AR045656A1 - Inhibidores de gamma secretasa - Google Patents

Inhibidores de gamma secretasa

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Publication number
AR045656A1
AR045656A1 ARP040103301A ARP040103301A AR045656A1 AR 045656 A1 AR045656 A1 AR 045656A1 AR P040103301 A ARP040103301 A AR P040103301A AR P040103301 A ARP040103301 A AR P040103301A AR 045656 A1 AR045656 A1 AR 045656A1
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AR
Argentina
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alkyl
substituted
unsubstituted
group
aryl
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ARP040103301A
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Schering Corp
Pharmacopeia Drug Discovery
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Application filed by Schering Corp, Pharmacopeia Drug Discovery filed Critical Schering Corp
Publication of AR045656A1 publication Critical patent/AR045656A1/es

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    • C07D401/14Heterocyclic 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 three or more hetero rings
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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    • A61P3/00Drugs for disorders of the metabolism
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • 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
    • C07D207/08Heterocyclic 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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • 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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    • C07D451/02Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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    • C07D471/00Heterocyclic 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
    • 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
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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
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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
    • C07D491/10Spiro-condensed systems

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  • Organic Chemistry (AREA)
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  • Animal Behavior & Ethology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pyrrole Compounds (AREA)

Abstract

Se describe un método de tratamiento de la Enfermedad de Alzheimer que utiliza uno o más compuestos del presente, y composiciones farmacéuticas que los comprenden. Reivindicación 1: Un compuesto de fórmula (1), o una de sus sales, solvatos o ésteres aceptables desde el punto de vista farmacéutico, en el cual: A) R1 se selecciona del grupo formado por: arilo no sustituido; arilo sustituido con uno o más grupos R5; heteroarilo no sustituido; y heteroarilo sustituido con uno o más grupos R5; B) R2 se selecciona del grupo formado por: alquilo; -XC(O)Y; -alquilen(C1-6)-XC(O)Y; -alquilen(C0-6)-cicloalquilen(C3-6)-alquilen(C0-6)-XC(O)Y; arilo; arilo sustituido con uno o más grupos R5; heteroarilo; heteroarilo sustituido con uno o más grupos R5; cicloalquilen-X-C(O)-Y; -CH2-X-C(O)-NR3-Y; -CH2-X-C(O)-Y; y -CH2-X-C(O)-NR3-Y; C) cada R3 se selecciona en forma independiente del grupo formado por: H; alquilo; -OH; -O-alquilo; acilo; aroilo; el resto (R3)2, junto con el átomo de carbono del anillo al cual se muestra unido en la fórmula (1), define un grupo carbonilo, -C(O)-, con la salvedad de que cuando m es un número entero superior a 1, como máximo un grupo carbonilo esté presente en el anillo que se muestra en la fórmula (1), halo; D) cada R3A y R3B se selecciona en forma independiente del grupo formado por: H; y alquilo; E) R5 se selecciona en forma independiente del grupo formado por: halo; -CF3; -OH; -O-alquilo; -OCF3; -CN; -NH2; -C(O)2alquilo; - C(O)NR6R7; -alquilen-NR6R7; -NR6C(O)alquilo; -NR6C(O)arilo; -NR6C(O)heteroarilo; y -NR6C(O)NR6R7; F) X se selecciona del grupo