AR065118A1 - Inhibidores de la proteina quinasa - Google Patents

Inhibidores de la proteina quinasa

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Publication number
AR065118A1
AR065118A1 ARP080100406A ARP080100406A AR065118A1 AR 065118 A1 AR065118 A1 AR 065118A1 AR P080100406 A ARP080100406 A AR P080100406A AR P080100406 A ARP080100406 A AR P080100406A AR 065118 A1 AR065118 A1 AR 065118A1
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AR
Argentina
Prior art keywords
independently
optionally
independently substituted
halogen
absent
Prior art date
Application number
ARP080100406A
Other languages
English (en)
Inventor
Tiansheng Wang
Chris Davis
Damian Fraysse
Luca Settimo
Juan Miguel Jimenez
Guy Bemis
Dean Boyall
Francois Maltais
Michael Mortimore
Ronald Knegtel
Stephen Yong
Original Assignee
Vertex Pharma
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Publication date
Application filed by Vertex Pharma filed Critical Vertex Pharma
Publication of AR065118A1 publication Critical patent/AR065118A1/es

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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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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    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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    • A61P35/00—Antineoplastic agents
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
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    • 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
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    • 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
    • C07D409/06—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 carbon chain containing only aliphatic carbon atoms
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    • 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
    • C07D417/06—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 only aliphatic carbon atoms
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    • C07—ORGANIC CHEMISTRY
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    • 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
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    • 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
    • C07D487/04—Ortho-condensed systems
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    • C07—ORGANIC CHEMISTRY
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    • 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

