AR077447A1 - Compuestos inhibidores de beta-secretasa, utiles para el tratamiento de enfermedades neurodegenerativas - Google Patents

Compuestos inhibidores de beta-secretasa, utiles para el tratamiento de enfermedades neurodegenerativas

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AR077447A1
AR077447A1 ARP100102351A ARP100102351A AR077447A1 AR 077447 A1 AR077447 A1 AR 077447A1 AR P100102351 A ARP100102351 A AR P100102351A AR P100102351 A ARP100102351 A AR P100102351A AR 077447 A1 AR077447 A1 AR 077447A1
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alkyl
alkynyl
alkenyl
alkylheteroaryl
alkylheterocyclyl
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Astrazeneca Ab
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    • 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
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    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
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    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D413/02—Heterocyclic 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
    • C07D413/10—Heterocyclic 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 aromatic rings
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    • 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
    • C07D417/10—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 carbon chain containing aromatic rings
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    • C07D471/02—Heterocyclic 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
    • C07D471/04—Ortho-condensed systems

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Abstract

Además la presente se refiere a métodos terapéuticos para el tratamiento y/o prevencion de patologías relacionadas con Abeta, tal como el síndrome de Down, angiopatía beta-amiloide tal como, pero sin limitarla a angiopatía amiloide cerebral o hemorragia cerebral hereditaria, trastornos asociados con trastornos asociados con disfuncion cognitiva, tal como, pero sin limitarlo a MCI (ôdisfuncion cognitiva leveö), enfermedad de Alzheimer, pérdida de memoria, síntomas de falta de atencion asociados con la enfermedad de Alzheimer; neurodegeneracion asociada con enfermedades tales como enfermedad de Alzheimer o demencia incluyendo demencia de origen mixto vascular y degenerativo, demencia pre-senil, demencia senil y demencia asociada con la enfermedad de Parkinson, parálisis supranuclear progresiva o degeneracion cortical basal. Reivindicacion 1: Un compuesto de acuerdo con la formula (1) en la cual A está seleccionado entre arilo y heteroarilo, donde dicho arilo o heteroarilo está opcionalmente sustituido con uno o más R1; B está seleccionado entre arilo y heteroarilo, donde dicho arilo o heteroarilo está opcionalmente sustituido con uno o más R2; C está seleccionado entre hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilo C0-6-cicloalquenilo C3-6, alquilo C0-6-cicloalquinilo C6, alquilarilo C0-6, alquilheteroarilo C0-6, alquilheterociclilo C0-6, alquilo C0-6OR4, alquilo C0-6CO2R4, alquilo C0-6N(R4)2, halogeno, alquilo C0-6CN, alquilo C0-6COR4, CHO, NO2, alquilo C0-6CON(R4)2, O(CO)OR4, O(CO)R4, O(CO)N(R4)2, NR4(CO)OR4, alquilo C0-6NR4(CO)R4, NR4(CO)N(R4)2, NR4(CO)(CO)R4, NR4(CO)(CO)N(R4)2, alquilo C0-6SR4, alquilo C0-6OSO2R4, alquilo C0-6SO3R4, alquilo C0-6SO2R4, alquilo C0-6SOR4, alquilo C0-6(SO2)N(R4)2, alquilo C0-6(SO)N(R4)2, alquilo C0-6NR4(SO2)N(R4)2, alquilo C0-6NR4(SO)R4, SF5 y OSF5, donde dicho alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilarilo C0-6, alquilheteroarilo C0-6, o alquilheterociclilo C0-6, están opcionalmente sustituidos con uno o más R3; R1 está seleccionado entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilo C0-6cicloalquenilo C3-6, alquilo C0-6-cicloalquinilo C6, alquilarilo C0-6, alquilheteroarilo C0-6, alquilheterociclilo C0-6, alquilo C0-6CO2R4, alquilo C0-6N(R4)2, alquilo C0-6OR4, halogeno, alquilo C0-6CN, alquilo C0-6COR4, CHO, NO2, alquilo C0-6CON(R4)2, O(CO)OR4, O(CO)R4, O(CO)N(R4)2, NR4(CO)OR4, alquilo C0-6NR4(CO)R4, NR4(CO)N(R4)2, NR4(CO)(CO)R4, NR4(CO)(CO)N(R4)2, alquilo C0-6SR4, alquilo C0-6OSO2R4, alquilo C0-6SO3R4, alquilo C0-6SO2R4, alquilo C0-6SOR4, alquilo C0-6(SO2)N(R4)2, alquilo C0-6(SO)N(R4)2, alquilo C0-6NR4(SO2)N(R4)2, alquilo C0-6NR4(SO)R4, SF5, y OSF5, donde dicho alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilarilo C0-6, alquilheteroarilo C0-6 o alquilheterociclilo C0-6 están opcionalmente sustituidos con uno o más R3; o dos R1 pueden formar conjuntamente con los átomos de carbono a los cuales están unidos un anillo cíclico o heterocíclico opcionalmente sustituido con uno o más R6; R2 está seleccionado entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilo