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AR053450A1 - Derivados de 3,4-dihidro-pirimido(4,5-d)pirimidin-2-(1h)-ona 1,5,7 trisustituidos como inhibidores de la quinasa p38 - Google Patents

Derivados de 3,4-dihidro-pirimido(4,5-d)pirimidin-2-(1h)-ona 1,5,7 trisustituidos como inhibidores de la quinasa p38

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AR053450A1
AR053450A1 ARP060101148A ARP060101148A AR053450A1 AR 053450 A1 AR053450 A1 AR 053450A1 AR P060101148 A ARP060101148 A AR P060101148A AR P060101148 A ARP060101148 A AR P060101148A AR 053450 A1 AR053450 A1 AR 053450A1
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alkyl
aryl
heteroaryl
cycloalkyl
optionally substituted
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Glaxo Group Ltd
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Abstract

Reivindicacion 1: Un compuesto de formulas (1) y (29 en las que G1 y G2 son independientemente N; G3 es NH; G4 es N; R1 es C(Z)N(R10')(CR10R20)vRb, C(Z)O(CR10R20)vRb, N(R10')C(Z)(CR10R20)vRb; N(R10')C(Z)N(R10')(CR10R20)vRb; o N(R10')OC(Z) (CR10R20)vRb; R1' se selecciona independientemente en cada caso entre halogeno, alquilo C1-4, alquilo C1-4 sustituido con halo, ciano, nitro, (CR10R20)v'NRdRd'; (CR10R20)v'C(O)R12, SR5, S(O)R5, S(O)2R5 o (CR10R20)v'OR13; Rb es un resto H, alquilo C1-10, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-10, arilo, aril-alquilo C1-10, heteroarilo, heteroaril-alquiloC1-10, heterociclo o heterociclil- alquilo C1-10, en el que los restos, excluyendo el H, pueden estar todos opcionalmente sustituidos; X es R2, OR2', S(O)mR2', (CH2) n'N(R10')S(O)mR2', (CH2)n'N(R10')C(O)R2', (CH2)n'NR4R14, (CH2)n'N(R2')(R2ö) o N(R10')-Rh-NH-C(=N-CN)NRqRq'; X1 es N(R11), O, S(O)m o CR10R20; Rh se selecciona entre un alquilo C1-10 opcionalmente sustituido -CH2-C(O)-CH2-, -CH2-O-CH2-, -CH2-C(O)N(R10') CH2-CH2-, -CH2-N(R10')C(O)CH2-, -CH2-CH(OR10')-CH2-, -CH2-C(O)O-CH2-CH2- o -CH2-CH2-O-C(O)CH2-; Rq y Rq' se seleccionan independientemente en cada caso entre un resto H, alquilo C1-10, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-10, cicloalquenilo C5-7, cicloalquenil C5-7-alquilo C1-10, arilo, aril-alquilo C1-10, heteroarilo, heteroaril-alquilo C1-10, heterociclo o heterociclil-alquilo C1-10, en los que todos los restos, excluyendo el H, están opcionalmente sustituidos, o Rq y Rq' junto con el N al que están unidos, forman un anillo opcionalmente sustituido de 5 a 7 miembros, donde el anillo puede contener un heteroátomo adicional seleccionado entre O, N o S; R2 es un resto H, alquilo C1- 10, cicloalquilo C3-7, cicloalquilalquilo C3-7, arilo, aril-alquilo C1-10, heteroarilo, heteroaril-alquilo C1-10, heterociclilo o heterociclil-alquilo C1-10, y en el que cada uno de estos restos, excluyendo el H, puede estar opcionalmente sustituido; o R2 es el resto (CR10R20)q'X1(CR10R20)qC(A1)(A2)(A3) o (CR10R20)q'C(A1)(A2)(A3); R2' es un resto H, alquilo C1-10, cicloalquilo C3-7, cicloalquilalquilo C3-7, arilo, aril-alquilo C1-10, heteroarilo, heteroaril-alquilo C1-10, heterociclilo o heterociclil-alquilo C1-10, y en el que cada uno de estos restos, excluyendo el H, puede estar opcionalmente sustituido; R2ö es un resto H, alquilo C1-10, cicloalquilo C3-7, cicloalquilalquilo C3-7, arilo, aril-alquilo C1-10, heteroarilo, heteroaril-alquilo C1-10, heterociclilo o heterociclil-alquilo C1-10, y en el que estos restos, excluyendo el H, pueden estar opcionalmente sustituidos; o donde R2ö es el resto (CR10R20) tX1(CR10R20)qC(A1)(A2)(A3); A1 es un alquilo C1-10 opcionalmente sustituido, heterociclo, heterocicloalquilo C1-10, heteroarilo, heteroaril-alquilo C1-10, arilo o aril-alquilo C1-10; A2 es un alquilo C1-10 opcionalmente sustituido, heterociclo, heterocicloalquilo C1-10, heteroarilo, heteroaril- alquilo C1-10, arilo o aril-alquilo C1-10; A3 es H o es un alquilo C1-10 opcionalmente sustituido; R3 es un resto alquilo C1-10, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-10, arilo, aril-alquilo C1-10, heteroaril-alquilo C1-10, o heterociclil- alquilo C1-10, y en el que cada uno de estos restos pueden estar opcionalmente sustituido; R4 y R14 se seleccionan cada uno independientemente en cada caso