AR059493A1 - Compuestos inhibidores de erk - Google Patents

Compuestos inhibidores de erk

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Publication number
AR059493A1
AR059493A1 ARP070100620A ARP070100620A AR059493A1 AR 059493 A1 AR059493 A1 AR 059493A1 AR P070100620 A ARP070100620 A AR P070100620A AR P070100620 A ARP070100620 A AR P070100620A AR 059493 A1 AR059493 A1 AR 059493A1
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Argentina
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substituted
alkyl
group
heteroaryl
cycloalkyl
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Schering Corp
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    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • 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
    • C07D207/10Heterocyclic 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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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    • A61P35/00Antineoplastic agents
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    • 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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    • C07D403/12Heterocyclic 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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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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 chain containing hetero atoms as chain links
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    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero 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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    • 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
    • C07DHETEROCYCLIC COMPOUNDS
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    • C07D417/14Heterocyclic 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 three or more hetero rings
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    • 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
    • C07D487/08Bridged systems

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  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Se revelan los inhibidores de ERK (quinasa reguladora de senal extracelular). También se revelan composicion farmacéutica y métodos para tratar el cáncer. Reivindicacion 1: Un compuesto de formula (1) o sus sales aceptables para uso farmacéutico, donde Y1, Y2 e Y3 se seleccionan cada uno independientemente del grupo que consiste en: CH=, -N= y -CR9=; z es 1 a 3; Q es un sustituyentes seleccionado del grupo que consiste en las formulas (2.1) a (2.16), cada Q1 representa un anillo seleccionado independientemente del grupo que consiste en: cicloalquilo, cicloalquilo sustituido, heterocicloalquilo, heterocicloalquilo sustituido, arilo, arilo sustituido, heteroarilo y heteroarilo sustituido, donde dichos anillos sustituidos están sustituidos con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: los restos R10, siempre que cuando Q1 sea arilo, heteroarilo, arilo sustituido o heteroarilo sustituido entonces los átomos de carbono en la union anular no sean sustituidos; Q2 representa un anillo seleccionado del grupo que consiste en: cicloalquilo, cicloalquilo sustituido, heterocicloalquilo y heterocicloalquilo sustituido, donde dichos anillos sustituidos están sustituidos con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: los restos R10; Z1 representa -(C(R24)2)w- donde cada R24 se selecciona independientemente del grupo que consiste en: H, alquilo y F y donde w es 1, 2 o 3 y generalmente w es 1 0 2 y comunmente w es 1 y donde en un ejemplo cada R24 es H y en otro ejemplo w es 1 y en otro ejemplo cada R24 es H y w es 1, preferentemente w es 1 y cada R24 es H; Z2 se selecciona del grupo que consiste en: -N(R44)-, -O- y -C(R46)2-; m es 1 a 6; n es 1 a 6; p es 0 a 6; t es 0, 1 o 2; R1 se selecciona del grupo que consiste en: (1) -CN, (2) -NO2, (3) -OR10, (4) -SR10, (5) -N(R10)2, (6) R10, (7) halo, (8) -CF3, (9) alquenilo; (10) -C(O)N(R10)2 donde cada R10 se