ES2353437T3 - Derivados de pirrolidina como inhibidores de erk. - Google Patents

Derivados de pirrolidina como inhibidores de erk. Download PDF

Info

Publication number
ES2353437T3
ES2353437T3 ES07750497T ES07750497T ES2353437T3 ES 2353437 T3 ES2353437 T3 ES 2353437T3 ES 07750497 T ES07750497 T ES 07750497T ES 07750497 T ES07750497 T ES 07750497T ES 2353437 T3 ES2353437 T3 ES 2353437T3
Authority
ES
Spain
Prior art keywords
substituted
alkyl
group
independently selected
heteroaryl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES07750497T
Other languages
English (en)
Inventor
Gerald W. Shipps, Jr.
Hugh Zhu
Alan Cooper
Robert Sun
Tong Wang
Li Xiao
James Wang
Joseph Kelly
Neng-Yang Shih
Youhao Dong
Yongqi Deng
M. Arshad Siddiqui
Ronald Doll
Jagdish Desai
Alan Hruza
Vincent S. Madison
Yang Nan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme Corp
Original Assignee
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Corp filed Critical Schering Corp
Application granted granted Critical
Publication of ES2353437T3 publication Critical patent/ES2353437T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic 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
    • C07D207/04—Heterocyclic 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
    • C07D207/10—Heterocyclic 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic 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
    • A61K31/4025—Heterocyclic 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07D401/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • 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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—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
    • C07D403/06—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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—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
    • 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
    • C07D405/12—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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—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
    • C07D409/12—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 linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • 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
    • C07D413/12—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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—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
    • 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
    • C07D417/12—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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—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
    • C07D417/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/08—Bridged systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • 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

