
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    • C07D413/06Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
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    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/12Heterocyclic 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
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    • C07ORGANIC CHEMISTRY
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    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04Ortho-condensed systems
    • C07D491/056Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Compuestos químicos que poseen actividad antagonista de Edg-1, y que, por consiguiente, son útiles debido a su actividad anticancerosa y por ende en los métodos de tratamiento del cuerpo humano o de animales. También se relaciona con procesos para la elaboración de dichos compuestos químicos, con composiciones farmacéuticas que los contienen y con su uso en la elaboración de medicamentos para la producción de un efecto anticanceroso en un animal de sangre caliente, tal como el hombre. Reivindicación 1: Un compuesto caracterizado porque responde a la fórmula (1) donde el Anillo A es carbociclilo o heterociclilo; en donde si dicho heterociclilo contiene una porción -NH- ese nitrógeno puede estar opcionalmente sustituido por un grupo seleccionado entre R6; R1se selecciona en forma independiente entre halo, nitro, ciano, hidroxi. amino, carboxi, carbamoilo, mercapto, sulfamoilo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alcoxi C1-6, hidrazinilo, ureido, N,N- di(alquil C1-3)ureido, alcanoilo C1-6, alcanoiloxi C1-6, N-(alquil C1-6)amino, N,N-(alquil C1-6)2amino, alcanoilamino C1-6, N-(alquil C1-6)carbamoilo, N,N-(alquil C1-6)2carbarnoilo, alquil C1-6S(O)a en donde a es entre 0 y 2, alcoxicarbonilo C1-6, N- (alquil C1-6)sulfamoilo, N,N-(alquil C1-6)2sulfamoilo, alquilsulfonilamino C1-6, carbociclilo, heterociclilo, en donde R1 puede estar sustituido opcionalmente en un carbono por uno o más R7, y en donde si dicho heterociclilo contiene una porción -NH- ese nitrógeno puede estar opcionalmente sustituido por un grupo seleccionado entre R8; n es 0-5; en donde los valores de R1 pueden ser iguales o diferente; R2 se selecciona entre alquilo C1-6, alquenilo C2-6 o alquinilo C2-6, carbociclilo, y heterociclilo; en donde R2 puede estar sustituido opcionalmente en un carbono por uno o más R9; en donde si dicho heterociclilo contiene una porción NH ese nitrógeno puede estar opcionalmente sustituido por un grupo seleccionado entre R19; R3 se selecciona entre hidrógeno, alquilo C1-6, alquenilo C2-6 o alquinilo C2-6, carbociclilo, heterociclilo; en donde R3 puede estar sustituido opcionalmente en un carbono por uno o más R11; en donde si dicho heterociclilo contiene una porción NH ese nitrógeno puede estar opcionalmente sustituido por un grupo seleccionado entre R20; o, como alternativa. R2 y R3 pueden formar, junto con el carbono al cual están unidos, un anillo carbocíclico C3-6, R4 se selecciona entre alquilo C1-6 o carbociclilo, en donde R4 puede estar sustituido opcionalmente en un carbono por uno o más R10; el Anillo D está fusionado al imidazol de fórmula (1) y es un anillo de 5-7 miembros; en donde si dicho anillo contiene una porción -NH- ese nitrógeno puede estar opcionalmente sustituido por un grupo seleccionado entre R14; R5 es un sustituyente sobre carbono y se selecciona en forma independiente entre halo, nitro, ciano, hidroxi, amino, carboxi, carbamoilo, mercapto, sulfamoilo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alcoxi