Compuestos farmacéuticamente activos como inhibidores AXL.

Los compuestos que tienen la fórmula general (I)**fórmula**

donde

A representa C-R10, N;

B representa C-R11, N;

D representa uno de los siguientes heterociclos**Fórmula**

R1, R4, R88, R92, R100 se seleccionan de forma mutuamente independiente a partir de -H, -F, -Cl, -Br, -I, -OH, -NH2, - NHR19, -NR19R20, -OCH3, -OC2H5, -OC3H7, -OCH

(CH3)2, -OC(CH3)3, -OC4H9, -NO2, -CHO, -COCH3, - COC2H5, -Ociclo-C3H5, -OCH2-ciclo-C3H5, -O-C2H4-ciclo-C3H5, -OPh, -COC3H7, -COCH(CH3)2, -COC(CH3)3, - COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH(CH3)2, -COOC(CH3)3, -OOC-CH3, -OOC-C2H5, -OOCC3H7, -OOC-CH(CH3)2, -OOC-C(CH3)3, -NHCH3, -NHC2H5, -NHC3H7, -NHCH(CH3)2, -NHC(CH3)3, -N(CH3)2, - N(C2H5)2, -N(C3H7)2, -N[CH(CH3)2]2, -N[C(CH3)3]2, -OCF3, -OC2F5, -CH2F, -CHF2, -CF3, -CH2Cl, -CH2Br, - CH2I, -CH2-CH2F, -CH2-CHF2, -CH2-CF3, -CH2-CH2Cl, -CH2-CH2Br, -CH2-CH2I, ciclo-C3H5, -CH2-ciclo-C3H5, - CH3, -C2H5, -C3H7, -CH(CH3)2, -C4H9, -CH2-CH(CH3)2, -CH(CH3)-C2H5, -C(CH3)3, -C5H11, -CH(CH3)-C3H7, - CH2-CH(CH3)-C2H5, -CH(CH3)-CH(CH3)2, -C(CH3)2-C2H5, -CH2-C(CH3)3, -CH(C2H5)2, -C2H4-CH(CH3)2, - C6H13, -C3H6-CH(CH3)2, -C2H4-CH(CH3)-C2H5, -CH(CH3)-C4H9, -CH2-CH(CH3)-C3H7, -CH(CH3)-CH2- CH(CH3)2, -CH(CH3)-CH(CH3)-C2H5, -CH2-CH(CH3)-CH(CH3)2, -CH2-C(CH3)2-C2H5, -C(CH3)2-C3H7, - C(CH3)2-CH(CH3)2, -C2H4-C(CH3)3, -CH(CH3)-C(CH3)3, -CH≥CH2, -CH2-CH≥CH2, -C(CH3)≥CH2, -CH≥CH-CH3, -C2H4-CH≥CH2, -CH2-CH≥CH-CH3, -CH≥CH-C2H5, -CH2-C(CH3)≥CH2, -CH(CH3)-CH≥CH, -CH≥C(CH3)2, - C(CH3)≥CH-CH3, -CH≥CH-CH≥CH2, -C3H6-CH≥CH2, -C2H4-CH≥CH-CH3, -CH2-CH≥CH-C2H5, -CH≥CH-C3H7, - CH2-CH≥CH-CH≥CH2, -CH≥CH-CH≥CH-CH3, -CH≥CH-CH2-CH≥CH2, -C(CH3)≥CH-CH≥CH2, -CH≥C(CH3)- CH≥CH2, -CH≥CH-C(CH3)≥CH2, -C2H4-C(CH3)≥CH2, -CH2-CH(CH3)-CH≥CH2, -CH(CH3)-CH2-CH≥CH2, -CH2- CH≥C(CH3)2, -CH2-C(CH3)≥CH-CH3, -CH(CH3)-CH≥CH-CH3, -CH≥CH-CH(CH3)2, -CH≥C(CH3)-C2H5, - C(CH3)≥CH-C2H5, -C(CH3)≥C(CH3)2, -C(CH3)2-CH≥CH2, -CH(CH3)-C(CH3)≥CH2, -C(CH3)≥CH-CH≥CH2, - CH≥C(CH3)-CH≥CH2,- CH≥CHC(CH3)≥CH2, -C4H8-CH≥CH2, -C3H6-CH≥CH-CH3, -C2H4-CH≥CH-C2H5, -CH2- CH≥CH-C3H7, -CH≥CH-C4H9, -C3H6-C(CH3)≥CH2, -C2H4-CH(CH3)-CH≥CH2, -CH2-CH(CH3)-CH2-CH≥CH2, - CH(CH3)-C2H4-CH≥CH2, -C2