selecciona independientemente y preferentemente cada R10 se selecciona independientemente del grupo que consiste en: (a) H, (b) alquilo, (c) heteroarilo, (d) arilo y (e) cicloalquilo, donde por ejemplo, cada R10 se selecciona del grupo que consiste en: H, metilo, butilo, i- propilo, piridilo, fenilo y ciclopropilo, donde, por ejemplo, dicho resto -C(O)N(R10)2 se selecciona del grupo que consiste en: -C(O)NH2, -C(O)NH(CH3), -C(O)NH(CH)(CH3)2, -C(O)NH(C4H9), -C(O)NH(C6H5), -C(O)NH(C3H5) y -C(O)NH(C5H4N); (11) arilalquenil-; R2 se selecciona del grupo que consiste en: (1) H, (2) -CN, (3) halo, (4) alquilo, (5) alquilo sustituido donde dicho alquilo sustituido está sustituido con 1 a 3 sustituyentes seleccionados del grupo que consiste en: (a) -OH, (b) -O- alquilo (por ej., -O-(alquilo C1-3), (c) -O-alquilo (por ej., -O-(alquilo C1-3)) sustituido con 1 a 3 átomos de F y (d) -N(R40)2 donde cada R40 se selecciona independientemente del grupo que consiste en: (i) H, (ii) alquilo C1-3 y (iii) -CF3, (6) alquinilo, (7) alquenilo, (8) -(CH2)mR11, (9) -N(R26)2, (10) -OR23, (11) -N(R26)C(O)R42, (12), cicloalquilo, (13) cicloalquilalquilo, y (14) formula (2); cada R3, R4, R5, R6 y R7 se selecciona independientemente del grupo que consiste en: (1) H, (2) alquenilo, (3) alquenilo sustituido, (4) alquilo, (5) alquilo sustituido, (6) cicloalquilo, (7) cicloalquilo sustituido, (8) cicloalquilalquil-, (9) cicloalquilalquil- sustituido, (10) heterocicloalquilo, (11) heterocicloalquilo sustituido, (12) heterocicloalquilalquil-, (13) heterocicloalquilalquil- sustituido, (14) -C(O)R10 donde en un ejemplo R10 se selecciona del grupo que consiste en: alquilo, (15) arilheteroaril-, (16) arilheteroaril- sustituido, (17) heteroarilaril-, tal como, por ejemplo, pirimidinilfenil-, pirazinilfenil-, piridinilfenil-, furanilfenil-, tienilfenil- y tiazolilfenil-, (18) heteroarilaril- sustituido, tal como, por ejemplo, pirimidinilfenil sustituido, pirazinilfenil- sustituido, piridinilfenil- sustituido, furanilfenil- sustituido, tienilfenil- sustituido, tiazolilfenil- sustituido y pirimidinilfenilo sustituido, (19) arilo, (20) arilo sustituido, (21) heteroarilo, (22) heteroarilo sustituido, (23) heteroarilheteroaril-, (24) heteroarilheteroaril- sustituido, (25) arilaminoheteroaril-, (26) arilaminoheteroaril- sustituido, (27) arilalquinil-, (28) arilalquinil- sustituido, (29) heteroarilalquinil- (30) heteroarilalquinil- sustituido, (31) -C(O)NHR28, (32) cicloalquilheteroarilaril-, (33) arilaril- sustituido, (34) arilalquenilaril-, (35) arilaril-, (36) arilalquil- sustituido, (37) arilalquil-, (38) -SO2arilo, (39) benzoheteroaril-C(O)-(heterocicloalquilo sustituido)-, (40) heterocicloalquilo sustituido, (41) heterocicloalquil-C(O)- alquil-, y (42) benzo[1,3]dioxolilo, donde dichos grupos sustituidos R3, R4, R5, R6 y R7, (7), (9), (11), (13), (16), (18), (20), (22). (24), (26), (28), (30), (33), (36), (39) y (40) están sustituidos con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: -CH2OH, CN, -OH, -NH2, alquilo, alquenilo, halo, -C(O)-NH-R28, -C(O)NH2, -C(O)OR28, -C(O)R28, -C(alquil)=NOH, -C(alquil)=NO(alquilo), alcoxi, hidroxil alquilo sustituido, dialquilamina, donde cada grupo alquilo se selecciona independientemente, -CF3, -SO2alquilo y -NHC(O)H, donde dichos grupos sustituidos R3, R4, R5, R6 y R7 (3) y (5) están sustituidos con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: -NH2, halo, - C(O)-NH-R28, -C(O)OR28 y -C(O)R28; R8 se selecciona del grupo que consiste en: H, -OH, alquilo, arilo, -N(R10)2 y -NR10C(O)R12, cada R9 se selecciona independientemente del grupo que consiste en: halogeno, -CN, -NO2, -OR10, -SR10, -N(R10)2 y R10; cada R10 se selecciona independientemente del grupo que consiste H, alquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, cicloalquilo, cicloalquilalquilo, heterocicloalquilo, heterocicloalquilalquilo, alquilheteroaril-, alquilaril-, alquilo sustituido, arilo sustituido, arilalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido, cicloalquilo sustituido, cicloalquilalquilo