CO5280089A1 - Antagonistas del receptor il-8 - Google Patents

Antagonistas del receptor il-8

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Publication number
CO5280089A1
CO5280089A1 CO01020681A CO01020681A CO5280089A1 CO 5280089 A1 CO5280089 A1 CO 5280089A1 CO 01020681 A CO01020681 A CO 01020681A CO 01020681 A CO01020681 A CO 01020681A CO 5280089 A1 CO5280089 A1 CO 5280089A1
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Colombia
Prior art keywords
alkyl
chloro
optionally substituted
aryl
heterocycle
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CO01020681A
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English (en)
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Qi
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Smithkline Beecham Corp
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Publication of CO5280089A1 publication Critical patent/CO5280089A1/es

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Abstract

Un compuesto de Fórmula (I):<EMI FILE="01020681_1" ID="1" IMF=JPEG >en la que:Rb es independientemente seleccionado del grupo que consiste en hidrógeno, NR6-R7, OH, ORa, alquilo C1-5, arilo, aril-alquilo C1-4, aril-alquenilo C2-4, cicloalquilo, cicloalquil-alquilo C1-5, heteroarilo, heteroaril-alquilo C1-4, heteroaril-alquenilo C2-4, heterociclo, hetero-ciclo-alquilo C1-4, y heterociclo-alquenilo C2-4, restos todos que pueden estar opcional e independientemente sustituidos de una a tres veces con un sustituyente seleccionado del grupo que consiste en halógeno, nitro, alquilo C1-4 halosustituido, alquilo C1-4, amino, amina mono- o di-sustituida con alquilo C1-4, ORa, C(O)Ra, NRaC(O)ORa, OC(O)NR6R7, hidroxilo, NR9C(O)Ra, S(O)m´Ra, C(O)NR6R7, C(O)OH, C(O)ORa, S(O)2NR6R7, y NHS(O)2Ra; o los dos sustituyentes Rb están unidos para formar un anillo de 3-10 miembros opcionalmente sustituido y que contiene independientemente, además de carbono, de 1 a 3 restos seleccionados del grupo que consiste en NRa, O, S, SO y SO2, y en el que el sustituyente puede estar opcionalmente insaturado;Ra es seleccionado del grupo que consiste en los restos alquilo, arilo, aril-alquilo C1-4 heteroarilo, hetero-aril-alquilo C1-4, heterociclo, COOR13, y heterociclo-alquilo C1-4, todos los cuales pueden estar opcionalmente sustituidos;m es un número entero que tiene un valor de 1 a 3; m' es 0 o un número entero que tiene un valor de 1 o 2; n es un número entero que tiene un valor de 1 a 3; q es 0 o un número entero que tiene un valor de 1 a 10; t es 0 o un número entero que tiene un valor de 1 ó 2; s es un número entero que tiene un valor de 1 a 3; R1 es independientemente seleccionado del grupo que consiste en hidrógeno, halógeno, nitro, ciano, alquilo C1-10, alquilo C1-10 halosustituido, alquenilo C2-10, alcoxilo C1-10, alcoxilo C1-10 halosustituido, azida, S(O)tR4, (CR8R8)qS(O)tR4, hidroxilo, alquilo C1-4, - 2 -sustituido con hidroxilo, arilo, aril-alquilo C1-4, aril-alquenilo C2-10, ariloxilo, aril-alquiloxilo C1-4, heteroarilo, heteroarilalquilo, heteroaril-alquenilo C2-10, hetero-aril-alquiloxilo C1-4, heterociclo, heterociclo-alquilo C1-4, heterociclo-alquiloxilo C1-4, heterociclo-alquenilo C2-10, (CR8R8)qNR4R5, (CR8R8)qC(O)NR4R5, alquenil C2-10- C(O)NR4R5, (CR8R8)qC(O)NR4R10, S(O)3R8, (CR8R8)qC(O)R11, alquenil C2-10-C(O)R11, alquenil C2-10-C(O)OR11, (CR8R8)q-C(O)OR11, (CR8R8)qOC(O)R11, (CR8R8)qNR4C(O)R11, (CR8R8)q-C(NR4)NR4R5, (CR8R8)qNR4C(NR5)R11, (CR8R8)qNHS(O)2R13, y (CR8R8)q- S(O)2NR4R5; o dos restos R1 pueden formar conjuntamente O-(CH2)SO o un anillo saturado o insaturado de 5 a 6 miembros, pudiendo estar opcionalmente sustituidos los restos alquilo, arilo, arilalquilo, heteroarilo y heterociclo;R4 y R5 son independientemente seleccionados del grupo que consiste en hidrógeno, alquilo C1-4 opcionalmente sustituido, arilo opcionalmente sustituido, aril-alquilo C1-4 opcionalmente