C0-6-cicloalquenilo C3-6, alquilo C0-6-cicloalquinilo C6, alquilarilo C0-6, alquilheteroarilo C0-6, alquilheterociclilo C0-6, alquilo C0-6CO2R4, alquilo C0-6N(R4)2, halogeno, alquilo C0-6CN, alquilo C0-6COR4, CHO, NO2, alquilo C0-6CON(R4)2, O(CO)OR4, O(CO)R4, O(CO)N(R4)2, R4(CO)OR4, alquilo C0-6NR4(CO)R4, NR4(CO)N(R4)2, NR4(CO)(CO)R4, NR4(CO)(CO)N(R4)2, alquilo C0-6SR4, alquilo C0-6OSO2R4, alquilo C0-6SO3R4, alquilo C0-6SO2R4, alquilo C0-6SOR4, alquilo C0-6(SO2)N(R4)2, alquilo C0-6(SO)N(R4)2, alquilo C0-6R4(SO2)N(R4)2, alquilo C0-6NR4(SO)R4 y alquilo C0-6OR4, donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilarilo C0-6, alquilheteroarilo C0-6 o alquilheterociclilo C0-6 están opcionalmente sustituidos con uno o más R3; o dos R2 pueden formar conjuntamente con los átomos a los cuales están unidos un anillo cíclico o heterocíclico opcionalmente sustituido con uno o más R6; R3 está seleccionado entre halogeno, NO2, CHO, alquilo C0-6CN, alquilo C0-6OR4, haloalquilo C1-6, alquilo C0-6N(R4)2, NR4C(O)R4, alquilo C0-6CO2R4, alquilo C0-6CON(R4)2, alquilo C0-6NR4(CO)R4, O(CO)N(R4)2, NR4(CO)OR4, NR4(CO)N(R4)2, O(CO)OR4, O(CO)R4, alquilo C0-6COR4, NR4(CO)(CO)R4, NR4(CO)(CO)N(R4)2, alquilo C0-6SR4, alquilo C0-6(SO2)N(R4)2, Oalquilo C2-6NR4(SO2)R4, alquilo C0-6(SO)N(R4)2, OSO2R4, SO3R4, alquilo C0-6NR4(SO2)N(R4)2, alquilo C0-6NR4(SO)R4, alquilo C0-6SO2R4, alquilo C0-6SOR4, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilo C0-6-cicloalquenilo C3-6, alquilo C0-6cicloalquinilo C6, alquilarilo C0-6, alquilheteroarilo C0-6 y alquilheterociclilo C0-6, donde dicho alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilarilo C0-6, alquilheteroarilo C0-6 o alquilheterociclilo C0-6 está opcionalmente sustituido con uno o más R6; R4 está seleccionado entre hidrogeno, alquilo C1-6, haloalquilo C1-3, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilo C0-6-cicloalquenilo C3-6, alquilo C0-6-cicloalquinilo C6, alquilarilo C0-6, alquilheteroarilo C0-6, alquilheterociclilo C0-6, alquilo C1-6OR5 y alquilo C1-6N(R5)2, donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilarilo C0-6, alquilheteroarilo C0-6 o alquilheterociclilo C0-6 están opcionalmente sustituidos con uno o más R6; o dos R4 pueden formar conjuntamente un anillo heterocíclico de 4 a 6 miembros que contiene uno o más heteroátomos seleccionados entre N, O o S, donde dicho anillo heterocíclico está sustituido con uno o más R6; R5 está seleccionado entre hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilo C0-6-cicloalquenilo C3-6, alquilo C0-6-cicloalquinilo C6, alquilarilo C0-6, alquilheterociclilo C0-6 y alquilheteroarilo C0-6, donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilo C0-6-cicloalquilo C3-6, alquilarilo C0-6, alquilheteroarilo C0-6 o alquilheterociclilo C0-6 están opcionalmente sustituidos con uno o más R6; o dos R5 pueden formar conjuntamente un anillo heterocíclico de 4 a 6 miembros que contiene uno o más heteroátomos seleccionados entre N, O o S, donde dicho anillo heterocíclico está opcionalmente sustituido con uno o más R6; R6 está seleccionado entre oxo, halogeno, nitro, CN, OR7, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilarilo C0-6, alquilheteroarilo C0-6, alquilo C0-6-cicloalquilo C3-6, alquilheterociclilo C0-6, haloalquilo C1-6, Oalquilo C2-6N(R7)2, N(R7)2, CON(R7)2, NR7(CO)R7, O(CO)alquilo C1-6, (CO)Oalquilo C1-6, COR7, SON(R7)2, (SO2)N(R7)2, NR7SO2R7, NR7SOR7, SO2R7, SOR7, (CO)alquilo C1-6N(R7)2, (SO2)alquilo C1-6N(R7)2, OSO2R7 y SO3R7, donde dicho alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquilarilo C0-6, alquilheteroarilo C0-6, alquilheterociclilo C0-6 o alquilo C0-6-cicloalquilo C3-6 están opcionalmente sustituidos con uno o más sustituyentes independientemente seleccionados entre halo, nitro, ciano, OR7, alquilo C1-6, haloalquilo C1-3, o haloalquilo OC1-3; R7 está seleccionado entre hidrogeno, alquilo C1-6, haloalquilo C1-3, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-6, cicloalquenilo C3-6, cicloalquinilo C6, arilo, heteroarilo y heterociclilo, donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-6, arilo, heteroarilo o heterociclilo están opcionalmente sustituidos con uno, dos o tres hidroxi, ciano, halogeno u Oalquilo C1-3; o dos R7 pueden formar conjuntamente un anillo heterocíclico de 4 a 6 miembros que contiene uno o más heteroátomos seleccionados entre N, O o S, donde dicho anillo heterocíclico está opcionalmente sustituido con uno o más sustituyentes independientemente seleccionados entre hidroxi, Oalquilo C1-3, ciano o halogeno; como base libre o una sal farmacéuticamente aceptable del mismo.
ARP100102351A 2009-07-02 2010-07-01 Compuestos inhibidores de beta-secretasa, utiles para el tratamiento de enfermedades neurodegenerativas AR077447A1 (es)