Un compuesto de formula 1.0: **Fórmula** o sus sales farmaceuticamente aceptables, donde: Y1, Y2, y Y3 se seleccionan cada uno independientemente del grupo que consiste en: -CH= y -CR9=; z es 1; Q es un sustituyente seleccionado del grupo que consiste en: **Fórmula** 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 estan sustituidos con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: los radicales R10; siempre que cuando Q1 es arilo, heteroarilo, arilo sustituido o heteroarilo sustituido los atomos de carbono en la union del anillo no estan sustituidos; Q2 representa un anillo seleccionado del grupo que consiste en: cicloalquilo, cicloalquilo sustituido, heterocicloalquilo, y heterocicloalquilo sustituido, donde dichos anillos sustituidos estan sustituidos con 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en: los radicales 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 o 2, y usualmente 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, preferiblemente 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 de 1 a 6; n es de 1 a 6; p es de 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 preferiblemente 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 -C(O)N(R10)2 radical 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) arilalquenilo-; R2 se selecciona del grupo que consiste en: (1) H, (2) -CN, (3) halo, (4) alquilo, (5) alquilo sustituido donde dicho alquilo sustituido esta sustituido con 1 a 3 sustituyentes seleccionados del grupo que consiste en: (a) -OH, (b) -O-alquilo (p. ej., -O-(alquilo C1-C3), (c) -Oalquilo (p. ej., -O-(alquilo C1-C3)) sustituido con 1 a 3 atomos de F, y (d) -N(R40)2 donde cada R40 se selecciona independientemente del grupo que consiste en: (i) H, (ii) alquilo C1-C3 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) **Fórmula** 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) cicloalquilalquilo-, (9) cicloalquilalquilo- sustituido, (10) heterocicloalquilo, (11) heterocicloalquilo sustituido, (12) heterocicloalquilalquilo-, (13) heterocicloalquilalquilo- sustituido, (14) -C(O)R10 donde en un ejemplo R10 se selecciona del grupo que consiste en: alquilo, (15) arilheteroarilo-, (16) arilheteroarilo- sustituido, (17) heteroarilarilo-, tal como, por ejemplo, pirimidinilfenilo-, pirazinilfenilo-, piridinilfenilo-, furanilfenilo-, tienilfenilo-, y tiazolilfenilo-, (18) heteroarilarilo- sustituido, tal como, por ejemplo, pirimidinilfenilo- sustituido, sustituido pirazinilfenilo-, sustituido piridinilfenilo-, sustituido furanilfenilo-, sustituido tienilfenilo-, sustituido tiazolilfenilo-, y sustituido pirimidinilfenilo, (19) arilo, (20) arilo sustituido, (21) heteroarilo, (22) heteroarilo sustituido, (23) heteroarilheteroarilo-, (24) sustituido heteroarilheteroarilo-, (25) arilaminoheteroarilo-, (26) sustituido arilaminoheteroarilo-, (27) arilalquinilo-, (28) sustituido arilalquinilo-, (29) heteroarilalquinilo-, (30) sustituido heteroarilalquinilo-, (31) -C(O)NHR28, (32) cicloalquilheteroarilarilo-, (33) sustituido arilarilo-, (34) arilalquenilarilo-, (35) arilarilo-, (36) arilalquilo- sustituido, (37) arilalquilo-, (38) -SO2arilo, (39) benzoheteroaril-C(O)-(heterocicloalquilo sustituido)-, (40) heterocicloalquilo sustituido, (41) heterocicloalquil-C(O)-alquilo-, y (42) benzo[1,3]dioxolilo, donde dichos grupos R3, R4, R5, R6 y R7 sustituidos (7), (9), (11), (13), (16), (18), (20), (22), (24), (26), (28), (30), (33), (36), (39) y (40) estan 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, hidroxilo alquilo sustituido, dialquilamina donde cada grupo alquilo se selecciona independientemente, -CF3, -SO2alquilo, y -NHC(O)H, donde dichos grupos R3, R4, R5, R6 y R7 sustituidos (3) y (5) estan 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 en: H, alquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, cicloalquilo, cicloalquilalquilo, heterocicloalquilo, heterocicloalquilalquilo, alquilheteroarilo-, alquilarilo-, alquilo sustituido, arilo sustituido, arilalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido, cicloalquilo sustituido, cicloalquilalquilo sustituido, heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, alquilheteroarilo- sustituido y alquilarilo- sustituido, y donde: dicho alquilo sustituido R10 esta 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, alquilheteroarilo- sustituido y alquilarilo- sustituido R10 estan 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, **Fórmula** 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; 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 es H ; 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, alquilheteroarilo-, alquilarilo-, alquilo sustituido, arilo sustituido, arilalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido, cicloalquilo sustituido, cicloalquilalquilo sustituido, heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, alquilheteroarilo- sustituido y alquilarilo- sustituido, y donde: dicho alquilo sustituido R38 esta 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, alquilheteroarilo- sustituido y alquilarilo- sustituido R38 estan 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- 30 N(R26)2, (15) -S(O)tR26, (16)-C(O)N(R32)(R26), (17) -NR32C(O)R26, (18) **Fórmula** y (19) -NHR20; R42 se selecciona del grupo que consiste en: alquilo, arilo, heteroarilo, y cicloalquilo; R44 se selecciona del grupo que consiste en: H, alquilo, cicloalquilo, y cicloalquilalquilo; y Cada R46 se selecciona independientemente del grupo que consiste en: H, alquilo, cicloalquilo, y cicloalquilalquilo; donde: cada alquilo incluyendo las porciones alquilicas de alquiloxi, arilalquilo, heteroarilalquilo, cicloalquilalquilo, heterocicloalquilalquilo, heterocicloalquil-C(O)-alquilo, alquilheteroarilo-, alquilarilo-, -C(alquil)=NOH, -C(alquil)=NO(alquilo), dialquilamina y -SO2alquilo significa un grupo hidrocarbonado alifatico que puede ser lineal o ramificado donde dicho grupo comprende de aproximadamente 1 a aproximadamente 20 atomos de carbono en la cadena; cada alcoxi o alquiloxi significa un grupo alquil-O-, es decir el enlace hacia el radical parental es a traves del ox
ES07750497T 2006-02-16 2007-02-13 Derivados de pirrolidina como inhibidores de erk. Active ES2353437T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US77404306P 2006-02-16 2006-02-16
US774043P 2006-02-16

Publications (1)

Publication Number Publication Date
ES2353437T3 true ES2353437T3 (es) 2011-03-02

Family

ID=38170991

Family Applications (1)

Application Number Title Priority Date Filing Date
ES07750497T Active ES2353437T3 (es) 2006-02-16 2007-02-13 Derivados de pirrolidina como inhibidores de erk.

