ES2628026T3 - Moduladores de transportadores del casete de unión a ATP - Google Patents

Moduladores de transportadores del casete de unión a ATP Download PDF

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Publication number
ES2628026T3
ES2628026T3 ES12152225.4T ES12152225T ES2628026T3 ES 2628026 T3 ES2628026 T3 ES 2628026T3 ES 12152225 T ES12152225 T ES 12152225T ES 2628026 T3 ES2628026 T3 ES 2628026T3
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Spain
Prior art keywords
oxo
carboxamide
quinoline
phenyl
tert
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Expired - Lifetime
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ES12152225.4T
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English (en)
Inventor
Sarah S. Hadida Ruah
Anna R. Hazlewood
Peter D. J. Grootenhuis
Fredrick F. Van Goor
Ashvani K. Singh
Jinglan Zhou
Jason Mccartney
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Vertex Pharmaceuticals Inc
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Vertex Pharmaceuticals Inc
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Application filed by Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc
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Publication of ES2628026T3 publication Critical patent/ES2628026T3/es
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
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    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
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    • A61K31/265—Esters, e.g. nitroglycerine, selenocyanates of carbonic, thiocarbonic, or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
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Abstract

Un compuesto de fórmula VA-1:**Fórmula** o una sal farmacéuticamente aceptable del mismo, en el que cada uno de WRW2 y WRW4 está seleccionado independientemente de hidrógeno, CN, CF3, halógeno, alquilo C1-C6 lineal o ramificado, cicloalifático de 3-12 miembros, fenilo, heteroarilo C5-C10 o heterocíclico C3-C7, en el que dicho heteroarilo o heterocíclico tiene hasta 3 heteroátomos seleccionados de O, S o N, en el que dichos WRW2 y WRW4 están independientemente y opcionalmente sustituidos con hasta tres sustituyentes seleccionados de -OR', -CF3, -OCF3, SR', S(O)R', SO2R', -SCF3, halógeno, CN, -COOR', - COR', -O(CH2)2N(R')(R'), -O(CH2)N(R')(R'), -CON(R')(R'), -(CH2)2OR', -(CH2)OR', CH2CN, fenilo opcionalmente sustituido o fenoxi, -N(R')(R'), -NR'C(O)OR', -NR'C(O)R', -(CH2)2N(R')(R') o -(CH2)N(R')(R'); y WRW5 está seleccionado de hidrógeno, -OH, NH2, CN, CHF2, NHR', N(R')2, -NHC(O)R', -NHC(O)OR', NHSO2R', -OR', CH2OH, CH2N(R')2, C(O)OR', SO2NHR' SO2N(R')2, CH2O(alquilo C1-C6) o CH2NHC(O)OR'; y X es un enlace RX es hidrógeno; R' está seleccionado independientemente de hidrógeno o un grupo opcionalmente sustituido seleccionado de un grupo alifático C1-C8, un anillo monocíclico de 3-8 miembros saturado, parcialmente insaturado, o completamente insaturado que tiene 0-3 heteroátomos seleccionados independientemente de nitrógeno, oxígeno, o azufre, o un sistema de anillo bicíclico de 8-12 miembros saturado, parcialmente insaturado, o completamente insaturado que tiene 0-5 heteroátomos seleccionados independientemente de nitrógeno, oxígeno, o azufre; o dos apariciones de R' tomadas junto con los átomos a los que están unidos para formar un anillo monocíclico o bicíclico opcionalmente sustituido de 3-12 miembros saturado, parcialmente insaturado, o completamente insaturado que tiene 0-4 heteroátomos seleccionados independientemente de nitrógeno, oxígeno, o azufre; siempre que:**Fórmula** de fórmula VA-1 no sea fenilo, 2-metilfenilo, 2,4-diclorofenilo, 2-bromofenilo, 4-bromofenilo, 2,4- dimetilfenilo, 2-etilfenilo, 3-ácido-carboxílico fenilo, 2-fluorofenilo, 3-etoxifenilo, 4-clorofenilo o 3- metoxifenilo;; y**Fórmula** de fórmula VA-1 no sea fenilo sustituido con -OCH2CH2Ph, -OCH2CH2(2-trifluorometil-fenil-OCH2CH2-(6,7- dimetoxi-1,2,3,4-tetrahidroisoquinolin-2-il), o 1H-pirazol-3-il sustituido.

Description

imagen1
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xvi) si R1, R3, R4, R5, R6 y R7 es cada uno hidrógeno y R2 es CF3 o OCF3, entonces Ar1 no es [3,5bis(trifluorometil)-1H-pirazol-1-il]fenilo; xvii) si R1, R2, R4, R5, R6 y R7 es cada uno hidrógeno y R3 es hidrógeno o CF3, entonces Ar1 no es un fenilo sustituido con -OCH2CH2Ph, -OCH2CH2(2-trifluorometil-fenilo), -OCH2CH2-(6,7-dimetoxi-1,2,3,4tetrahidroisoquinolin-2-ilo) o 1H-pirazol-3-ilo sustituido; y xviii) se excluyen los dos siguientes compuestos:
imagen7
y
2. Compuesto y definiciones
Como se usa en el presente documento, deben aplicarse las siguientes definiciones, a menos que se indique lo contrario.
El término “transportador de ABC”, como se usa en el presente documento, significa una proteína transportadora de ABC o un fragmento de la misma que comprende al menos un dominio de unión, en el que dicha proteína o fragmento de la misma está presente in vivo o in vitro. El término “dominio de unión”, como se usa en el presente documento, significa un dominio sobre el transportador de ABC que puede unirse a un modulador. Véase, por ejemplo, Hwang, T. C. y col., J. Gen. Physiol. (1998): 111(3), 477-90.
El término “CFTR”, como se usa en el presente documento, significa regulador de la conductancia transmembrana de la fibrosis quística o una mutación del mismo que es capaz de regular la actividad, que incluye, pero no se limita a, F508-CFTR y G551D-CFTR (véase, por ejemplo, http://www.genet.sickkids.on.ca/cftr/, para mutaciones CFTR).
El término “modular”, como se usa en el presente documento, significa aumentar o disminuir por una cantidad medible.
Para los fines de la presente invención, los elementos químicos se identifican según la tabla periódica de los elementos, versión CAS, Handbook of Chemistry and Physics, 75ª ed. Adicionalmente, los principios generales de la química orgánica se describen en “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, y “March's Advanced Organic Chemistry”, 5ª ed., Ed.: Smith, M.B. y March, J., John Wiley & Sons, Nueva York: 2001.
Como se describe en el presente documento, los compuestos de la invención pueden estar opcionalmente sustituidos con uno o más sustituyentes, tal como se ilustra generalmente anteriormente, o como se ejemplifica por clases particulares, subclases y especies de la invención. Se apreciará que la expresión “opcionalmente sustituido” se usa indistintamente con el término “sustituido o sin sustituir”. En general, el término “sustituido”, si va precedido por el término “opcionalmente” o no, se refiere a la sustitución de radicales hidrógeno en una estructura dada con el radical de un sustituyente especificado. A menos que se indique lo contrario, un grupo opcionalmente sustituido puede tener un sustituyente en una cada posición sustituible del grupo, y cuando más de una posición en cualquier estructura dada puede estar sustituida con más de un sustituyente seleccionado de un grupo especificado, el sustituyente puede ser tanto el mismo como diferente en cada posición. Combinaciones de sustituyentes concebidas por la presente invención son preferentemente aquellas combinaciones que producen la formación de compuestos estables o químicamente factibles. El término “estable”, como se usa en el presente documento, se refiere a compuestos que no están sustancialmente alterados cuando se someten a condiciones para permitir su producción, detección y preferentemente su recuperación, purificación y uso para uno o más de los fines desvelados en el presente documento. En algunos casos, un compuesto estable o compuesto químicamente factible es uno que no está sustancialmente alterado cuando se mantiene a una temperatura de 40 ºC o menos, en ausencia de humedad u otras condiciones químicamente reactivas, durante al menos una semana.
El término “alifático” o “grupo alifático”, como se usa en el presente documento, significa una cadena lineal (es decir, sin ramificar) o cadena de hidrocarburo ramificada, sustituida o sin sustituir, que está completamente saturada o que contiene una o más unidades de insaturación, o un hidrocarburo monocíclico o hidrocarburo bicíclico que está completamente saturado o que contiene una o más unidades de insaturación, pero que no es aromático (también denominado en el presente documento “carbociclo”, “cicloalifático” o “cicloalquilo”), que tiene un único punto de unión con el resto de la molécula. A menos que se especifique de otro modo, grupos alifáticos contienen 1-20
8
imagen8
5
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65
sobre el grupo alifático de R° están seleccionados de NH2, NH(alifático C1-4), N(alifático C1-4)2, halógeno, alifático C14, OH, O(alifático C1-4), NO2, CN, CO2H, CO2(alifático C1-4), O(haloalifático C1-4) o haloalifático C1-4, en los que cada uno de los grupos alifáticos C1-4 anteriores de R° está sin sustituir.
Un grupo alifático o heteroalifático, o un anillo heterocíclico no aromático, puede contener uno o más sustituyentes. Sustituyentes adecuados sobre el carbono saturado de un grupo alifático o heteroalifático, o de un anillo heterocíclico no aromático, están seleccionados de aquellos enumerados anteriormente para el carbono insaturado de un grupo arilo o heteroarilo y adicionalmente incluyen los siguientes: =O, =S, =NNHR*, =NN(R*)2, =NNHC(O)R*, =NNHCO2(alquilo), =NNHSO2(alquilo) o =NR*, en los que cada R* está seleccionado independientemente de hidrógeno o un alifático C1-6 opcionalmente sustituido. Sustituyentes opcionales sobre el grupo alifático de R* están seleccionados de NH2, NH(alifático C1-4), N(alifático C1-4)2, halógeno, alifático C1-4, OH, O(alifático C1-4), NO2, CN, CO2H, CO2(alifático C1-4), O(haloalifático C1-4) o halo(alifático C1-4), en los que cada uno de los grupos alifáticos C1-4 anteriores de R* está sin sustituir.
Sustituyentes opcionales sobre el nitrógeno de un anillo heterocíclico no aromático están seleccionados de -R+, N(R*)2, -C(O)R+, -CO2R+, -C(O)C(O)R+, -C(O)CH2C(O)R+, -SO2R+, -SO2N(R+)2, -C(=S)N(R+)2, -C(=NH)-N(R+)2 o NR+SO2R+; en los que R+ es hidrógeno, un alifático C1-6 opcionalmente sustituido, fenilo opcionalmente sustituido, O(Ph) opcionalmente sustituido, -CH2(Ph) opcionalmente sustituido, -(CH2)1-2(Ph) opcionalmente sustituido; -CH=CH(Ph) opcionalmente sustituido; o un heteroarilo o anillo heterocíclico de 5-6 miembros sin sustituir que tiene uno a cuatro heteroátomos independientemente seleccionados de oxígeno, nitrógeno o azufre, o, a pesar de la definición anterior, dos apariciones independientes de R+, sobre el mismo sustituyente o sustituyentes diferentes, tomadas conjuntamente con el (los) átomo(s) a los que cada grupo R+ está unido, forman un anillo de cicloalquilo, heterociclilo, arilo o heteroarilo de 3-8-miembros que tiene 0-3 heteroátomos independientemente seleccionados de nitrógeno, oxígeno o azufre. Sustituyentes opcionales sobre el grupo alifático o el anillo de fenilo de R+ están seleccionados de NH2, NH(alifático C1-4), N(alifático C1-4)2, halógeno, alifático C1-4, OH, O(alifático C1-4), NO2, CN, CO2H, CO2(alifático C1-4), O(haloalifático C1-4) o halo(alifático C1-4), en los que cada uno de los anteriores grupos alifáticos C1-4 de R+ está sin sustituir.
El término “cadena de alquilideno” se refiere a una cadena de carbono lineal o ramificada que puede estar completamente saturada o tener una o más unidades de insaturación y tiene dos puntos de unión al resto de la molécula. El término “espirocicloalquilideno” se refiere a un anillo carbocíclico que puede estar completamente saturado o tener una o más unidades de insaturación y tiene dos puntos de unión del mismo átomo de carbono del anillo al resto de la molécula.
Como se ha detallado anteriormente, en algunos casos, dos apariciones independientes de R° (o R+, o cualquier otra variable similarmente definida en el presente documento), se toman conjuntamente junto con el (los) átomo(s) a los que cada variable está unida para formar un anillo de cicloalquilo, heterociclilo, arilo o heteroarilo de 3-8-miembros que tiene 0-3 heteroátomos independientemente seleccionados de nitrógeno, oxígeno o azufre. Anillos a modo de ejemplo que se forman cuando dos apariciones independientes de R° (o R+, o cualquier otra variable similarmente definida en el presente documento) se toman conjuntamente con el (los) átomo(s) a los que cada variable está unida incluyen, pero no se limitan a, las siguientes: a) dos apariciones independientes de R° (o R+, o cualquier otra variable similarmente definida en el presente documento) que están unidas al mismo átomo y se toman conjuntamente con aquel átomo para formar un anillo, por ejemplo, N(R°)2, en la que ambas apariciones de R° se toman conjuntamente con el átomo de nitrógeno para formar un grupo piperidin-1-ilo, piperazin-1-ilo o morfolin-4-ilo; y b) dos apariciones independientes de R° (o R+, o cualquier otra variable similarmente definida en el presente documento) que están unidas a diferentes átomos y se toman conjuntamente con ambos de aquellos átomos para formar un anillo, por ejemplo, en el que un grupo fenilo está sustituido con dos apariciones de OR°
imagen9
estas dos apariciones de R° se toman conjuntamente con los átomos de oxígeno a los que están unidos para formar un anillo condensado que contiene oxígeno de 6 miembros:
imagen10
Se apreciará que puede formarse una variedad de otros anillos cuando dos apariciones independientes de R° (o R+, o cualquier otra variable similarmente definida en el presente documento) se toman conjuntamente con el (los) átomo(s) a los que cada variable está unida y que los ejemplos detallados anteriormente no pretenden ser limitantes.
Un enlace de sustituyente en, por ejemplo, un sistema de anillos bicíclicos, como se muestra más adelante, significa
10
imagen11
imagen12
imagen13
en donde el anillo A2 está condensado al anillo A1 a través de dos átomos del anillo adyacentes.
55 En otras realizaciones, W es un enlace o es una cadena de alquilideno C1-6 opcionalmente sustituida en la que una o dos unidades de metileno están opcionalmente e independientemente sustituidas con O, NR', S, SO, SO2, o COO, CO, SO2NR', NR'SO2, C(O)NR', NR'C(O), OC(O), OC(O)NR' y RW es R' o halógeno. En todavía más realizaciones, cada aparición de WRW es independientemente -alquilo C1-C3, perhaloalquilo C1-C3, -O(alquilo C1-C3), -CF3, -OCF3, -SCF3, -F, -Cl, -Br o -COOR', -COR', -O(CH2)2N(R')(R'), -O(CH2)N(R')(R'), -CON(R')(R'), -(CH2)2OR', -(CH2)OR', anillo aromático monocíclico o bicíclico opcionalmente sustituido, arilsulfona opcionalmente sustituida, anillo de heteroarilo de 5 miembros opcionalmente sustituido, -N(R')(R'), -(CH2)2N(R')(R') o -(CH2)N(R')(R').
En algunas realizaciones, m es 0. O, m es 1. O, m es 2. En algunas realizaciones, m es 3. En todavía otras realizaciones, m es 4.
65 En una realización, R5 es X-RX. En algunas realizaciones, R5 es hidrógeno. O, R5 es un grupo alifático C1-8
13 5
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65
opcionalmente sustituido. En algunas realizaciones, R5 es alifático C1-4 opcionalmente sustituido. O, R5 es bencilo.
En algunas realizaciones, R6 es hidrógeno. O, R6 es un grupo alifático C1-8 opcionalmente sustituido. En algunas realizaciones, R6 es alifático C1-4 opcionalmente sustituido. En ciertas otras realizaciones, R6 es -(O-alifático C1-4) o (S-alifático C1-4). Preferentemente, R6 es -OMe o -SMe. En ciertos otras realizaciones, R6 es CF3.
En una realización, R1, R2, R3 y R4 son simultáneamente hidrógeno. En otra realización, R6 y R7 son ambos simultáneamente hidrógeno.
En otra realización, R1, R2, R3, R4 y R son simultáneamente hidrógeno. En otra realización, R1, R2, R3, R4, R5 y R6 son simultáneamente hidrógeno.
En otra realización, R2 es X-RX, en el que X es -SO2NR'-y RX es R'; es decir, R2 es -SO2N(R')2. En una realización, los dos R' en su interior tomados conjuntamente forman un anillo de 5-7 miembros opcionalmente sustituido con 0-3 heteroátomos adicionales seleccionados de nitrógeno, oxígeno o azufre. O, R1, R3, R4, R5 y R6 son simultáneamente hidrógeno y R2 es SO2N(R')2.
En algunas realizaciones, X es un enlace o es una cadena de alquilideno C1-6 opcionalmente sustituida en la que una
o dos unidades de metileno no adyacentes están opcionalmente e independientemente sustituidas con O, NR', S, SO2 o COO, CO y RX es R' o halógeno. En todavía más realizaciones, cada aparición de XRX es independientemente -alquilo C1-3, -O(alquilo C1-3), -CF3, -OCF3, -SCF3, -F, -Cl, -Br, OH; -COOR', -COR', -O(CH2)2N(R')(R'), -O(CH2)N(R')(R'), -CON(R')(R'), -(CH2)2OR', -(CH2)OR', fenilo opcionalmente sustituido, -N(R')(R'), -(CH2)2N(R')(R') o -(CH2)N(R')(R').
En algunas realizaciones, R7 es hidrógeno. En ciertos otras realizaciones, R7 es alifático C1-4 lineal o ramificado.
En algunas realizaciones, RW está seleccionado de halógeno, ciano, CF3, CHF2, OCHF2, Me, Et, CH(Me)2, CHMeEt, n-propilo, t-butilo, OMe, OEt, OPh, O-fluorofenilo, O-difluorofenilo, O-metoxifenilo, O-tolilo, O-bencilo, SMe, SCF3, SCHF2, SEt, CH2CN, NH2, NHMe, N(Me)2, NHEt, N(Et)2, C(O)CH3, C(O)Ph, C(O)NH2, SPh, SO2-(amino-piridilo), SO2NH2, SO2Ph, SO2NHPh, SO2-N-morfolino, SO2-N-pirrolidilo, N-pirrolilo, N-morfolino, 1-piperidilo, fenilo, bencilo, (ciclohexil-metilamino)metilo, 4-metil-2,4-dihidro-pirazol-3-on-2-ilo, bencimidazol-2-ilo, furan-2-ilo, 4-metil-4H[1,2,4]triazol-3-ilo, 3-(4'-clorofenil)-[1,2,4]oxadiazol-5-ilo, NHC(O)Me, NHC(O)Et, NHC(O)Ph, NHSO2Me, 2-indolilo, 5indolilo, -CH2CH2OH, -OCF3, O-(2,3-dimetilfenilo), 5-metilfurilo, -SO2-N-piperidilo, 2-tolilo, 3-tolilo, 4-tolilo, O-butilo, NHCO2C(Me)3, CO2C(Me)3, isopropenilo, n-butilo, O-(2,4-diclorofenilo), NHSO2PhMe, O-(3-cloro-5-trifluorometil-2piridilo), fenilhidroximetilo, 2,5-dimetilpirrolilo, NHCOCH2C(Me)3, O-(2-terc-butil)fenilo, 2,3-dimetilfenilo, 3,4dimetilfenilo, 4-hidroximetilfenilo, 4-dimetilaminofenilo, 2-trifluorometilfenilo, 3-trifluorometilfenilo, 4trifluorometilfenilo, 4-cianometilfenilo, 4-isobutilfenilo, 3-piridilo, 4-piridilo, 4-isopropilfenilo, 3-isopropilfenilo, 2metoxifenilo, 3-metoxifenilo, 4-metoxifenilo, 3,4-metilendioxifenilo, 2-etoxifenilo, 3-etoxifenilo, 4-etoxifenilo, 2metiltiofenilo, 4-metiltiofenilo, 2,4-dimetoxifenilo, 2,5-dimetoxifenilo, 2,6-dimetoxifenilo, 3,4-dimetoxifenilo, 5-cloro-2metoxifenilo, 2-OCF3-fenilo, 3-trifluorometoxi-fenilo, 4-trifluorometoxifenilo, 2-fenoxifenilo, 4-fenoxifenilo, 2-fluoro-3metoxi-fenilo, 2,4-dimetoxi-5-pirimidilo, 5-isopropil-2-metoxifenilo, 2-fluorofenilo, 3-fluorofenilo, 4-fluorofenilo, 3cianofenilo, 3-clorofenilo, 4-clorofenilo, 2,3-difluorofenilo, 2,4-difluorofenilo, 2,5-difluorofenilo, 3,4-difluorofenilo, 3,5difluorofenilo, 3-cloro-4-fluoro-fenilo, 3,5-diclorofenilo, 2,5-diclorofenilo, 2,3-diclorofenilo, 3,4-diclorofenilo, 2,4diclorofenilo, 3-metoxicarbonilfenilo, 4-metoxicarbonilfenilo, 3-isopropiloxicarbonilfenilo, 3-acetamidofenilo, 4-fluoro-3metilfenilo, 4-metanosulfinil-fenilo, 4-metanosulfonil-fenilo, 4-N-(2-N,N-dimetilaminoetil)carbamoilfenilo, 5-acetil-2tienilo, 2-benzotienilo, 3-benzotienilo, furan-3-ilo, 4-metil-2-tienilo, 5-ciano-2-tienilo, N'-fenilcarbonil-N-piperazinilo, -NHCO2Et, -NHCO2Me, N-pirrolidinilo, -NHSO2(CH2)2 N-piperidina, -NHSO2(CH2)2 N-morfolina, -NHSO2(CH2)2N(Me)2, COCH2N(Me)COCH2NHMe, -CO2Et, O-propilo, -CH2CH2NHCO2C(Me)3, hidroxi, aminometilo, pentilo, adamantilo, ciclopentilo, etoxietilo, C(Me)2CH2OH, C(Me)2CO2Et, -CHOHMe, CH2CO2Et, -C(Me)2CH2NHCO2C(Me)3, O(CH2)2OEt, O(CH2)2OH, CO2Me, hidroximetilo, 1-metil-1-ciclohexilo, 1-metil-1-ciclooctilo, 1-metil-1-cicloheptilo, C(Et)2C(Me)3, C(Et)3, CONHCH2CH(Me)2, 2-aminometilfenilo, etenilo, 1-piperidinilcarbonilo, etinilo, ciclohexilo, 4-metilpiperidinilo, -OCO2Me, -C(Me)2CH2NHCO2CH2CH(Me)2, -C(Me)2CH2NHCO2CH2CH2CH3, -C(Me)2CH2NHCO2Et, C(Me)2CH2NHCO2Me, -C(Me)2CH2NHCO2CH2C(Me)3, -CH2NHCOCF3, -CH2NHCO2C(Me)3, C(Me)2CH2NHCO2(CH2)3CH3, C(Me)2CH2NHCO2(CH2)2OMe, C(OH) (CF3)2, -C(Me)2CH2NHCO2CH2-tetrahidrofuran3-ilo, C(Me)2CH2O(CH2)2OMe o 3-etil-2,6-dioxopiperidin-3-ilo.
