ES2189165T3 - Nuevos compuestos macrociclicos como inhibidores de metaloproteasa. - Google Patents

Nuevos compuestos macrociclicos como inhibidores de metaloproteasa.

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ES2189165T3
ES2189165T3 ES98921183T ES98921183T ES2189165T3 ES 2189165 T3 ES2189165 T3 ES 2189165T3 ES 98921183 T ES98921183 T ES 98921183T ES 98921183 T ES98921183 T ES 98921183T ES 2189165 T3 ES2189165 T3 ES 2189165T3
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compounds
inhibitors
metaloproteasa
macrociclic
new
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Chu-Bio Xue
Carl P Decicco
Robert J Cherney
Elizabeth Arner
William F Degrado
Jingwu Duan
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Bristol Myers Squibb Pharma Co
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Bristol Myers Squibb Pharma Co
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Abstract

Un compuesto, y una de sus formas de sal farmacéuticamente aceptable, seleccionado de: 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[glicina - n - pentil éster] - ciclopentadecano - 13 - N - hidroxi - carboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[N - 4 - fenil - 1 - butilamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[5 - metoxitriptamina] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[1 - (2, 5 - dimetoxifenil) - 2 - glicina - amidoetanol] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[glicina - t - butil éster] - ciclopentadecano - 13 - N - hidroxi - carboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[ácido L - glutámico - a, g - di - t - butil éster] -ciclopenta - decano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[glicina] - ciclopentadecano - 13 N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[N - 2 - fenil - 1 - butilamida] - ciclopentadecano - 13 - N - hidroxicarboxamida 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[2 - (2 - aminoetil) - 1 - metilpirrol] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[2 - (2 - aminoetil)bencenosulfonamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[L - ácido glutámico - g - ciclohexil éster - N - metil amida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[L - fenilalanina - p - fluoro - N metilamida] - ciclopentadecano - 13 - N - hidrixicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[L - fenilalanina - p - metoxi - N (S) - a - metilbencilamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[N - ciclohexilmetil amida] - ciclopentadecano - 13 - N - hidroxi - carboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[N - 3 - fenil - 1 - propil - amida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[N - 3, 3 - difenilpropil amida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[N - (2 - aminoetilamino)etil pirrolidina] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[L - 3(2¿ - nafti1)alanina - N - metil amida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[etil - 4 - amino - 1 - piperidina carboxilato] - ciclopentade cano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[5 - metil - triptamina] - ciclopentadecano - 13 - N - hidroxi - carboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[N - 4 - trifluorometilbencil amida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[L - ácido glutámico] - ciclopentadecano - 13 - N - hidroxi - carboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[2 - (dietilamino)etil - 4 - amino benzoato] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[6 - fluorotriptamina] - ciclopentadecano - 13 - N - hidroxi - carboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 -isobutil - 2[6 - metoxi triptamina] - ciclopentadecano - 13 - N - hidroxi - carboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2[triptamina] - ciclopentadecano 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - 4 - metilpiperazinamida)carboxamida] - ciclo - pentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (L - alanina - N - morfolinamida)carboxamida] - ciclopenta - decano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (L - valina - N - morfolinamida)carboxamida] - ciclopenta - decano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (L - terc - butilglicina - N morfolinamida)carboxamida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (b - alanina - N - morfolinamida)carboxamida] - ciclopenta - decano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (etoxicarbonil - N - morfolinamida)carboxamida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (2 - hidroxi - 2 - feniletil)carboxamida]ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 3S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - 4 - bencilpiperazinamida)carboxamida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - 4 - fenilpiperazinamida)carboxamida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - 4 - (2 - piridil)piperazinamida)carboxamida] ciclopentadecano - 13 - N -hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (a - ciclopropanoetiloxicarboxamida - b - alanina) - carboxamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - {N - [glicina - N - 4 - (1 - piperidinil)piperidinamida] - carboxamida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (R - isopropiloxicarbonil N - morfolinamida)carboxamida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (S - isopropiloxicarbonil N - morfolinamida)carboxamida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (2 - tiazol - 4 - ácido acético)carboxamida]ciclopenta - decano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo- 9 - oxa - 14 - isobutil - 2 - [N - (a - ciclopropanoetiloxicarboxamida - b - alanina - N - dimetilamida)carboxamida]ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (a - ciclopropanoetiloxicarboxamida - b - alanina - N - morfolinamida)carboxamida]ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (2 - tiazol - 4 - acetil - N morfolinamida)carboxamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (L - serina - N - morfolinamida)carboxamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - piperidinamida - 3 - ácido carboxílico) - carboxamida]ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - 2, 6 - dimetilmorfolinamida)carboxamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - 4 - etoxicarbonilpiperazinamida) - carboxamida]ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - 4 - etoxicarbonilpiperidinamida) carboxamida]ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - {N - [4 - (1 morfolinil)fenil]carboxamida}ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - {N - [glicina - N - (4 - (1 - morfolinil)anilida)carboxamida] ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - (glicina - N - piperidinamida - 4 - ácido carboxílico) - carboxamida] -ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [N - metilcarboxamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [alanina - N - metilamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [metilcarboxi] - ciclopentadecano 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [glicina - N - metilamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [2 - N - morfolinoetilcarboxamida] - ciclopentadecano - 13 - N - hidroxicarboxamida; 2S, 13S, 14R - 1, 7 - diaza - 8, 15 - dioxo - 9 - oxa - 14 - isobutil - 2 - [3 - N - morfolinopropilcarboxamida] - ciclopentadecano - 13 - N - hidroxicarbox
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