AR060612A1 - Inhibidores de la quinasa c- fms - Google Patents

Inhibidores de la quinasa c- fms

Info

Publication number
AR060612A1
AR060612A1 ARP070101693A ARP070101693A AR060612A1 AR 060612 A1 AR060612 A1 AR 060612A1 AR P070101693 A ARP070101693 A AR P070101693A AR P070101693 A ARP070101693 A AR P070101693A AR 060612 A1 AR060612 A1 AR 060612A1
Authority
AR
Argentina
Prior art keywords
alkyl
4alkyl
cancer
ch2ch2ora
na1a2
Prior art date
Application number
ARP070101693A
Other languages
English (en)
Original Assignee
Janssen Pharmaceutica Nv
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 Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv
Publication of AR060612A1 publication Critical patent/AR060612A1/es

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    • 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
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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    • C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—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 two 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
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    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
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    • 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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    • 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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    • 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
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    • 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
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    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/99—Enzyme inactivation by chemical treatment

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  • Chemical & Material Sciences (AREA)
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  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
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  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
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  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Virology (AREA)

Abstract

La presente se refiere a los compuestos inhibidores de quinasa C-FMS, una composicion farmacéutica y uso del compuesto para preparar medicamentos. Estos compuestos son utiles para tratar enfermedades autoinmunes; y enfermedades con un componente inflamatorio; para tratar la metástasis del cáncer ovárico, cáncer uterino, cáncer de mama, cáncer de prostata, cáncer de pulmon, cáncer de colon, cáncer de estomago, leucemia de células pilosas; y para tratar el dolor, incluyendo dolor oseo, originado por metástasis de tumores u osteoartritis, o dolor visceral, inflamatorio y neurogénico; como así también osteoporosis, enfermedad de Paget y otras enfermedades en las cuales la sorcion osea media la morbilidad, que incluyen artritis reumatoide y otras formas de artritis inflamatoria, osteoartritis, falla de protesis, sarcoma osteolítico, mieloma y metástasis de tumores en hueso. Reivindicacion 1: Los compuestos novedosos de formula 1 o su solvato, hidrato, tautomero o sal aceptable para uso farmacéutico, donde: W es como en formulas (2) donde cada R4 es dependientemente H, F, Cl, Br, I, OH, OCH3, OCH2CH3, Salquilo C1-4, SOalquilo C1-4, SO2alquilo C1-4, -alquilo C1-3, CO2Rd, CONReRf, C:::CRg, o CN; donde Rd es H o - alquilo C1-3; Re es H o -alquilo C1-3; Rf es H o -alquilo C1-3; y Rg es H -CH2OH, o -CH2CH2OH; R2 es cicloalquilo, cicloalquenilo espiro-sustituido, heterociclilo, piperidinilo espiro-sustituido, tiofenilo, dihidrosulfonopiranilo, fenilo, furanilo, tetrahidropiridilo o dihidropiranilo, cualquiera de los cuales puede estar independientemente sustituido con uno o dos de cada uno de los siguientes: cloro, fluoro, hidroxi, alquilo C1-3 y alquilo C1-4; Z es H, F o CH3; J es CH o N; X es como en formulas (3); Rz es H o -alquilo C1-4, donde ambos Rz pueden tener o bien estereoquímica syn o anti; en forma alternativa ambos Rz en una relacion syn pueden tomarse juntos para formar -(CH2)n-, donde n es 2 o 3; R3 es H, alquilo C1-4, CH2CH2NH2, CH2CH2ORa, -COCH3, CONH2 o CO2Ra; R9 es H, alquilo C1-4, ORa, -NA1A2, NA1SO2C1-4alquilo, A1COalquilo C1-4, -NHCH2CH2OCH2CH3, -N(CH2CH2OH)2, -N(CH3)CH2CH2OCH3, -NHCH2CH2SO2CH3, -NHCH2CON(CH3)2, o R3 y R9 pueden tomarse juntos para formar oxo, - OCH2CH2O- u OCH2C(Ra)2CH2O-; R10 es H, -alquilo C1-4, ORa, -CN, -NA1A2, -SO2CH3, -COORa, -CO2CH3, -CH2-NA1A2, -CONA1A2, -CH2ORa, -Oalquilo C1-4ORa, -NHCH2CH2CO2Ra, -NHCH2CH2ORa, -NRaCH2CH2NA1A2, -Oalquilo C1-4NA1A2, -OCH2CO2Ra, -CH2CO2Ra, - CH2CH2SO2alquilo C1-4, -SO2CH2CH2NA1A2, -SOCH2CH2NA1A2, -SCH2CH2NA1A2, -NHSO2CH2CH2NAA2, fenilo, imidazolilo, tiazolilo, 4H-[1,2,4]oxadiazol-5-onilo, 4H-pirrolo[2,3-b]pirazinilo, piridinilo, [1,3,4]oxadiazolilo, 4H-[1,2,4]triazolilo, tetrazolilo, pirazolilo, [1,3,5]triazinilo y [1,3,4]tiadiazolilo; A1 es H, -alquilo C1-4 o CH2CH2ORa; A2 es H, -alquilo C1-4, CORa, CH2CON(CH3)2, CH2CH2ORa, -CH2CH2SaIquiIo C1-4, -CH2CH2SOalquilo C1-4 o -CH2CH2SO2alquilo C1-4; en forma alternativa, A1 y A2 pueden tomarse junto con su N unido para formar un anillo heterocíclico seleccionado de los siguientes de formula (4) donde Ra es H o alquilo C1-4; Raa es H o alquilo C1-4; y Rbb H, -alquilo C1-4, -CH2CH2OCH2CH2OCH3, -CH2CO2H, -C(O)alquilo C1-4 o - CH2C(O)alquilo C1-4.
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