Country Status (17)

Country Link
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)
AU (1) AU2007218059A1 (es)
CA (1) CA2642762A1 (es)
DE (1) DE602007009932D1 (es)
ES (1) ES2353437T3 (es)
HK (1) HK1117159A1 (es)
IL (1) IL193413A0 (es)
MX (1) MX2008010635A (es)
TW (1) TW200745089A (es)
WO (1) WO2007097937A1 (es)
ZA (1) ZA200807457B (es)

Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8546404B2 (en) 2005-12-13 2013-10-01 Merck Sharp & Dohme Compounds that are ERK inhibitors
CA2706453A1 (en) * 2007-11-30 2009-06-11 Schering Corporation Braf biomarkers
RU2525389C2 (ru) * 2008-02-21 2014-08-10 Мерк Шарп И Доум Корп. Соединения, которые являются ингибиторами erk
DE102008022221A1 (de) 2008-05-06 2009-11-12 Universität des Saarlandes Inhibitoren der humanen Aldosteronsynthase CYP11B2
US9229008B2 (en) 2008-08-19 2016-01-05 Merck Sharp & Dohme Corp. IL-8 level as a determinant of responsivity of a cancer to treatment
EP2626072B1 (en) * 2009-04-02 2019-12-04 Merck Patent GmbH Piperidine and piperazine derivatives as autotaxin inhibitors
WO2011002067A1 (ja) * 2009-07-02 2011-01-06 武田薬品工業株式会社 複素環化合物およびその用途
US8609675B2 (en) 2009-07-02 2013-12-17 Merck Sharp & Dohme Corp. Fused Tricyclic Compounds as novel mTOR inhibitors
WO2011041152A1 (en) 2009-09-30 2011-04-07 Schering Corporation Novel compounds that are erk inhibitors
CN104945382B (zh) * 2009-10-14 2020-02-07 默沙东公司 提高p53活性的取代的哌啶和其用途
US8541404B2 (en) 2009-11-09 2013-09-24 Elexopharm Gmbh Inhibitors of the human aldosterone synthase CYP11B2
US9062015B2 (en) 2009-12-14 2015-06-23 Merck Patent Gmbh Inhibitors of sphingosine kinase
CN101812007B (zh) * 2010-04-27 2011-11-23 浙江大学 氨基吡咯类化合物及其制备方法
EP2608669B1 (en) 2010-08-23 2016-06-22 Merck Sharp & Dohme Corp. NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
CN103635472B (zh) 2011-02-28 2018-01-12 阵列生物制药公司 丝氨酸/苏氨酸激酶抑制剂
CN103732592A (zh) 2011-04-21 2014-04-16 默沙东公司 胰岛素样生长因子-1受体抑制剂
EP2736338B1 (en) 2011-07-26 2019-01-23 Merck Sharp & Dohme Corp. FUSED TRICYCLIC COMPOUNDS AS mTOR INHIBITORS
RU2014108140A (ru) 2011-08-04 2015-09-10 Эррэй Биофарма Инк. Соединение на основе хинозолина в качестве ингибиторов серен-треониновых киназ
GB201113538D0 (en) 2011-08-04 2011-09-21 Karobio Ab Novel estrogen receptor ligands
US8987274B2 (en) 2011-10-28 2015-03-24 Merck Sharp & Dohme Corp Macrocycles that increase p53 activity and the uses thereof
WO2013096150A1 (en) 2011-12-21 2013-06-27 Merck Sharp & Dohme Corp. Substituted piperidines as hdm2 inhibitors
WO2013109142A1 (en) 2012-01-16 2013-07-25 Stichting Het Nederlands Kanker Instituut Combined pdk and mapk/erk pathway inhibition in neoplasia
RS61500B1 (sr) 2012-03-01 2021-03-31 Array Biopharma Inc Inhibitori serinske/treoninske kinaze
MX369989B (es) 2012-08-27 2019-11-27 Array Biopharma Inc Inhibidores de serina/treonina cinasa para el tratamiento de enfermedades hiperproliferativas.
AU2013361694B2 (en) 2012-12-20 2017-10-26 Merck Sharp & Dohme Corp. Substituted imidazopyridines as HDM2 inhibitors
WO2015041534A1 (en) 2013-09-20 2015-03-26 Stichting Het Nederlands Kanker Instituut P90rsk in combination with raf/erk/mek
WO2015041533A1 (en) 2013-09-20 2015-03-26 Stichting Het Nederlands Kanker Instituut Rock in combination with mapk-pathway
JP6427197B2 (ja) 2013-10-03 2018-11-21 クラ オンコロジー， インコーポレイテッド Ｅｒｋの阻害剤および使用方法
CN103922928A (zh) * 2013-10-31 2014-07-16 北京利和知信科技有限公司 适用于制备烯烃聚合催化剂的环取代醚酸酯化合物
WO2015074081A1 (en) 2013-11-18 2015-05-21 Bair Kenneth W Benzopiperazine compositions as bet bromodomain inhibitors
BR122019007990B1 (pt) 2013-11-18 2021-05-04 Forma Therapeutics, Inc Composto, e, composição farmacêutica
WO2015156674A2 (en) 2014-04-10 2015-10-15 Stichting Het Nederlands Kanker Instituut Method for treating cancer
WO2015178770A1 (en) 2014-05-19 2015-11-26 Stichting Het Nederlands Kanker Instituut Compositions for cancer treatment
US10864179B2 (en) 2015-10-01 2020-12-15 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Histone deacetylase inhibitors for the use in the treatment of drug resistant melanoma
WO2017099591A1 (en) 2015-12-07 2017-06-15 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Treatment of inhibitor resistant braf-mutant cancers
WO2017204626A1 (en) 2016-05-24 2017-11-30 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Combination therapy - combined map2k4/map3k1 and mek/erk inhibition
CN111646979B (zh) * 2018-01-23 2021-08-31 深圳市塔吉瑞生物医药有限公司 取代的哒嗪酮化合物