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Abstract

Se refiere a compuestos utiles como inhibidores de la proteína quinasa, PKC-theta, GSK-3. Además provee composiciones farmacéuticamente aceptables que comprenden dichos compuestos y métodos de utilizacion de las composiciones para el tratamiento de varias enfermedades, condiciones o trastornos, como Alzheimer, Parkinson, trastorno bipolar, esclerosis lateral amiotrofica, esclerosis multiple, esquizofrenia, artritis reumatoidea, colon irritable, leucemia de célula T, linfomas y diabetes. También provee los procesos para preparar los compuestos. Reivindicacion 1: Un compuesto representado por la formula estructural (1) o una sal farmacéuticamente aceptable del mismo, caracterizado porque: B es un anillo heteroaromático monocíclico, un anillo heteroaromático bicíclico 6,6 o un anillo heteroaromático bicíclico 6,5 donde B está opcional e independientemente sustituido con R12' e independiente y opcionalmente, e independientemente sustituido con uno o más grupos R12 además de R3, y el punto de union a -C(Z)- del anillo bicíclico 6,5 está en el anillo de 6 miembros; Z es O o S; R1 es -H, halogeno, -CN, -NO2, o -T1-Q1; T1 está ausente o es un grupo alifático C1-10, donde hasta tres unidades metileno de T1 están opcional e independientemente reemplazadas por G donde G es -O-, -S-, -S(O)-, -S(O)2-, -N(R4)- o -C(O)-; T1 está opcional e independientemente sustituido con uno o más JT1; Q1 está ausente, o es un anillo monocíclico de 3-8 miembros, saturado, parcialmente insaturado o completamente insaturado que tiene 0-3 heteroátomos seleccionados independientemente entre nitrogeno, oxígeno y azufre, o es un sistema anular bicíclico de 8-12 miembros saturado, parcialmente insaturado o completamente insaturado que tiene 0-5 heteroátomos seleccionados independientemente entre nitrogeno, oxígeno y azufre, donde Q1 está opcional e independientemente sustituido con J1 e independiente y opcionalmente, e independientemente sustituido con uno o más grupos R13; J1 es -Y1-M1; Y1 está ausente, o es oxo, o un grupo alifático C1-10 donde hasta tres unidades metileno de Y1 están opcional e independientemente reemplazadas con G1 donde G1 es -N(R$)-, -O-, -S-, -C(O)-, -S(O)- o -S(O)2-, Y1 está opcional e independientemente sustituido con uno o más JT1; M1 es un grupo alifático C1-6, cicloalifático C3-8, halo alifático C1-4, -O(halo alifático C1-4), heterociclilo de 3-8 miembros, heteroarilo de 5-6, fenilo, -OR$, -SR$, -N(R$)2, -C(O)R$, -C(O)2R$, - C(O)N(R$)2, -OC(O)R$, -OC(O)N(R$)2, -NR$C(O)R$, -NR$C(O)2R$, -NR$C(O)N(R$)2, -SO2N(R$)2, -NR$S(O)2R$, -S(O)R$, S(O)2R$, -P(O)R$, -P(O)2R$, -P(O)(R$)2 o -PO(OR$)2; M1 está opcional e independientemente sustituido con uno o más J; o M1 está ausente, es halogeno, -N(O)2 o -CN; R2 es -H, halogeno, -CN, -N(O)2 o alquilo C1-6 opcional e Independientemente sustituido; R3 es halogeno, -CN, -NO2 o -T2-Q2; T2 está ausente o es un grupo alifático C1-10, donde hasta tres unidades metileno de T2 están opcional e independientemente reemplazadas por G' donde G' es O-, -S-, -S(O)-, -S(O)2-, -N(R4)- o -C(O)-; T2 está opcional e independientemente sustituidas con uno o más JT2; Q2 está ausente, es un anillo monocíclico de 3-8 miembros, saturado, parcialmente insaturado o completamente insaturado que tiene 0-3 heteroátomos seleccionados independientemente entre nitrogeno, oxígeno y azufre, o un sistema anular bicíclico de 8-12 miembros saturado, parcialmente insaturado o completamente insaturado que tiene 0-5 heteroátomos seleccionados independientemente entre nitrogeno, oxígeno y azufre, donde Q2 está opcional e independientemente sustituido con J2 y opcional e independientemente, e independientemente sustituido con uno o más grupos R13; donde, cuando R1 y R2 son -H, R12 está ausente, R12' está ausente, Z es O, R3 es -T2-Q2 entonces -T2-Q2 no está ausente, -NHCH2CH(OH)CH2OH, o el resto de formula (2); J2 es -Y2-M2; Y2 está ausente, es oxo, o un grupo alifático C1-10, donde hasta dos unidades metileno de Y2 están opcional e independientemente reemplazadas con G1' donde G1' es -N(R$)-, -O-, -S-, -C(O)-, -S(O)- o -S(O)2-, Y2 está opcional e independientemente sustituido con uno o más JT2; M2 es un grupo alifático C1-6, cicloalifático C3-8, halo alifático C1-4, -O(halo alifático C1-4), un heterociclilo, heteroarilo, arilo de 3-8 miembros, -OR$, -SR$, -N(R$)2, C(O)R$, -C(O)2R$, -C(O)N(R$)2, -OC(O)R$, -OC(O)N(R$)2, -NR$C(O)R$, -NR$C(O)2R$, -NR$C(O)N(R$)2, - SO2N(R$)2, -NR$S(O)2R$, -S(O)R$, -S(O)2R$, -P(O)R$, -P(O)2R$, -P(O)(R$)2, o -PO(OR$)2; donde M2 está opcional e independientemente sustituido con uno o más J; o M2 está ausente, es halogeno, -N(O)2 o -CN; cada J es independientemente halogeno, un grupo alifático C1-6, cicloalifático C3-6, -NO2, -CN, -N(R$)2, -OR$, -C(O)R$, -C(O)N(R$)2, -C(O)2R$, oxo, -O(halo alifático C1-4), o halo alifático C1-4; R4 es -H o un alquilo C1-6 opcional e independientemente sustituido; cada JT1 es independientemente halogeno, -CN, -N(O)2, o hidroxilo; cada JT2 es independientemente halogeno, -CN, -N(O)2, o hidroxilo; cada R$ es independientemente -H o alquilo C1-6; cada R12 es independientemente halogeno, amino, aminoalquilo, alquilaminoalquilo, alcoxilo, hidroxilo, -CN, -NO2, o alquilo C1-6 opcional e independientemente sustituido; cada R12' es independientemente halogeno, amino, aminoalquilo, alcoxilo, hidroxilo, -CN, -NO2, o un grupo alifático C1-10 opcional e independientemente sustituido donde hasta tres unidades metileno están opcional e independientemente reemplazadas con G' donde G' es -O-, -S(O)p-, -N(R4)- o -C(O)-, y cada unidad metileno está opcional e independientemente sustituida con uno o más JT3; o cada R12' es un grupo cicloalifático, fenilo, heteroarilo, cada una independiente y opcionalmente sustituido con uno o más JT4; cada JT3 es independientemente halogeno, -CN, -NO2, cicloalifático, o fenilo; cada JT4 es independientemente halogeno, alquilo C1-6, o alcoxilo C1-6; cada R13 es independientemente halogeno, amino, aminoalquilo, alcoxilo, hidroxilo, -CN, -NO2, oxo o alquilo C1-6 opcional e independientemente sustituido; y p es 0, 1 o 2; con la condicion de que el compuesto no sea (2-amino-5-(3,4-dimetoxifenil)piridin-3-il)(6-aminopiridin-3-il)metanona, (2-amino-5-bromopiridin-3-il)(6-(2-metoxietilamino)piridin-3-il)metanona, (2-amino-5-(3,4-dimetoxifenil)piridin-3-il)(6-(2-metoxietilamino)piridin-3-il)metanona, (2- amino-5-(3,4-dimetoxifenil)piridin-3-il)(6-(isobutilamino)piridin-3-il)metanona, (2-amino-5-bromopiridin-3-iI)(6-fluoropiridin-3-il)metanona, metanona (2-amino-5-cloro-3-piridinil)-4-piridinil-, bencenosulfonamida, N-[2-[(2-amino-3- pirimidinil)carbonil]-5-cloro-3-piridinil]-4-cloro-(trifluorometil) o metanona, (2-amino-5-cloro-3-piridinil)-4-piridinil-.
ARP080100406A 2007-01-31 2008-01-31 Inhibidores de la proteina quinasa AR065118A1 (es)

Applications Claiming Priority (4)

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US89864307P 2007-01-31 2007-01-31
US91386707P 2007-04-25 2007-04-25
US96931207P 2007-08-31 2007-08-31
US1489307P 2007-12-19 2007-12-19

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AR065118A1 true AR065118A1 (es) 2009-05-20

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US (4) US8188071B2 (es)
EP (2) EP2121613A2 (es)
JP (3) JP2010518014A (es)
AR (1) AR065118A1 (es)
AU (1) AU2008210455A1 (es)
CA (1) CA2677096A1 (es)
MX (1) MX2009008253A (es)
NZ (1) NZ578744A (es)
TW (1) TW200848415A (es)
WO (1) WO2008094992A2 (es)

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