sustituido, heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, alquilheteroarilsustituido y alquilaril- sustituido y donde: dicho alquilo sustituido R10 está sustituido con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: -NH2, -NHR20, -NO2, -CN, -OR26, halo, -C(O)-NH-R26, - C(O)OR26 y -C(O)R26 y dichos arilo sustituido, arilalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido, cicloalquilo sustituido, cicloalquilalquilo sustituido, heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, alquilheteroarilsustituido y alquilaril- sustituido R10 están sustituidos con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: (1) -NH2, (2) -NO2, (3) -CN, (4) -OH, (5) -OR20, (6) -OCF3, (7) -CF3, (8) -C(O)R38, (9) alquilo, (10) alquenilo, (11) halo, (12) -C(O)-NH-R26, (13) -C(O)OR38, (14) -C(O)-NR32- (C(R30)2)n-N(R38)2, (15) -S(O)tR38, (16) -C(O)-NR32-R38, (17) -NR32-C(O)-R38, (18) -C(=N)N(R32)(R38) y (19) -NHR20, R11 se selecciona del grupo que consiste en: F, -OH, -CN, -OR10, -NHNR1R10, -SR10 y heteroarilo; R12 se selecciona del grupo que consiste en: alquilo, arilo, heteroarilo, cicloalquilo, cicloalquilalquilo, heterocicloalquilo y heterocicloalquilalquilo; R14 se selecciona del grupo que consiste en: alquilo, arilo, heteroarilo, cicloalquilo, cicloalquilalquil-, heterocicloalquilo, alquilheterocicloalquilo, heterocicloalquilalquil-, alquilheteroaril- y alquilaril-; R15 se selecciona del grupo que consiste en: H, -OH, alquilo, arilo, heteroarilo, cicloalquilo, cicloalquilalquil-, heterocicloalquilo y heterocicloalquilalquil-, alquilheteroaril- y alquilaril-; R20 representa alquilo; R23 se selecciona del grupo que consiste en: H, alquilo, arilo, cicloalquilo y cicloalquilalquil-; cada R26 se selecciona independientemente del grupo que consiste en: H y alquilo; R28 es alquilo; cada R30 se selecciona independientemente del grupo que consiste en: H, alquilo y F; cada R32 se selecciona independientemente del grupo que consiste en: H y alquilo; cada R35 se selecciona independientemente del grupo que consiste en: H y alquilo C1-6; R36 se selecciona del grupo que consiste en: H y alquilo; cada R38 se selecciona independientemente del grupo que consiste en: H, alquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, cicloalquilo, cicloalquilalquilo, heterocicloalquilo, heterocicloalquilalquilo, alquilheteroaril-, alquilaril-, alquilo sustituido, arilo sustituido, arilalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido, cicloalquilo sustituido, cicloalquilalquilo sustituido, heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, alquilheteroarilsustituido y alquilaril- sustituido y donde: dicho alquilo sustituido R38 está sustituido con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: -NH2, -NO2, -CN, -OR26, halo, -C(O)-NH-R28, -C(O)OR28 y -C(O)R28 y dichos arilo sustituido, arilalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido, cicloalquilo sustituido, cicloalquilalquilo sustituido, heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, alquilheteroaril sustituido y alquilaril- sustituido R38 están sustituidos con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: (1) -NH2, (2) -NO2, (3) -CN, (4) -OH, (5) -OR20, (6) -OCF3, (7) -CF3, (8) -C(O)R26, (9) alquilo, (10) alquenilo, (11) halo, (12) -C(O)-NH-R26, (13) -C(O)OR26, (14) -C(O)-NR32- (C(R30)2)n-N(R26)2, (15) -S(O)tR26, (16) -C(O)N(R32)(R26), (17) -NR32C(O)R26, (18) -C(=N)N(R32)(R26) y (19) -NHR20; R42 se selecciona del grupo que consiste en: alquilo, arilo, heteroarilo y cicloalquilo; R44 se selecciona del grupo que consiste H, alquilo, cicloalquilo y cicloalquilalquilo; y cada R46 se selecciona independientemente del grupo que consiste en H alquilo, cicloalquilo y cicloalquilalquilo.
ARP070100620A 2006-02-16 2007-02-14 Compuestos inhibidores de erk AR059493A1 (es)

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US (1) US7807672B2 (es)
EP (1) EP1984331B1 (es)
JP (1) JP2009528280A (es)
KR (1) KR20080103996A (es)
CN (1) CN101415674A (es)
AR (1) AR059493A1 (es)
AT (1) ATE485268T1 (es)
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