En una realización, R' es hidrógeno.
En una realización, R' es un grupo alifático C1-C8, opcionalmente sustituido con hasta 3 sustituyentes seleccionados de halógeno, CN, CF3, CHF2, OCF3 o OCHF2, en el que hasta dos unidades de metileno de dicho alifático C1-C8 están opcionalmente sustituidas con -CO-, -CONH(alquil C1-C4)-, -CO2-, -OCO-, -N(alquil C1-C4)CO2-, -O-, -N(alquil C1-C4)CON(alquil C1-C4)-, -OCON(alquil C1-C4)-, -N(alquil C1-C4)CO-, -S-, -N(alquil C1-C4)-, -SO2N(alquil C1-C4)-, N(alquil C1-C4)SO2-o -N(alquil C1-C4)SO2N(alquil C1-C4)-.
En una realización, R' es un anillo monocíclico de 3-8 miembros saturado, parcialmente insaturado, o completamente insaturado, que tiene 0-3 heteroátomos independientemente seleccionados de nitrógeno, oxígeno o
14
azufre, en el que R' está opcionalmente sustituido con hasta 3 sustituyentes seleccionados de halógeno, CN, CF3, CHF2, OCF3, OCHF2 o alquilo C1-C6, en el que hasta dos unidades de metileno de dicho alquilo C1-C6 están opcionalmente sustituidas con -CO-, -CONH(alquil C1-C4)-, -CO2-, -OCO-, -N(alquil C1-C4)CO2-, -O-, -N(alquil C1C4)CON(alquil C1-C4)-, -OCON(alquil C1-C4)-, -N(alquil C1-C4)CO-, -S-, -N(alquil C1-C4)-, -SO2N(alquil C1-C4)-,
5 N(alquil C1-C4)SO2-o -N(alquil C1-C4)SO2N(alquil C1-C4)-.
En una realización, R' es un sistema de anillos bicíclicos de 8-12 miembros saturado, parcialmente insaturado, o completamente insaturado, que tiene 0-5 heteroátomos independientemente seleccionados de nitrógeno, oxígeno o azufre; en el que R' está opcionalmente sustituido con hasta 3 sustituyentes seleccionados de halógeno, CN, CF3,
10 CHF2, OCF3, OCHF2 o alquilo C1-C6, en el que hasta dos unidades de metileno de dicho alquilo C1-C6 están opcionalmente sustituidas con -CO-, -CONH(alquil C1-C4)-, -CO2-, -OCO-, -N(alquil C1-C4)CO2-, -O-, -N(alquil C1C4)CON(alquil C1-C4)-, -OCON(alquil C1-C4)-, -N(alquil C1-C4)CO-, -S-, -N(alquil C1-C4)-, -SO2N(alquil C1-C4)-, N(alquil C1-C4)SO2-o -N(alquil C1-C4)SO2N(alquil C1-C4)-.
15 En una realización, dos apariciones de R' se toman conjuntamente con el (los) átomo(s) a los que están unidas para formar un anillo monocíclico o bicíclico de 3-12 miembros saturado, parcialmente insaturado, o completamente insaturado, opcionalmente sustituido que tiene 0-4 heteroátomos independientemente seleccionados de nitrógeno, oxígeno o azufre, en el que R' está opcionalmente sustituido con hasta 3 sustituyentes seleccionados de halógeno, CN, CF3, CHF2, OCF3, OCHF2 o alquilo C1-C6, en el que hasta dos unidades de metileno de dicho alquilo C1-C6
20 están opcionalmente sustituidas con -CO-, -CONH(alquil C1-C4)-, -CO2-, -OCO-, -N(alquil C1-C4)CO2-, -O-, -N(alquil C1-C4)CON(alquil C1-C4)-, -OCON(alquil C1-C4)-; -N(alquil C1-C4)CO-, -S-, -N(alquil C1-C4)-, -SO2N(alquil C1-C4)-, N(alquil C1-C4)SO2-o -N(alquil C1-C4)SO2N(alquil C1-C4)-.
En el presente documento se describen compuestos de fórmula IIA o fórmula IIb: 25
imagen14
35 En el presente documentos se describen compuestos de fórmula IIIA, fórmula IIIB, fórmula IIIC, fórmula IIID, o fórmula IIIE:
imagen15
15
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imagen17
5
10
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25
30
35
40
45
50
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60
65
imagen18
18
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5
10
15
20
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30
35
40
45
50
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60
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20
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Tabla 1
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El compuesto 433 es el compuesto de la invención; el resto de compuestos de la Tabla 1 son compuestos comparativos.
Nº comp.
Nombre
1
N-[5-(5-cloro-2-metoxi-fenil)-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
2
N-(3-metoxi-4-tert-butil-fenilo)-4-oxo-1H-quinolina-3-carboxamida
3
N-[2-(2-metoxifenoxi)-5-(trifluorometilo)fenilo]-4-oxo-1H-quinolina-3-carboxamida
4
N-(2-morfolinofenilo)-4-oxo-1H-quinolina-3-carboxamida
5
N-[4-(2-hidroxi-1,1-dimetilo-etil)fenilo]-4-oxo-1H-quinolina-3-carboxamida
6
N-[3-(hidroximetilo)-4-tert-butil-fenilo]-4-oxo-1H-quinolina-3-carboxamida
7
N-(4-benzoilamino-2,5-dietoxi-fenilo)-4-oxo-1H-quinolina-3-carboxamida
8
N-(3-amino-4-etil-fenilo)-4-oxo-1H-quinolina-3-carboxamida
9
4-oxo-N-(3-sulfamoilfenilo)-1H-quinolina-3-carboxamida
10
1,4-dihidro-N-(2,3,4,5-tetrahidro-1H-benzo[b]azepin-8-il)-4-oxoquinolina-3-carboxamida
11
4-oxo-N-[2-[2-(trifluorometilo)fenilo]fenilo]-1H-quinolina-3-carboxamida
12
N-[2-(4-dimetiloaminofenilo)fenilo]-4-oxo-1H-quinolina-3-carboxamida
13
N-(3-ciano-4-tert-butil-fenilo)-4-oxo-1H-quinolina-3-carboxamida
14
[5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-tert-butil-fenilo]acido aminoformico metilo ester
15
N-(2-metoxi-3-piridil)-4-oxo-1H-quinolina-3-carboxamida
16
4-oxo-N-(2-propilfenilo)-1H-quinolina-3-carboxamida
17
N-(5-amino-2-propoxi-fenilo)-4-oxo-1H-quinolina-3-carboxamida
18
N-(9H-fluoren-1-il)-4-oxo-1H-quinolina-3-carboxamida
19
4-oxo-N-(2-quinolil)-1H-quinolina-3-carboxamida
20
N-[2-(2-metilofenoxi)fenilo]-4-oxo-1H-quinolina-3-carboxamida
21
4-oxo-N-[4-(2-piridilsulfamoil)fenilo]-quinolina-3-carboxamida
22
Acido 4-Oxo-1,4-dihidro-quinolina-3-carboxílio N-(1’,2’-dihidrospiro[ciclopropano-1,3’-[3H]indol]-6’yl)-amida
23
N-[2-(2-etoxifenilo)-5-hidroxi-4-tert-butil-fenilo]-4-oxo-1H-quinolina-3-carboxamida
24
4-oxo-N-(3-pirrolidin-1-ilsulfonilfenilo)-1H-quinolina-3-carboxamida
25
N-[2-(3-acetilaminofenilo)fenilo]-4-oxo-1H-quinolina-3-carboxamida
26
4-oxo-N-[2-(1-piperidil)fenilo]-1H-quinolina-3-carboxamida
27
N-[1-[2-[metil-(2-metilaminoacetil)-amino]acetil]-1H-indol-6-il]-4-oxo-1H-quinolina-3carboxamida
28
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformico 2-metoxietil ester
29
1-isopropil-4-oxo-N-fenil-1H-quinolina-3-carboxamida
30
[2-isopropil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformico metil ester
31
4-oxo-N-(p-tolil)-1H-quinolina-3-carboxamida
32
N-(5-cloro-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
33
N-(1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
34
N-[4-(1,1-dietilpropil)-2-fluoro-5-hidroxi-fenil]-4-hidroxi-quinolina-3-carboxamida
31
5
10
15
20
25
30
35
40
45
50
55
60
65
Nº comp.
Nombre
35
1,4-dihidro-N-(2,3,4,5-tetrahidro-5,5-dimetil-1H-benzo[b]azepin-8-il)-4-oxoquinolina-3-carboxamida
36
N-(2-isopropilfenil)-4-oxo-1H-quinolina-3-carboxamida
37
N-(1H-indol-7-il)-4-oxo-1H-quinolina-3-carboxamida
38
N-[2-(1H-indol-2-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
39
[3-[(2,4-dimetoxi-3-quinolil)carbonilamino]-4-tert-butil-fenil]acido aminoformico tert-butil ester
40
N-[2-(2-hidroxietil)fenil]-4-oxo-1H-quinolina-3-carboxamida
41
N-(5-amino-2-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
42
N-[2-[[3-cloro-5-(trifluorometil)-2-piridil]oxi]fenil]-4-oxo-1H-quinolina-3-carboxamida
43
N-[2-(3-etoxifenil)-5-hidroxi-4-tert-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
44
N-(2-metilbenzotiazol-5-il)-4-oxo-1H-quinolina-3-carboxamida
45
N-(2-ciano-3-fluoro-fenil)-4-oxo-1H-quinolina-3-carboxamida
46
N-[3-cloro-5-(2-morfolinoetilsulfonilamino)fenil]-4-oxo-1H-quinolina-3-carboxamida
47
N-[4-isopropil-2-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
48
N-(6-cloro-2-fluoro-fenil)-4-oxo-1H-quinolina-3-carboxamida
49
N-[2-(2,6-dimetoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
50
4-oxo-N-(2,4,6-trimetilfenil)-1H-quinolina-3-carboxamida
51
6-[(4-metil-1-piperidil)sulfonil]-4-oxo-N-(5-terc-butil-1H-indol-6-il)-1H-quinolina-3-carboxamida
52
N-[2-(m-tolil)fenil]-4-oxo-1H-quinolina-3-carboxamida
53
4-oxo-N-(4-piridil)-1H-quinolina-3-carboxamida
54
4-oxo-N-(8-thia-7,9-diazabiciclo[4.3.0]nona-2,4,6,9-tetraen-5-il)-1H-quinolina-3-carboxamida
55
N-(3-amino-2-metoxi-5-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
56
1,4-dihidro-N-(1,2,3,4-tetrahidro-6-hidroxinaftalen-7-il)-4-oxoquinolina-3-carboxamida
57
N-[4-(3-etil-2,6-dioxo-3-piperidil)fenil]-4-oxo-1H-quinolina-3-carboxamida
58
N-[3-amino-4-(trifluorometoxi)fenil]-4-oxo-1H-quinolina-3-carboxamida
59
N-[2-(5-isopropil-2-metoxi-fenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
60
[4-isopropil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformico tert-butil ester
61
N-(2,3-dimetilfenil)-4-oxo-1H-quinolina-3-carboxamida
62
4-oxo-N-[3-(trifluorometoxi)fenil]-1H-quinolina-3-carboxamida
63
N-[2-(2,4-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
64
4-oxo-N-(2-oxo-1,3-dihidrobenzoimidazol-5-il)-1H-quinolina-3-carboxamida
65
4-oxo-N-[5-(3-piridil)-1H-indol-6-il]-1H-quinolina-3-carboxamida
66
N-(2,2-difluorobenzo[1,3]dioxol-5-il)-4-oxo-1H-quinolina-3-carboxamida
67
6-etil-4-hidroxi-N-(1H-indol-6-il)quinolina-3-carboxamida
68
3-[2-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido benzoico metil ester
69
N-(3-amino-4-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
70
4-oxo-N-[2-(4-piridil)fenil]-1H-quinolina-3-carboxamida
71
3-[2-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido benzoico isopropil ester
32
5
10
15
20
25
30
35
40
45
50
55
60
65
Nº comp.
Nombre
72
N-(2-etilfenil)-4-oxo-1H-quinolina-3-carboxamida
73
4-oxo-N-(2-fenil-3H-benzoimidazol-5-il)-1H-quinolina-3-carboxamida
74
4-oxo-N-[5-(trifluorometil)-2-piridil]-1H-quinolina-3-carboxamida
75
4-oxo-N-(3-quinoil)-1H-quinolina-3-carboxamida
76
N-[2-(3,4-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
77
N-(5-fluoro-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
78
4-oxo-N-(2-sulfamoilfenil)-1H-quinolina-3-carboxamida
79
N-[2-(4-fluoro-3-metil-fenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
80
N-(2-metoxifenil)-4-oxo-1H-quinolina-3-carboxamida
81
4-oxo-N-(3-propionilaminofenil)-1H-quinolina-3-carboxamida
82
N-(4-dietilamino-2-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
83
N-[2-(3-cianofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
84
N-(4-metil-2-piridil)-4-oxo-1H-quinolina-3-carboxamida
85
N-[2-(3,4-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
86
N-[4-[2-(aminometil)fenil]fenil]-4-oxo-1H-quinolina-3-carboxamida
87
4-oxo-N-(3-fenoxifenil)-1H-quinolina-3-carboxamida
88
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformico tert-butil ester
89
N-(2-ciano-5-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
90
4-oxo-N-(2-tert-butilfenil)-1H-quinolina-3-carboxamida
91
N-(3-cloro-2,6-dietil-fenil)-4-oxo-1H-quinolina-3-carboxamida
92
N-[2-fluoro-5-hidroxi-4-(1-metilciclohexil)-fenil]-4-oxo-1H-quinolina-3-carboxamida
93
N-[2-(5-ciano-2-tienilo)fenil]-4-oxo-1H-quinolina-3-carboxamida
94
N-(5-amino-2-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
95
N-(2-cianofenil)-4-oxo-1H-quinolina-3-carboxamida
96
N-[3-(cianometil)-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
97
N-[2-(2,4-dimetoxipirimidin-5-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
98
N-(5-dimetilamino-2-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
99
4-oxo-N-(4-pentilfenil)-1H-quinolina-3-carboxamida
100
N-(1H-indol-4-il)-4-oxo-1H-quinolina-3-carboxamida
101
N-(5-amino-2-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
102
N-[2-[3-(4-clorofenil)-1,2,4-oxadiazol-5-il]fenil]-4-oxo-1H-quinolina-3-carboxamida
103
5-fluoro-N-(5-hidroxi-2,4-ditert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
104
N-(2-metil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
105
1,4-dihidro-N-(3,4-dihidro-2H-benzo[b][1,4]oxazin-6-il)-4-oxoquinolina-3-carboxamida
106
N-(2-ciano-4,5-dimetoxi-fenil)-4-oxo-1H-quinolina-3-carboxamida
107
terc-butil ester de ácido 7-[(4-oxi-1H-quinolin-3-il)carbonilamino]-1,2,3,4-tetrahidroisoquinolina-2-carboxílico
108
terc-butil ester de ácido 4,4-dimetil-7-[(4-oxo-1H-quinolin-3-il)carbonilamino]-1,2,3,4-tetrahidroquinolina-1carboxílico
33
5
10
15
20
25
30
35
40
45
50
55
60
65
Nº comp.
Nombre
109
N-(1-acetil-2,3,4,5-tetrahidro-5,5-dimetil-1H-benzo[b]azepin-8-il)-1,4-dihidro-4-oxoquinolina-3-carboxamida
110
N-[4-(cianometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
111
4-oxo-N-[2-(trifluorometil)fenil]-1H-quinolina-3-carboxamida
112
6-etoxi-4-hidroxi-N-(1H-indol-6-il)quinolina-3-carboxamida
113
N-(3-metil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
114
[4-(2-etoxifenil)-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformico tert-butil ester
115
N-[2-(2-furil)fenil]-4-oxo-1H-quinolina-3-carboxamida
116
5-hidroxi-N-(1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
117
N-(3-dimetilamino-4-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
118
N-[2-(1H-indol-6-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
119
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformicoetil ester
120
N-(2-metoxi-5-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
121
N-(3,4-diclorofenil)-4-oxo-1H-quinolina-3-carboxamida
122
N-(3,4-dimetoxifenil)-4-oxo-1H-quinolina-3-carboxamida
123
N-[2-(3-furil)fenil]-4-oxo-1H-quinolina-3-carboxamida
124
6-fluoro-4-oxo-N-(5-terc-butil-1H-indol-6-il)-1 H-quinolina-3-carboxamida
125
N-(6-etil-2-piridil)-4-oxo-1H-quinolina-3-carboxamida
126
N-[3-hidroxi-4-[2-(2-metoxietoxi)-1,1-dimetil-etil]-fenil]-4-oxo-1H-quinolina-3-carboxamida
127
[5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-tert-butil-fenil]acido aminoformico etil ester
128
1,6-dimetil-4-oxo-N-(2-fenilfenil)-1H-quinolina-3-carboxamida
129
[2-etil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformico metil ester
130
4-hidroxi-N-(1H-indol-6-il)-5,7-bis(trifluorometil)quinolina-3-carboxamida
131
N-(3-amino-5-cloro-fenil)-4-oxo-1H-quinolina-3-carboxamida
132
N-(5-acetilamino-2-etoxi-fenil)-4-oxo-1H-quinolina-3-carboxamida
133
N-[3-cloro-5-[2-(1-piperidil)etilsulfonilamino]fenil]-4-oxo-1H-quinolina-3-carboxamida
134
N-[2-(4-metilsulfinilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
135
N-(2-benzo[1,3]dioxol-5-ilfenil)-4-oxo-1H-quinolina-3-carboxamida
136
N-(2-hidroxi-3,5-ditert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
137
6-[(4-fluorofenil)-metil-sulfamoil]-N-(5-hidroxi-2,4-ditert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
138
N-[2-(3,5-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
139
N-[2-(2,4-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
140
N-(4-ciclohexilfenil)-4-oxo-1H-quinolina-3-carboxamida
141
[2-metil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformico etil ester
142
4-oxo-N-(2-sec-butilfenil)-1H-quinolina-3-carboxamida
143
N-(2-fluoro-5-hidroxi-4-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
144
N-(3-hidroxifenil)-4-oxo-1H-quinolina-3-carboxamida
145
éster etílico de ácido 6-[(4-oxo-1H-quinolin-3-il)carbonilamino]-1H-indol-4-carboxílico
34
5
10
15
20
25
30
35
40
45
50
55
60
El compuesto 433 es el compuesto de la invención; el resto de compuestos de la Tabla 1 son compuestos comparativos.
Nº comp.
Nombre
146
4-oxo-N-(1,7,9-triazabiciclo[4.3.0]nona-2,4,6,8-tetraen-5-il)-1H-quinolins-3-carboxamida
147
N-[2-(4-fluorofenoxi)-3-piridil]-4-oxo-1H-quinolina-3-carboxamida
148
4-oxo-N-[5-(1-piperidilcarbonil)-1H-indol-6-il]-1H-quinolina-3-carboxamida
149
N-(3-acetilamino-4-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
150
4-oxo-N-[4-[2,2,2-trifluoro-1-hidroxi-1-(trifluorometil)etil]fenil]-1H-quinolina-3-carboxamida
151
N-[2-(4-metil-2-tienilo)fenil]-4-oxo-1H-quinolina-3-carboxamida
152
4-oxo-N-(2-oxo-3H-benzooxazol-6-il)-1H-quinolina-3-carboxamida
153
N-[4-(1,1-dietil-2,2-dimetil-propil)-2-fluoro-5-hidroxi-fenil]-4-hidroxi-quinolina-3-carboxamida
154
N-[3,5-bis(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
155
4-oxo-N-(2-piridil)-1H-quinolina-3-carboxamida
156
4-oxo-N-[2-[2-(trifluorometoxi)fenil]fenil]-1H-quinolina-3-carboxamida
157
N-(2-etil-5-metilamino-fenil)-4-oxo-1H-quinolina-3-carboxamida
158
4-oxo-N-(5-fenil-1H-indol-6-il)-1H-quinolina-3-carboxamida
159
éster metílico de ácido [7-[(4-oxo-1H-quinolin-3-il)carbonilamino]tetralin-1-il]aminoformico
160
N-(3-amino-4-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
161
N-[3-(2-etoxietoxi)-4-tert-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
162
N-(6-metoxi-3-piridil)-4-oxo-1H-quinolina-3-carboxamida
163
N-[5-(aminometil)-2-(2-etoxifenil)-fenil]-4-oxo-1H-quinolina-3-carboxamida
164
4-oxo-N-[3-(trifluorometil)fenil]-1H-quinolina-3-carboxamida
165
4-oxo-N-(4-sulfamoilfenil)-1H-quinolina-3-carboxamida
166
4-[2-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido benzoico metil ester
167
N-(3-amino-4-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
168
4-oxo-N-(3-piridil)-1H-quinolina-3-carboxamida
169
N-(1-metil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
170
N-(5-cloro-2-piridil)-4-oxo-1H-quinolina-3-carboxamida
171
N-[2-(2,3-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
172
N-(2-(benzo[b]tiofen-2-il)fenil)-1,4-dihidro-4-oxoquinolina-3-carboxamida
173
N-(6-metil-2-piridil)-4-oxo-1H-quinolina-3-carboxamida
174
N-[2-(5-acetil-2-tienilo)fenil]-4-oxo-1H-quinolina-3-carboxamida
175
ácido 4-Oxo-1,4-dihidro-quinolina-3-carboxílico N-(1’-Acetil-1’,2’-dihidrospiro[ciclopropano-1,3’-3Hindol]6’-il)-amida
176
4-oxo-N-[4-(trifluorometoxi)fenil]-1H-quinolina-3-carboxamida
177
N-(2-butoxifenil)-4-oxo-1H-quinolina-3-carboxamida
178
4-oxo-N-[2-(2-tert-butilfenoxi)fenil]-1H-quinolina-3-carboxamida
179
N-(3-carbamoilfenil)-4-oxo-1H-quinolina-3-carboxamida
180
N-(2-etil-6-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
35
15
25
35
45
55
Nº comp.