C1-6, alcanoilo C1-6, alcanoiloxi C1-6, N-(alquil C1-6)amino, N,N-(alquil C1-6)2amino, alcanoilamino C1-6, N-(alquil C1-6)carbamoilo, N,N-(alquil C1-6)2carbarnoilo, alquil C1-6S(O)a en donde a es entre 0 y 2, alcoxicarbonilo C1-6, heterociclilcarbonilo, N-(alquil C1-6)sulfamoilo, N,N-(alquil C1-6)2sulfamoilo, alquilsulfonilamino C1-6, carbociclilo o heterociclilo, o dos R5 pueden formar junto con los átomos de carbono del anillo D a los cuales están unidos un anillo carbociclilo o heterociclilo de 5 a 8 miembros; en donde R5 puede estar sustituido opcionalmente en un carbono por uno o más R15; y en donde si dicho heterociclilo o anillo heterocíclico contiene una porción -NH- ese nitrógeno puede estar opcionalmente sustituido por un grupo seleccionado entre R16; m es 0-5; en donde los valores de R5 pueden ser iguales o diferentes, R7, R9, R11 y R15 se seleccionan en forma independiente entre halo, nitro, ciano, hidroxi, amino, carboxi, carbamoilo, mercapto, sulfamoilo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alcoxi C1-6, alcanoilo C1-6, alcanoiloxi C1-6, N-(alquil C1-6)amino, N,N-(alquil C1-6)2amino, alcanoilamino C1-6, N-(alquil C1-6)carbamoilo, N,N-(alquil C1- 6)2carbarnoilo, alquil C1-6S(O)a en donde a es entre 0 y 2, alcoxicarbonilo C1-6, N-(alquil C1-6)sulfamoilo, N,N-(alquil C1-6)2sulfamoilo, alquilsulfonilamino C1-6, carbociclilo o heterociclilo, en donde R7, R9, R11 y R15 pueden estar opcionalmente sustituidos sobre carbono en forma independiente por uno o más R17; y en donde si dicho heterociclilo contiene una porción -NH- ese nitrógeno puede estar opcionalmente sustituido por un grupo seleccionado entre R18; R6, R8, R13, R14, R16, R18, R19 y R20 se seleccionan en forma independiente entre alquilo C1-6, alcanoilo C1-6, alquilsulfonilo C1-6, alcoxicarbonilo C1-6, carbamoilo, N-(alquil C1-6)carbamoilo, N,N-(alquil C1-6)carbamoilo, bencilo, benciloxicarbonilo, benzoilo y fenilsulfonil; R10 se selecciona entre halo, nitro, hidroxi, amino, carboxi, mercapto, sulfamoilo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alcanoilo C1-6, alcanoiloxi C1-6, N-(alquil C1-6)amino, N,N-(alquil C1-6)2amino, alcanoilamino C1-6, N-(alquil C1- 6)carbamoilo, N,N-(alquil C1-6)2carbarnoilo, alquil C1-6S(O)a en donde a es entre 0 y 2, alcoxicarbonilo C1-6, N-(alquil C1-6)sulfamoilo, N,N-(alquil C1-6)2sulfamoilo, alquilsulfonilamino C1-6, carbociclilo o heterociclilo, en donde R10 puede estar sustituido opcionalmente en un carbono por uno o más R12; y en donde si dicho heterociclilo contiene una porción -NH- ese nitrógeno pude estar opcionalmente sustituido por un grupo seleccionado entre R13; R12 y R13 se seleccionan entre halo, nitro, ciano, hidroxi, trifluorometoxi, trifluorometilo, amino, carboxi, carbamoilo, mercapto, sulfamoilo, metilo, etilo metoxi, etoxi, acetilo, acetoxi, metilamino, etilamino, dimetilamino, dietilamino, N-metil-N-etilamino, acetilamino, N-metilcarbamoilo, N-etilcarbamoilo, N,N-dimetilcarbamoilo, N,N-dietilcarbamoilo, N-metil-N-etilcarbamoilo, metiltio, etiltio, metilsulfinilo, etilsulfinilo, mesilo, etilsulfonilo, metoxicarbonilo, etoxicarbonilo, N-metilsulfamoilo, N-etilsulfamoilo, N,N- dimetilsulfamoilo, N,N-dietilsulfamoilo o N-metil-N-etilsulfamoilo; o una sal aceptable para uso farmacéutico del mismo; con la salvedad de que el compuesto no sea 4-metil-N-[(1-metil-1H-bencimidazol-2-il)fenilmetil]bencensulfonamida.
ARP070104984A 2006-11-10 2007-11-08 COMPUESTOS HETEROCICLICOS eTILES COMO AGENTES ANTICANCEROSOS AR063625A1 (es)