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UA108363C2 (uk) 2009-10-08 2015-04-27 Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування
US8415483B2 (en) 2010-12-22 2013-04-09 Astrazeneca Ab Compounds and their use as BACE inhibitors
AU2012296529A1 (en) 2011-08-17 2014-02-20 Amgen Inc. Heteroaryl sodium channel inhibitors
WO2013054108A1 (en) 2011-10-10 2013-04-18 Astrazeneca Ab Mono-fluoro beta-secretase inhibitors
US9000184B2 (en) 2012-06-20 2015-04-07 Astrazeneca Ab Cyclohexane-1,2′-naphthalene-1′,2″-imidazol compounds and their use as BACE inhibitors
US9000185B2 (en) 2012-06-20 2015-04-07 Astrazeneca Ab Cycloalkyl ether compounds and their use as BACE inhibitors
US9000183B2 (en) 2012-06-20 2015-04-07 Astrazeneca Ab Cyclohexane-1,2′-indene-1′,2″-imidazol compounds and their use as BACE inhibitors
US9000182B2 (en) 2012-06-20 2015-04-07 Astrazeneca Ab 2H-imidazol-4-amine compounds and their use as BACE inhibitors
US10548882B2 (en) 2012-06-21 2020-02-04 Astrazeneca Ab Camsylate salt
CN108658784B (zh) * 2018-04-26 2020-12-18 联化科技股份有限公司 (r)-1-(4-甲基苯基)乙胺的合成方法

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US20090176850A1 (en) * 2005-11-21 2009-07-09 Astrazeneca Ab Novel 2-Amino-Imidazole-4-One Compounds And Their Use In The Manufacture Of A Medicament To Be Used In The Treatment Of Cognitive Impairment, Alzheimer's Disease, Neurodegeneration And Dementia
TW200831484A (en) * 2006-12-20 2008-08-01 Astrazeneca Ab New compounds
WO2008076043A1 (en) * 2006-12-20 2008-06-26 Astrazeneca Ab Novel 2-amino-5,5-diaryl-imidazol-4-ones
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