Nombre
181
4-oxo-N-[2-(p-tolil)fenil]-1H-quinolina-3-carboxamida
182
N-[2-(4-fluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
183
terc-butil éster de ácido 7-[(4-oxo-1H-quinolin-3-il)carbonilamino]-1,2,3,4-tetrahidroquinolina-1carboxílico
184
N-(1H-indol-6-il)-4-oxo-2-(trifluorometil)-1H-quinolina-3-carboxamida
185
N-(3-morfolinosulfonilfenil)-4-oxo-1H-quinolino-3-carboxamida
186
N-(3-ciclopentil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
187
N-(1-acetil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
188
éster etílico de ácido 6-[(4-oxo-1H-quinolin-3-il)carbonilamino]-1H-indol-5-carboxílico
189
N-(4-benziloxifenil)-4-oxo-1H-quinolina-3-carboxamida
190
N-[2-(3-cloro-4-fluoro-fenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
191
4-oxo-N-(5-quinolil)-1H-quinolina-3-carboxamida
192
N-(3-metil-2-piridil)-4-oxo-1H-quinolina-3-carboxamida
193
N-(2,6-dimetoxi-3-piridil)-4-oxo-1H-quinolina-3-carboxamida
194
N-(4-cianofenil)-4-oxo-1H-quinolina-3-carboxamida
195
N-(5-metil-2-piridil)-4-oxo-1H-quinolina-3-carboxamida
196
N-[5-(3,3-dimetilbutanoilamino)-2-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
197
4-oxo-N-[6-(trifluorometil)-3-piridil]-1H-quinolina-3-carboxamida
198
N-(4-fluorofenil)-4-oxo-1H-quinolina-3-carboxamida
199
N-[2-(o-tolil)fenil]-4-oxo-1H-quinolina-3-carboxamida
200
1,4-dihidro-N-(1,2,3,4-tetrahidro-1-hidroxinaftalen-7-il)-4-oxoquinolina-3-carboxamida
201
N-(2-ciano-3-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
202
N-[2-(5-cloro-2-metoxi-fenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
203
N-(1-bencil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
204
N-(4,4-dimetilcroman-7-yi)-4-oxo-1H-quinolina-3-carboxamida
205
N-[2-(4-metoxifenoxi)-5-(trifluorometil)fenil]-4-oxo-1H-quinollne-3-carboxamida
206
N-[2-(2,3-dimetilfenoxi)-3-pirldil]-4-oxo-1H-quinolina-3-carboxamida
207
éster etílico de ácido 2-[6-[(4-oxo-1H-quinolin-3-il)carbonilamino]-1H-indol-3-il]acético
208
N-[4-(2-adamantil)-5-hidroxi-2-metil-fenil]-4-oxo-1H-quinolina-3-carboxamida
209
N-[4-(hidroximetil)fenil]-4-oxo-1H-quinolina-3-carboxamida
210
2,4-dimetoxi-N-(2-fenilfenil)-quinolina-3-carboxamida
211
N-(2-metoxi-5-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
212
N-[3-(3-metil-5-oxo-1,4-dihidropirazol-1-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
213
N-[2-(2,5-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
214
N-(3-meltilsulfonilaminofenil)-4-oxo-1H-quinolina-3-carboxamida
215
4-oxo-N-fenil-1H-quinolina-3-carboxamida
216
N-(3H-benzoimidazol-2-il)-4-oxo-1H-quinolina-3-carboxamida
217
N-(1H-indazol-5-yi)-4-oxo-1H-quinolina-3-carboxamida
218
6-fluoro-N-[2-fluoro-5-hidroxi-4-(1-metilciclohexil)-fenil]-4-oxo-1H-quinolina-3-carboxamida
36
5
10
15
20
25
30
35
40
45
50
55
60
219
4-oxo-N-pirazin-2-il-1H-quinolina-3-carboxamida
220
N-(2,3-dihidroxi-4,6-ditert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
221
[5-[(4-oxi-1H-quinolin-3-il)carbonilamino]-2-propil-fenil]acido aminoformico metil ester
222
N-(3-cloro-2-ciano-fenil)-4-oxo-1H-quinolina-3-carboxamida
223
N-[2-(4-metilsulfanilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
224
4-oxo-N-[4-[2-[(2,2,2-trifluoroacetil)aminometil]fenil]fenil]-1H-quinolina-3-carboxamida
225
[2-isopropil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformico etil ester
226
4-oxo-N-(4-propilfenil)-1H-quinolina-3-carboxamida
227
N-[2-(3H-benzoimidazol-2-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
228
N-[2-(hidroxi-fenil-metil)fenil]-4-oxo-1H-quinolina-3-carboxamida
229
N-(2-metilsulfanilfenil)-4-oxo-1H-quinolina-3-carboxamida
230
N-(2-meti-1H-indol-5-il)-4-oxo-1H-quinolina-3-carboxamida
231
3-[4-hidroxi-2-[(4-oxo-1H-quinolin-3-il)carbonilamino]-5-tert-butil-fenil]acido benzoico metil ester
232
N-(5-acetilamino-2-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
233
N-(1-acetilindolin-6-il)-4-oxo-1H-quinolina-3-carboxamida
234
4-oxo-N-[5-(trifluorometil)-1 H-indol-6-il]-1 H-quinolina-3-carboxamida
235
N-(6-isopropil-3-piridil)-4-oxo-1H-quinolina-3-carboxamida
236
4-oxo-N-[4-(trifluorometil)fenil]-1H-quinolina-3-carboxamlde
237
N-[5-(2-metoxifenil)-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
238
terc-butil éster de ácido 7’-[(4-oxo-1H-quinolin-3-ylcarbonil)amino]-spiro[piperidina-4,4’(1’H)-quinolina], 2’,3’-dihidrocarboxílico
239
[4-isopropil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformicometil ester
240
N-(2-benziloxifenil)-4-oxo-1H-quinolina-3-carboxamida
241
4-oxo-N-(8-quinolil)-1H-quinolina-3-carboxamida
242
N-(5-amino-2,4-dicloro-fenil)-4-oxo-1H-quinolina-3-carboxamida
243
N-(5-acetilamino-2-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
244
4-oxo-N-(6,7,8,9-tetrahidro-5H-carbazol-2-il)-1H-quinolina-3-carboxamida
245
N-[2-(2,4-diclorofenoxi)fenil]-4-oxo-1H-quinolina-3-carboxamida
246
N-(3,4-dimetilfenil)-4-oxo-1H-quinolina-3-carboxamida
247
4-oxo-N-[2-(2-fenoxifenil)fenil]-1H-quinolina-3-carboxamida
248
N-(3-acetilamino-4-metil-fenil)-4-oxo-1H-quinolina-3-carboxamlde
249
[4-etil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformicometil ester
250
N-(5-acetilamino-2-metoxi-fenil)-4-oxo-1H-quinolina-3-carboxamida
251
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformicoIsobutil ester
252
N-(2-benzoilfenil)-4-oxo-1H-quinolina-3-carboxamida
253
4-oxo-N-[2-[3-(triffluorometoxi)fenil]fenil]-1H-quinolina-3-carboxamida
254
6-fluoro-N-(5-fluoro-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
255
N-(5-hidroxi-2,4-ditert-butil-fenil)-4-oxo-6-pirrolidin-1-ilsulfonil-1H-quinolina-3-carboxamida
37
5
10
15
20
25
30
35
40
45
50
55
60
65
256
N-(1H-benzotriazol-5-il)-4-oxo-1H-quinolina-3-carboxamida
257
N-(4-fluoro-3-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
258
N-indolin-6-il-4-oxo-1H-quinolina-3-carboxamida
259
4-oxo-N-(3-sec-butil-1H-indol-6-il)-1H-quinolina-3-carboxamida
260
N-(5-amino-2-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
261
N-[2-(3,4-dimetilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
262
1,4-dihidro-N-(3,4-dihidro-3-oxo-2H-benzo[b][1,4]tiazin-6-il)-4-oxoquinolina-3-carboxamida
263
N-(4-bromo-2-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
264
N-(2,5-dietoxifenil)-4-oxo-1H-quinolina-3-carboxamida
265
N-(2-benzilfenil)-4-oxo-1H-quinolina-3-carboxamida
266
N-[5-hidroxi-4-tert-butil-2-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
267
4-oxo-N-(4-fenoxiphanil)-1H-quinolina-3-carboxamida
268
4-oxo-N-(3-sulfamoil-4-tert-butil-fenil)-1H-quinolina-3-carboxamida
269
[4-isopropil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformicoetil ester
270
N-(2-ciano-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
271
N-(3-amino-4-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
272
N-[3-(2-morfolinoetilsulfonilamino)-5-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
273
terc-butil éster de ácido [7-[(4-oxo-1H-quinolin-3-il)carbonilamino]tetralin-1-il]aminofórmico
274
4-oxo-6-pirrolidin-1-ilsulfonil-N-(5-terc-butil-1H-indol-6-il)-1H-quinolina-3-carboxamida
275
4-benziloxi-N-(3-hidroxi-4-tert-butil-fenil)-quinolina-3-carboxamida
276
N-(4-morfolinosulfonilfenil)-4-oxo-1H-quinolina-3-carboxamida.
277
N-[2-(3-fluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
278
4-oxo-N-[2-[3-(trifluorometil)fenil]fenil]-1H-quinolina-3-carboxamida
279
N-[2-(2-metilsulfanilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
280
4-oxo-N-(6-quinolil)-1H-quinolina-3-carboxamida
281
N-(2,4-dimetilfenil)-4-oxo-1H-quinolina-3-carboxamida
282
N-(5-amino-2-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
283
N-[2-(3-metoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
284
N-(1H-indazol-6-il)-4-oxo-1H-quinolina-3-carboxamida
285
N-[2-(2,3-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
286
1,4-dihidro-N-(1,2,3,4-tetrahidronaftalen-5-il)-4-oxoquinolina-3-carboxamida
287
N-[2-fluoro-5-hidroxi-4-(1-metilciclohexil)-fenil]-5-hidroxi-4-oxo-1H-quinolina-3-carboxamida
288
N-(5-fluoro-2-metoxicarboniloxi-3-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
289
N-(2-fluoro-4-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
290
N-[2-(3-isopropilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
291
N-(2-cloro-5-hidroxi-4-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
292
N-(5-cloro-2-fenoxi-plienil)-4-oxo-1H-quinolina-3-carboxamida
38
5
10
15
20
25
30
35
40
45
50
55
60
65
Nº comp.
Nombre
293
4-oxo-N-[2-(1H-pirrol-1-il)fenil]-1H-quinolina-3-carboxamida
294
N-(1H-indol-5-il)-4-oxo-1H-quinolina-3-carboxamida
295
4-oxo-N-(2-pirrolidin-1-ilfenil)-1H-quinolina-3-carboxamida
296
2,4-dimetoxi-N-(2-tert-butilfenil)-quinolina-3-carboxamida
297
N-[2-(2,5-dimetil-1H-pirrol-1-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
298
[2-etil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformico etil ester
299
4-oxo-N-(1,2,3,4-tetrahidroquinolin-7-il)-1H-quinolina-3-carboxamida
300
N-(4,4-dimetil-1,2,3,4-tetrahidroquinolin-7-il)-4-oxo-1H-quinolina-3-carboxamida
301
N-[4-(4-metil-4H-1,2,4-triazol-3-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
302
N-[2-[4-(hidroximetil)fenil]fenil]-4-oxo-1H-quinolina-3-carboxamida
303
N-(2-acetil-1,2,3,4-tetrahidroisoquinolin-7-il)-4-oxo-1H-quinolina-3-carboxamida
304
[4-(2-etoxifenil)-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenilmetil]acido aminoformico tert-butil ester
305
N-[2-(4-metoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
306
N-[2-(3-etoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
307
N-[2-(3-clorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
308
N-[2-(cianometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
309
N-(3-isoquinolil)-4-oxo-1H-quinolina-3-carboxamida
310
4-oxo-N-(4-sec-butilfenil)-1H-quinolina-3-carboxamida
311
N-[2-(6-metil-2-furil)fenil]-4-oxo-1H-quinolina-3-carboxamida
312
N-[2-(2,4-dimetoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
313
N-[2-(2-fluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
314
N-(2-etil-6-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
315
N-(2,6-dimetilfenil)-4-oxo-1H-quinolina-3-carboxamida
316
N-(6-acetilamino-2-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
317
N-(2,6-diclorofenil)-4-oxo-1H-quinolina-3-carboxamida
318
4-oxo-N-[3-[2-(1-piperidil)etilsulfonilamino]-5-(trifluorometil)fenil)-1H-quinolina-3-carboxamida
319
6-fluoro-N-(2-fluoro-5-hidroxi-4-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
320
4-oxo-N-(2-terc-butil-1H-indol-6-il)-1H-quinolina-3-carboxamida
321
N-[2-(4-benzoilpiperazin-1-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
322
N-(2-etil-6-sec-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
323
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformico metil ester
324
N-(4-butilfenil)-4-oxo-1H-quinolina-3-carboxamida
325
N-(2,6-dietilfenil)-4-oxo-1H-quinolina-3-carboxamida
326
N-[2-(4-metilsulfonilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
327
N-[5-(2-etoxifenil)-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
328
N-(3-acetilfenil)-4-oxo-1H-quinolina-3-carboxamida
329
N-[2-(o-tolyl)benzooxazol-5-il]-4-oxo-1H-quinolina-3-carboxamida
39
5
10
15
20
25
30
35
40
45
50
55
60
65
Nº comp.
Nombre
330
N-(2-clorofenil)-4-oxo-1H-quinolina-3-carboxamida
331
N-(2-carbamoilfenil)-4-oxo-1H-quinolina-3-carboxamida
332
N-(4-etinilfenil)-4-oxo-1H-quinolina-3-carboxamida
333
N-[2-[4-(cianometil)fenil]fenil]-4-oxo-1H-quinolina-3-carboxamida
334
terc-butil éster de ácidó 7’-[(4-oxo-1H-quinolin-3-ilcarbonil)amino]-spiro[piperidina-4,4’(1’H)-1-acetilquinolina], 2’,3’-dihidrocarboxílico
335
N-(2-carbamoil-5-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
336
N-(2-butilfenil)-4-oxo-1H-quinolina-3-carboxamida
337
N-(5-hidroxi-2,4-ditert-butil-fenil)-N-metil-4-oxo-1H-quinolina-3-carboxamida.
338
N-(3-metil-1H-indol-4-il)-4-oxo-1H-quinolina-3-carboxamida
339
N-(3-ciano-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
340
N-(3-metilsulfonilamino-4-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
341
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformico neopentil ester
342
N-[5-(4-isopropilfenil)-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
343
N-[5-(isobutilcarbamoil)-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
344
N-[2-(2-etoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
345
6-fluoro-4-hidroxi-N-(1H-indol-6-il)quinolina-3-carboxamida
346
4-oxo-N-fenil-7-(trifluorometil)-1H-quinolina-3-carboxamida
347
N-[5-[4-(2-dimetilaminoetilcarbamoil)fenil]-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
348
N-[2-(4-etoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
349
4-oxo-N-(2-fenilsulfonilfenil)-1H-quinolina-3-carboxamida
350
N-(1-naftil)-4-oxo-1H-quinolina-3-carboxamida
351
N-(5-etil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
352
2-[6-[(4-oxo-1H-quinolin-3-il)carbonilamino]-1H-indol-3-il]ácido etilaminoformico terc-butil ester
353
[3-[(4-oxo-1H-quinolin-3-il)carbonilamino]-4-tert-butil-fenil]acido aminoformico tert-butil ester
354
N-[2-[(ciclohexil-metil-amino)metil]fenil]-4-oxo-1H-quinolina-3-carboxamida
355
N-[2-(2-metoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
356
N-(5-metilamino-2-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
357
N-(3-isopropil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
358
6-cloro-4-hidroxi-N-(1H-indol-6-il)quinolina-3-carboxamida
359
N-[3-(2-dimetilaminoetilsulfonilamino)-5-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
360
N-[4-(difluorometoxi)fenil]-4-oxo-1H-quinolina-3-carboxamida
361
N-[2-(2,5-dimetoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
362
N-(2-cloro-4-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
363
N-[2-(2-fluoro-3-metoxi-fenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
364
N-(2-metil-8-quinolil)-4-oxo-1H-quinolina-3-carboxamida
365
N-(2-acetilfenil)-4-oxo-1H-quinolina-3-carboxamida
366
4-oxo-N-[2-[4-(trifluorometil)fenil]fenil]-1H-quinolina-3-carboxamida
40
5
10
15
20
25
30
35
40
45
50
55
60
Nº comp.
Nombre
367
N-[2-(3,5-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
368
N-(3-amino-4-propoxi-fenil)-4-oxo-1H-quinolina-3-carboxamida
369
N-(2,4-dicloro-6-ciano-fenil)-4-oxo-1H-quinolina-3-carboxamida
370
N-(3-clorofenil)-4-oxo-1H-quinolina-3-carboxamida
371
4-oxo-N-[2-(trifluorometilsulfanil)fenil]-1H-quinolina-3-carboxamida
372
N-[2-(4-metil-1-piperidil)fenil]-4-oxo-1H-quinolina-3-carboxamida
373
N-indan-4-il-4-oxo-1H-quinolina-3-carboxamida
374
4-hidroxi-N-(1H-indol-6-il)-2-metilsulfanil-quinolina-3-carboxamida
375
1,4-dihidro-N-(1,2,3,4-tetrahidronaftalen-6-il)-4-oxoquinolina-3-carboxamida
376
4-oxo-N-(2-fenilbenzooxazol-5-il)-1H-quinolina-3-carboxamida
377
6,8-difluoro-4-hidroxi-N-(1H-indol-6-il)quinolina-3-carboxamida
378
N-(3-amino-4-metoxi-fenil)-4-oxo-1H-quinolina-3-carboxamida
379
N-[3-acetilamino-5-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
380
N-(2-etoxiphonil)-4-oxo-1H-quinolina-3-carboxamida
381
4-oxo-N-(5-terc-butil-1H-indol-6-il)-1H-quinolina-3-carboxamida
382
[5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-propil-fenil]acido aminoformicoetil ester
383
N-(3-etil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
384
N-[2-(2,5-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
385
N-[2-(2,4-difluorofenoxi)-3-piridil]-4-oxo-1H-quinolina-3-carboxamida
386
N-(3,3-dimetilindolin-6-il)-4-oxo-1H-quinolina-3-carboxamida
387
N-[2-metil-3-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
388
4-oxo-N-[2-[4-(trifluorometoxi)fenil]fenil]-1H-quinolina-3-carboxamida
389
N-(3-benzilfenil)-4-oxo-1H-quinolina-3-carboxamida
390
N-[3-(aminometil)-4-tert-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
391
N-[2-(4-isobutilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
392
N-(6-cloro-3-piridil)-4-oxo-1H-quinolina-3-carboxamida
393
N-[5-amino-2-(2-etoxifenil)-fenil]-4-oxo-1H-quinolina-3-carboxamida
394
1,6-dimetil-4-oxo-N-fenil-1H-quinolina-3-carboxamida
395
N-[4-(1-adamantil)-2-fluoro-5-hidroxi-fenil]-4-hidroxi-quinolina-3-carboxamida
396
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamlno]fenil]-propil]acido aminoformicotetrahidrofuran-3ilmetil ester
397
4-oxo-N-(4-fenilfenil)-1H-quinolina-3-carboxamida
398
4-oxo-N-[2-(p-tolilsulfonilamino)fenil]-1H-quinolina-3-carboxamida
399
N-(2-isopropil-5-metilamino-fenil)-4-oxo-1H-quinolina-3-carboxamida
400
N-(6-morfolino-3-piridil)-4-oxo-1H-quinolina-3-carboxamida
401
N-[2-(2,3-dimetilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
402
4-oxo-N-(5-fenil-2-piridil)-1H-quinolina-3-carboxamida
41
5
10
15
20
25
30
35
40
45
50
55
60
Nº comp.
Nombre
403
N-[2-fluoro-5-hidroxi-4-(1-metilciclooctil)-fenil]-4-hidroxi-quinolina-3-carboxamida
404
N-[5-(2,6-dimetoxifenil)-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
405
N-(4-clorofenil)-4-oxo-1H-quinolina-3-carboxamida
406
6-[(4-fluorofenil)-metil-sulfamoil]-4-oxo-N-(5-terc-butil-1H-indol-6-il)-1H-quinolina-3-carboxamida
407
N-(2-fluoro-5-hidroxi-4-tert-butil-fenil)-5-hidroxi-4-oxo-1H-quinolina-3-carboxamida
408
N-(3-metoxifenil)-4-oxo-1H-quinolina-3-carboxamida
409
N-(5-dimetilamino-2-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
410
4-oxo-N-[2-(4-fenoxifenil)fenil]-1H-quinolina-3-carboxamida
411
7-cloro-4-oxo-N-fenil-1H-quinolina-3-carboxamida
412
éster etílico de ácido 6-[(4-oxo-1H-quinolin-3-il)carbonilamino]-1H-indol-7-carboxílico
413
4-oxo-N-(2-fenoxifenil)-1H-quinolina-3-carboxamida
414
N-(3H-benzoimidazol-5-il)-4-oxo-1H-quinolina-3-carboxamida
415
N-(3-hidroxi-4-tert-butil-fenil)-4-metoxi-quinolina-3-carboxamida
416
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformico propil ester
417
N-(2-(benzo[b]tiofen-3-il)fenil)-1,4-dihidro-4-oxoquinolina-3-carboxamida
418
N-(3-dimetilaminofenil)-4-oxo-1H-quinolina-3-carboxamida
419
N-(3-acetilaminofenil)-4-oxo-1H-quinolina-3-carboxamida
420
2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-acido propanoico etil ester
421
N-[5-metoxi-4-tert-butil-2-(trifluorometil)fenil)-4-oxo-1H-quinolina-3-carboxamida
422
N-(5,6-dimetil-3H-benzoimidazol-2-il)-4-oxo-1H-quinolina-3-carboxamida
423
N-[3-(2-etoxietil)-1H-indol-6-il]-4-oxo-1H-quinolina-3-carboxamida
424
N-[2-(4-clorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
425
N-(4-isopropilfenil)-4-oxo-1H-quinolina-3-carboxamida
426
N-(4-cloro-5-hidroxi-2-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
427
terc-butil éster de ácido 5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-1,2,3,4-tetrahidroisoquinolina-2carboxílico
428
N-(3-hidroxi-tert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
429
N-[3-amino-5-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
430
N-(2-isopropil-6-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
431
N-(3-aminofenil)-4-oxo-1H-quinolina-3-carboxamida
432
N-[2-(4-isopropilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
433
N-(5-hidroxi-2,4-ditert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
434
N-(2,5-dimetilfenil)-4-oxo-1H-quinolina-3-carboxamida
435
N-[2-(2-fluorofenoxi)-3-piridil]-4-oxo-1H-quinolina-3-carboxamida
436
N-[2-(3,4-dimetoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
437
N-benzo[1,3]dioxol-5-il-4-oxo-1 H-quinolina-3-carboxamida
438
N-[5-(difluorometil)-2,4-ditert-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
42
5
10
15
20
25
30
35
40
45
50
55
60
Nº comp.