entre un resto H, alquilo C1-10, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-4, arilo, aril-alquilo C1-4, heterociclo, heterocicloalquilo C1-4, heteroarilo o heteroaril-alquilo C1-4, y en los que cada uno de estos restos, excluyendo el H, puede estar opcionalmente sustituido; o R4 y R14 junto con el N al que están unidos, forman un anillo heterocíclico opcionalmente sustituido de 4 a 7 miembros, en donde el anillo opcionalmente contiene un heteroátomo adicional seleccionado entre O, S o N; R4' y R14' se seleccionan independientemente en cada caso entre H o alquilo C1-4, o R4' y R14' junto con el N al que están unidos, forman un anillo heterocíclico de 5 a 7 miembros, donde el anillo opcionalmente contiene un heteroátomo adicional seleccionado a partir de NR9'; R5 se selecciona independientemente en cada caso entre H, alquilo C1-4, alquenilo C2-4, alquinilo C2-4 o NR4'R14', excluyendo los restos SR5 que son SNR4'R14'; S(O)2R5 que son SO2H y S(O)R5 que son SOH; R9' se selecciona independientemente en cada caso entre H o alquilo C1-4; R10 y R20 se seleccionan independientemente en cada caso entre H o alquilo C1-4; R10' se selecciona independientemente en cada caso entre H o alquilo C1-4; R11 se selecciona independientemente en cada caso entre H o alquilo C1-4; R12 se selecciona independientemente en cada caso entre un resto H, alquilo C1-4, alquilo C1-4 sustituido con halo, alquenilo C2-4, alquinilo C2-4, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-4, cicloalquenilo C5-7, cicloalquenil C5-7-alquilo C1-4, arilo, aril-alquilo C1-4, heteroarilo, heteroaril-alquilo C1-4, heterociclilo o heterociclil-alquilo C1-4, y en el que cada uno de estos restos, excluyendo el H, puede estar opcionalmente sustituido; R13 se selecciona independientemente en cada caso entre un resto H, alquilo C1-4, alquilo C1-4 sustituido con halo, alquenilo C2-4, alquinilo C2-4, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-4, cicloalquenilo C5-7, cicloalquenil C5-7- alquilo C1-4, arilo, aril-alquilo C1-4, heteroarilo, heteroaril-alquilo C1-4, heterociclilo o heterociclil-alquilo C1-4, y en el que cada uno de estos restos, excluyendo el H, puede estar opcionalmente sustituido; cada uno de Rd y Rd' se selecciona independientemente en cada caso entre un resto H, alquilo C1-4, cicloalquilo C3-6, cicloalquil C3-6-alquilo C1-4 y en los que cada uno de estos restos, excluyendo el H, puede estar opcionalmente sustituido; o Rd y Rd' junto con el N al que están unidos forman un anillo heterocíclico opcionalmente sustituido de 5 a 6 miembros, donde dicho anillo contiene opcionalmente un heteroátomo más seleccionado entre O, S o NR9'; g es 0 o un numero entero que tiene el valor 1, 2, 3, o 4; n' se selecciona independientemente en cada caso entre 0 y un numero entero que tiene un valor de 1 a 10; m se selecciona independientemente en cada caso entre 0 y un entero que tiene un valor de 1 o 2; q es 0 o un entero que tiene un valor de 1 a 10; q' es 0 o un numero entero que tiene un valor de 1 a 6; t es un numero entero que tiene un valor de 2 a 6; v es 0 o un numero entero que tiene el valor 1 o 2; v' se selecciona independientemente en cada caso entre 0 o un entero que tiene un valor de1 o 2; Z se selecciona independientemente en cada caso entre O o S; o una de sus sales farmacéuticamente aceptables, solvatos o derivados fisiologicamente funcionales.
ARP060101148A 2005-03-25 2006-03-23 Derivados de 3,4-dihidro-pirimido(4,5-d)pirimidin-2-(1h)-ona 1,5,7 trisustituidos como inhibidores de la quinasa p38 AR053450A1 (es)

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CN1847229B (zh) 2000-10-23 2011-05-04 史密丝克莱恩比彻姆公司 2，4，8-三取代-8H-吡啶并[2，3-d]嘧啶-7-酮化合物
EP2258687B1 (en) 2002-02-12 2012-12-26 Glaxosmithkline LLC Nicotinamide derivates useful as P38 inhibitors
EP1499320B1 (en) * 2002-04-19 2007-08-22 Smithkline Beecham Corporation Novel compounds
CN101495475A (zh) * 2005-03-25 2009-07-29 葛兰素集团有限公司 制备吡啶并[2,3-d]嘧啶-7-酮和3,4-二氢嘧啶并[4,5-d]嘧啶-2(1H)-酮衍生物的方法
PE20061193A1 (es) * 2005-03-25 2006-12-02 Glaxo Group Ltd DERIVADOS DE 3,4-DIHIDROPIRIMIDO[4,5-d]PIRIMIDIN-2-[1H]-0NA COMO INHIBIDORES DE QUINASA p38
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