formado por: -O-; -NH-; -N-alquilo; y -O-alquileno; G) Y se selecciona del grupo formado por: 1) -NR6R7; 2) - N(R3)CH2)bNR6R7 en la que b es 2-6; 3) arilo no sustituido; 4)heteroarilo no sustituido; 5) -alquilo; -cicloalquilo; 7) arilalquilo no sustituido; 8) arilcicloalquilo no sustituido; 9) heteroarilalquilo no sustituido; 10) heteroarilcicloalquilo no sustituido; 11) arilheterocicloalquilo no sustituido; 12) arilo sustituido; 13) heteroarilo sustituido; 14) arilalquilo sustituido; 15) arilcicloalquilo sustituido; 16) heteroarilalquilo sustituido; 17) heteroarilcicloalquilo sustituido; y 18) arilheterocicloalquilo sustituido; 19) heterocicloalquil alquilo sustituido; 20) heteroaril alquil no sustituido; 21) heterocicloalquil alquil arilo no sustituido; 22) heterocicloalquilo no sustituido; y 23) cicloalquilo no sustituido, en los que el resto arilo de dichos grupos sustituidos 12), 14), 15), 18) y 21) de dicho grupo Y, y el resto heteroarilo de dichos grupos sustituidos 13), 16), 17) y 20) de dicho grupo Y, se sustituyen con uno o más sustituyentes seleccionados en forma independiente del grupo formado por: halo; -CF3; -OH; -O-alquilo; -OCF3; -CN; -NH2; -C(O)2(C1-6)alquilo; -C(O)NR6R7; -alquilen(C1-6)-NR6R7; -NR6C(O)alquilo; -NR6C(O)arilo; -NR6C(O)heteroarilo; -NR6C(O)NR6R7; y alquilo; o Y se selecciona del grupo formado por las fórmulas (2); H) R6 y R7 se seleccionan en forma independiente del grupo formado por: H; alquilo; alquilo sustituido con 1 a 4 grupos hidroxi, con la salvedad de que uno de los grupos hidroxi esté unido a un carbono al cual está unido, además, un nitrógeno; cicloalquilo; arilalquilo; heteroarilalquilo; la fórmula (3); la fórmula 4); y heterocicloalquilo; I) cada R8 se selecciona en forma independiente del grupo formado por: H; alquilo; alquilo sustituido con 1 a 4 grupos hidroxi; arilo; -OH; -O-alquilo; -C(O)O-alquilo; si r es superior a 1, por lo menos dos grupos R8, junto con el átomo o átomos de carbono del anillo al cual están unidos definen un anillo, en el cual uno o más átomos de carbono de dicho anillo pueden reemplazarse en forma independiente entre sí por -O- o -C(O)O-, y dicho anillo puede estar sustituido con 1 a 4 grupos hidroxi; J) cada R9 se selecciona en forma independiente del grupo formado por: H; alquilo; alquilo sustituido con 1 a 4 grupos hidroxi; cicloalquilo; cicloalquilo sustituido con 1 a 4 grupos hidroxi; arilalquilo; heteroarilalquilo; -C(O)O-alquilo; alquilen-O-alquilen-OH; arilo sustituido con uno o más grupos R5; heteroarilo sustituido con uno o más grupos R5; heteroarilo no sustituido; arilo no sustituido; -alquilen-C(O)O-alquilo; y hidroxialquil-O-alquilo; K) cada R10 se selecciona en forma independiente del grupo formado por: H; y alquilo; L) R11 se selecciona del grupo formado por: 1) arilo no sustituido; 2) arilo sustituido; 3) heteroarilo no sustituido; 4) alquilo; 5) cicloalquilo; 6) arilalquilo no sustituido; 7) arilcicloalquilo no sustituido; 8) heteroarilalquilo no sustituido; 9) heteroarilcicloalquilo no sustituido; 10) arilheterocicloalquilo no sustituido; 11) alcoxialquilo; 12) heteroarilo sustituido; 13) arilalquilo sustituido; 14) arilcicloalquilo sustituido; 15) heteroarilalquilo sustituido; y 16) arilheterocicloalquilo sustituido, en los que el resto arilo de dichos grupos sustituidos 2), 13), 14) y 16) de dicho grupo R11, y el resto heteroarilo de dichos grupos sustituidos 12) y 15) de dicho grupo R11, se sustituyen con uno o más sustituyentes seleccionados en forma independiente del grupo formador por: halo; -CF3; -OH; -O-alquilo; -OCF3; -CN; -NH2; -C(O)2(C1-6)alquilo; -C(O)NR6R7; -alquilen(C1-6)-NR6R7; -NR6C(O)alquilo; -NR6C(O)arilo; -NR6C(O)heteroarilo; y -NR6C(O)NR6R7; M) m es 0 a 3, y si m es mayor que 1, m restos pueden ser idénticos o diferentes entre sí; n es 0 a , y si n es mayor que 1, n restos pueden ser idénticos o diferentes entre sí; o es 0 a 3, y si o es mayor que 1, o restos pueden ser idénticos o diferentes