Nombre
439
N-(4-metoxifenil)-4-oxo-1H-quinolina-3-carboxamida
440
N-(2,2,3,3-tetrafluoro-2,3-dihidrobenzo[b][1,4]dioxin-6-il)-1,4-dihidro-4-oxoquinolina-3-carboxamida
441
N-[3-metilsulfonilamino-5-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
442
4-oxo-N-[3-(1-piperidilsulfonil)fenil]-1H-quinolina-3-carboxamida
443
4-oxo-N-quinoxalin-6-il-1H-quinolina-3-carboxamida
444
5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-tert-butil-acido benzoico metil ester
445
N-(2-isopropenilfenil)-4-oxo-1H-quinolina-3-carboxamida
446
N-(1,1-dioxobenzotiofen-6-il)-4-oxo-1H-quinolina-3-carboxamida
447
N-(3-cianofenil)-4-oxo-1H-quinolina-3-carboxamida
448
4-oxo-N-(4-tert-butilfenil)-1H-quinolina-3-carboxamida
449
N-(m-tolil)-4-oxo-1H-quinolina-3-carboxamida
450
N-[4-(1-hidroxietil)fenil]-4-oxo-1H-quinolina-3-carboxamida
451
N-(4-ciano-2-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
452
4-oxo-N-(4-vinilfenil)-1H-quinolina-3-carboxamida
453
N-(3-amino-4-cloro-fenil)-4-oxo-1H-quinolina-3-carboxamida
454
N-(2-metil-5-fenil-fenil)-4-oxo-1H-quinolina-3-carboxamida
455
N-[4-(1-adamantil)fenil]-4-oxo-1H-quinolina-3-carboxamida
456
4-oxo-N-[3-(trifluorometilsulfanil)fenil]-1H-quinolina-3-carboxamida
457
N-(4-morfolinofenil)-4-oxo-1H-quinolina-3-carboxamida
458
N-[3-(2-hidroxietoxi)-4-tert-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
459
N-(o-tolil)-4-oxo-1H-quinolina-3-carboxamida
460
[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformico butil ester
461
4-oxo-N-(2-fenilfenil)-1H-quinolina-3-carboxamida
462
N-(3-dimetilamino-4-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
463
N-(4-etilfenil)-4-oxo-1H-quinolina-3-carboxamida
464
5-hidroxi-N-(5-hidroxi-2,4-ditert-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
465
[5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-tert-butil-fenilmetil]acido aminoformico tert-butil ester
466
N-(2,6-diisopropilfenil)-4-oxo-1H-quinolina-3-carboxamida
467
N-(2,3-dihidrobenzofuran-5-il)-4-oxo-1H-quinolina-3-carboxamida
468
1-metil-4-oxo-N-fenil-1H-quinolina-3-carboxamida
469
4-oxo-N-(2-fenilfenil)-7-(trifluorometil)-1H-quinolina-3-carboxamida
470
4-oxo-N-(4-fenilsulfanilfenil)-1H-quinolina-3-carboxamida
471
[3-[(4-oxo-1H-quinolin-3-il)carbonilamino]-4-propil-fenil]acido aminoformico metil ester
472
[4-etil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]acido aminoformico etil ester
473
1-isopropil-4-oxo-N-(2-tert-butilfenil)-1H-quinolina-3-carboxamida
474
N-(3-metil-2-oxo-3H-benzooxazol-5-il)-4-oxo-1H-quinolina-3-carboxamida
475
N-(2,5-dicloro-3-piridil)-4-oxo-1H-quinolina-3-carboxamida
43
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En un vial de 2 dracmas, se añadió el ácido arilborónico correspondiente (0,58 mmoles) seguido de KF (110 mg, 1,9 mmoles). Los sólidos se suspendieron en THF (2 ml), y a continuación se añadió 2-bromoanilina (70 µl, 0,58 mmoles). El vial se purgó con argón durante 1 min. Se añadió P(tBu)3 (100 µl, 10 % de sol. en hexanos), seguido de Pd2(dba)3 (900 µl, 0,005 M en THF). El vial se purgó de nuevo con argón y se cerró. El vial se agitó en un agitador orbital a temperatura ambiente durante 30 min y se calentó en un bloque térmico a 80 ºC durante 16 h. A continuación, el vial se enfrió a 20 ºC y la suspensión se pasó a través de una almohadilla de Celite. La almohadilla se lavó con EtOAc (5 ml). Los extractos orgánicos se combinaron y se concentraron a vacío dando una amina en bruto que se usó sin más purificación.
La siguiente tabla incluye las aminas preparadas siguiendo el esquema general anterior.
Producto
Nombre Método
F-1
4’-Metil-bifenil-2-ilamina A
F-2
3’-Metil-bifenil-2-ilamina A
F-3
2’-Metil-bifenil-2-ilamina A
F-4
2’,3’-Dimetil-bifenil-2-ilamina A
F-5
(2’-Amino-bifenil-4-il)-metanol A
F-6
N*4’*,N*4’*-Dimetil-bifenil-2,4’-diamina B
F-7
2’-Trifluorometil-bifenil-2-ilamina B
F-8
(2’-Amino-bifenil-4-il)-acetonitrilo A
F-9
4’-Isobutil-bifenil-2-ilamina A
F-10
3’-Trifluorometil-bifenil-2-ilamina B
F-11
2-Piridin-4-il-fenilamina B
F-12
2-(1H-Indol-5-il)-fenilamina B
F-13
3’,4’-Dimetil-bifenil-2-ilamina A
F-14
4’-Isopropil-bifenil-2-ilamina A
F-15
3’-Isopropil-bifenil-2-ilamina A
F-16
4’-Trifluorometil-bifenil-2-ilamina B
F-17
4’-Metoxi-bifenil-2-ilamina B
F-18
3’-Metoxi-bifenil-2-ilamina B
F-19
2-Benzo[1,3]dioxol-5-il-fenilamina B
F-20
3’-Etoxi-bifenil-2-ilamina B
F-21
4’-Etoxi-bifenil-2-ilamina B
F-22
2’-Etoxi-bifenil-2-ilamina B
F-23
4’-Metilsulfanil-bifenil-2-ilamina B
F-24
3’,4’-Dimetoxi-bifenil-2-ilamina B
F-25
2’,6’-Dimetoxi-bifenil-2-ilamina B
F-26
2’,5’-Dimetoxi-bifenil-2-ilamina B
F-27
2’,4’-Dimetoxi-bifenil-2-ilamina B
F-28
5’-Cloro-2’-metoxi-bifenil-2-ilamina B
F-29
4’-Trifluorometoxi-bifenil-2-ilamina B
F-30
3’-Trifluorometoxi-bifenil-2-ilamina B
F-31
4’-Fenoxi-bifenil-2-ilamina B
128 129
Producto
Nombre Método
F-32
2’-Fluoro-3’-metoxi-bifenil-2-ilamina B
F-33
2’-Fenoxy-bifenil-2-ilamina B
F-34
2-(2,4-Dimetoxi-pirimidin-5-il)-fenilamina B
F-35
5’-Isopropil-2’-metoxi-bifenil-2-ilamina B
F-36
2’-Trifluorometoxi-bifenil-2-ilamina B
F-37
4’-Fluoro-bifenil-2-ilamina B
F-38
3’-Fluoro-bifenil-2-ilamina B
F-39
2’-Fluoro-bifenil-2-ilamina B
F-40
2’-Amino-bifenil-3-carbonitrilo B
F-41
4’-Fluoro-3’-metil-bifenil-2-ilamina B
F-42
4’-Cloro-bifenil-2-ilamina B
F-43
3’-Cloro-bifenil-2-ilamina B
F-44
3’,5’-Difluoro-bifenil-2-ilamina B
F-45
2’,3’-Difluoro-bifenil-2-ilamina B
F-46
3’,4’-Difluoro-bifenil-2-ilamina B
F-47
2’,4’-Difluoro-bifenil-2-ilamina B
F-48
2’,5’-Difluoro-bifenil-2-ilamina B
F-49
3’-Cloro-4’-fluoro-bifenil-2-ilamina B
F-50
3’,5’-Dicloro-bifenil-2-ilamina B
F-51
2’,5’-Dicloro-bifenil-2-ilamina B
F-52
2’,3’-Dicloro-bifenil-2-ilamina B
F-53
3’,4’-Dicloro-bifenil-2-ilamina B
F-54
Ester metil 2’-Amino-bifenil-4-acido carboxílico B
F-55
Ester metil 2’-Amino-bifenil-3-acido carboxílico B
F-56
2’-Metilsulfanil-bifenil-2-ilamina B
F-57
N-(2’-Amino-bifenil-3-il)-acetamida B
F-58
4’-Metanosulfinil-bifenil-2-ilamina B
F-59
2’,4’-Dicloro-bifenil-2-ilamina B
F-60
4’-Metanosulfonil-bifenil-2-ilamina B
F-61
Ester isopropil 2’-Amino-bifenil-2-acido carboxílico B
F-62
2-Furan-2-il-fenilamine B
F-63
1-[5-(2-Amino-fenil)-tiofen-2-il]-etanona B
F-64
2-Benzo[b]tiofen-2-il-fenilamine B
F-65
2-Benzo[b]tiofen-3-il-fenilamine B
F-66
2-Furan-3-il-fenilamine B
F-67
2-(4-Metil-tiofen-2-il)-fenilamina B
F-68
5-(2-Amino-fenil)-tiofene-2-carbonitrilo B
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Amina
Nombre
J-18
2-terc-butilbencenamina
J-19
2,4,6-trimetilbencenamina
J-20
5,6-dimetil-1H-benzo[d]imidazol-2-amina
J-21
2,3-dihidro-1H-inden-4-amina
J-22
2-sec-butil-6-etilbencenamina
J-23
quinolin-5-amina
J-24
4-(benciloxi)bencenamina
J-25
2’-Metoxi-bifenil-2-ilamina
J-26
benzo[c][1,2,5]tiadiazol-4-amina
J-27
3-benzilbencenamina
J-28
4-isopropilbencenamina
J-29
2-(fenilsulfonil)bencenamina
J-30
2-metoxibencenamina
J-31
4-amino-3-etilbenzonitrilo
J-32
4-metilpiridin-2-amina
J-33
4-clorobencenamina
J-34
2-(benciloxi)bencenamina
J-35
2-amino-6-clorobenzonitrilo
J-36
3-metilpiridin-2-amina
J-37
4-aminobenzonitrilo
J-38
3-cloro-2,6-dietilbencenamina
J-39
3-fenoxibencenamina
J-40
2-bencilbencenamina
J-41
2-(2-fluorofenoxi)piridin-3-amina
J-42
5-cloropiridin-2-amina
J-43
2-(trifluorometil)bencenamina
J-44
(4-(2-aminofenil)piperazin-1-il)(fenil)metanona
J-45
1H-benzo[d][1,2,3]triazol-5-amina
J-46
2-(1H-indol-2-il)bencenamina
J-47
4-Metil-bifenil-3-ilamina
J-48
piridin-3-amina
J-49
3,4-dimetoxibencenamina
J-50
3H-benzo[d]imidazol-5-amina
J-51
3-aminobenzonitrilo
J-52
6-cloropiridin-3-amina
J-53
o-toluidina
J-54
1H-indol-5-amina
134 135 136 137 138 139
Amina
Nombre
J-56
2-metoxipiridin-3-amina
J-57
2-butoxibencenamina
J-58
2,6-dimetilbencenamina
J-59
2-(metiltio)bencenamina
J-60
2-(5-metilfuran-2-il)bencenamina
J-61
3-(4-aminofenil)-3-etilpiperidina-2,6-diona
J-62
2,4-dimetilbencenamina
J-63
5-fluoropiridin-2-amina
J-64
4-ciclohexilbencenamina
J-65
4-Amino-bencenosulfonamida
J-66
2-etilbencenamina
J-67
4-fluoro-3-metilbencenamina
J-68
2,6-dimetoxipiridin-3-amina
J-69
4-terc-butilbencenamina
J-70
4-sec-butilbencenamina
J-71
5,6,7,8-tetrahidronaftalen-2-amina
J-72
3-(Pirrolidina-1-sulfonil)-fenilamina
J-73
4-Adamantan-1-il-fenilamina
J-74
3-amino-5,6,7,8-tetrahidronaftalen-2-ol
J-75
benzo[d] [1,3]dioxol-5-amina
J-76
5-cloro-2-fenoxibencenamina
J-77
N1-tosilbenceno-1,2-diamina
J-78
3,4-dimetilbencenamina
J-79
2-(trifluorometiltio)bencenamina
J-80
1H-indol-7-amina
J-81
3-metoxibencenamina
J-82
quinolin-8-amina
J-83
2-(2,4-difluorofenoxi)piridin-3-amina
J-84
2-(4-aminofenil)acetonitrilo
J-85
2,6-diclorobencenamina
J-86
2,3-dihidrobenzofuran-5-amina
J-87
p-toluidina
J-88
2-metilquinolin-8-amina
J-89
2-terc-butilbencenamina
J-90
3-clorobencenamina
J-91
4-terc-butil-2-clorobencenamina
J-92
2-Amino-bencenosulfonamida
Amina
Nombre
J-93
1-(2-aminofenil)etanona
J-94
m-toluidina
J-95
2-(3-cloro-5-(trifluorometil)piridin-2-iloxi)bencenamina
J-96
2-amino-6-melhilbenzonitrilo
J-97
2-(prop-1-en-2-il)bencenamina
J-98
4-Amino-N-piridin-2-il-bencenosulfonamida
J-99
2-etoxibencenamina
J-100
nafthalen-1-amina
J-101
Bifenil-2-ilamina
J-102
2-(trifluorometil)-4-isopropilbencenamina
J-103
2,6-dietilbencenamina
J-104
5-(trifluorometil)piridin-2-amina
J-105
2-aminobenzamida
J-106
3-(trifluorometoxi)bencenamina
J-107
3,5-bis(trifluorometil)bencenamina
J-108
4-vinilbencenamina
J-109
4-(trifluorometil)bencenamina
J-110
2-morfolinobencenamina
J-111
5-amino-1H-benzo[d]imidazol-2(3H)-ona
J-112
quinolin-2-amina
J-113
3-metil-1H-indol-4-amina
J-114
piracin-2-amina
J-115
1-(3-aminofenil)etanona
J-116
2-etil-6-isopropilbencenamina
J-117
2-(3-(4-clorofenil)-1,2,4-oxadiazol-5-il)bencenamina
J-118
N-(4-amino-2,5-dietoxifenil)benzamida
J-119
5,6,7,8-tetrahidronaftalen-1-amina
J-120
2-(1H-benzo[d]imidazol-2-il)bencenamina
J-121
1,1-Dioxo-1H-1lambda*6*-benzo[b]tiofen-6-ilamina
J-122
2,5-dietoxibencenamina
J-123
2-isopropil-6-metilbencenamina
J-124
terc-butil 5-amino-3,4-dihidroisoquinolina-2(1H)-carboxilato
J-125
2-(2-aminofenil)etanol
J-126
(4-aminofenil)metanol
J-127
5-metilpiridin-2-amina
J-128
2-(pirrolidin-1-il)bencenamina
J-129
4-propilbencenamina
Amina
Nombre
J-130
3,4-diclorobencenamina
J-131
2-fenoxibencenamina
J-132
Bifenil-2-ilamina
J-133
2-clorobencenamina
J-134
2-amino-4-metilbenzonitrilo
J-135
(2-aminofenil)(fenil)metanona
J-136
anilina
J-137
3-(trifluorometiltio)bencenamina
J-138
2-(2,5-dimetil-1H-pirrol-1-il)bencenamina
J-139
4-(Morfoline-4-sulfonil)-fenilamina
J-140
2-metilbenzo[d]tiazol-5-amina
J-141
2-amino-3,5-diclorobenzonitrilo
J-142
2-fluoro-4-metilbencenamina
J-143
6-etilpiridin-2-amina
J-144
2-(1H-pirrol-1-il)bencenamina
J-145
2-metil-1H-indol-5-amina
J-146
quinolin-6-amina
J-147
1H-benzo[d]imidazol-2-amina
J-148
2-o-tolilbenzo[d]oxazol-5-amina
J-149
5-fenilpiridin-2-amina
J-150
Bifenil-2-ilamina
J-151
4-(difluorometoxi)bencenamina
J-152
5-terc-butil-2-metoxibencenamina
J-153
2-(2-terc-butilfenoxi)bencenamina
J-154
3-aminobenzamida
J-155
4-morfolinobencenamina
J-156
6-aminobenzo[d]oxazol-2(3H)-ona
J-157
2-fenil-3H-benzo[d]imidazol-5-amina .
J-158
2,5-dicloropiridin-3-amina
J-159
2,5-dimetilbencenamina
J-160
4-(feniltio)bencenamina
J-161
9H-fluoren-1-amina
J-162
2-(4-aminofenil)-1,1,1,3,3,3-hexafluoropropan-2-ol
J-163
4-bromo-2-etilbencenamina
J-164
4-metoxibencenamina
J-165
3-(Piperidina-1-sulfonil)-fenilamina
J-166
quinoxalin-6-amina
Amina
Nombre
J-167
6-(trifluorometil)piridin-3-amina
J-168
3-(trifluorometil)-2-metilbencenamina
J-169
(2-aminofenil)(fenil)metanol
J-170
anilina
J-171
6-metoxipiridin-3-amina
J-172
4-butilbencenamina
J-173
3-(Morfoline-4-sulfonil)-fenilamina
J-174
2,3-dimetilbencenamina
J-175
anilina
J-176
Bifenil-2-ilamina
J-177
2-(2,4-diclorofenoxi)bencenamina
J-178
piridin-4-amina
J-179
2-(4-metoxifenoxi)-5-(trifluorometil)bencenamina
J-180
6-metilpiridin-2-amina
J-181
5-cloro-2-fluorobencenamina
J-182
6-morfolinopiridin-3-amina
J-183
6-morfolinopiridin-3-amina
J-184
anilina
J-185
1H-indazol-5-amina
J-186
2-[(Ciclohexil-metil-amino)-metil]-fenilamina
J-187
2-fenilbenzo[d]oxazol-5-amina
J-188
naftalen-2-amina
J-189
2-aminobenzonitrilo
J-190
N1,N1-dietil-3-metilbenceno-1,4-diamina
J-191
anilina
J-192
2-butilbencenamina
J-193
1-(4-aminofenil)etanol
J-194
2-amino-4-metilbenzamida
J-195
quinolin-3-amina
J-196
2-(piperidin-1-il)bencenamina
J-197
3-Amino-bencenosulfonamida
J-198
2-etil-6-metilbencenamina
J-199
Bifenil-4-ilamina
J-200
2-(o-toliloxi)bencenamina
J-201
5-amino-3-metilbenzo[d]oxazol-2(3H)-ona
J-202
4-etilbencenamina
Amina
Nombre
J-203
2-isopropilbencenamina
J-204
3-(trifluorometil)bencenamina
J-205
2-amino-6-fluorobenzonitrilo
J-206
2-(2-aminofenil)acetonitrilo
J-207
2-(4-fluorofenoxi)piridin-3-amina
J-208
anilina
J-209
2-(4-metilpiperidin-1-il)bencenamina
J-210
4-fluorobencenamina
J-211
2-propilbencenamina
J-212
4-(trifluorometoxi)bencenamina
J-213
3-aminofenol
J-214
2,2-difluorobenzo[d][1,3]dioxol-5-amina
J-215
2,2,3,3-tetrafluoro-2,3-dihidrobenzo[b][1,4]dioxin-6-amina
J-216
N-(3-aminofenil)acetamida
J-217
1-(3-aminofenil)-3-metil-1H-pirazol-5(4H)-one
J-218
5-(trifluorometil)benceno-1,3-diamina
J-219
5-terc-butil-2-metoxibenceno-1,3-diamina
J-220
N-(3-amino-4-etoxifenil)acetamida
J-221
N-(3-Amino-fenil)-metanesulfonamida
J-222
N-(3-aminofenil)propionamida
J-223
N1,N1-dimetilbenceno-1,3-diamina
J-224
N-(3-amino-4-metoxifenil)acetamida
J-225
benceno-1,3-diamina
J-226
4-metilbenceno-1,3-diamina
J-227
1H-indol-6-amina
J-228
6,7,8,9-tetrahidro-5H-carbazol-2-amina
J-229
1H-indol-6-amina
J-230
1H-indol-6-amina
J-231
1H-indol-6-amina
J-232
1H-indol-6-amina
J-233
1H-indol-6-amina
J-234
1H-indol-6-amina
J-235
1H-indol-6-amina
J-236
1H-indol-6-amina
J-237
1H-indol-6-amina
J-238
H-indol-6-amina
imagen119
Compuesto de la formula I
Acido Amina
2
A-1 C-2
3
A-1 J-17
4
A-1 J-110
5
A-1 G-2
6
A-1 E-8
7
A-1 J-118
8
A-1 D-7
9
A-1 J-197
11
A-1 F-7
12
A-1 F-6
13
A-1 E-2
15
A-1 J-56
16
A-1 J-211
18
A-1 J-161
19
A-1 J-112
20
A-1 J-200
21
A-1 J-98
23
A-1 C-15
24
A-1 J-72
25
A-1 F-57
26
A-1 J-196
29
A-21 J-208
31
A-1 J-87
32
A-1 B-21
33
A-1 J-227
34
A-1 C-19
36
A-1 J-203
37
A-1 J-80
38
A-1 J-46
39
A-17 D-10
40
A-1 J-125
42
A-1 J-95
43
A-1 C-16
44
A-1 J-140
45
A-1 J-205
47
A-1 J-102
48
A-1 J-181
141 142 143 144 145 146 147 148 149 150 151
Compuesto de la formula I
Acido Amina
49
A-1 F-25
50
A-1 J-19
51
A-7 B-24
52
A-1 F-2
53
A-1 J-178
54
A-1 J-26
55
A-1 J-219
56
A-1 J-74
57
A-1 J-61
58
A-1 D-4
59
A-1 F-35
60
A-1 D-11
61
A-1 J-174
62
A-1 J-106
63
A-1 F-47
64
A-1 J-111
66
A-1 J-214
67
A-10 J-236
68
A-1 F-55
69
A-1 D-8
70
A-1 F-11
71
A-1 F-61
72
A-1 J-66
73
A-1 J-157
74
A-1 J-104
75
A-1 J-195
76
A-1 F-46
77
A-1 B-20
78
A-1 J-92
79
A-1 F-41
80
A-1 J-30
81
A-1 J-222
82
A-1 J-190
83
A-1 F-40
84
A-1 J-32
85
A-1 F-53
86
A-1 J-15
Compuesto de la formula I
Acido Amina
87
A-1 J-39
88
A-1 G-3
89
A-1 J-134
90
A-1 J-18
91
A-1 J-38
92
A-1 C-13
93
A-1 F-68
95
A-1 J-189
96
A-1 B-9
97
A-1 F-34
99
A-1 J-4
100
A-1 J-182
102
A-1 J-117
103
A-2 C-9
104
A-1 B-4
106
A-1 J-11
107
A-1 DC-6
108
A-1 DC-3
109
A-1 DC-4
110
A-1 J-84
111
A-1 J-43
112
A-11 J-235
113
A-1 B-7
114
A-1 D-18
115
A-1 F-62
116
A-3 J-229
118
A-1 F-12
120
A-1 J-1
121
A-1 J-130
122
A-1 J-49
123
A-1 F-66
124
A-2 B-24
125
A-1 J-143
126
A-1 C-25
128
A-22 J-176
130
A-14 J-233
131
A-1 J-240
Compuesto de la formula I
Acido Amina
132
A-1 J-220
134
A-1 F-58
135
A-1 F-19
136
A-1 C-8
137
A-6 C-9
138
A-1 F-44
139
A-1 F-59
140
A-1 J-64
142
A-1 J-10
143
A-1 C-7
144
A-1 J-213
145
A-1 B-18
146
A-1 J-55
147
A-1 J-207
150
A-1 J-162
151
A-1 F-67
152
A-1 J-156
153
A-1 C-23
154
A-1 J-107
155
A-1 J-3
156
A-1 F-36
160
A-1 D-6
161
A-1 C-3
162
A-1 J-171
164
A-1 J-204
165
A-1 J-65
166
A-1 F-54
167
A-1 J-226
168
A-1 J-48
169
A-1 B-1
170
A-1 J-42
171
A-1 F-52
172
A-1 F-64
173
A-1 J-180
174
A-1 F-63
175
A-1 DC-2
176
A-1 J-212
177
A-1 J-57
Compuesto de la formula I
Acido Amina
178
A-1 J-153
179
A-1 J-154
180
A-1 J-198
181
A-1 F-1
182
A-1 F-37
183
A-1 DC-1
184
A-15 J-231
185
A-1 J-173
186
A-1 B-15
187
A-1 B-3
188
A-1 B-25
189
A-1 J-24
190
A-1 F-49
191
A-1 J-23
192
A-1 J-36
193
A-1 J-68
194
A-1 J-37
195
A-1 J-127
197
A-1 J-167
198
A-1 J-210
199
A-1 F-3
200
A-1 H-1
201
A-1 J-96
202
A-1 F-28
203
A-1 B-2
204
A-1 C-5
205
A-1 J-179
206
A-1 J-8
207
A-1 B-17
208
A-1 C-12
209
A-1 J-126
210
A-17 J-101
211
A-1 J-152
212
A-1 J-217
213
A-1 F-51
214
A-1 J-221
215
A-1 J-136
Compuesto de la formula I
Acido Amina
216
A-1 J-147
217
A-1 J-185
218
A-2 C-13
219
A-1 J-114
220
A-1 C-26
222
A-1 J-35
223
A-1 F-23
224
A-1 I-1
226
A-1 J-129
227
A-1 J-120
228
A-1 J-169
229
A-1 J-59
230
A-1 J-145
231
A-1 C-17
233
A-1 J-239
234
A-1 B-22
235
A-1 E-9
236
A-1 J-109
240
A-1 J-34
241
A-1 J-82
242
A-1 D-2
244
A-1 J-228
245
A-1 J-177
246
A-1 J-78
247
A-1 F-33
250
A-1 J-224
252
A-1 J-135
253
A-1 F-30
254
A-2 B-20
255
A-8 C-9
256
A-1 J-45
257
A-1 J-67
259
A-1 B-14
261
A-1 F-13
262
A-1 DC-7
263
A-1 J-163
Compuesto de la formula I
Acido Amina
264
A-1 J-122
265
A-1 J-40
266
A-1 C-14
267
A-1 J-7
268
A-1 E-7
270
A-1 B-5
271
A-1 D-9
273
A-1 H-2
274
A-8 B-24
276
A-1 J-139
277
A-1 F-38
278
A-1 F-10
279
A-1 F-56
280
A-1 J-146
281
A-1 J-62
283
A-1 F-18
284
A-1 J-16
285
A-1 F-45
286
A-1 J-119
287
A-3 C-13
288
A-1 C-6
289
A-1 J-142
290
A-1 F-15
291
A-1 C-10
292
A-1 J-76
293
A-1 J-144
294
A-1 J-54
295
A-1 J-128
296
A-17 J-12
297
A-1 J-138
301
A-1 J-14
302
A-1 F-5
303
A-1 J-13
304
A-1 E-1
305
A-1 F-17
306
A-1 F-20
307
A-1 F-43
308
A-1 J-206
Compuesto de la formula I
Acido Amina
309
A-1 J-5
310
A-1 J-70
311
A-1 J-60
312
A-1 F-27
313
A-1 F-39
314
A-1 J-116
315
A-1 J-58
317
A-1 J-85
319
A-2 C-7
320
A-1 B-6
321
A-1 J-44
322
A-1 J-22
324
A-1 J-172.
