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AR035773A1 - Compuestos diamino ciclico, composicion farmaceutica y su uso en la fabricacion de un medicamento util para modular la actividad de una quimioquina - Google Patents

Compuestos diamino ciclico, composicion farmaceutica y su uso en la fabricacion de un medicamento util para modular la actividad de una quimioquina

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Publication number
AR035773A1
AR035773A1 ARP010105969A ARP010105969A AR035773A1 AR 035773 A1 AR035773 A1 AR 035773A1 AR P010105969 A ARP010105969 A AR P010105969A AR P010105969 A ARP010105969 A AR P010105969A AR 035773 A1 AR035773 A1 AR 035773A1
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Argentina
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substituted
crr
alkyl
appears
alkynyl
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ARP010105969A
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Bristol Myers Squibb Pharma Co
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    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
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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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Abstract

Un compuesto diamino cíclico de la fórmula (1) o un estereoisómero o una sal aceptable para uso farmacéutico del mismo, donde: el anillo B es un grupo cicloalquilo de 3 a 8 átomos de carbono, donde el grupo cicloalquilo está saturado o parcialmente insaturado; o un heterociclo de 3 a 7 átomos, donde el heterociclo está saturado o parcialmente insaturado, conteniendo dicho heterociclo un heteroátomo seleccionado entre -O-, -S-, -S(=O), -S(=O)2 y -N(R4)- y optativamente el heterociclo contiene un -C(O)-; el anillo B está sustituido con 0-2 R5; Z se selecciona entre un enlace, -C(O)-, -C(O)NH-, -C(S)NH-, -SO2- y -SO2NH-; R1a y R1b se seleccionan independientemente entre H, alquilo C1-4, cicloalquilo C1-4, CF3, o como alternativa, R1a y R1b se toman juntos para formar =O; R1 se selecciona entre un grupo arilo C6-10 sustituido con 0-5 R6 y un sistema heteroarilo de 5-10 miembros que contiene 1-4 heteroátomos seleccionados entre N, O, y S, sustituido con 0-3 R6; R2 se selecciona entre un grupo arilo C6-10 sustituido con 0-5 R7 y un sistema heteroarilo de 5-10 miembros que contiene 1-4 heteroátomos seleccionados entre N, O, y S, sustituido con 0-3 R7; R4 se selecciona entre H, alquilo C1-6, alquenilo C3-8, alquinilo C3-8, (CRR)qOH, (CRR)tSH, (CRR)tOR4d, (CHR)tSR4d, (CRR)tNR4aR4a, (CRR)qC(O)OH, (CRR)rC(O)R4b, (CRR)rC(O)NR4aR4a, (CRR)tOC(O)NR4aR4a, (CRR)tNR4aC(O)OR4d, (CRR)tNR4aC(O)R4b, (CRR)tC(O)OR4b, (CRR)tOC(O)R4b, (CRR)rS(O)pR4b, (CRR)rS(O)2NR4aR4a, (CRR)rNR4aS(O)2R4b, haloalquilo C1-6, un residuo carbocíclico (CRR)r-C3-10 sustituido con 0-3 R4e, y un sistema heterocíclico (CHR)r de 4-10 miembros que contiene 1-4 heteroátomos seleccionados