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AR074209A1 - Derivados de pirimidina utiles para el tratamiento del cancer - Google Patents

Derivados de pirimidina utiles para el tratamiento del cancer

Info

Publication number
AR074209A1
AR074209A1 ARP090104510A ARP090104510A AR074209A1 AR 074209 A1 AR074209 A1 AR 074209A1 AR P090104510 A ARP090104510 A AR P090104510A AR P090104510 A ARP090104510 A AR P090104510A AR 074209 A1 AR074209 A1 AR 074209A1
Authority
AR
Argentina
Prior art keywords
nrere
nrcrc
nrg
membered
orc
Prior art date
Application number
ARP090104510A
Other languages
English (en)
Inventor
Ioannis Sapountzis
Heinz Stadtmueller
Bodo Betzemeier
Original Assignee
Boehringer Ingelheim Int
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 Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int
Publication of AR074209A1 publication Critical patent/AR074209A1/es

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • 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
    • C07D403/12—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
    • C07D405/14—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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Transplantation (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Son apropiados para el tratamiento de enfermedades que se distinguen por una proliferacion celular excesiva o anomala, así como su utilizacion para la fabricacion de un medicamento con las propiedades mencionadas anteriormente. Reivindicacion 1: Compuestos caracterizados porque tienen la formula general (1) en donde A significa un radical, eventualmente sustituido con uno o varios R1 iguales o diferentes, seleccionados del grupo compuesto por arilo C6-15 y heteroarilo de 5-12 miembros, X es O, S o CH2; R1 significa H o un radical seleccionado del grupo compuesto por Ra, Rb y Ra sustituido con uno o varios Rc y/o Rb iguales o diferentes; R2 es un radical seleccionado del grupo compuesto por Ra y Ra sustituido con uno o multiples Rb y/o Rc iguales o diferentes; y cada Ra está seleccionado independientemente de los demás, del grupo consistente en alquilo C1-6, cicloalquilo C3-10, cicloalquilalquilo C4-16, arilo C6-10, arilalquilo C7-16, heteroalquilo de 2-6 miembros, heterocicloalquilo de 3-8 miembros, heterocicloalquilalquilo de 4-14 miembros, heteroarilo de 5-12 miembros y heteroarilalquilo de 6-18 miembros; cada Rb es un radical apropiado y seleccionado en cada caso de forma independiente entre sí del grupo compuesto por =O, -ORc, haloalcoxi C1-3-oxi, -OCF3, =S, -SRc, =NRc, =NORc, =NNRcRc, =NN(Rg)C(O)NRcRc, -NRcRc, -ONRcRc, -N(ORc)Rc, -N(Rg)NRcRc, halogeno, -CF3, -CN, -NC, -OCN, -SCN, -NO, -NO2, =N2, -N3, -S(O)Rc, -S(O)ORc, -S(O)2Rc, -S(O)2ORc, -S(O)NRcRc, -S(O)2NRcRc, -OS(O)Rc, -OS(O)2Rc, -OS(O)2ORc, -OS(O)NRcRc, -OS(O)2NRcRc, -C(O)Rc, -C(O)ORc, -C(O)SRc, -C(O)NRcRc, -C(O)N(Rg)NRcRc, -C(O)N(Rg)ORc, -C(NRg)NRcRc, -C(NOH)Rc, -C(NOH)NRcRc, -OC(O)Rc, -OC(O)ORc, -OC(O)SRc, -OC(O)NRcRc, -OC(NRg)NRcRc, -SC(O)Rc, -SC(O)ORc, -SC(O)NRcRc, -SC(NRg)NRcRc, -N(Rg)C(O)Rc, -N[C(O)Rc]2, -N(ORg)C(O)Rc, -N(Rg)C(NRg)Rc, -N(Rg)N(Rg)C(O)Rc, -N[C(O)Rc]NRcRc, -N(Rg)C(S)Rc, -N(Rg)S(O)Rc, -N(Rg)S(O)ORc, -N(Rg)S(O)2Rc, -N[S(O)2Rc]2, -N(Rg)S(O)2ORc, -N(Rg)S(O)2NRcRc, -N(Rg)[S(O)2]2Rc, -N(Rg)C(O)ORc, -N(Rg)C(O)SRc, -N(Rg)C(O)NRcRc, -N(Rg)C(O)NRgNRcRc, -N(Rg)N(Rg)C(O)NRcRc, -N(Rg)C(S)NRcRc, -[N(Rg)C(O)]2Rc, -N(Rg)[C(O)]2Rc, -N{[C(O)]2Rc}2, -N(Rg)[C(O)]2ORc, -N(Rg)[C(O)]2NRcRc, -N{[C(O)]2ORc}2, -N{[C(O)]2NRcRc}2, -[N(Rg)C(O)]2ORc, -N(Rg)C(NRg)ORc, -N(Rg)C(NOH)Rc, -N(Rg)C(NRg)SRc