AR059229A1 - Derivados de piperidinilo como moduladores de la actividad del receptor de quimiocina - Google Patents

Derivados de piperidinilo como moduladores de la actividad del receptor de quimiocina

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Publication number
AR059229A1
AR059229A1 ARP070100372A ARP070100372A AR059229A1 AR 059229 A1 AR059229 A1 AR 059229A1 AR P070100372 A ARP070100372 A AR P070100372A AR P070100372 A ARP070100372 A AR P070100372A AR 059229 A1 AR059229 A1 AR 059229A1
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AR
Argentina
Prior art keywords
cr8r8
alkyl
heterocyclyl
nr14r14
rcf3
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ARP070100372A
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English (en)
Inventor
Percy H Carter
Joseph B Santella
Rul-Qin Liu
John Hynes
Cullen L Cavallaro
John V Duncia
Daniel S Gardner
Stuart Dodd
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Bristol Myers Squibb Co
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Publication of AR059229A1 publication Critical patent/AR059229A1/es

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Abstract

Moduladores de piperidinilo substituidos de MIP-1alfa o CCR-1 o estereoisomeros o sales farmacéuticamente aceptables de los mismos y composicion farmacéutica. Estos compuestos son utiles para tratar y prevenir enfermedades inflamatorias tales como asma y enfermedades alérgicas, así como patologías autoinmunes tales como artritis reumatoide y rechazo al transplante usando los modulares aquí descritos. Reivindicacion 1: Un compuesto de la formula (1) o estereoisomeros o profárrmacos o formas de sales farmacéuticamente aceptables de los mismos, caracterizado porque: la línea punteada representa un enlace doble opcional; T es como se muestra en los restos de formulas (2), R1 es alquilo, cicloalquilo, arilo, heterociclilo o heteroarilo, todos los cuales pueden ser opcionalmente substituidos con 0-5 R1a; R1a cada que se presenta, se selecciona independientemente de alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)O(CR8R8)rR10, -O(CF2)rCF3, -O(CR8R8)rR10, -OH, -SH, -S(CR8R8)rR10, -S(O)3H, -P(O)3H2, -C(=O)NR9R9, NR9R9, -S(O)NR9R9, -NR9S(O)2(CF2)rCF3, -C(=O)NR9S(O)2R6, -S(O)2NR9C(=O)OR6, -S(O)2NR9C(=O)NR9R9, -C(=O)NR9S(O)2(CF2)rCF3, -C(=O)(CR8R8)rR10, -NR9C(=O)H, -NR9C(=O)(CR8R8)rR10, -OC(=O)(CR8R8)rR10, -C(=NR14)NR9R9, -NHC(=NR14)NR14R14, -S(=O)(CR8R8)rR10, -S(O)2(CR8R8)rR10, -NR9C(=O)OR8, -NR9S(O)2R8, -S(O)2NR9C(O)R6, ariloxi o arilalquilo, en donde el arilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, ariloxi y arilalquilo pueden ser opcionalmente substituidos con 0-3 R1b; R1b cada que se presenta, se selecciona independientemente alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)O(CR8R8)rR10, -O(CF2)rCF3, - O(CR8R8)rR10, -OH, -SH, -S(CR8R8)rR10, -S(O)3H, -P(O)3H2, -C(=O)NR9R9, NR9R9, -S(O)NR9R9, -NR9S(O)2(CF2)rCF3, -C(=O)NR9S(O)2R6, -S(O)2NR9C(=O)OR6, -S(O)2NR9C(=O)NR9R9, -C(=O)NR9S(O)2(CF2)rCF3, -C(=O)(CR8R8)rR10, -NR9C(=O)H, -NR9C(=O)(CR8R8)rR10, - OC(=O)(CR8R8)rR10, -C(=NR14)NR9R9, -NHC(=NR14)NR14R14, -S(=O)(CR8R8)rR10, -S(O)2(CR8R8)rR10, -NR9C(=O)OR8, -NR9S(O)2R8, ariloxi o arilalquilo; R2 es alquilo, cicloalquilo, cicloalquilalquilo, o alquenilo, en donde el alquilo puede ser