entre N, O y S, sustituido con 0-2 R4e; R4a, cada vez que aparece, se selecciona independientemente entre H, metilo sustituido con 0-1 R4c, alquilo C2-6 sustituido con 0-3 R4e, alquenilo C3-8 sustituido con 0-3 R4e, alquinilo C3-8 sustituido con 0-3 R4e, un residuo carbocíclico (CH2)r-C3-10 sustituido con 0-4 R4e, y un sistema heterocíclico (CHR)r de 4-10 miembros que contiene 1-4 heteroátomos seleccionados entre N, O, y S, sustituido con 0-2 R4e; R4b, cada vez que aparece, se selecciona entre H, alquilo C1-6 sustituido con 0-3 R4e, alquenilo C3-8 sustituido con 0-3 R4e, alquinilo C3-8 sustituido con 0-3 R4e, un residuo carbocíclico (CH2)r-C3-6 sustituido con 0-2 R4e, y un sistema heterocíclico (CHR)r de 4-10 miembros que contiene 1-4 heteroátomos seleccionados entre N, O y S, sustituido con 0-2 R4e; R4c se selecciona independientemente entre -C(O)R4b, -C(O)OR4d, -C(O)NR4fR4f y -(CH2)rfenilo; R4d, cada vez que aparece, se selecciona entre metilo, -CF3, alquilo C1-6 sustituido con 0-3 R4e, alquenilo C3-8 sustituido con 0-3 R4e, alquinilo C3-8 sustituido con 0-3 R4e, y un residuo carbocíclico C3-10 sustituido con 0-3 R4e; R4e, cada vez que aparece, se selecciona entre alquilo C1-6, alquenilo C2-8, alquinilo C2-8, (CH2)rcicloalquilo C3-6, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rO-alquilo C1-5, OH, SH, (CH2)rS-alquilo C1-5, (CH2)rNR4fR4f, -C(O)R4i, -C(O)OR4j, -C(O)NR4hR4h, -OC(O)NR4hR4h, -NR4hC(O)NR4hR4h, -NR4hC(O)OR4j, y (CH2)rfenilo; R4f, cada vez que aparece, se selecciona entre H, alquilo C1-6, cicloalquilo C3-6 y fenilo; R4h, cada vez que aparece, se selecciona independientemente entre H, alquilo C1-6, alquenilo C3-8, alquinilo C3-8 y un residuo carbocíclico (CH2)r-C3-10; R4i, cada vez que aparece, se selecciona independientemente entre H, alquilo C1-6, alquenilo C3-8, alquinilo C3-8 y un residuo carbocíclico (CH2)r-C3-6; R4j, cada vez que aparece, se selecciona entre CF3, alquilo C1-6, alquenilo C3-8, alquinilo C3-8 y un residuo carbocíclico C3-10; R5, cada vez que aparece, se selecciona independientemente entre H, alquilo C1-6, alquenilo C2-8, alquinilo C2-8, (CRR)rOH, (CRR)rSH, (CRR)rOR5d, (CRR)rSR5d, (CRR)rNR5aR5a, (CRR)rC(O)OH, (CRR)rC(O)R5b, (CRR)rC(O)NR5aR5a, (CRR)rNR5aC(O)R5b, (CRR)rOC(O)NR5aR5a, (CRR)rNR5aC(O)OR5d, (CRR)rNR5aC(O)NR5aR5a, (CRR)rNR5aC(O)H, (CRR)rC(O)OR5b, (CRR)rOC(O)R5b, (CRR)rS(O)pR5b, (CRR)rS(O)2NR5aR5a, (CRR)rNR5aS(O)2R5b, (CRR)rNR5aS(O)2NR5aR5a, haloalquilo C1-6, un residuo carbocíclico (CRR)r-C3-10 sustituido con 0-3 R5c y un sistema heterocíclico (CRR)r de 5-10 miembros que contiene 1-4 heteroátomos seleccionados entre N, O y S, sustituido con 0-2 R5c; R5a, cada vez que aparece, se selecciona independientemente entre H, metilo sustituido con 0-1 R5g, alquilo C2-6 sustituido con 0-2 R5e, alquenilo C3-8 sustituido con 0-2 R5e, alquinilo C3-10 sustituido con 0-2 R5e, un residuo carbocíclico (CH2)r-C3-10 sustituido con 0-5 R5e y un