Family Cites Families (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2306108A (en) 1995-10-13 1997-04-30 Merck & Co Inc Treatment of Raf-mediated cancers with imidazole derivatives
AU3215197A (en) 1996-05-30 1998-01-05 Merck & Co., Inc. A method of treating cancer
GB2323845A (en) 1997-03-31 1998-10-07 Merck & Co Inc MEK inhibiting lactones
JP2001510168A (ja) 1997-07-18 2001-07-31 ノボ ノルディスク アクティーゼルスカブ ＦＶＩＩａ媒介性細胞内シグナル伝達経路に関連する反対条件の処理のためのＦＶＩＩａ又はＦＶＩＩａｉの使用
GB9716557D0 (en) 1997-08-06 1997-10-08 Glaxo Group Ltd Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity
JP4783532B2 (ja) 2000-02-05 2011-09-28 バーテックス ファーマシューティカルズ インコーポレイテッド Ｅｒｋのインヒビターとして有用なピラゾール組成物
EP1207864A2 (en) 2000-02-05 2002-05-29 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of erk
JP2003527379A (ja) 2000-03-15 2003-09-16 ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー Ｍｅｘ阻害物質としての５−アミド置換ジアリールアミン類
TWI310684B (en) 2000-03-27 2009-06-11 Bristol Myers Squibb Co Synergistic pharmaceutical kits for treating cancer
US6897231B2 (en) * 2000-07-31 2005-05-24 Signal Pharmaceuticals, Inc. Indazole derivatives as JNK inhibitors and compositions and methods related thereto
US7211594B2 (en) * 2000-07-31 2007-05-01 Signal Pharmaceuticals, Llc Indazole compounds and compositions thereof as JNK inhibitors and for the treatment of diseases associated therewith
US20050009876A1 (en) * 2000-07-31 2005-01-13 Bhagwat Shripad S. Indazole compounds, compositions thereof and methods of treatment therewith
ZA200301696B (en) 2000-09-15 2004-04-28 Vertex Pharma Isoxazoles and their use as inhibitors of erk.
MXPA03002294A (es) 2000-09-15 2005-09-08 Vertex Pharma Compuestos de pirazol utiles como inhibidores de proteina cinasa.
EP1345922B1 (en) * 2000-12-21 2006-05-31 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
MY130778A (en) * 2001-02-09 2007-07-31 Vertex Pharma Heterocyclic inhibitiors of erk2 and uses thereof
US6982274B2 (en) * 2001-04-16 2006-01-03 Eisai Co., Ltd. 1H-indazole compound
US6706711B2 (en) 2001-04-27 2004-03-16 Vertex Pharmaceuticals Incorporated Pyrazole derived kinase inhibitor
MXPA03009846A (es) 2001-04-27 2004-05-05 Vertex Pharma Derivados de triazol inhibidores de cinasa y usos de los mismos.
US6750239B2 (en) 2001-08-03 2004-06-15 Vertex Pharmaceuticals Incorporated Pyrazole-derived kinase inhibitors and uses thereof
MXPA04001088A (es) 2001-08-03 2004-05-20 Vertex Pharma Derivados de pirazol como inhibidores de cinasa y uso de los mismos.
EP1438295B1 (en) 2001-10-23 2012-08-15 Merck Serono SA Azole derivatives and pharmaceutical compositions containing them
US20030187026A1 (en) * 2001-12-13 2003-10-02 Qun Li Kinase inhibitors
AU2003237121A1 (en) * 2002-04-26 2003-11-10 Vertex Pharmaceuticals Incorporated Pyrrole derivatives as inhibitors of erk2 and uses thereof
AU2003233605A1 (en) 2002-05-24 2003-12-12 The University Of Utah Research Foundation Mitogen activated protein kinase inhibitor compositions for lymphoma therapy
IL164209A0 (en) * 2002-05-31 2005-12-18 Eisai Co Ltd Pyrazole derivatives and pharmaceutical compositions containing the same