325
A-1 J-103
326
A-1 F-60
328
A-1 J-115
329
A-1 J-148
330
A-1 J-133
331
A-1 J-105
332
A-1 J-9
333
A-1 F-8
334
A-1 DC-5
335
A-1 J-194
336
A-1 J-192
337
A-1 C-24
338
A-1 J-113
339
A-1 B-8
344
A-1 F-22
345
A-2 J-234
346
A-12 J-6
348
A-1 F-21
349
A-1 J-29
350
A-1 J-100
351
A-1 B-23
352
A-1 B-10
353
A-1 D-10
354
A-1 J-186
Compuesto de la formula I
Acido Amina
355
A-1 J-25
357
A-1 B-13
358
A-24 J-232
360
A-1 J-151
361
A-1 F-26
362
A-1 J-91
363
A-1 F-32
364
A-1 J-88
365
A-1 J-93
366
A-1 F-16
367
A-1 F-50
368
A-1 D-5
369
A-1 J-141
370
A-1 J-90
371
A-1 J-79
372
A-1 J-209
373
A-1 J-21
374
A-16 J-238
375
A-1 J-71
376
A-1 J-187
377
A-5 J-237
378
A-1 D-3
380
A-1 J-99
381
A-1 B-24
383
A-1 B-12
384
A-1 F-48
385
A-1 J-83
387
A-1 J-168
388
A-1 F-29
389
A-1 J-27
391
A-1 F-9
392
A-1 J-52
394
A-22 J-170
395
A-1 C-20
397
A-1 J-199
398
A-1 J-77
400
A-1 J-183
401
A-1 F-4
Compuesto de la formula I
Acido Amina
402
A-1 J-149
403
A-1 C-22
405
A-1 J-33
406
A-6 B-24
407
A-3 C-7
408
A-1 J-81
410
A-1 F-31
411
A-13 J-191
412
A-1 B-19
413
A-1 J-131
414
A-1 J-50
417
A-1 F-65
418
A-1 J-223
419
A-1 J-216
420
A-1 G-1
421
A-1 C-18
422
A-1 J-20
423
A-1 B-16
424
A-1 F-42
425
A-1 J-28
426
A-1 C-11
427
A-1 J-124
428
A-1 C-1
429
A-1 J-218
430
A-1 J-123
431
A-1 J-225
432
A-1 F-14
433
A-1 C-9
434
A-1 J-159
435
A-1 J-41
436
A-1 F-24
437
A-1 J-75
438
A-1 E-10
439
A-1 J-164
440
A-1 J-215
441
A-1 D-19
442
A-1 J-165
Compuesto de la formula I
Acido Amina
443
A-1 J-166
444
A-1 E-6
445
A-1 J-97
446
A-1 J-121
447
A-1 J-51
448
A-1 J-69
449
A-1 J-94
450
A-1 J-193
451
A-1 J-31
452
A-1 J-108
453
A-1 D1
454
A-1 J-47
455
A-1 J-73
456
A-1 J-137
457
A-1 J-155
458
A-1 C-4
459
A-1 J-53
461
A-1 J-150
463
A-1 J-202
464
A-3 C-9
465
A-1 E-4
466
A-1 J-2
467
A-1 J-86
468
A-20 J-184
469
A-12 J-132
470
A-1 J-160
473
A-21 J-89
474
A-1 J-201
475
A-1 J-158
477
A-1 J-63
478
A-1 B-11
479
A-4 J-230
480
A-23 J-175
481
A-1 J-188
483
A-1 C-21
484
A-1 D-14
B-26-I
A-1 B-26
B-27-I
A-1 B-27
imagen120
imagen121
imagen122
imagen123
imagen124
imagen125
imagen126
imagen127
imagen128
imagen129
imagen130
imagen131
imagen132
imagen133
imagen134
imagen135
imagen136
imagen137
imagen138
A continuación se muestran los datos de RMN para compuestos seleccionados en la Tabla 2-A:
Nº de Comp.
Datos de NMR
2
1H NMR (300 MHz, CDCl3) δ 12.53 (s, 1H), 11.44 (br d, J = 6.0 Hz, 1H), 9.04 (d, J = 6.7 Hz, 1H), 8.43 (d, J = 7.8 Hz, 1H), 7.51 (t, J = 7.3 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H), 7.33-7.21 (m, 3H), 7.10 (d, J = 8.2 Hz, 1H), 3.79 (s, 3H), 1.36 (s, 9H)
5
H NMR (400 MHz, DMSO-d6) δ 12.94 (bs, 1H), 12.41 (s, 1H), 8.88 (s, 1H), 8.34 (dd, J = 8, 1 Hz, 1H), 7.82 (ddd, J = 8, 8, 1 Hz, 1H), 7.75 (d, J = 8 Hz, 1H), 7.64 (dd, J = 7, 2 HZ, 2H), 7.54 (ddd, J = 8, 8, 1 Hz, 1H), 7.35 (dd, J = 7, 2 Hz, 2H), 4.66 (t, J = 5 Hz, 1H), 3.41 (d, J = 5 Hz, 2H), 1.23 (s, 6H).
8
1H NMR (CD3OD, 300 MHz) δ 8.86 (s, 1H), 8.42 (d, J = 8.5 Hz, 1H), 7.94 (s, 1H), 7.81 (t, J = 8.3 Hz, 1H), 7.67 (d, J = 8.3 Hz, 1H), 7.54 -7.47 (m, 2H), 7.38 (d, J = 8.5 Hz, 1H), 2.71 (q, J = 7.7 Hz, 2H), 1.30 (t, J= 7.4 Hz, 3H).
10
H NMR (400 MHz, DMSO-d6) δ 13.02 (d, J = 6.4 Hz, 1H), 12.58 (s, 1H), 8.87 (d, J = 6.8 Hz, 1H), 8.33 (dd, J = 8.1, 1.2 Hz, 1H), 7.89-7.77 (m, 3H), 7.56 (t, J = 8.1 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 3.23 (m, 2H), 2.81 (m, 2H), 1.94 (m, 2H), 1.65 (m, 2H)
13
H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 12.68 (s, 1H), 8.89 (s, 1H), 8.35 (t, J = 2.5 Hz, 1H), 8.32 (d, J = 1.1 Hz, 1H), 7.85-7.76 (m, 3H), 7.58-7.54 (m, 2H), 1.47 (s, 9H)
14
H NMR (400 MHz, DMSO-d6) δ 1.32.(s, 9H), 3.64 (s, 3H), 7.36 (d, J = 8.4 Hz, 1H), 7.55 (m, 3H), 7.76 (d, J = 8.0 Hz, 1H), 7.83 (m, 1H), 8.33 (d, J = 7.0 Hz, 1H), 8.69 (s, 1H), 8.87 (d, J = 6.7 Hz, 1H), 12.45 (s, 1H), 12.97 (s, 1H)
27
H NMR (400 MHz, DMSO-d6) δ 13.20 (d, J = 6.7 Hz, 1H), 12.68 (s, 1 H), 8.96-8.85 (m, 4H), 8.35 (d, J = 7.9 Hz, 1H), 7.91-7.77 (m, 3H), 7.64-7.54 (m, 3H), 6.82 (m, 1H), 5.05 (s, 0.7H), 4.96 (s, 1.3H), 4.25 (t, J = 5.6 Hz, 1.3H), 4.00 (t, J = 5.7 Hz, 0.7H), 3.14 (s, 2H), 3.02 (s, 1H), 2.62 (t, J = 5.2 Hz, 2H), 2.54 (t, J = 5.4 Hz, 1 H)
29
H NMR (400 MHz, CDCl3) δ 9.0 9 (s, 1H), 8.62 (dd, J = 8.1 and 1.5 Hz, 1H), 7.83-7.79 (m, 3H), 7.57 (d, J = 7.2 Hz, 1H), 7.38 (t, J =7.6 Hz, 2H), 7.14 (t, J = 7.4 Hz, 2H), 5.05 (m, 1H), 1.69 (d, J =6.6 Hz, 6H)
32
H NMR (400 MHz, DMSO-d6) δ 12.93 (d, J = 6.6 Hz, 1H), 12.74 (s, 1H), 11.27 (s, 1H), 8.91 (d, J = 6.7 Hz, 1H), 8.76 (s, 1H), 8.37 (d, J = 8.1 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.70 (s, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.38 (m, 1H), 6.40 (m, 1H)
170 171 172 173 174 175 176 177
Nº de Comp.
Datos de NMR
33
H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 12.47 (s, 1H), 11.08 (s, 1H), 8.90 (s, 1H), 8.35 (dd, J = 8.1, 1.1 Hz, 1H), 8.20 (t, J = 0.8 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.30 (t, J = 2.7 Hz, 1H), 7.06 (dd, J = 8.4, 1.8 Hz, 1H), 6.39 (m, 1H)
35
H NMR (400 MHz, DMSO-d6) δ 13.01 (d, J = 6.7 Hz, 1H), 12.37 (s, 1H), 8.86 (d, J = 6.8 Hz, 1H), 8.33 (dd, J = 8.1, 1.3 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.36 (s, 1H), , 7.19 (d, J = 8.4 Hz, 1H), 7.08 (d, J = 8.2 Hz, 1H), 3.29 (m, 2H), 1.85 (m, 1H), 1.73-1.53 (m, 3H), 1.21 (s, 3H), 0.76 (t, J = 7.4 Hz, 3H)
43
H NMR (400 MHz, DMSO-d6) δ 12.77 (s, 1H), 11.94 (s, 1H), 9.56 (s, 1H), 8.81 (s, 1H), 8.11 (dd, J = 8.2, 1.1 Hz, 1H), 7.89 (s, 1H), 7.79-7.75 (m, 1 H), 7.70 (d, J = 7.7 Hz, 1H), 7.49-7.45 (m, 1H), 7.31 (t, J = 8.1 Hz, 1H), 7.00 (s, 1 H), 6.93-6.87 (m, 3H), 4.07 (q, J = 7.0 Hz, 2H), 1.38 (s, 9H), 1.28 (t, J = 7.0 Hz, 3H)
47
H NMR (400 MHz, DMSO-d6) δ 1.24 (d, J = 6.9 Hz, 6H), 3.00 (m, 1H), 7.55 (m, 3H), 7.76 (d, J = 7.7 Hz, 1H), 7.83 (m, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.33 (d, J = 9.2 Hz, 1 H), 8.89 (s, 1H), 12.65 (s, 1H), 12.95 (s, 1H)
56
H NMR (400 MHz, DMSO-d6) δ 12.81 (d, J = 6.7 Hz, 1H), 12.27 (s, 1H), 9.62 (s, 1H), 8.82 (d, J = 6.7 Hz, 1H), 8.32 (dd, J = 8.2, 1.3 Hz, 1H), 8.07 (s, 1H), 7.80 (t, J = 8.4 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H), 6.58 (s, 1H), 2.62 (m, 4H), 1.71 (m, 4H)
58
H NMR (400 MHz, DMSO-d6) δ 12.95 (d, J = 6.6 Hz, 1 H), 12.39 (s, 1H), 8.86 (d, J = 6.8 Hz, 1H), 8.33 (d, J = 7.3 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.29 (d, J = 2.5 Hz, 1H), 7.07 (dd, J = 8.7, 1.3 Hz, 1H), 6.91 (dd, J = 8.8, 2.5 Hz, 1H), 5.44 (br s, 2H)
64
H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 12.41 (s, 1H), 10.63 (s, 1H), 10.54 (s, 1H), 8.86 (s, 1H), 8.33 (d, J = 8.1 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.69 (s, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.04 (d, J = 8.3 Hz, 1H), 6.90 (d, J = 8.3 Hz, 1H)
69
H NMR (400 MHz, DMSO-d6) δ 13.06 (d, J = 6.5 Hz, 1H), 12.51 (s, 1H), 8.88 (d, J = 6.6 Hz, 1H), 8.33 (dd, J = 8.1, 1.0 Hz, 1H), 7.85-7.74 (m, 3H), 7.55 (t, J = 8.1 Hz, 1H), 7.38 (dd, J = 8.4, 1.9 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 3.03 (septet, J = 6.8 Hz, 1H), 1.20 (d, J = 6.7 Hz, 6H)
76
1H-NMR (CDCl3, 300 MHz) δ 8.84 (d, J = 6.6 Hz, 1H), 8.31 (d, J = 6.2 Hz, 1H), 8.01 (d, J = 7.9 Hz, 1H), 7.44-7.13 (m, 8H), 6.78 (d, J = 7.5 Hz, 1H).
77
H NMR (400 MHz, DMSO-d6) δ 6.40 (m, 1H), 7.36 (t, J = 2.7 Hz, 1H), 7.43 (d, J = 11.8 Hz, 1H), 7.55 (t, J=8.1 Hz, 1H), 7.80 (m, 2H), 8.36 (d, J = 9.2 Hz, 1H), 8.65 (d, J = 6.8 Hz, 1H), 8.91 (s, 1H), 11.19 (s, 1H), 12.72 (s, 1H), 12.95 (s, 1H)
88
H NMR (400 MHz, DMSO-d6) δ 12.96 (d, J = 6.6 Hz, 1H), 12.42 (s, 1H), 8.89 (d, J = 6.7 Hz, 1H), 8.33 (dd, J = 8.1, 1.2 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.66 (d, J = 8.7 Hz, 2H), 7.54 (t, J = 8.1 Hz, 1H), 7.34 (d, J = 8.7 Hz, 2H), 6.67 (t, J = 6.3 Hz, 1H), 3.12 (d, J = 6.3 Hz, 2H), 1.35 (s, 9H), 1.22 (s, 6H)
90
1H NMR (400 MHz, DMSO-d6) δ 11.98 (s, 1H), 8.89 (s, 1H), 8.34 (dd, J = 8.2, 1.1 Hz, 1H), 7.84-7.75 (m, 2H), 7.59 (dd, J = 7.8, 1.5 Hz, 1H), 7.55-7.51 (m, 1H), 7.42 (dd, J = 7.9, 1.5 Hz, 1H), 7.26-7.21 (m, 1H), 7.19-7.14 (m, 1H), 1.43 (s, 9H)
96
1H NMR (400 MHz, DMSO-d6) δ 12.58 (s, 1H), 11.11 (s, 1H), 8.89 (s, 1H), 8.35 (dd, J = 8.1, 1.1 Hz, 1H), 8.22 (d, J = 1.5 Hz, 1H), 7.83-7.74 (m, 2H), 7.56-7.51 (m, 2H), 7.30 (d, J = 2.3 Hz, 1H), 7.13 (dd, J = 8.5, 1.8 Hz, 1H), 4.03 (d, J = 0.5 Hz, 2H)
103
H NMR (400 MHz, DMSO-d6) δ 1.37 (s, 9H), 1.38 (s, 9H), 7.08 (s, 1H), 7.17 (s, 1H), 7.74 (m, 1H), 7.86 (m, 1H), 7.98 (dd, J = 9.2, 2.9 Hz, 1H), 8.90 (d, J = 6.7 Hz, 1H), 9.21 (s, 1H), 11.71 (s, 1H), 13.02 (d, J = 6.7 Hz, 1H)
104
1H NMR (400 MHz, DMSO-d6) δ 12.93 (d, J = 6.6 Hz, 1H), 12.41 (s, 1H), 10.88 (s, 1H), 8.88 (d, J = 6.7 Hz, 1H), 8.36-8.34 (m, 1H), 8.05 (d, J = 0.8 Hz, 1H), 7.84-7.75 (m, 2H), 7.56-7.52 (m, 1H), 7.35 (d, J = 8.3 Hz, 1H), 7.01 (dd, J = 8.4, 1.9 Hz, 1H), 6.07-6.07 (m, 1H), 2.37 (s, 3H)
Nº de Comp.
Datos de NMR
107
H NMR (400 MHz, DMSO-d6) δ 12.52 (s, 1H), 8.87 (s, 1H), 8.33 (dd, J = 8.2, 1.1 Hz, 1H), 7.81 (t, J = 8.3 Hz, 1H), 7.75 (d, J = 7.7 Hz, 1H), 7.57-7.51 (m, 3H), 7.15 (d, J = 8.3 Hz, 1H), 4.51 (s, 2H), 3.56 (t, J = 5.7 Hz, 2H), 2.75 (t, J = 5.5 Hz, 2H), 1.44 (s, 9H)
109
H NMR (400 MHz, DMSO-d6) δ 12.97 (brs, 1H), 12.45 (s, 1H), 8.89 (s, 1H), 8.33 (dd, J = 8.2, 1.1 Hz, 1H), 7.88 (s, 1H), 7.82 (t, J = 8.4 Hz, 1H), 7.75 (d, J = 7.7 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.43 (m, 1H), 7.31 (d, J = 8.5 Hz, 1 H), 4.01 (m, 1H), 3.41 (m, 1H), 2.21 (s, 3H), 1.85 (m, 1H), 1.68-1.51 (m, 3H), 1.23 (s, 3H), 0.71 (t, J = 7.4 Hz, 3H)
113
1H NMR (400 MHz, DMSO-d6) δ 12.92 (d, J = 6.6 Hz, 1H), 12.46 (s, 1), 10.72 (d, J = 1.5 Hz, 1H), 8.89 (d, J = 6.7 Hz, 1H), 8.35 (dd, J = 8.1, 1.2 Hz, 1H), 8.13 (d, J = 1.5 Hz, 1H), 7.84-7.75 (m, 2H), 7.56-7.52 (m, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.07-7.04 (m, 2H), 2.25 (d, J = 0.9 Hz, 3H)
114
1H NMR (300 MHz, DMSO-d6): δ 12.65 (d, J = 6.9 Hz, 1H), 11.60 (s, 1H), 9.33 (s, 1H), 8.71 (d, J = 6.6 Hz, 1H), 8.36 (d, J = 1.8 Hz, 1H), 8.03 (d, J = 7.8 Hz, 1H), 7.66 (t, J = 7.2 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 7.12 (m, 2H), 6.97 (m, 3H), 3.97 (m, 2H), 1.45 (s, 9H), 1.06 (t, J = 6.6 Hz, 3H).
126
H NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 12.33 (s, 1H), 9.49 (s, 1H), 8.88 (s, 1H), 8.35 (dd, J = 8.7, 0.5 Hz, 1H), 7.86-7.82 (m, 1H), 7.77 (d, J = 7.8 Hz, , 7.58-7.54 (m, 1H), 7.40 (d, J = 2.2 Hz, 1H), 7.11 (d, J = 8.5 Hz, 1H), 6.98 (dd, J = 8.4, 2.2 Hz, 1H), 3.67 (s, 2H), 3.51-3.47 (m, 2H), 3.44-3.41 (m, 2H), 3.36 (s, 3H), 1.33 (s, 6H)
127
H NMR (400 MHz, DMSO-d6) δ 1.23 (t, J = 7.0 Hz, 3H), 1.32 (s, 9H), 4.10 (q, J = 7.0 Hz, 2H), 7.36 (d, J = 8.5 Hz, 1H), 7.54 (m, 3H), 7.76 (d, J = 7.9 Hz, 1H), 7.82 (m, 1H) 8.33 (d, J = 9.2 Hz, 1H), 8.64 (s, 1H), 8.87 (s, 1H), 12.45 (s, 1H), 12.99 (s, 1H)
129
1H-NMR (CD3OD, 300 MHz) δ 8.83 (s, 1H), 8.41 (d, J = 8.1 Hz, 1H), 7.80 (m, 2H), 7.65 (d, J = 8.1 Hz, 1H), 7.55 (m, 2H), 7.22 (d, J = 8.1 Hz, 1H), 3.76 (s, 3H, OMe), 2.62 (q, J = 7.5 Hz, 2H), 1.21 (t, J = 7.5 Hz, 3H).