opcionalmente substituido con -OH; R3, cada que se presenta, es alquilo; o cualquiera de los dos R3's enlazados al mismo átomo de carbono pueden formar un anillo de 3 hasta 6 miembros; W es hidrogeno, F, -OH, -CN, -NH2; R5 es halo, -CN o -Oalquilo; o W y un R5 se toman junto con los átomos de carbono a los cuales cada uno se enlaza para formar un anillo que contiene oxígeno de 3 hasta 6 miembros en donde el anillo puede ser opcionalmente substituido con uno o más R5's; R6, cada que se presenta, es independientemente alquilo, cicloalquilo, cicloalquilalquilo, arilo, arilalquilo, heteroarilo o heteroarilalquilo; R8, cada que se presenta, es independientemente H o alquilo; R9, cada que se presenta, es independientemente hidrogeno, alquilo, cicloalquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, heterociclilo o heterociclilalquilo, en donde el arilo, arilalquilo, heteroarilo, heteroarilalquilo, heterociclilo o heterociclilalquilo pueden ser opcionalmente substituidos con 0-5 R9a, y el heteroarilo, heteroarilalquilo heterociclilo o heterociclilalquilo contiene 1-4 heteroátomos seleccionados de N, O, y S; R9a, cada que se presenta, se selecciona independientemente de alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)O(CR8R8)rR14, -O(CF2)rCF3, -O(CR8R8)rR14, -OH, -SH, -S(CR8R8)rR14, -S(O)3H, -P(O)3H2, -C(=O)NR14R14, - NR14R14, -S(O)NR14R14, -NR14S(O)2(CF2)rCF3, -C(=O)NR14S(O)2R6, -S(O)2NR14C(=O)OR6, -S(O)2NR14C(=O)NR14R14, -C(=O)NR14S(O)2(CF2)rCF3, -C(=O)(CR8R8)rR14, -NR14C(=O)H, -NR14C(=O)(CR8R8)rR14, -OC(=O)(CR8R8)rR14, -C(=NR14)NR14R14, -NHC(=NR14)R14R14, - S(=O)(CR8R8)rR14, -S(O)2(CR8R8)rR14, -NR14C(=O)OR8, -NR14S(O)2R8, ariloxi o arilalquilo; R10, cada que se presenta, se selecciona independientemente de alquilo, arilo, arilalquilo, heterociclilo o heterociclilalquilo, en donde el alquilo, arilo, arilalquilo, heterociclilo o heterociclilalquilo pueden ser opcionalmente substituidos con 0-3 R10a, y el heterociclilo o heterociclilalquilo contiene 1-4 heteroátomos seleccionados de N, O, y S; R10a, cada que se presenta, se selecciona independientemente de alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)O(CR8R8)rR14, -O(CF2)rCF3, - O(CR8R8)rR14, -OH, -SH, -S(CR8R8)rR14, -S(O)3H, -P(O)3H2, -C(=O)NR14R14, -NR14R14, -S(O)NR14R14, -NR14S(O)2(CF2)rCF3, -C(=O)NR14S(O)2R6, -S(O)2NR14C(=O)OR6, -S(O)2NR14C(=O)NR14R14, -C(=O)NR14S(O)2(CF2)rCF3, -C(=O)(CR8R8)rR14, -NR14C(=O)H, - NR14C(=O)(CR8R8)rR14, -OC(=O)(CR8R8)rR14, -C(=NR14)NR14R14, -NHC(=NR14)R14R14, -S(=O)(CR8R8)rR14, -S(O)2(CR8R8)rR14, -NR14C(=O)OR8, -NR14S(O)2R8, ariloxi o arilalquilo; R14, cada que se presenta, se selecciona independientemente de H, alquilo, cicloalquilo o fenilo; m, cada que se presenta, es 0-2; n es 1-3; y r es 0-5.
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WO2007092681A2 (en) 2007-08-16
MX2008009512A (es) 2009-02-26
EP2471774B1 (en) 2016-08-24
EP2471774A1 (en) 2012-07-04
AU2007212236A1 (en) 2007-08-16
BRPI0707307A2 (pt) 2011-05-03
US20090298833A1 (en) 2009-12-03
IL192976A (en) 2015-05-31
TWI424993B (zh) 2014-02-01
EP2049486A2 (en) 2009-04-22
EA019192B1 (ru) 2014-01-30
NO20083359L (no) 2008-10-15
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CA2651987C (en) 2014-09-23

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