US7196092B2 (en) 2002-09-04 2007-03-27 Schering Corporation N-heteroaryl pyrazolopyrimidines as cyclin dependent kinase inhibitors
US7205308B2 (en) 2002-09-04 2007-04-17 Schering Corporation Trisubstituted 7-aminopyrazolopyrimidines as cyclin dependent kinase inhibitors
EP1539756B1 (en) 2002-09-19 2007-11-14 Schering Corporation Imidazopyridines as cyclin dependent kinase inhibitors
DE602004024374D1 (de) 2003-03-13 2010-01-14 Vertex Pharma Zusammensetzungen zur verwendung als protein-kinase-inhibitoren
WO2005002673A1 (en) 2003-07-03 2005-01-13 Astex Therapeutics Limited Raf kinase inhibitors
JP2007521331A (ja) * 2003-11-19 2007-08-02 シグナル ファーマシューティカルズ，エルエルシー 複数キナーゼの標的化による疾患及び障害の治療方法
EP1715871A1 (en) 2003-12-22 2006-11-02 Gilead Sciences, Inc. Kinase inhibitor phosphonate conjugates
JP2007530595A (ja) * 2004-03-26 2007-11-01 バーテックス　ファーマシューティカルズ　インコーポレイテッド Ｅｒｋ２のピリジンインヒビターおよびそれらの使用
JP2007532615A (ja) 2004-04-13 2007-11-15 アステックス、セラピューティックス、リミテッド 医薬化合物
EP3305776B1 (en) * 2004-05-14 2019-09-25 Vertex Pharmaceuticals Incorporated Pyrrole compounds as inhibitors of erk protein kinases and pharmaceutical compositions containing these compounds
AU2005245877B2 (en) 2004-05-14 2010-06-03 Vertex Pharmaceuticals, Incorporated Prodrugs of pyrrolylpyrimidine ERK protein kinase inhibitors
WO2006040569A1 (en) 2004-10-14 2006-04-20 Astex Therapeutics Limited Thiophene amide compounds for use in the treatment or prophylaxis of cancers
US7501415B2 (en) 2004-12-23 2009-03-10 Vertex Pharmaceuticals Incorporated Selective inhibitors of ERK protein kinase and uses thereof
CN100377868C (zh) * 2005-03-24 2008-04-02 中国科学院物理研究所 用于磁性/非磁性/磁性多层薄膜的核心复合膜及其用途
WO2006136008A1 (en) 2005-05-24 2006-12-28 University Health Network Salicylic acid hydrazones as inhibitors of the erk mapkinase pathway and for the treatment of cancer
US8217042B2 (en) * 2005-11-11 2012-07-10 Zentaris Gmbh Pyridopyrazines and their use as modulators of kinases
US8546404B2 (en) * 2005-12-13 2013-10-01 Merck Sharp & Dohme Compounds that are ERK inhibitors
NZ569087A (en) * 2005-12-13 2011-09-30 Schering Corp Polycyclic indazole derivatives that are ERK inhibitors
EP2018872A4 (en) * 2006-04-20 2010-06-09 Takeda Pharmaceutical PHARMACEUTICAL PRODUCT
US7601852B2 (en) * 2006-05-11 2009-10-13 Kosan Biosciences Incorporated Macrocyclic kinase inhibitors
BRPI0713119A2 (pt) * 2006-06-30 2012-04-17 Schering Corp piperidinas substituìdas que aumentam a atividade de p53 e os usos destas
US7671832B2 (en) * 2006-07-10 2010-03-02 Philips Lumileds Lighting Company, Llc Multi-colored LED backlight with color-compensated clusters near edge
EP2548558A1 (en) 2007-03-28 2013-01-23 Pharmacyclics, Inc. Nitrogen-containing condensed heterocyclic as inhibitors of bruton's tyrosine kinase
CN101790526A (zh) 2007-06-08 2010-07-28 雅培制药有限公司 用作激酶抑制剂的5-杂芳基取代的吲唑化合物
CN101772501A (zh) 2007-06-18 2010-07-07 先灵公司 杂环化合物及其作为erk抑制剂的用途
RU2525389C2 (ru) 2008-02-21 2014-08-10 Мерк Шарп И Доум Корп. Соединения, которые являются ингибиторами erk