131
1H NMR (300 MHz, DMSO-d6) δ 12.37 (s, 1H), 8.81 (s, 1H), 8.30 (d, J = 8.1 Hz, 1H), 7.77 (m, 2H), 7.52 (t, J = 7.2 Hz, 1H), 7.09 (s, 1H), 6.74 (s, 1H), 6.32 (s, 1H), 5.47 (s, 2H).
135
1H-NMR (CDCl3, 300 MHz) δ 8.86 (d, J = 6.6 Hz, 1H), 8.32 (d, J = 6.2 Hz, 1H), 8.07 (d, J = 7.9 Hz, 1H), 7.47 -7.24 (m, 6H), 6.95 -6.83 (m, 3H), 5.95 (s, 2H).
136
H NMR (400 MHz, DMSO-d6) δ 1.29 (s, 9H), 1.41 (s, 9H), 7.09 (d, J = 2.4 Hz, 1H), 7.47 (d, J = 2.3 Hz, 1H), 7.57 (t, J = 8.1 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.85 (t, J = 8.4 Hz, 1H), 8.36 (d, J = 9.5 Hz, 1H), 8.93 (d, J = 6.8 Hz, 1H), 9.26 (s, 1H), 12.66 (s, 1H), 13.04 (d, J = 6.6 Hz, 1H)
141
H NMR (400 MHz, DMSO-d6) δ 12.96 (d, J = 6.6 Hz, 1H), 12.42 (s, 1H), 8.87 (d, J = 6.8 Hz, 1H), 8.33 (dd, J = 8.1, 1.2 Hz, 1H), 7.85-7.75 (m, 3H), 7.55 (t, J = 8.1 Hz, 1H), 7.46 (dd, J = 8.2, 2.2 Hz, 1H), 7.16 (d, J = 8.5 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 2.18 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H)
143
H NMR (400 MHz, DMSO-d6) δ 12.96 (d, J = 6.8 Hz, 1H), 12.56 (s, 1H), 9.44 (s, 1H), 8.87 (d, J = 6.8 Hz, 1H), 8.34 (dd, J = 8.2, 1.3 Hz, 1H), 8.08 (d, J = 7.4 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.00 (d, J = 13.3 Hz, 1H), 1.34 (s, 9H)
150
1H-NMR (DMSO d6, 300 MHz) δ 8.86 (d, J = 6.9 Hz, 1H), 8.63 (s, 1H), 8.30 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.7 Hz, 2H), 7.82-7.71 (m, 2H), 7.64 (d, J = 8.4 Hz, 2H), 7.52 (td, J =1.2Hz, 1H).
157
1H-NMR (CD30D, 300 MHz) δ 8.91 (s, 1H), 8.57 (s, 1H), 8.45 (d, J = 8.3 Hz, 1H), 7.83 (t, J = 7.2 Hz, 1H), 7.69 (d, J = 9.0 Hz, 1H), 7.57 (t, J = 7.9 Hz, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.16 (d, J = 6.0 Hz, 1H), 3.08 (s, 3H, NMe), 2.94 (q, J = 7.4 Hz, 2H), 1.36 (t, J = 7.4 Hz, 3H).
161
H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 12.41 (s, 1H), 8.88 (s, 1H), , 8.33 (dd, J = 8.2, 1.2 Hz, 1H), 7.84-7.80 (m, 1H), 7.75 (d, J = 7.9 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), , 7.44 (s, 1H), 7.19 (s, 2H), 4.13 (t, J = 4.6 Hz, 2H), 3.79 (t, J = 4.6 Hz, 2H), 3.54 (q, J = 7.0 Hz, 2H), 1.36 (s, 9H), 1.15 (t, J = 7.0 Hz, 3H)
Nº de Comp.
Datos de NMR
163
1H-NMR (300 MHz, DMSO-d6) δ 12.87 (d, J = 6.3 Hz, 1H), 11.83 (s, 1H), 8.76 (d, J = 6.3 Hz, 1H), 8.40 (s, 1H), 8.26 (br s, 2H), 8.08 (dd, J = 8.4 Hz, J = 1.5 Hz, 1H), 7.75(m, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.47-7.37 (m, 2H), 7.24 (d, J = 0.9 Hz, 1H), 7.15 (dd, J = 7.5 Hz, J = 1.8 Hz, 1H), 7.10 (d, J = 8.1 Hz, 1H), 7.02 (dt, J = 7.5 Hz, J = 0.9 Hz, 1H), 4.07 (m, 4H), 1.094 (t, J = 6.9 Hz, 3H).
167
H NMR (400 MHz, DMSO-d6) δ 2.03 (s, 3H), 4.91 (s, 2H), 6.95 (m, 3H), 7.53 (m, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.81 (m, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.84 (s, 1H), 12.20 (s, 1H), 12.90 (s, 1H)
169
1H NMR (400 MHz, DMSO-d6) 5 12.94 (d, J = 5.3 Hz, 1H), 12.51 (s, 1H), 8.89 (d, J = 6.3 Hz, 1H), 8.36 (dd, J = 8.1, 1.1 Hz, 1H), 8.06 (t, J = 0.7 Hz, 1H), 7.85-7.75 (m, 2H), 7.57-7.51 (m, 2H), 7.28 (d, J = 3.1 Hz, 1H), 7.24 (dd, J = 8.4, 1.8 Hz, 1H), 6.39 (dd, J = 3.1, 0.8 Hz, 1H), 3.78 (s, 3H)
178
1H NMR (400 MHz, DMSO-d6) δ 12.86 (s, 1H), 8.89 (d, J = 6.8 Hz, 1H), 8.65 (dd, J=8.1, 1.6 Hz, 1H), 8.19 (dd,J=8.2, 1.3Hz, 1H),7.80-7.71(m, 2H),7.48-7.44(m,2H),7.24-7.20(m, 1H),7.16-7.09(m, 2H),7.04-7.00 (m, 1H), 6.80 (dd, J = 8.0, 1.3 Hz, 1H), 6.69 (dd, J = 8.1, 1.4Hz, 1H), 1.45 (s, 9H)
183
1H NMR (400 MHz, DMSO-d6) δ 12.42 (s, 1H), 8.88 (s, 1H), 8.33 (dd, J = 8.2,1.1 Hz, 1H), 8.06(d, J = 2.1 Hz, 1H), 7.84-7.75 (m, 2H), 7.56-7.52 (m, 1H), 7.38 (dd, J = 8.2, 2.1 Hz, 1H), 7.08 (d, J = 8.3 Hz, 1H), 3.66-3.63 (m, 2H), 2.70 (t, J = 6.5 Hz, 2H), 1.86-1.80 (m, 2H), 1.51 (s, 9H)
186
H NMR (400 MHz, DMSO-d6) δ 12.93 (s, 1H), 12.47 (s, 1H), 10.72 (s, 1H), 8.89 (s, 1H), 8.35 (dd, J = 8.2, 1.1 Hz, 1H), 8.13 (d, J = 1.6 Hz, 1H), 7.82 (t, J = 8.2 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.50(d, J = 8.4 Hz, 1H), 7.05-7.02(m, 2H), 3.19 (quintet, J = 8.2 Hz, 1H), 2.08(m, 2H), 1.82-1.60 (m, 6H)
187
1H NMR (400 MHz, DMSO-d6) δ 12.63 (s, 1H), 8.91 (s, 1H), 8.87-8.87 (m, 1H), 8.36 (dd, J = 8.2, 1.2 Hz, 1H), 7.85-7.75 (m, 3H), 7.64-7.53 (m, 3H), 6.71 (dd, J = 3.7, 0.5 Hz, 1H), 2.67 (s, 3H)
188
H NMR (400 MHz, DMSO-d6) δ 12.84 (s, 1H), 12.73 (d, J = 6.6 Hz, 1H), 11.39 (s, 1H), 8.85 (d, J = 6.7 Hz, 1H), 8.61 (s, 1H), 8.33 (d, J = 6.8 Hz, 1H), 8.23 (s, 1H), 7.80 (t, J = 8.4 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H), 7.43 (m, 1H), 6.54 (m, 1 H), 4.38 (q, J = 7.1 Hz, 2H), 1.36 (t, J = 7.1 Hz, 3H)
204
H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 12.37 (s, 1H), 8.87 (d, J = 1.2 Hz, 1H), 8.32 (d, J = 8.2 Hz, 1H), 7.82 (dd, J = 8.2, 7.0 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.32-7.28 (m, 2H), 7.05 (d, J = 8.4 Hz, 1H), 4.16 (t, J = 4.9 Hz, 2H), 1.78 (t, J = 4.9 Hz, 2H), 1.29 (s, 6H),
207
H NMR (400 MHz, DMSO-d6) δ 12.92 (br s, 1H), 12.50 (s, 1H), 10.95 (s, 1H), 8.89 (s, 1H), 8.35 (dd, J = 8.2, 1.1 Hz, 1H), 8.17 (d, J = 1.5 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.21 (d, J = 2.3 Hz, 1H), 7.06 (dd, J = 8.5, 1.8 Hz, 1H), 4.09 (q, J = 7.1 Hz, 2H), 3.72 (s, 2H), 1.20 (t, J = 7.1 Hz, 3H)
215
H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 12.50 (s, 1H), 8.89 (s, 1H), 8.34 (dd, J = 8.1, 1.1 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 7.75 (m, 3H), 7.55 (t, J = 8.1 Hz, 1H), 7.37 (t, J = 7.9 Hz, 2H), 7.10 (t, J = 6.8 Hz, 1H)
220
H NMR (400 MHz, DMSO-d6) δ 12.99 (d, J = 6.6 Hz, 1H), 12.07 (s, 1H), 8.93 (d, J = 6.8 Hz, 1H), 8.35 (d, J = 7.1 Hz, 1H), 8.27 (s, 1H), 8.12 (s, 1H), 7.85-7.77 (m, 2H), 7.54 (td, J = 7.5, 1.2 Hz, 1H), 6.81 (s, 1H), 1.37 (d, J = 3.9 Hz, 9H), 1.32 (d, J = 17.1 Hz, 9H)
225
1H NMR (CD3OD, 300 MHz) δ 8.79 (s, 1H), 8.37 (d, J = 7.9 Hz, 1H), 7.75 (m, 2H), 7.61 (d, J = 8.3 Hz, 1H), 7.5 (m, 2H), 7.29 (d, J = 8.3 Hz, 1H), 4.21 (q, J = 7.2, 2H), 3.17 (m, 1H), 1.32 (t, J = 7.2 Hz, 3H), 1.24 (d, J = 6.9 Hz, 6H).
232
1H-NMR (CD3OD, 300 MHz) δ 8.87 (s, 1H), 8.45 (d, J= 8.25, 1H), 8.27 (m, 1H), 7.83 (t, J = 6.88, 1H), 7.67 (d, J= 8.25, 1H), 7.54 (t, J= 7.15, 1H), 7.39 (d, J= 6.05, 1H), 7.18 (d, J= 8.5, 1H), 2.77 (t, J= 6.87, 2H), 2.03 (s, 3H), 1.7 (q, 2H), 1.04 (t, J= 7.42, 3H)
233
1H NMR (400 MHz, DMSO-d6) δ 12.75 (d, J = 13.6 Hz, 1H), 8.87 (s, 1H), 8.32-8.28 (m, 2H), 7.76-7.70 (m, 2H), 7.60 (d, J = 7.8 Hz, 1H), 7.49-7.45 (m, 1H), 7.18 (d, J = 8.4 Hz, 1H), 4.11 (t, J = 8.3 Hz, 2H), 3.10 (t, J = 7.7 Hz, 2H), 2.18 (s, 3H)
234
1H NMR (400 MHz, DMSO-d6) δ 12.49 (s, 1H), 11.50 (s, 1H), 8.90 (s, 1H), 8.36-8.34 (m, 2H), 7.97 (s, 1H), 7.85-7.81 (m, 1H), 7.77-7.75 (m, 1H), 7.56-7.50 (m, 2H), 6.59-6.58 (m, 1H)
Nº de Comp.
Datos de NMR
235
H NMR (400 MHz, DMSO-d6) δ 13.09 (d, J = 6.5 Hz, 1H), 12.75 (s, 1H), 9.04 (s, 1H), 8.92 (d, J = 6.8 Hz, 1H), 8.42 (d, J = 7.1 Hz, 1H), 8.34 (d, J = 6.9 Hz, 1H), 7.85 (t, J = 8.4 Hz, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.63-7.56 (m, 2H), 3.15 (m, 1H), 1.29 (d, J = 6.9 Hz, 6H)
238
H NMR (400 MHz, DMSO-d6) 12.93 (d, J = 6.4 Hz, 1H), 12.29 (s, 1H), 8.85 (d, J = 6.7 Hz, 1H), 8.32 (d, J = 8.1 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.75 (d, J = 7.9 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.17 (m, 2H), 6.94 (m, 1H), 3.79 (m, 2H), 3.21-2.96 (m, 4H), 1.91-1.76 (m, 4H), 1.52 (m, 2H), 1.43 (s, 9H)
242
H NMR (400 MHz, DMSO-d6) δ 12.95 (d, J = 6.6 Hz, 1H), 12.65 (s, 1H), 8.87 (d, J = 6.8 Hz, 1H), 8.34 (dd, J = 8.1, 1.1 Hz, 1H), 8.17 (s, 1H), 7.83 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.37 (s, 1H), 5.60 (s, 2H)
243
1H-NMR (CD30D, 300 MHz) δ 8.87 (s, 1H), 8.45 (d, J= 8.25, 1H), 8.27 (m, 1H), 7.83 (t, J= 6.88, 1H), 7.67 (d, J= 8.25, 1H), 7.54 (t, J= 7.15, 1H), 7.39 (d, J= 6.05, 1H), 7.18 (d, J= 8.5, 1H), 2.77 (t, J= 6.87, 2H), 2.03 (s, 3H), 1.7 (q, 2H), 1.04 (t, J= 7.42, 3H) NMR Shows regio isomer
244
H NMR (400 MHz, DMSO-d6) δ 12.89 (s, 1 H), 12.42 (s, 1H), 10.63 (s, 1H), 8.88 (d, J = 6.7 Hz, 1H), 8.35 (d, J = 8.2 Hz, 1H), 8.03 (d, J = 1.6 Hz, 1 H), 7.82 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1 H), 7.29 (d, J = 8.3 Hz, 1H), 7.02 (dd, J = 8.4, 1.8 Hz, 1 H), 2.69 (t, J = 5.3 Hz, 2H), 2.61 (t, J = 5.0 Hz, 2H), 1.82 (m, 4H)
248
H NMR (400 MHz, DMSO-d6) δ 12.95 (d, J = 6.6 Hz, 1H), 12.42 (s, 1H), 9.30 (s, 1H), 8.86 (d, J = 6.8 Hz, 1H), 8.33 (dd, J = 8.1, 1.3 Hz, 1H), 7.85-7.81 (m, 2H), 7.76 (d, J = 7.8 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.49 (dd, J = 8.2, 2.2 Hz, 1H), 7.18 (d, J = 8.3 Hz, 1H), 2.18 (s, 3H), 2.08 (s, 3H)
259
H NMR (400 MHz, DMSO-d6) δ 0.86 (t, J = 7.4 Hz, 3H), 1.29 (d, J = 6.9 Hz, 3H), 1.67 (m, 2H), 2.88 (m, 1H), 7.03 (m, 2H), 7.53 (m, 2H), 7.80 (m, 2H), 8.13 (s, 1H), 8.35 (d, J = 8.2 Hz, 1H), 8.89 (s, 1H), 10.75 (s, 1H), 12.45 (s, 1H), 12.84 (s, 1H)
260
H NMR (400 MHz, DMSO-d6) δ 13.23 (d, J = 6.6 Hz, 1H), 12.20 (s, 1H), 10.22 (br s, 2H), 8.88 (d, J = 6.8 Hz, 1H), 8.34 (d, J = 7.8 Hz, 1H), 7.86-7.80 (m, 3H), 7.56-7.52 (m, 2H), 7.15 (dd, J = 8.5, 2.4 Hz, 1H), 1.46 (s, 9H)
261
1H-NMR (d6-DMSO, 300 MHz) δ 11.99 (s, 1H, NH), 8.76 (s, J = 6.6 Hz, 1H), 8.26 (d, J = 6.2 Hz, 1H), 8.09 (d, J = 7.9 Hz, 1 H), 7.72 -7.63 (m, 2H), 7.44 -7.09 (m, 7H), 2.46 (s, 3H), 2.25 (s, 3H).
262
1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 12.53 (s, 1H), 10.62 (s, 1H), 8.88 (s, 1H), 8.33 (dd, J = 8.2, 1.2 Hz, 1H), 7.85-7.75 (m, 2H), 7.57-7.50 (m, 2H), 7.34-7.28 (m, 2H), 3.46 (s, 2H)
266
H NMR (400 MHz, DMSO-d6) δ 12.94 (d, J = 6.6 Hz, 1H), 12.57 (s, 1H), 10.37 (s, 1H), 8.88 (d, J = 6.8 Hz, 1H), 8.34-8.32 (m, 1H), 7.99 (s, 1H), 7.85-7.81 (m, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.56-7.52 (m, 1H), 7.38 (s, 1H), 1.37 (s, 9H)
268
H NMR (400 MHz, DMSO-d6) δ 13.02 (s, 1H), 12.62 (s, 1H), 8.91 (s, 1H), 8.34 (dd, J = 8.1, 1.1 Hz, 1H), 8.22 (d, J = 2.4 Hz, 1H), 8.14 (dd, J = 8.8, 2.4 Hz, 1H), 7.84 (t, J = 8.3 Hz, 1 H), 7.77 (d, J = 7.8 Hz, 1H), 7.65-7.54 (m, 4H), 1.52 (s, 9H)
271
H NMR (400 MHz, DMSO-d6) δ 1.38 (s, 9H), 4.01 (s, 2H), 7.35 (s, 2H), 7.55 (m, 1H), 7.65 (s, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.83 (m, 1H), 8.33 (d, J = 7.6 Hz, 1H), 8.86 (d, J = 6.8 Hz, 1H), 12.49 (s, 1H), 13.13 (s, 1H)
272
1H-NMR (d6-Acetone, 300 MHz) δ 8.92 (d, J= 6.6 Hz, 1H), 8.39 (d, J= 7.8 Hz, 1H), 7.94 (s, 1H), 7.79 (s, 1H), 7.77 (s, 2H), 7.53 (m, 1H), 7.36 (s, 1H), 3.94-3.88 (m, 5H), 3.64-3.59 (m, 3H), 3.30 (m, 4H).
274
H NMR (400 MHz, DMSO-d6) δ 13.21 (d, J = 6.6 Hz, 1H), 11.66 (s, 1H), 10.95 (s, 1H), 9.00 (d, J = 6.5 Hz, 1H), 8.65 (d, J = 2.1 Hz, 1H), 8.18 (dd, J = 8.7, 2.2 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.57 (m, 2H), 7.31 (t, J = 2.7 Hz, 1H), 6.40 (t, J = 2.0 Hz, 1H), 3.19 (m, 4H), 1.67 (m, 4H), 1.46 (s, 9H)
275
H NMR (400 MHz, DMSO-d6) δ 12.23 (s, 1H), 9.47 (s, 1H), 9.20 (s, 1H), 8.43 (d, J = 7.9 Hz, 1H), 7.79 (t, J = 2.0 Hz, 2H), 7.56 (m, 1H), 7.38-7.26 (m, 6H), 7.11 (d, J = 8.4 Hz, 1H), 6.99 (dd, J = 8.4, 2.1 Hz, 1H), 5.85 (s, 2H), 1.35 (s, 9H)
Nº de Comp.
Datos de NMR
282
1H NMR (CD3OD, 300 MHz) δ 8.90 (s, 1 H), 8.51 (s, 1H), 8.44 (d, J = 7.9 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.56 (t, J = 7.7 Hz, 2H), 7.42 (d, J = 7.9 Hz, 1H), 7.07 (d, J = 5.8 Hz, 1H), 2.93 (q, J = 7.4 Hz, 2H), 1.36 (t, J = 7.5 Hz, 3H).
283
1H-NMR (CDCl3, 300 MHz) δ 8.82 (d, J = 6.6 Hz, 1H), 8.29 (d, J = 6.2 Hz, 1H), 8.06 (d, J = 7.9 Hz, 1H), 7.43 -7.24 (m, 6H), 7.02 (m, 2H), 6.87 -6.81 (dd, 2H), 3.76 (s, 3H).
287
H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H), 13.28 (d, J = 6.6 Hz, 1H), 11.72 (d, J = 2.2 Hz, 1H), 9.42 (s, 1H), 8.87 (d, J = 6.9 Hz, 1H), 8.04 (d, J = 7.4 Hz, 1H), 7.67 (t, J = 8.2 Hz, 1H), 7.17 (dd, J = 8.3, 0.8 Hz, 1H), 7.01 (d, J = 13.7 Hz, 1H), 6.81 (dd, J = 8.1, 0.8 Hz, 1H), 2.10 (m, 2H), 1.63-1.34 (m, 8H), 1.26 (s, 3H)
288
H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 12.85 (s, 1H), 8.98 (s, 1H), 8.43 (dd, J = 8.1, 1.1 Hz, 1H), 8.34 (dd, J = 10.3, 3.1 Hz, 1H), 7.93 (t, J = 8.4 Hz, 1H), 7.86 (d, J = 7.7 Hz, 1H), 7.66 (t, J = 8.1 Hz, 1H), 7.03 (dd, J = 10.7, 3.2 Hz, 1H), 4.06 (s, 3H), 1.42 (s, 9H)
295
H NMR (400 MHz, DMSO-d6) δ 1.98 (m, 4H), 3.15 (m, 4H), 7.04 (m, 2H), 7.17 (d, J = 7.8 Hz, 1H), 7.52 (m, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.81 (m, 1H), 8.19 (dd, J = 7.9, 1.4 Hz, 1H), 8.33 (d, J = 8.1 Hz, 1H), 8.88 (d, J = 6.7 Hz, 1H), 12.19 (s, 1 H), 12.87 (s, 1H)
299
1H NMR (400 MHz, DMSO-d6) (δ 12.93-12.88 (m, 1H), 12.18 (s, 1H), 8.83 (d, J = 6.8 Hz, 1H), 8.38-8.31 (m, 1H), 7.85-7.67 (m, 2H), 7.57-7.51 (m, 1H), 6.94 (s, 1H), 6.81-6.74 (m, 2H), 3.19-3.16 (m, 2H), 2.68-2.61 (m, 2H), 1.80-1.79 (m, 2H)
300
H NMR (400 MHz, DMSO-d6) δ 13.23 (d, J = 6.6 Hz, 1H), 12.59 (s, 1H), 8.87 (d, J = 6.8 Hz, 1H), 8.33 (d, J = 7.7 Hz, 1H), 7.86-7.79 (m, 3H), 7.58-7.42 (m, 3H), 3.38 (m, 2H), 1.88 (m, 2H), 1.30 (s, 6H)
303
H NMR (400 MHz, DMSO-d6) δ 12.96 (d, J = 6.5 Hz, 1H), 12.47 (s, 0.4H), 12.43 (s, 0. 6H), 8.87 (dd, J = 6.7, 2.3 Hz, 1H), 8.33 (d, J = 8.1 Hz, 1H), 7.82 (t, J = 8.2 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.62-7.52 (m, 3H), 7.17 (d, J = 8.3 Hz, 1H), 4.66 (s, 0.8H), 4.60 (s, 1.2H), 3.66 (t, J = 5.9 Hz, 2H), 2.83 (t, J = 5.8 Hz, 1.2H), 2.72 (t, J = 5.9 Hz, 0.8H), 2.09 (m, 3H)
304
1H NMR (300 MHz, DMSO-d6) δ 11.70 (s, 1H), 8.74 (s, 1H), 8.15 (s, 1H), 8.07 (m, 1H), 7.72 (m, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.45-7.31 (m, 3H), 7.15-6.95 (m, 5H), 4.17 (d, J = 6.0 Hz, 2H), 4.02 (q, J = 6.9 Hz, 2H), 1.40 (s, 9H), 1.09 (t, J = 6.9 Hz, 3H).