y -N(Rg)C(NRg)NRcRc, cada Rc es, de forma independiente entre sí, H o un radical sustituido eventualmente con uno o multiples Rd y/o Re iguales o diferentes seleccionados del grupo compuesto por alquilo C1-6, cicloalquilo C3-10, cicloalquilalquilo C4-11, arilo C6-10, arilalquilo C7-16, heteroalquilo de 2-6 miembros, heterocicloalquilo de 3-8 miembros, heterocicloalquilo de 4-14 miembros, heteroarilo de 5-12 miembros y heteroaril-alquilo de 6-18 miembros, cada Rd es un radical apropiado y está seleccionado, de modo independiente entre sí, del grupo compuesto por =O, -ORe, haloalquil C1-3-oxi, -OCF3, =S, -SRe, =NRe, =NORe, =NNReRe, =NN(Rg)C(O)NReRe, -NReRe, -ONReRe, -N(Rg)NReRe, halogeno, -CF3, -CN, -NC, -OCN, -SCN, -NO, -NO2, =N2, -N3, -S(O)Re, -S(O)ORe, -S(O)2Re, -S(O)2ORe, -S(O)NReRe, -S(O)2NReRe, -OS(O)Re, -OS(O)2Re, -OS(O)2ORe, -OS(O)NReRe, -OS(O)2NReRe, -C(O)Re, -C(O)ORe, -C(O)SRe, -C(O)NReRe, -C(O)N(Rg)NReRe, -C(O)N(Rg)ORe, -C(NRg)NReRe, -C(NOH)Re, -C(NOH)NReRe, -OC(O)Re, -OC(O)ORe, -OC(O)SRe, -OC(O)NReRe, -OC(NRg)NReRe, -SC(O)Re, -SC(O)ORe, -SC(O)NReRe, -SC(NRg)NReRe, -N(Rg)C(O)Re, -N[C(O)Re]2, -N(ORg)C(O)Re, -N(Rg)C(NRg)Re, -N(Rg)N(Rg)C(O)Re, -N[C(O)Re]NReRe, -N(Rg)C(S)Re, -N(Rg)S(O)Re, -N(Rg)S(O)ORe, -N(Rg)S(O)2Re, -N[S(O)2Re]2, -N(Rg)S(O)2ORe, -N(Rg)S(O)2NReRe, -N(Rg)[S(O)2]2Re, -N(Rg)C(O)ORe, -N(Rg)C(O)SRe, -N(Rg)C(O)NReRe, -N(Rg)C(O)NRgNReRe, -N(Rg)N(Rg)C(O)NReRe, -N(Rg)C(S)NReRe, -[N(Rg)C(O)]2Re, -N(Rg)[C(O)]2Re, -N{[C(O)]2Re}2, -N(Rg)[C(O)]2ORe, -N(Rg)[C(O)]2NReRe, -N{[C(O)]2ORe}2, -N{[C(O)]2NReRe}2, -[N(Rg)C(O)]2ORe, -N(Rg)C(NRg)ORe, -N(Rg)C(NOH)Re, -N(Rg)C(NRg)SRe y -N(Rg)C(NRg)NReRe, cada Re es, de modo independiente entre sí, H o un radical eventualmente sustituido con uno o multiples Rf y/o Rg iguales o diferentes seleccionados del grupo compuesto por alquilo C1-6, cicloalquilo C3-8, cicloalquilalquilo C4-11, arilo C6-10, arilalquilo C7-16, heteroalquilo de 2-6 miembros, heterocicloalquilo de 3-8 miembros, heterocicloalquilalquilo de 4-14 miembros, heteroarilo de 5-12 miembros o heteroarilalquilo de 6-18 miembros, cada Rf es un radical adecuado y en cada caso independientemente uno de otro, se selecciona del grupo consistente en halogeno y -CF3; y cada Rg es, independientemente entre sí, H, alquilo C1-6, cicloalquilo C3-8, cicloalquilalquilo C4-11, arilo C6-10, arilalquilo C7-16, heteroalquilo de 2-6 miembros, heterocicloalquilo de 3-8 miembros, heterocicloalquilo de 4-14 miembros, heteroarilo de 5-12 miembros o heteroarilalquilo de 6-18 miembros, eventualmente en forma de sus tautomeros, sus racematos, sus enantiomeros, sus diastereoisomeros y sus mezclas, así como eventualmente sus sales por adicion de ácidos farmacologicamente inocuos.
ARP090104510A 2008-11-24 2009-11-23 Derivados de pirimidina utiles para el tratamiento del cancer AR074209A1 (es)

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US (2) US20110288109A1 (es)
EP (1) EP2367799B1 (es)
AR (1) AR074209A1 (es)
ES (1) ES2690341T3 (es)
TW (1) TW201024281A (es)
WO (1) WO2010058030A1 (es)

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US8785464B2 (en) 2014-07-22
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US20140038993A1 (en) 2014-02-06
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