sustituido, heteroarilo opcionalmente sustituido, heteroaril-alquilo C1-4 opcionalmente sustituido, heterociclo y heterociclo alquilo C1-4; o R4 y R5 junto con el nitrógeno al que están unidos forman un anillo de 5 a 7 miembros que puede comprender opcionalmente un heteroátomo adicional seleccionado entre O, N y S; R6 y R7 son independientemente seleccionados del grupo que consiste en hidrógeno, alquilo C1-4, heteroarilo, arilo, alquilarilo, y alquil-heteroalquilo C1-4; o R6 y R7 junto con el nitrógeno al que están unidos forman un anillo de 5 a 7 miembros, anillo que puede contener opcionalmente un heteroátomo adicional seleccionado entre oxígeno, nitrógeno y azufre y que puede estar opcionalmente sustituido;Y es seleccionado del grupo que consiste en CR14R15, NR14, O, CO, y S(O)t;R8 es hidrógeno o alquilo C1-4;R9 es alquilo C1-4;R10 es alquil C1-10-C(O)2R8;R11 es seleccionado del grupo que consiste en hidrógeno, alquilo C1-4 opcionalmente sustituido, arilo opcionalmente sustituido, aril-alquilo C1-4 opcionalmente sustituido, heteroarilo opcionalmente sustituido, heteroaril-alquilo C1-4 opcionalmente sustituido, heterociclo opcionalmente sustituido, y heterociclo-alquilo C1-4 opcionalmente sustituido;R12 es seleccionado del grupo que consiste en hidrógeno, alquilo C1-4, arilo, aril-alquilo C1-4, heteroarilo, heteroaril-alquilo C1-4, heterociclo y heterociclo-alquilo C1-4;R13 es seleccionado del grupo que consiste en alquilo C1-4, arilo, aril-alquilo C1-4, heteroarilo, heteroaril-alquilo C1-4, heterociclo, y heterociclo-alquilo C1-4; yR14 y R15 son independientemente seleccionados del grupo que consiste en hidrógeno, alquilo C1-4 opcionalmente sustituido, ORa, y NR4R5; o R14 y R15 junto con el(los) átomo(s) al(a los) que están unidos pueden formar un anillo de 4 a 7 miembros que puede contener opcionalmente un heteroátomo adicional que es seleccionado del grupo que consiste en oxigeno, nitrógeno y azufre, anillo que puede estar opcionalmente sustituido;o una sal farmacéuticamente aceptable del mismo. Un compuesto de acuerdo con la Reivindicación 1, que es seleccionado del grupo que consiste en: N-(3-aminosulfonil-4-cloro-2-hidroxifenil)-N' -ciclohexilurea;N-(3-aminosulfonil-4-cloro-2-hidroxifenil)-N' - (1-adamantu) urea;N- (3-aminosulfonil-4-cloro-2-hidroxifenil) -N' - (tetrahidro-2-piranil) urea;N-(4-cloro-2-hidroxi-3-sulfamilfenil),-N´- (3-tetrahidrofuril) urea;6-cloro-2-hidroxi-3-[3-(2-metil-ciclopropil)-ureido]- -bencenosulfonamida;N-(4-cloro-2-hidroxi-3-sulfamilfenil)-N' -ciclohexilurea;6-cloro-2-hidroxi-3-[3-(2,2,3,3-tetrametil-ciclopropil)-ureido]-bencenosulfonamida;6-cloro-2-hidroxi-3-(3-piperidin-4-il-ureido) -benceno-sulfonamida;N-(4-cloro-2-hidroxi-3-sulfamilfenil)-N´-(4-metil-ciclohexil) urea;6-cloro-2-hidroxi-3-[3-(3-metoxi-ciclohexil)ureido]-bencenosulfonamida;N- (4-cloro-2 -hidroxi -3-sulfamilfenil) -N´-ciclopentilurea;N- (4-cloro-2-hidroxi-3-sulfamilfenil) -N' -ciclobutilurea;N-(4-cloro-2-hidroxi-3-sulfamilfenil) -N' -ciclopropilurea;éster terc-butílico del ácido 4-[6-cloro-3-(3-ciclopentil-ureido)-2-hidroxi-bencenosulfonil] -piperazina-1 -carboxílico;1- (4-cloro-2-hidroxi-3- (piperazina-1-sulfonil)-fenil] -3-ciclopentil -urea;éster terc-butílico del ácido 4-(6-cloro-3-(3-ciclobutil-ureido)-2-hidroxi-bencenosulfonil] -piperazina-1-carboxílico;3-{3-[(1S,2S)-2-benciloxi-ciclohexil]-ureido}-6-cloro-2-hidroxi- bencenosulfonamida; y6-cloro-3-(3-ciclobutil-ureido)-2-hidroxi-N,N'-dimetil--bencenosulfonamida.
CO01020681A 2000-03-16 2001-03-14 Antagonistas del receptor il-8 CO5280089A1 (es)

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RU2017106172A (ru) * 2014-07-31 2018-08-28 Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед Применение антагонистов cxcr2 для предотвращения и/или лечения периферической невропатии, вызванной химиотерапией (cipn)
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