sistema heterocíclico (CH2)r de 5-10 miembros que contiene 1-4 heteroátomos seleccionados entre N, O y S, sustituido con 0-3 R5e; R5b, cada vez que aparece, se selecciona entre alquilo C1-6 sustituido con 0-3 R5e, alquenilo C3-8 sustituido con 0-2 R5e, alquinilo C3-8 sustituido con 0-2 R5e, un residuo carbocíclico (CH2)r-C3-6 sustituido con 0-2 R5e y un sistema heterocíclico (CH2)r de 5-6 miembros que contiene 1-4 heteroátomos seleccionados entre N, O y S, sustituido con 0-3 R5e; R5c, cada vez que aparece, se selecciona entre alquilo C1-6, alquenilo C2-8, alquinilo C2-8, (CH2)rcicloalquilo C3-6, Cl, Br, I, F, (CF2)rCF3, NO2, CN, (CH2)rNR5fR5f, (CH2)rOH, (CH2)rO-alquilo C1-4, (CH2)rS-alquilo C1-4, (CH2)rC(O)OH, (CH2)rC(O)R5b, (CH2)rC(O)NR5fR5f, (CH2)rNR5fC(O)R5b, (CH2)rC(O)O-alquilo C1-4, (CH2)rOC(O)R5b, (CH2)rC(=NR5f)NR5fR5f, (CH2)rS(O)pR5b, (CH2)rNHC(=NR5f)NR5fR5f, (CH2)rS(O)2NR5fR5f, (CH2)rNR5fS(O)2R5b y (CH2)rfenilo sustituido con 0-3 R5e; R5d, cada vez que aparece, se selecciona entre metilo, CF3, alquilo C2-6 sustituido con 0-2 R5e, alquenilo C3-8 sustituido con 0-2 R5e, alquinilo C3-8 sustituido con 0-2 R5e, un residuo carbocíclico C3-10 sustituido con 0-3 R5e; R5e, cada vez que aparece, se selecciona entre alquilo C1-6, alquenilo C2-8, alquinilo C2-8, cicloalquilo C3-6, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rO-alquilo C1-5, OH, SH, (CH2)rS-alquilo C1-5, (CH2)rNR5fR5f y (CH2)rfenilo; R5f, cada vez que aparece, se selecciona entre H, alquilo C1-6, y cicloalquilo C3-6; R5g se selecciona independientemente entre -C(O)R5b, -C(O)OR5d, -C(O)NR5fR5f y (CH2)rfenilo; R, cada vez que aparece, se selecciona entre H, alquilo C1-6 sustituido con R5e, alquenilo C2-8, alquinilo C2-8, (CH2)rcicloalquilo C3-6 y (CH2)rfenilo sustituido con R5e; R6, cada vez que aparece, se selecciona entre alquilo C1-8, alquenilo C2-8, alquinilo C2-8, (CH2)rcicloalquilo C3-6, Cl, Br, I, F, NO2, CN, (CR'R')rNR6aR6a, (CR'R')rOH, (CR'R')rO(CR'R')rR6d, (CR'R')rSH, (CR'R')rC(O)H, (CR'R')rS(CR'R')rR6d, (CR'R')rSC(O)(CR'R')rR6b, (CR'R')rC(O)OH, (CR'R')rC(O)(CR'R')rR6b, (CR'R')rNR6aR6a, (CR'R')rC(O)NR6aR6a, (CR'R')rNR6fC(O)(CR'R')rR6b, (CR'R')rC(O)O(CR'R')rR6d, (CR'R')rOC(O)(CR'R')rR6b, (CR'R')rOC(O)NR6a(CR'R')rR6d, (CR'R')rNR6aC(O)NR6a(CR'R')rR6d, (CR'R')rNR6aC(S)NR6a(CR'R')rR6d, (CR'R')rNR6fC(O)O(CR'R')rR6b, (CR'R')rC(=NR6f)NR6aR6a, (CR'R')rNHC(=NR6f)NR6fR6f, (CR'R')rS(O)p(CR'R')rR6b, (CR'R')rS(O)2NR6aR6a, (CR'R')rNR6fS(O)2NR6aR6a, (CR'R')rNR6fS(O)2(CR'R')rR6b, haloalquilo C1-6, alquenilo C2-8 sustituido con 0-3 R', alquinilo C2-8 sustituido con 0-3 R' y (CR'R')rfenilo sustituido con 0-3 R6e; como alternativa, se pueden unir dos R6 sobre átomos adyacentes de R1 para formar un acetal cíclico; R6a, cada vez que aparece, se selecciona entre H, metilo sustituido con 0-1 R6g, alquilo C2-6 sustituido con 0-2 R6e, alquenilo C3-8 sustituido con 0-2 R6e, alquinilo C3-8 sustituido con 0-2 R6e, un residuo