307
1H-NMR (CDCl3, 300 MHz) δ 8.81 (d, J = 6.6 Hz, 1H), 8.30 (d, J = 6.2 Hz, 1H), 8.02 (d, J = 7.9 Hz, 1H), 7.44-7.26 (m, 9H), 6.79 (d, J = 7.5 Hz, 1H).
318
1H-NMR (d6-Acetone, 300 MHz) δ 8.92 (bs, 1H), 8.40 (d, J= 8.1 Hz, 1H), 8.05 (bs, 1H), 7.94 (bs, 1H), 7.78 (bs, 2H), 7.52 (m, 1H), 7.36 (bs, 1H), 3.97 (t, J = 7.2 Hz, 2H), 3.66 (t, J= 8 Hz, 2H), 3.31-3.24 (m, 6H), 1.36-1.31 (m, 4H).
320
1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 12.44 (s, 1H), 10.86 (s, 1H), 8.90 (s, 1H), 8.35 (dd, J = 8.2, 1.0 Hz, 1H), 8.12 (t, J = 0.8 Hz, 1H), 7.84-7.75 (m, 2H), 7.56-7.52 (m, 1H), 7.37 (d, J = 8.3 Hz, 1H), 6.99 (dd, J = 8.4, 1.9 Hz, 1H), 6.08-6.07 (m, 1H), 1.35 (s, 9H)
321
H NMR (400 MHz, DMSO-d6) δ 2.93 (m, 4H), 3.72 (m, 4H), 7.10 (m, 2H), 7.27 (d, J = 7.8 Hz, 1H), 7.51 (m, 6H), 7.74 (d, J = 8.2 Hz, 1H), 7.81 (m, 1H), 8.40 (d, J = 8.1 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H), 8.88 (d, J = 6.7 Hz, 1H), 12.69 (s, 1H), 12.86 (s, 1H)
323
H NMR (400 MHz, DMSO-d6) δ 12.94 (br s, 1H), 12.44 (s, 1H), 8.89 (s, 1H), 8.33 (dd, J = 8.2, 1.1 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.54 (t, J = 8.1 Hz, 1H), 7.35 (d, J = 8.7 Hz, 2H), 7.02 (t, J = 6.3 Hz, 1 H), 3.50 (s, 3H), 3.17 (d, J = 6.2 Hz, 2H), 1.23 (s, 6H)
334
H NMR (400 MHz, DMSO-d6) δ 13.02 (br s, 1H), 12.46 (s, 1H), 8.89 (s, 1H), 8.33 (dd, J = 8.2, 1.1 Hz, 1H), 7.89 (s, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.44 (m, 1H), 7.37 (d, J = 8.6 Hz, 1 H), 3.85 (m, 2H), 3.72 (t, J = 6.0 Hz, 2H), 3.18-3.14 (m, 2H), 2.23 (s, 3H), 1.93 (t, J = 5.7 Hz, 2H), 1.79 (m, 2H), 1.53 (m, 2H), 1.43 (s, 9H)
Nº de Comp.
Datos de NMR
337
H NMR (400 MHz, DMSO-d6) δ 12.19 (s, 1H), 9.35 (s, 1H), 8.22 (dd, J = 8.1, 1.1 Hz, 1H), 8.08 (s, 1H), 7.74-7.70 (m, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.44-7.40 (m, 1H), 7.23 (s, 1H), 3.31 (s, 3H), 1.37 (s, 9H), 1.36 (s, 9H)
351
1H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 12.34 (s, 1H), 10.96 (s, 1H), 8.91 (s, 1H), 8.48 (s, 1H), 8.37 (d, J = 8.1 Hz, 1H), 7.84-7.76 (m, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.39 (s, 1 H), 7.26 (t, J = 2.6 Hz, 1H), 6.34 (s, 1H), 2.89-2.84 (m, 2H), 1.29 (t, J = 7.4 Hz, 3H)
353
1H NMR (400 MHz, DMSO-d6) δ 11.90 (s, 1H), 9.30 (s, 1H), 8.88 (s, 1H), 8.34 (dd, J = 8.2, 1.1 Hz, 1H), 7.84-7.71 (m, 3H), 7.55-7.50 (m, 1H), 7.28-7.26 (m, 1H), 7.20-7.17 (m, 1H), 1.47 (s, 9H), 1.38 (s, 9H)
356
1H-NMR (CD3OD, 300 MHz) δ 8.89 (s, 1H), 8.59 (s, 1H), 8.45 (d, J = 8.3 Hz, 1H), 7.83 (t, J = 7.2 Hz, 1H), 7.69 (d, J = 9.0 Hz, 1H), 7.57 (t, J = 7.9 Hz, 1H), 7.42 (d, J = 8.5 Hz, 1H), 7.17 (d, J = 6.0 Hz, 1H), 3.09 (s, 3H, NMe), 2.91 (t, J = 7.4 Hz, 2H), 1.76 (m, 2H), 1.09 (t, J = 7.4 Hz, 3H).
357
H NMR (400 MHz, DMSO-d6) 5 12.91 (d, J = 6.6 Hz, 1H), 12.45 (s, 1H), 10.73 (d, J = 1.9 Hz, 1H), 8.89 (d, J = 6.7 Hz, 1H), 8.35 (dd, J = 8.1, 1.3 Hz, 1H), 8.13 (d, J = 1.6 Hz, 1 H), 7.83 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.57-7.51 (m, 2H), 7.06-7.02(m, 2H), 3.12 (septet, J = 6.6 Hz, 1H), 1.31 (d, J = 6.9 Hz, 6H)
363
1H-NMR (CDCl3, 300 MHz) δ 8.86 (d, J = 6.6 Hz, 1H), 8.24 (d, J = 6.2 Hz, 1H), 8.14 (d, J = 7.9 Hz, 1H), 7.43 -7.16 (m, 5H), 7.02-6.92 (m, 2H), 6.83 (d, J = 7.9 Hz, 2H), 3.87 (s, 3H).
368
H NMR (400 MHz, DMSO-d6) δ 12.97 (d, J = 6.6 Hz, 1H), 12.36 (s, 1H), 8.86 (d, J = 6.7 Hz, 1H), 8.33 (dd, J = 8.1, 1.0 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.62 (s, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.25 (dd, J = 8.7, 2.2 Hz, 1H), 7.01 (d, J = 8.8 Hz, 1H), 3.98 (t, J = 6.5 Hz, 2H), 1.78 (sextet, J = 6.9 Hz, 2H), 1.02 (t, J = 7.4 Hz, 3H)
375
H NMR (400 MHz, DMSO-d6) δ 12.93 (d, J = 6.2 Hz, 1H), 12.35 (s, 1H), 8.86 (d, J = 6.7 Hz, 1H), 8.33 (d, J = 6.9 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.47-7.43 (m, 2H), 7.04 (d, J = 8.2 Hz, 1H), 2.71 (m, 4H), 1.75 (m, 4H)
378
H NMR (400 MHz, DMSO-d6) δ 12.98 (d, J = 6.6 Hz, 1H), 12.39 (s, 1H), 8.86 (d, J = 6.7 Hz, 1H), 8.33 (dd, J = 8.1, 1.2 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 7.77 (d, J = 7.7 Hz, 1H), 7.69 (s, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.31 (dd, J = 8.8, 2.4 Hz, 1H), 7.06 (d, J = 8.8 Hz, 1H), 3.85 (s, 3H)
379
1H NMR (300 MHz, DMSO-d6) δ 12.79 (s, 1H), 10.30 (s, 1H), 8.85 (s, 1H), 8.32 (d, J = 7.8 Hz, 1H), 8.06 (s, 1H), 7.93 (s, 1H), 7.81 (t, J = 7.8 Hz, 1H), 7.74 (d, J = 6.9 Hz, 1H), 7.73 (s, 1H), 7.53 (t, J = 6.9 Hz, 1H), 2.09 (s, 3H).
381
H NMR (400 MHz, DMSO-d6) δ 12.78 (br s, 1H), 11.82 (s, 1H), 10.86 (s, 1H), 8.83 (s, 1H), 8.28 (dd, J = 8.1, 1.0 Hz, 1H), 7.75 (t, J = 8.3 Hz, 1H), 7.69 (d, J = 7.7 Hz, 1H),, 7.49-7.43 (m, 3H), 7.23 (m, 1H), 6.32 (m, 1H), 1.39 (s, 9H)
382
1H NMR (CD3OD, 300 MHz) δ 8.83 (s, 1H), 8.40 (d, J = 7.4 Hz, 1H), 7.81 -7.25 (m, 2H), 7.65 (d, J = 8.3 Hz, 1H), 7.51 (d, J = 8.2, 1H), 7.24 (d, J = 8.3, 1H), 2.58 (t, J = 7.7 Hz, 2H), 2.17 (s, 3H), 1.60 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H).
383
H NMR (400 MHz, DMSO-d6) δ 1.27 (t, J = 7.5 Hz, 3H), 2.70 (q, J = 7.7 Hz, 2H), 7.05 (m, 2H), 7.47 (d, J = 8.4 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 8.13 (s, 1H), 8.35 (d, J = 6.9 Hz, 1H), 8.89 (d, J = 6.7 Hz, 1H), 10.73 (s, 1H), 12.46 (s, 1H), 12.91 (s, 1H)
386
H NMR (400 MHz, DMSO-d6) δ 13.18 (d, J = 6.8 Hz, 1H), 12.72 (s, 1H), 8.88 (d, J = 6.8 Hz, 1H), 8.34 (d, J = 8.1 Hz, 1H), 8.09 (s, 1H), 7.86-7.79 (m, 2H), 7.58-7.50 (m, 2H), 7.43 (d, J = 8.2 Hz, 1 H), 3.51 (s, 2H), 1.36 (s, 6H)
393
1H NMR (300 MHz, MeOH) δ 8.78 (s, 1H), 8.45 (d, J = 2.1 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 7.71 (t, J = 6.9, Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.39 (m, 3H), 7.18 (m, 2H), 7.06 (m, 2H), 4.02 (m, 2H), 1.13 (t, J = 6.9, Hz, 3H);
Nº de Comp.
Datos de NMR
399
1H-NMR (CD3OD, 300 MHz) δ 8.91 (s, 1H), 8.51 (s, 1H), 8.42 (d, J = 8.3 Hz, 1H), 7.84 (t, J = 7.2 Hz, 1H), 7.67 (d, J = 9.0 Hz, 1H), 7.56 (t, J = 7.9 Hz, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.24 (d, J = 6.0 Hz, 1H), 3.48 (m, 1H), 3.09 (s, 3H, NMe), 1.39 (d, J = 6.8 Hz, 6H).
412
H NMR (400 MHz, DMSO-d6) δ 12.81-12.79 (m, 2H), 10.96 (s, 1H), 8.87 (d, J = 6.7 Hz, 1H), 8.35 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.83-7.73 (m, 3H), 7.53 (t, J = 8.1 Hz, 1H), 7.36 (m, 1H), 6.52 (m, 1 H), 4.51 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H)
415
H NMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 9.46 (s, 1H), 8.99 (s, 1H), 8.43-8.41 (m, 1H), 7.94-7.88 (m, 2H), 7.65-7.61(m,1H),7.38(d,J =2.1Hz, 1H), 7.10(d,J =8.4 Hz, 1H), 6.96(dd, 1H), 4.08(s, 3H), 1.35(s, 9H)
420
H NMR (400 MHz, DMSO-d6) δ 12.91 (bs, 1H), 12.51 (s, 1H), 8.89 (s, 1H), 8.33 (dd, J = 8, 1 Hz, 2H), 7.82 (ddd, J = 8, 8, 1 Hz, 1H), 7.75 (dd, J = 8, 1 Hz, 1H), 7.70 (d, J = 9 Hz, 2H), 7.54 (ddd, J = 8, 8, 1 Hz, 1H), 4.09 (q, J = 7 Hz, 2H), 1.51 (s, 6H), 1.13 (t, J = 7 Hz, 3H).
423
H NMR (400 MHz, DMSO-d6) δ 12.91 (br s, 1 H), 12.48 (s, 1H), 10.81 (d, J = 1.8 Hz, 1H), 8.89 (s, 1H), 8.35 (dd, J = 8.2, 1.1 Hz, 1H), 8.14 (d, J = 1.6 Hz, 1H), 7.82 (t, J = 7.6 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.56-7.48 (m, 2H), 7.11 (d, J = 2.2 Hz, 1H), 7.05 (dd, J = 8.5, 1.8 Hz, 1H), 3.62 (t, J = 7.3 Hz, 2H), 3.48 (q, J = 7.0 Hz, 2H), 2.91 (t, J = 7.3 Hz, 2H), 1.14 (t, J = 7.0 Hz, 3H)
425
1H-NMR (DMSO d6, 300 MHz) δ 8.84 (s, 1H), 8.29 (d, J = 8.1 Hz, 1H), 7.78-7.70 (m, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.50 (t, J = 7.8 Hz, 1H), 7.20 (d, J = 8.7 Hz, 2H), 2.85 (h, J = 6.9 Hz, 1H), 1.19 (d, J = 6.9 Hz, 6H).
427
H NMR (400 MHz, DMSO-d6) δ 1.45 (s, 9H), 2.84 (t, J = 5.9 Hz, 2H), 3.69 (m, 2H), 4.54 (s, 1H), 6.94 (d, J = 7.5 Hz, 1H), 7.22 (t, J = 7.9 Hz, 1H), 7.55 (m, 1H), 7.77 (d, J = 7.7 Hz, 1H), 7.83 (m, 1H), 8.24 (d, J = 8.0 Hz, 1H), 8.37 (d, J = 9.2 Hz, 1 H), 8.91 (s, 1 H), 12.36 (s, 1 H), 12.99 (s, 1H)
428
1H NMR (300 MHz, CD3OD) δ 12.30 (s, 1H), 8.83 (s, 1H), 8.38 (d, J = 7.4 Hz, 1H), 7.78 (app dt, J = 1.1, 7.1 Hz, 1H), 7.64 (d, J = 8..3 Hz, 1H), 7.53 (app t, J = 7.5 Hz, 1H), 7.21 (br d, J = 0.9 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 6.98 (dd, J = 2.1, 8.4 Hz, 1H), 1.38 (s, 9H)
429
H NMR (400 MHz, DMSO-d6) δ 13.13 (d, J = 6.8 Hz, 1H), 12.63 (s, 1H), 8.86 (d, J = 6.8 Hz, 1H), 8.33 (d, J = 7.0 Hz, 1H), 7.84 (t, J = 8.3 Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.56 (t, J = 8.1 Hz, 1H), 7.51 (s, 1H), 7.30 (s, 1H), 6.77 (s, 1H)
433
H NMR (400 MHz, DMSO-d6) δ 12.87 (br s, 1H), 11.82 (s, 1H), 9.20 (s, 1H), 8.87 (s, 1H), 8.33 (dd, J = 8.2, 1.1 Hz, 1H), 7.81 (t, J = 8.3 Hz, 1H), 7.75 (d, J = 7.7 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H), 7.17 (s, 1H), 7.10 (s, 1H), 1.38 (s, 9H), 1.36 (s, 9H)
438
H NMR (400 MHz, DMSO-d6) δ 12.97 (d, J = 6.6 Hz, 1H,12.08 (s, 1H), 8.90 (d, J = 6.8 Hz, 1H), 8.35-8.34 (m, 1H), 8.03 (s, 1H), 7.85-7.81 (m, 1H), 7.77-7.71 (m, 1H), 7.58-7.44 (m, 2H), 1.46 (s, 9H), 1.42 (s, 9H)
441
1H-NMR (d6-Acetone, 300 MHz) δ 11.90 (br s, 1H), 8.93 (br s, 1H), 8.42 (d, J = 8.1 Hz, 1H), 8.08 (s, 1 H), 7.92 (s, 1H), 7.79 (m, 2H), 7.57 (m, 1H), 7.36 (s, 1H), 3.13 (s, 3H).
444
H NMR (400 MHz, DMSO-d6) δ 12.56 (s, 1H), 12.17 (br d, J = 6 Hz, 1H), 8.89 (d, J = 6 Hz, 1H), 8.42 (dd, J = 9, 2 Hz, 1H), 7.77 (d, J = 2 Hz, 1H), 7.68 (dd, J = 9, 2 Hz, 1H), 7.60 (ddd, J = 9, 9, 2 Hz, 1H), 7.46-7.40 (m, 3H), 3.47 (s, 3H), 1.35 (s, 9H).
448
H NMR (400 MHz, DMSO-d6) δ 12.96 (br s, 1H), 12.42 (s, 1H), 8.88 (s, 1H), 8.33 (dd, J = 8.2, 1.1 Hz, 1H), 7.82 (t, J = 8.3 Hz, 1H), 7.75 (d, J = 7.7 Hz, 1H), 7.66 (d, J = 8.7 Hz, 2H), 7.54 (t, J = 8.1 Hz, 1H), 7.39 (d, J = 8.7 Hz, 2H), 1.29 (s, 9H)
453
H NMR (400 MHz, DMSO-d6) 12.95 (d, J = 6.5 Hz, 1H), 12.38 (s, 1H), 8.86 (d, J = 6.8 Hz, 1H), 8.33 (d, J = 8.1 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.28 (d, J = 2.4 Hz, 1H), 7.15 (d, J = 8.6 Hz, 1H), 6.94 (dd, J = 8.6, 2.4 Hz, 1H)
458
H NMR (400 MHz, DMSO-d6) δ 12.97 (d, J = 7.1 Hz, 1H), 12.39 (s, 1H), 8.88 (d, J = 6.8 Hz, 1H), 8.33 (d, J = 7.9 Hz, 1H), 7.83 (t, J = 7.6 Hz, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.47 (s, 1H), 7.17 (s, 2H), 4.04 (t, J = 5.0 Hz, 2H), 3.82 (t, J = 5.0 Hz, 2H), 1.36 (s, 9H)
Nº de Comp.
Datos de NMR
461
1H-NMR (d6-DMSO, 300 MHz) δ 11.97 (s, 1H), 8.7 (s, 1H), 8.30 (d, J = 7.7 Hz, 1H), 8.07 (d, J = 7.7 Hz, 1H), 7.726 -7.699 (m, 2H), 7.446 -7.357 (m, 6H), 7.236-7.178 (m, 2H). 13C-NMR (d6-DMSO, 75 MHz) d 176.3, 163.7, 144.6, 139.6, 138.9, 136.3, 134.0, 133.4, 131.0, 129.8, 129.2, 128.4, 128.1, 126.4, 126.0, 125.6, 124.7, 123.6, 119.6, 111.2.
463
1H-NMR (DMSO d6, 300 MHz) δ 8.83 (s, 1H), 8.29 (d, J = 7.8 Hz, 1H), 7.78-7.70 (m, 2H), 7.61 (d, J = 7.8 Hz, 2H), 7.51 (t, 1H), 7.17 (d, J = 8.1 Hz, 2H), 2.57 (q, J = 7.5 Hz, 2H), 1.17 (t, J = 7.5 Hz,1H), 0.92 (t, J = 7.8 Hz, 3H).
464
H NMR (400 MHz, DMSO-d6) δ 1.37 (s, 9H), 1.38 (s, 9H), 6.80 (dd, J = 8.1, 0.9 Hz, 1H), 7.15 (m, 3H), 7.66 (t, J = 8.2 Hz, 1H), 8.87 (d, J = 6.9 Hz, 1H), 9.24 (s, 1H), 11.07 (s, 1H), 13.23 (d, J = 6.5 Hz, 1H), 13.65 (s, 1H)
465
H NMR (400 MHz, DMSO-d6) δ 12.94 (d, J = 6.0 Hz, 1H), 12.40 (s, 1H), 8.87 (d, J = 6.8 Hz, 1H), 8.33 (d, J = 8.2 Hz, 1H), 7.84-7.75 (m, 3H), 7.57-7.43 (m, 2H), 7.31 (d, J = 8.6 Hz, 1H), 4.40 (d, J = 5.8 Hz, 2H), 1.44 (s, 9H), 1.38 (s, 9H)
471
1H-NMR (CD3OD, 300 MHz) δ 8.87 (s, 1H), 8.44 (d, J= 8.25, 1H), 8.18 (m, 1H), 7.79 (t, J= 6.88, 1H), 7.67 (d, J= 8.25, 1H), 7.54 (t, J= 7.15, 1H), 7.23 (d, J= 6.05, 1H), 7.16 (d, J= 8.5, 1H), 3.73 (s, 3H), 2.75 (t, J= 6.87, 2H), 1.7 (q, 2H), 1.03 (t, J= 7.42, 3H)
476
H NMR (400 MHz, DMSO-d6) δ 13.00 (d, J = 6.4 Hz, 1H), 12.91 (s, 1H), 10.72 (s, 1H), 8.89 (d, J = 6.8 Hz, 1H), 8.34 (d, J = 8.2 Hz, 1H), 8.16 (s, 1H), 7.85-7.75 (m, 2H), 7.56-7.54 (m, 1H), 7.44 (s, 1H), 1.35 (s, 9H)
478
H NMR (400 MHz, DMSO-d6) δ 1.40 (s, 9H), 6.98 (d, J = 2.4 Hz, 1H), 7.04 (dd, J = 8.6, 1.9 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.66 (d, J = 8.6 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.83 (t, J = 8.3 Hz, 1H), 8.13 (d, J = 1.7 Hz, 1H), 8.35 (d, J = 8.1 Hz, 1H), 8.89 (d, J = 6.7 Hz, 1H), 10.74 (s, 1H), 12.44 (s, 1H), 12.91 (s, 1H)
484
1H NMR (300 MHz, DMSO-d6) δ 12.90 (d, J = 6.3 Hz, 1H), 12.21 (s, 1H), 8.85 (d, J = 6.8 Hz, 1H), 8.31 (d, J = 8.0 Hz, 1H), 7.79 (app dt, J = 12, 8.0 Hz, 1H), 7.72 (d, J = 8.3 Hz, 1H), 7.52 (dd, J = 6.9, 8.1 Hz, 1H), 7.05 (d, J = 8.3 Hz, 1H), 6.94 (s with fine str, 1H), 1H), 6.90 (d with fine str, J = 8.4 Hz, 1H), 2.81 (s, 3H), 1.34 (s, 9H)
485
1H NMR (300 MHz, CDCl3) δ 13.13 (br s, 1H), 12.78 (s, 1H), 8.91 (br s, 1H), 8.42 (br s, 1H), 8.37 (d, J = 8.1 Hz, 1H), 7.72-7.58 (m, 2H), 7.47-7.31 (m, 3H), 3.34 (s, 6H), 1.46 (s, 9H)
B) Ensayos para detectar y medir las propiedades de corrección de F508-CFTR de compuestos
I) Métodos ópticos de potencial de membrana para ensayar las propiedades de modulación de F508-CFTR de compuestos
El ensayo de potencial de membrana óptica utilizó sensores de FRET sensibles al voltaje descritos por Gonzalez y Tsien (véase, Gonzalez, J. E. y R. Y. Tsien (1995) “Voltage sensing by fluorescence resonance energy transfer in single cells” Biophys J 69(4): 1272-80, y Gonzalez, J. E. y R. Y. Tsien (1997) “Improved indicators of cell membrane potential that use fluorescence resonance energy transfer” Chem Biol 4(4): 269-77) en combinación con instrumentación para medir cambios de fluorescencia tales como el lector de la sonda de voltaje/iones (VIPR) (véase, Gonzalez, J. E., K. Oades, y col. (1999) “Cell-based assays and instrumentation for screening ion-channel targets" Drug Discov Today 4(9): 431-439).
