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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Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of AR059229A1 publication Critical patent/AR059229A1/es

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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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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    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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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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CA2651987C (en) 2014-09-23
NZ570036A (en) 2011-06-30
KR101348491B1 (ko) 2014-01-06
US20090298833A1 (en) 2009-12-03
TWI424993B (zh) 2014-02-01
EP2471774B1 (en) 2016-08-24
MX2008009512A (es) 2009-02-26
EA019192B1 (ru) 2014-01-30
EP2471773B1 (en) 2016-03-23
EA200801757A1 (ru) 2009-08-28
JP2009526764A (ja) 2009-07-23
US20110245226A1 (en) 2011-10-06
EP2471773A1 (en) 2012-07-04
EP2471774A1 (en) 2012-07-04
EP2049486A2 (en) 2009-04-22
US20070208056A1 (en) 2007-09-06
NO20083359L (no) 2008-10-15
CA2651987A1 (en) 2007-08-16
PE20071236A1 (es) 2007-12-14
WO2007092681A3 (en) 2009-03-12
KR20080095890A (ko) 2008-10-29

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