carbocíclico (CH2)r-C3-10 sustituido con 0-5 R6e y un sistema heterocíclico (CH2)r de 5-10 miembros que contiene 1-4 heteroátomos seleccionados entre N, O y S, sustituido con 0-2 R6e; R6b, cada vez que aparece, se selecciona entre H, alquilo C1-6 sustituido con 0-2 R6e, alquenilo C3-8 sustituido con 0-2 R6e, alquinilo C3-8 sustituido con 0-2 R6e, un residuo carbocíclico (CH2)r-C3-6 sustituido con 0-3 R6e y un sistema heterocíclico (CH2)r de 5-6 miembros que contiene 1-4 heteroátomos seleccionados entre N, O y S, sustituido con 0-2 R6e; R6d, cada vez que aparece, se selecciona entre alquenilo C3-8 sustituido con 0-2 R6e, alquinilo C3-8 sustituido con 0-2 R6e, metilo, CF3, alquilo C2-6 sustituido con 0-3 R6e, un residuo carbocíclico (CH2)r-C3-10 sustituido con 0-3 R6e y un sistema heterocíclico (CH2)r de 5-6 miembros que contiene 1-4 heteroátomos seleccionados entre N, O y S, sustituido con 0-3 R6e; R6e, cada vez que aparece, se selecciona entre alquilo C1-6, alquenilo C2-8, alquinilo C2-8, (CH2)rcicloalquilo C3-6, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rO-alquilo C1-5, OH, SH, (CH2)rS-alquilo C1-5, (CH2)rNR6fR6f y (CH2)rfenilo; R6f, cada vez que aparece, se selecciona entre H, alquilo C1-5, y cicloalquilo C3-6 y fenilo; R6g se selecciona independientemente entre -C(O)R6b, -C(O)OR6d, -C(O)NR6fR6f y (CH2)rfenilo; R7, cada vez que aparece, se selecciona entre alquilo C1-8, alquenilo C2-8, alquinilo C2-8, (CH2)rcicloalquilo C3-6, Cl, Br, I, F, NO2, CN, (CR'R')rNR7aR7a, (CR'R')rOH, (CR'R')rO(CR'R')rR7d, (CR'R')rSH, (CR'R')rC(O)H, (CR'R')rS(CR'R')rR7d, (CR'R')rC(O)OH, (CR'R')rC(O)(CR'R')rR7b, (CR'R')rC(O)NR7aR7a, (CR'R')rNR7fC(O)(CR'R')rR7b, (CR'R')rC(O)O(CR'R')rR7d, (CR'R')rOC(O)(CR'R')rR7b, (CR'R')rOC(O)NR7a(CR'R')rR7a, (CR'R')rNR7aC(O)NR7a(CR'R')rR7a, (CR'R')rNR7fC(O)O(CR'R')rR7b, (CR'R')rC(=NR7f)NR7aR7a, (CR'R')rNHC(=NR7f)NR7fR7f, (CR'R')rS(O)p(CR'R')rR7b, (CR'R')rS(O)2NR7aR7a, (CR'R')rNR7aS(O)2NR7aR7a, (CR'R')rNR7fS(O)2(CR'R')rR7b, haloalquilo C1-6, alquenilo C2-8 sustituido con 0-3 R', alquinilo C2-8 sustituido con 0-3 R' y (CR'R')rfenilo sustituido con 0-3 R7e; como alternativa, se pueden unir dos R7 sobre átomos adyacentes de R2 para formar un acetal cíclico; R7a, cada vez que aparece, se selecciona independientemente entre H, metilo sustituido con 0-1 R7g, alquilo C2-6 sustituido con 0-2 R7e, alquenilo C3-8 sustituido con 0-2 R7e, alquinilo C3-8 sustituido con 0-2 R7e, un residuo carbocíclico (CH2)r-C3-10 sustituido con 0-5 R7e y un sistema heterocíclico (CH2)r de 5
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US6706712B2 (en) 2004-03-16
US20030004151A1 (en) 2003-01-02
US20040110736A1 (en) 2004-06-10
US7045521B2 (en) 2006-05-16
US20060135502A1 (en) 2006-06-22
HUP0303652A2 (hu) 2004-03-01
CA2432369A1 (en) 2002-08-08
WO2002060859A2 (en) 2002-08-08
US7572813B2 (en) 2009-08-11
JP2004523534A (ja) 2004-08-05

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