entre sí; de modo tal que m + n + o es 1, 2, 3 ó 4; N) p es 0 a 4, y si mayor que 1, p restos pueden ser idénticos o diferentes entre sí; O) r es 0 a 4, y si mayor que 1, r restos pueden ser idénticos o diferentes entre sí; P) s es 0 a 3, y si es mayor que 1, s restos pueden ser idénticos o diferentes entre sí; y Q) Z se selecciona del grupo formado por: 1) heterocicloalquilo no sustituido; 2) heterocicloalquilo sustituido; 3) -NH2; 4) -NH(alquilo); 5) -N(alquilo)2 en el que cada alquilo es idéntico o diferente; 6) -NH(cicloalquilo no sustituido); 7) - NH(cicloalquilo sustituido); 8) -N(alquil)(cicloalquilo no sustituido); 9) -N(alquil)(cicloalquilo sustituido); 10) -NH(aralquilo no sustituido); 11) -NH(aralquilo sustituido); 12) -N(alquil)(aralquilo); 13) -NH(heterocicloalquilo no sustituido); 14) -NH(heterocicloalquilo sustituido); 15) -N(alquil)(heterocicloalquilo no sustituido); 16)-N(alquil)(heterocicloalquilo sustituido); 17) -NH(heteroaralquilo no sustituido); 18) -NH(heteroaralquilo sustituido); 19) -NH-alquilen-(cicloalquilo no sustituido); 20) -NH-alquilen-(cicloalquilo sustituido); 21) -N(alquil)alquilen-(cicloalquilo no sustituido); 22) -N(alquil)alquilen-(cicloalquilo sustituido); 23) -NHalquilen-(heterocicloalquilo no sustituido); 24) -NHalquilen-(heterocicloalquilo sustituido); 25) -N(alquil)alquilen-(heterocicloalquilo no sustituido); 26) -N(alquil)alquilen-(heterocicloalquilo sustituido); 27) heterocicloalquilo benzofusionado no sustituido; y 28) heterocicloalquilo benzofusionado sustituido; 29) H; y 30) - N(hidroxialquilo)2, en el que cada alquilo puede ser idéntico o diferente, en los que dicho resto heterocicloalquilo sustituido de los sustituyentes 2), 14), 16), 24), 26) y 27) del grupo Z, y dicho resto cicloalquilo sustituido de los sustituyentes 7), 9), 20) y 22) del grupo Z, y dicho resto arilo sustituido del sustituyente 11) del grupo Z, y dicho resto heteroarilo sustituido del sustituyente 18) del grupo Z, están sustituidos con 1 a 3 grupos seleccionados en forma independiente del grupo formado por: alquilo; -OH; -Oalquilo; -OC(O)alquilo; -OC(O)arilo; -NH2; -NH(alquilo); -N(alquilo)2 en el que cada alquilo es idéntico o diferente; -NHC(O)alquilo; -N(alquil)C(O)alquilo; -NHC(O)arilo; -N(alquil)C(O)arilo; -C(O)alquilo; -C(O)arilo; - C(O)NH2; -C(O)NH(alquilo); -C(O)N(alquilo)2 en el que cada alquilo es idéntico o diferente; -C(O)2alquilo; -alquilen-C(O)Oalquilo; piperidinilo; pirrolidinilo; 1,1-etilendioxi; arilo; heteroarilo; e -O-CH2CH2-O-, en el cual ambos átomos de oxígeno están unidos al mismo átomo de carbono, y siempre que los restos arilo y heteroarilo de dicho grupo Z no estén sustituidos con dicho grupo -O-CH2CH2-O-.
ARP040103301A 2003-09-16 2004-09-15 Inhibidores de gamma secretasa AR045656A1 (es)

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US10/663,042 US20040171614A1 (en) 2002-02-06 2003-09-16 Novel gamma secretase inhibitors

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US (1) US20040171614A1 (es)
EP (1) EP1663975A1 (es)
JP (1) JP2007519607A (es)
KR (1) KR20060106814A (es)
CN (1) CN101061097A (es)
AR (1) AR045656A1 (es)
AU (1) AU2004274449A1 (es)
CA (1) CA2538590A1 (es)
IL (1) IL174270A0 (es)
MX (1) MXPA06003058A (es)
PE (1) PE20050377A1 (es)
TW (1) TW200519087A (es)
WO (1) WO2005028440A1 (es)
ZA (1) ZA200602193B (es)

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US7256186B2 (en) * 2002-02-06 2007-08-14 Schering Corporation Gamma secretase inhibitors
US20040171614A1 (en) * 2002-02-06 2004-09-02 Schering-Plough Corporation Novel gamma secretase inhibitors
US7521481B2 (en) 2003-02-27 2009-04-21 Mclaurin Joanne Methods of preventing, treating and diagnosing disorders of protein aggregation
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TW200519087A (en) 2005-06-16
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CA2538590A1 (en) 2005-03-31
KR20060106814A (ko) 2006-10-12
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