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US86536406P 2006-11-10 2006-11-10
US89569907P 2007-03-19 2007-03-19
US94779507P 2007-07-03 2007-07-03
US95383807P 2007-08-03 2007-08-03

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US (1) US20100029643A1 (es)
EP (1) EP2094670A1 (es)
JP (1) JP2010509301A (es)
KR (1) KR20090089338A (es)
AR (1) AR063625A1 (es)
AU (1) AU2007319061A1 (es)
BR (1) BRPI0718759A2 (es)
CA (1) CA2668785A1 (es)
EC (1) ECSP099382A (es)
IL (1) IL198658A0 (es)
MX (1) MX2009004906A (es)
NO (1) NO20091703L (es)
PE (1) PE20081492A1 (es)
TW (1) TW200827340A (es)
WO (1) WO2008056150A1 (es)

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DE102007037579B4 (de) * 2007-08-09 2012-05-16 Emc Microcollections Gmbh Neue Benzimidazol-2-yl-alkylamine und ihre Anwendung als mikrobizide Wirkstoffe
EP2349484A2 (en) * 2008-07-15 2011-08-03 Novartis AG Heteroaryl derivatives as dgat1 inhibitors
US8288627B2 (en) * 2009-05-13 2012-10-16 Monsanto Technology Llc Plants and seeds of hybrid corn variety CH532948
KR101632318B1 (ko) 2009-11-05 2016-06-27 재단법인 의약바이오컨버젼스연구단 벤조헤테로사이클 유도체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 암 예방 및 치료용 조성물
WO2012116440A1 (en) 2011-03-03 2012-09-07 Zalicus Pharmaceuticals Ltd. Benzimidazole inhibitors of the sodium channel
US9051311B2 (en) 2012-03-09 2015-06-09 Amgen Inc. Sulfamide sodium channel inhibitors
EP3759095A1 (en) 2018-03-01 2021-01-06 Annapurna Bio Inc. Compounds and compositions for treating conditions associated with apj receptor activity
CN113490668A (zh) * 2018-10-05 2021-10-08 安娜普尔纳生物股份有限公司 用于治疗与apj受体活性有关的疾病的化合物和组合物
WO2021145785A1 (ru) * 2020-01-17 2021-07-22 Борис Славинович ФАРБЕР Производные бензимидазолов, их соли, проявляющие анигериатрическое действие
CN113461611B (zh) * 2021-07-08 2023-02-28 江苏法安德医药科技有限公司 一种咪喹莫特中间体的合成方法

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US7884207B2 (en) * 2004-06-18 2011-02-08 3M Innovative Properties Company Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines
EP1798226A4 (en) * 2004-08-04 2009-06-17 Taisho Pharmaceutical Co Ltd TRAIZOL DERIVATIVE
WO2007112322A2 (en) * 2006-03-28 2007-10-04 Allergan, Inc. Indole compounds having sphingosine-1-phosphate (s1p) receptor agonist and/or antagonist biological activity
WO2007122401A1 (en) * 2006-04-21 2007-11-01 Astrazeneca Ab Imidazole derivatives for use as edg-1 antagonists

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WO2008056150A1 (en) 2008-05-15
EP2094670A1 (en) 2009-09-02
IL198658A0 (en) 2010-02-17
TW200827340A (en) 2008-07-01
NO20091703L (no) 2009-05-29
MX2009004906A (es) 2009-07-09
CA2668785A1 (en) 2008-05-15
US20100029643A1 (en) 2010-02-04
JP2010509301A (ja) 2010-03-25
KR20090089338A (ko) 2009-08-21
BRPI0718759A2 (pt) 2013-12-03
ECSP099382A (es) 2009-07-31
AU2007319061A1 (en) 2008-05-15
PE20081492A1 (es) 2008-12-07

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