Also Published As

Publication number Publication date
TW200745089A (en) 2007-12-16
IL193413A0 (en) 2009-05-04
US7807672B2 (en) 2010-10-05
JP2009528280A (ja) 2009-08-06
CN101415674A (zh) 2009-04-22
CA2642762A1 (en) 2007-08-30
EP1984331A1 (en) 2008-10-29
DE602007009932D1 (de) 2010-12-02
ZA200807457B (en) 2009-09-30
AU2007218059A1 (en) 2007-08-30
ATE485268T1 (de) 2010-11-15
WO2007097937A1 (en) 2007-08-30
US20070232610A1 (en) 2007-10-04
AR059493A1 (es) 2008-04-09
HK1117159A1 (en) 2009-01-09
KR20080103996A (ko) 2008-11-28
MX2008010635A (es) 2008-10-28
EP1984331B1 (en) 2010-10-20

Similar Documents

Publication Publication Date Title
ES2353437T3 (es) Derivados de pirrolidina como inhibidores de erk.
AR068046A1 (es) Derivados policiclicos de indazol y su uso como inhibidores de erk para el tratamiento del cancer
AR056891A1 (es) Derivados policiclicos de indazol que son inhibidores de erk
AR061847A1 (es) Derivados de pirimidina 2- amino -5- sustituida. como inhibidores de quinasas. composiciones farmaceuticas.
AR109424A2 (es) Pirimidil ciclopentanos hidroxilados y metoxilados como inhibidores de la proteína quinasa akt
PE20070808A1 (es) COMPUESTOS DERIVADOS DE ISOQUINOLINA COMO INHIBIDORES DE Rho-QUINASA
PE20071286A1 (es) Composicion para inducir tolerancia viral en plantas
CO6180439A2 (es) Derivados de quinuclidinol como antagonistas de receptores muscarinicos
AR049125A1 (es) Heterociclos biciclicos nitrogenados inhibidores de la aromatasa.
AR050181A1 (es) Derivados de urea ciclicos sustituidos, su preparacion y su uso farmaceutico como inhibidores de quinasa
TNSN06019A1 (en) Pharmaceutical compounds
CO6190515A2 (es) Derivados indolicos con anilo unido en las posiciones 4,5 y sus metodos de uso
UY31750A (es) Compuestos y composiciones como inhibidores de quinasa
AR023703A1 (es) N-carboniloximetilesteres de nitroetilendiaminas y nitroguanidinas, proceso para su preparacion, composicion parasiticida, una preparacion en combinacionpara controlar parasitos en animales de sangre caliente, uso de dichos compuestos y compuestos intermediarios para su uso en dicho proceso de prepa
BRPI0519288A2 (pt) compostos heterocÍclicos como antagonistas de ccr2b
AR055053A1 (es) Compuestos indol sustituidos con actividad inhibidora de nos. composiciones farmaceuticas.
CO5630023A2 (es) Fenil quinolinas y su uso como agentes estrogenicos
CO6150144A2 (es) Inhibidores de proteina tirosina fosfatasa humana y metodos de uso
AR071739A1 (es) Inhibidores de transcriptasa reversa
AR060050A1 (es) Compuestos moduladores del receptor de s1p y uso de los mismos
NI201000011A (es) Derivados de pirimidina 934.
PE20090216A1 (es) Compuestos triazolil aminopirimidina
CO6020016A1 (es) Derivados de 1,2,4,5 tetrahidro-3h-benzapezinas su procedimiento de preparacion y las composiciones farmaceuticas que las contienen
CO5690593A2 (es) Nuevos derivados de pirimidin 2-amina
CO6150147A2 (es) Derivados de 5,6-bisaril-2-piridin-carboxamida su preparacion y su aplicacion en terapeutica como antagonistas de los receptores de urotensina ii