Estos ensayos sensibles al voltaje se basan en el cambio en la transferencia de energía por resonancia de fluorescencia (FRET) entre el colorante sensible al voltaje soluble en la membrana, DiSBAC2(3), y un fosfolípido fluorescente, CC2-DMPE, que está unido a la capa externa de la membrana plasmática y actúa de donante de FRET. Cambios en el potencial de la membrana (Vm) hacen que el DiSBAC2(3) negativamente cargado se distribuya a través de la membrana plasmática y, por consiguiente, cambie la cantidad de transferencia de energía de CC2-DMPE. Los cambios en la emisión de fluorescencia se monitorizaron usando VIPR™ II, que es un manipulador de líquidos integrado y detector fluorescente diseñado para realizar los cribados basados en células en placas de microtitulación de 96 ó 384 pocillos.
Identificación de compuestos de corrección
Para identificar moléculas pequeñas que corrigen el defecto del tráfico asociado a F508-CFTR, se desarrolló un formato de ensayo de HTS de una sola adición. Las células se incubaron en medio sin suero durante 16 h a 37 ºC
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Claims (5)

  1. imagen1
    imagen2
    Nº de Comp.
    Nombre
    2
    N-(3-metoxi-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    4
    N-(2-morfolinofenil)-4-oxo-1H-quinolina-3-carboxamida
    5
    N-[4-(2-hidroxi-1,1-dimetil-etil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    6
    N-[3-(hidroximetil)-4-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    8
    N-(3-amino-4-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    9
    4-oxo-N-(3-sulfamoilfenil)-1H-quinolina-3-carboxamida
    11
    4-oxo-N-[2-[2-(trifluorometil)fenil]fenil]-1H-quinolina-3-carboxamida
    12
    N-[2-(4-dimetilaminofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    13
    N-(3-ciano-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    14
    Ester metílico de ácido [5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-terc-butil-fenil]aminofórmico
    16
    4-oxo-N-(2-propilfenil)-1H-quinolina-3-carboxamida
    23
    N-[2-(2-etoxifenil)-5-hidroxi-4-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    24
    4-oxo-N-(3-pirrolidin-1-ilsulfonilfenil)-1H-quinolina-3-carboxamida
    25
    N-[2-(3-acetilaminofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    26
    4-oxo-N-[2-(1-piperidil)fenil]-1H-quinolina-3-carboxamida
    28
    Ester metoxietílico de ácido[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]propil]aminofórmico
    30
    Ester metílico de ácido [2-isopropil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminofórmico
    31
    4-oxo-N-(p-tolil)-1H-quinolina-3-carboxamida
    36
    N-(2-isopropilfenil)-4-oxo-1H-quinolina-3-carboxamida
    38
    N-[2-(1H-indol-2-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
    40
    N-[2-(2-hidroxietil)fenil]-4-oxo-1H-quiriolina-3-carboxamida
    41
    N-(5-amino-2-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    43
    N-[2-(3-etoxifenil)-5-hidroxi-4-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    47
    N-[4-isopropil-2-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    49
    N-[2-(2,6-dimetoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    60
    terc-butil ester de ácido [4-isopropil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminofórmico
    62
    4-oxo-N-[3-(trifluorometoxi)fenil]-1H-quinolina-3-carboxamida
    63
    N-[2-(2,4-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    68
    Ester metílico de ácido3-[2-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]benzoico
    69
    N-(3-amino-4-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    70
    4-oxo-N-[2-(4-piridil)fenil]-1H-quinolina-3-carboxamida
    71
    Ester ispropílico de ácido 3-[2-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]benzoico
    76
    N-[2-(3,4-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    81
    4-oxo-N-(3-propionilaminofenil)-1H-quinolina-3-carboxamida
    83
    N-[2-(3-cianofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    85
    N-[2-(3,4-dichlorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    Nº de comp.
    Nombre
    86
    N-[4-[2-(aminometil)fenil]fenil]-4-oxo-1H-quinolina-3-carboxamida
    87
    4-oxo-N-(3-fenoxifenil)-1H-quinolina-3-carboxamida
    88
    terc-butil ester de ácido [2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]aminofórmico
    90
    4-oxo-N-(2-terc-butilfenil)-1H-quinolina-3-carboxamida
    93
    N-[2-(5-ciano-2-tienil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    94
    N-(5-amino-2-metil-fenil)-4-oxo-1H-quinoilhe-3-carboxamida
    95
    N-(2-cianofenil)-4-oxo-1H-quinolina-3-carboxamida
    97
    N-[2-(2,4-dimetoxipirimidin-5-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
    98
    N-(5-dimetilamino-2-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    99
    4-oxo-N-(4-pentilfenil)-1H-quinolina-3-carboxamida
    100
    N-(1H-indol-4-il)-4-oxo-1H-quinolina-3-carboxamida
    101
    N-(5-amino-2-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    102
    N-[2-[3-(4-clorofenil)-1,2,4-oxadiazol-5-il]fenil]-4-oxo-1H-quinolina-3-carboxamida
    110
    N-[4-(cianometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    111
    4-oxo-N-[2-(trifluorometil)fenil]-1H-quinolina-3-carboxamida
    112
    6-etoxi-4-hidroxi-N-(1H-indol-6-il)quinolina-3-carboxamida
    113
    N-(3-metil-1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
    114
    terc-butil éster de ácido [4-(2-etoxifenil)-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminofórmico
    115
    N-[2-(2-furil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    116
    5-hidroxi-N-(1H-indol-6-il)-4-oxo-1H-quinolina-3-carboxamida
    117
    N-(3-dimetilamino-4-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    118
    N-[2-(1H-indol-6-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
    119
    Ester etílico de ácido[2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]aminofórmico
    123
    N-[2-(3-furil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    126
    N-[3-hidroxi-4-[2-(2-metoxietoxi)-1,1-dimetil-etil]-fenil]-4-oxo-1H-quinolina-3-carboxamida
    127
    Ester etílico de ácido [5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-terc-butil-fenil]aminoformico
    129
    Ester metílico de ácido [2-etil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    134
    N-[2-(4-metilsulfinilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    135
    N-(2-benzo[1,3]dioxol-5-ilfenil)-4-oxo-1H-quinolina-3-carboxamida
    138
    N-[2-(3,5-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    139
    N-[2-(2,4-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    140
    N-(4-ciclohexilfenil)-4-oxo-1H-quinolina-3-carboxamida
    141
    Ester etílico de ácido 2-metil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    142
    4-oxo-N-(2-sec-butilfenil)-1H-quinolina-3-carboxamida
    143
    N-(2-fluoro-5-hidroxi-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    144
    N-(3-hidroxifenil)-4-oxo-1H-quinolina-3-carboxamida
    149
    N-(3-acetilamino-4-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    150
    4-oxo-N-[4-[2,2,2-trifluoro-1-hidroxi-1-(trifluorometil)etil]fenil]-1H-quinolina-3-carboxamida
    Nº de comp.
    Nombre
    156
    4-oxo-N-[2-[2-(trifluorometoxi)fenil]fenil]-1H-quinolina-3-carboxamida
    157
    N-(2-etil-5-metilamino-fenil)-4-oxo-1H-quinolina-3-carboxamida
    160
    N-(3-amino-4-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    161
    N-[3-(2-etoxietoxi)-4-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    163
    N-[5-(aminometil)-2-(2-etoxifenil)-fenil]-4-oxo-1H-quinolina-3-carboxamida
    166
    Ester metílico de ácido 4-[2-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]benzoico
    167
    N-(3-amino-4-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    171
    N-[2-(2,3-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    172
    N-(2-(benzo[b]tiofen-2-il)fenil)-1,4-dihidro-4-oxoquinolina-3-carboxamida
    174
    N-[2-(5-acetil-2-tienilo)fenil]-4-oxo-1H-quinolina-3-carboxamida
    182
    N-[2-(4-fluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    185
    N-(3-morfolinosulfonilfenil)-4-oxo-1H-quinolino-3-carboxamida
    190
    N-[2-(3-cloro-4-fluoro-fenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    194
    N-(4-cianofenil)-4-oxo-1H-quinolina-3-carboxamida
    196
    N-[5-(3,3-dimetilbutanoilamino)-2-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    198
    N-(4-fluorofenil)-4-oxo-1H-quinolina-3-carboxamida
    202
    N-[2-(5-cloro-2-metoxi-fenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    209
    N-[4-(hidroximetil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    213
    N-[2-(2,5-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    214
    N-(3-meltilsulfonilaminofenil)-4-oxo-1H-quinolina-3-carboxamida
    221
    Ester metílico de ácido [5-[(4-oxi-1H-quinolin-3-il)carbonilamino]-2-propil-fenil]aminoformico
    223
    N-[2-(4-metilsulfanilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    224
    4-oxo-N-[4-[2-[(2,2,2-trifluoroacetil)aminometil]fenil]fenil]-1H-quinolina-3-carboxamida
    225
    Ester etílico de ácido [2-isopropil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    226
    4-oxo-N-(4-propilfenil)-1H-quinolina-3-carboxamida
    227
    N-[2-(3H-benzoimidazol-2-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
    228
    N-[2-(hidroxi-fenil-metil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    231
    Ester metílico de ácido 3-[4-hidroxi-2-[(4-oxo-1H-quinolin-3-il)carbonilamino]-5-terc-butilfenil]benzoico
    232
    N-(5-acetilamino-2-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    236
    4-oxo-N-[4-(trifluorometil)fenil]-1H-quinolina-3-carboxamlda
    239
    Ester metílico de ácido[4-isopropil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    242
    N-(5-amino-2,4-dicloro-fenil)-4-oxo-1H-quinolina-3-carboxamida
    243
    N-(5-acetilamino-2-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    247
    4-oxo-N-[2-(2-fenoxifenil)fenil]-1H-quinolina-3-carboxamida
    248
    N-(3-acetilamino-4-metil-fenil)-4-oxo-1H-quinolina-3-carboxamlda
    249
    Ester metílico de ácido [4-etil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    Nº de comp.
    Nombre
    251
    [2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]acido aminoformicoIsobutil ester
    253
    4-oxo-N-[2-[3-(triffluorometoxi)fenil]fenil]-1H-quinolina-3-carboxamida
    260
    N-(5-amino-2-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    263
    N-(4-bromo-2-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    265
    N-(2-benzilfenil)-4-oxo-1H-quinolina-3-carboxamida
    266
    N-[5-hidroxi-4-terc-butil-2-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    268
    4-oxo-N-(3-sulfamoil-4-terc-butil-fenil)-1H-quinolina-3-carboxamida
    269
    Ester etílico de ácido [4-isopropil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    271
    N-(3-amino-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    277
    N-[2-(3-fluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    278
    4-oxo-N-[2-[3-(trifluorometil)fenil]fenil]-1H-quinolina-3-carboxamida
    279
    N-[2-(2-metilsulfanilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    282
    N-(5-amino-2-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    283
    N-[2-(3-metoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    285
    N-[2-(2,3-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    289
    N-(2-fluoro-4-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    291
    N-(2-cloro-5-hidroxi-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    293
    4-oxo-N-[2-(1H-pirrol-1-il)fenil]-1H-quinolina-3-carboxamida
    295
    4-oxo-N-(2-pirrolidin-1-ilfenil)-1H-quinolina-3-carboxamida
    298
    Ester etílico de ácido [2-etil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    302
    N-[2-[4-(hidroximetil)fenil]fenil]-4-oxo-1H-quinolina-3-carboxamida
    304
    terc-butil ester de ácido[4-(2-etoxifenil)-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenilmetil]aminoformico
    305
    N-[2-(4-metoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    306
    N-[2-(3-etoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    307
    N-[2-(3-clorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    308
    N-[2-(cianometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    310
    4-oxo-N-(4-sec-butilfenil)-1H-quinolina-3-carboxamida
    312
    N-[2-(2,4-dimetoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    313
    N-[2-(2-fluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    316
    N-(6-acetilamino-2-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    321
    N-[2-(4-benzoilpiperazin-1-il)fenil]-4-oxo-1H-quinolina-3-carboxamida
    323
    Ester metílico de ácido [2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]aminoformico
    324
    N-(4-butilfenil)-4-oxo-1H-quinolina-3-carboxamida
    326
    N-[2-(4-metilsulfonilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    330
    N-(2-clorofenil)-4-oxo-1H-quinolina-3-carboxamida
    333
    N-[2-[4-(cianometil)fenil]fenil]-4-oxo-1H-quinolina-3-carboxamida
    336
    N-(2-butilfenil)-4-oxo-1H-quinolina-3-carboxamida
    Nº de comp.
    Nombre
    340
    N-(3-metilsulfonilamino-4-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    341
    Neopentil éster de ácido [2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]aminoformico
    344
    N-[2-(2-etoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    348
    N-[2-(4-etoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    353
    terc-butil ester de ácido [3-[(4-oxo-1H-quinolin-3-il)carbonilamino]-4-terc-butil-fenil]aminoformico
    354
    N-[2-[(ciclohexil-metil-amino)metil]fenil]-4-oxo-1H-quinolina-3-carboxamida
    355
    N-[2-(2-metoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    356
    N-(5-metilamino-2-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    361
    N-[2-(2,5-dimetoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    362
    N-(2-cloro-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    363
    N-[2-(2-fluoro-3-metoxi-fenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    366
    4-oxo-N-[2-[4-(trifluorometil)fenil]fenil]-1H-quinolina-3-carboxamida
    367
    N-[2-(3,5-diclorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    382
    Ester etílico de ácido [5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-propil-fenil]aminoformico
    384
    N-[2-(2,5-difluorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    388
    4-oxo-N-[2-[4-(trifluorometoxi)fenil]fenil]-1H-quinolina-3-carboxamida
    390
    N-[3-(aminometil)-4-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    393
    N-[5-amino-2-(2-etoxifenil)-fenil]-4-oxo-1H-quinolina-3-carboxamida
    396
    tetrahidrofuran-3-ilmetil ester de ácido [2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamlno]fenil]-propil] aminoformico
    397
    4-oxo-N-(4-fenilfenil)-1H-quinolina-3-carboxamida
    399
    N-(2-isopropil-5-metilamino-fenil)-4-oxo-1H-quinolina-3-carboxamida
    409
    N-(5-dimetilamino-2-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    410
    4-oxo-N-[2-(4-fenoxifenil)fenil]-1H-quinolina-3-carboxamida
    416
    propil ester de ácido [2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]aminoformico
    417
    N-(2-(benzo[b]tiofen-3-il)fenil)-1,4-dihidro-4-oxoquinolina-3-carboxamida
    418
    N-(3-dimetilaminofenil)-4-oxo-1H-quinolina-3-carboxamida
    419
    N-(3-acetilaminofenil)-4-oxo-1H-quinolina-3-carboxamida
    420
    Ester etílico de ácido 2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propanoico
    421
    N-[5-metoxi-4-terc-butil-2-(trifluorometil)fenil)-4-oxo-1H-quinolina-3-carboxamida
    424
    N-[2-(4-clorofenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    425
    N-(4-isopropilfenil)-4-oxo-1H-quinolina-3-carboxamida
    426
    N-(4-cloro-5-hidroxi-2-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    428
    N-(3-hidroxi-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    431
    N-(3-aminofenil)-4-oxo-1H-quinolina-3-carboxamida
    432
    N-[2-(4-isopropilfenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    436
    N-[2-(3,4-dimetoxifenil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    Nº de comp.
    Nombre
    438
    N-[5-(difluorometil)-2,4-diterc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    442
    4-oxo-N-[3-(1-piperidilsulfonil)fenil]-1H-quinolina-3-carboxamida
    444
    Ester metílico de ácido 5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-terc-butil-benzoico
    447
    N-(3-cianofenil)-4-oxo-1H-quinolina-3-carboxamida
    448
    4-oxo-N-(4-terc-butilfenil)-1H-quinolina-3-carboxamida
    450
    N-[4-(1-hidroxietil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    451
    N-(4-ciano-2-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    453
    N-(3-amino-4-cloro-fenil)-4-oxo-1H-quinolina-3-carboxamida
    457
    N-(4-morfolinofenil)-4-oxo-1H-quinolina-3-carboxamida
    458
    N-[3-(2-hidroxietoxi)-4-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    460
    Butil éster de ácido [2-metil-2-[4-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]-propil]aminoformico
    461
    4-oxo-N-(2-fenilfenil)-1H-quinolina-3-carboxamida
    462
    N-(3-dimetilamino-4-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    463
    N-(4-etilfenil)-4-oxo-1H-quinolina-3-carboxamida
    465
    terc-butil ester de ácido [5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-terc-butil-fenilmetil]aminoformico
    471
    Ester metílico de ácido [3-[(4-oxo-1H-quinolin-3-il)carbonilamino]-4-propil-fenil]aminoformico
    472
    Ester etílico de ácido [4-etil-3-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    476
    N-(2-ciano-5-hidroxi-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    484
    N-(3-metilamino-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    485
    N-(3-dimetilamino-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    o una sal farmacéuticamente aceptable de cualquiera de los anteriormente mencionados.
  2. 13. El compuesto de acuerdo con la reivindicación 10, en el que el compuesto está seleccionado de:
    Nº de comp.
    Nombre
    2
    N-(3-metoxi-4-tert-butil-fenilo)-4-oxo-1H-quinolina-3-carboxamida
    8
    N-(3-amino-4-etil-fenilo)-4-oxo-1H-quinolina-3-carboxamida
    13
    N-(3-ciano-4-tert-butil-fenilo)-4-oxo-1H-quinolina-3-carboxamida
    14
    Ester metílico de ácido [5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-tert-butil-fenilo]aminoformico
    30
    Ester metílico de ácido [2-isopropil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminofórmico
    31
    4-oxo-N-(p-tolil)-1H-quinolina-3-carboxamida
    69
    N-(3-amino-4-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    117
    N-(3-dimetilamino-4-isopropil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    127
    Ester etílico de ácido [5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-terc-butil-fenil]aminoformico
    129
    Ester metílico de ácido [2-etil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    140
    N-(4-ciclohexilfenil)-4-oxo-1H-quinolina-3-carboxamida
    Nº de comp.
    Nombre
    141
    Ester etílico de ácido 2-metil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    149
    N-(3-acetilamino-4-etil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    160
    N-(3-amino-4-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    167
    N-(3-amino-4-metil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    221
    Ester metílico de ácido [5-[(4-oxi-1H-quinolin-3-il)carbonilamino]-2-propil-fenil]aminoformico
    225
    Ester etílico de ácido [2-isopropil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    226
    4-oxo-N-(4-propilfenil)-1H-quinolina-3-carboxamida
    248
    N-(3-acetilamino-4-metil-fenil)-4-oxo-1H-quinolina-3-carboxamlda
    271
    N-(3-amino-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    298
    Ester etílico de ácido [2-etil-5-[(4-oxo-1H-quinolin-3-il)carbonilamino]fenil]aminoformico
    310
    4-oxo-N-(4-sec-butilfenil)-1H-quinolina-3-carboxamida
    324
    N-(4-butilfenil)-4-oxo-1H-quinolina-3-carboxamida
    382
    Ester etílico de ácido [5-[(4-oxo-1H-quinolin-3-il)carbonilamino]-2-propil-fenil]aminoformico
    425
    N-(4-isopropilfenil)-4-oxo-1H-quinolina-3-carboxamida
    428
    N-(3-hidroxi-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    448
    4-oxo-N-(4-terc-butilfenil)-1H-quinolina-3-carboxamida
    462
    N-(3-dimetilamino-4-propil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    463
    N-(4-etilfenil)-4-oxo-1H-quinolina-3-carboxamida
    484
    N-(3-metilamino-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    o una sal farmacéuticamente aceptable de cualquiera de los anteriormente mencionados.
  3. 14. El compuesto de acuerdo con la reivindicación 11, en el que el compuesto es
    Nº de comp.
    Nombre
    23
    N-[2-(2-etoxifenil)-5-hidroxi-4-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    43
    N-[2-(3-etoxifenil)-5-hidroxi-4-terc-butil-fenil]-4-oxo-1H-quinolina-3-carboxamida
    143
    N-(2-fluoro-5-hidroxi-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    266
    N-[5-hidroxi-4-terc-butil-2-(trifluorometil)fenil]-4-oxo-1H-quinolina-3-carboxamida
    291
    N-(2-cloro-5-hidroxi-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    426
    N-(4-cloro-5-hidroxi-2-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    476
    N-(2-ciano-5-hidroxi-4-terc-butil-fenil)-4-oxo-1H-quinolina-3-carboxamida
    o una sal farmacéuticamente aceptable de cualquiera de los anteriormente mencionados.
  4. 15.
    Una composición farmacéutica que comprende un compuesto de acuerdo con cualquiera de las reivindicaciones 1 a 14, o una sal farmacéuticamente aceptable del mismo, y un vehículo o adyuvante farmacéuticamente aceptable.
  5. 16.
    La composición de acuerdo con la reivindicación 15, en la que dicha composición comprende un agente adicional seleccionado de un agente mucolítico, broncodilatador, un antibiótico, un agente anti-infeccioso, un agente antiinflamatorio, un modulador de CFTR, o un agente nutricional.
    imagen3
    imagen4
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