H4-CH≥C(CH3)2, -C2H4-C(CH3)≥CH-CH3, -CH2-CH(CH3)-CH≥CH-CH3, -CH(CH3)- CH2-CH≥CH-CH3, -CH2-CH≥CH-CH(CH3)2, -CH2-CH≥C(CH3)-C2H5, -CH2-C(CH3)≥CH-C2H5, -CH(CH3)- CH≥CH-C2H5, -CH≥CH-CH2-CH(CH3)2, -CH≥CH-CH(CH3)-C2H5, -CH≥C(CH3)-C3H7, -C(CH3)≥CH-C3H7, -CH2- CH(CH3)-C(CH3)≥CH2, -CH(CH3)-CH2-C(CH3)≥CH2, -CH(CH3)-CH(CH3)-CH≥CH2, -CH2-C(CH3)2-CH≥CH2, - C(CH3)2-CH2-CH≥CH2, -CH2-C(CH3)≥C(CH3)2, -CH(CH3)-CH≥C(CH3)2, -C(CH3)2-CH≥CH-CH3, -CH(CH3)- C(CH3)≥CH-CH3, -CH≥C(CH3)-CH(CH3)2, -C(CH3)≥CH-CH(CH3)2, -C(CH3)≥C(CH3)-C2H5, -CH≥CH-C(CH3)3, - C(CH3)2-C(CH3)≥CH2, -CH(C2H5)-C(CH3)≥CH2, -C(CH3)(C2H5)-CH≥CH2, -CH(CH3)-C(C2H5)≥CH2, -CH2- C(C3H7)≥CH2, -CH2-C(C2H5)≥CH-CH3, -CH(C2H5)-CH≥CH-CH3, -C(C4H9)≥CH2, -C(C3H7)≥CH-CH3, - C(C2H5)≥CH-C2H5, -C(C2H5)≥C(CH3)2, -C[C(CH3)3]≥CH2, -C[CH(CH3)(C2H5)]≥CH2, -C[CH2-CH(CH3)2]≥CH2, - C2H4-CH≥CH-CH≥CH2, -CH2-CH≥CHCH2- CH≥CH2, -CH≥CH-C2H4-CH≥CH2, -CH2-CH≥CH-CH≥CH-CH3, - CH≥CH-CH2-CH≥CH-CH3, -CH≥CH CH≥CH-C2H5, -CH2-CH≥CH-C(CH3)≥CH2, -CH2-CH≥C(CH3)-CH≥CH2, - CH2-C(CH3)≥CH-CH≥CH2, -CH(CH3)-CH≥CH-CH≥CH2, -CH≥CH-CH2-C(CH3)≥CH2, -CH≥CH-CH(CH3)-CH≥CH2, -CH≥C(CH3)-CH2-CH≥CH2, -C(CH3)≥CH-CH2-CH≥CH2, -CH≥CH-CH≥C(CH3)2, -CH≥CH-C(CH3)≥CH-CH3, - CH≥C(CH3)-CH≥CH-CH3, -C(CH3)≥CH-CH≥CH-CH3, -CH≥C(CH3)-C(CH3)≥CH2, -C(CH3)≥CH-C(CH3)≥CH2, - C(CH3)≥C(CH3)-CH≥CH2, -CH≥CH-CH≥CH-CH≥CH2, -C≡CH, -C≡C-CH3, -CH2-C≡-CH, -C2H4-C≡CH, -CH2-C≡CCH3, -C≡C-C2H5, -C3H6-C≡CH, -C2H4-C≡C-CH3, -CH2-C≡C-C2H5, -C≡C-C3H7, -CH(CH3)-C≡CH, -CH2- CH(CH3)-C≡CH, -CH(CH3)-CH2-C≡CH, -CH(CH3)-C≡C-CH3, -C4H8-C≡CH, -C3H6-C≡C-CH3, -C2H4-C≡C-C2H5, - CH2-C≡C-C3H7, -C≡C-C4H9, -C2H4-CH(CH3)-C≡CH, -CH2-CH(CH3)-CH2-C≡CH, -CH(CH3)-C2H4-C≡CH, -CH2- CH(CH3)-C≡C-CH3, -CH(CH3)-CH2-C≡C-CH3, -CH(CH3)-C≡C-C2H5, -CH2-C≡CCH(CH3)2, -C≡C-CH(CH3)-C2H5, -C≡C-CH2-CH(CH3)2, -C≡C-C(CH3)3, -CH(C2H5)-C≡C-CH3,- C(CH3)2-C≡CCH3, -CH(C2H5)-CH2-C≡CH, -CH2- CH(C2H5)-C≡CH, -C(CH3)2-CH2-C≡CH, -CH2-C(CH3)2-C≡CH, -CH(CH3)-CH(CH3)-C≡CH, -CH(C3H7)-C≡CH, - C(CH3)(C2H5)-C≡CH, -C≡C-C≡CH, -CH2-C≡C-C≡CH, -C≡CC≡C-CH3, -CH(C≡CH)2, -C2H4-C≡C-C≡CH, -CH2- C≡C-CH2-C≡CH, -C≡C-C2H4-C≡CH, -CH2-C≡C-C≡C-CH3, -C≡C-CH2-C≡C-CH3, -C≡C-C≡C-C2H5, -C≡CCH( CH3)-C≡CH, -CH(CH3)-C≡C-C≡CH, -CH(C≡CH)-CH2-C≡CH, -C(C≡CH)2-CH3, -CH2-CH(C≡CH)2, -CH(C≡CH)- C≡C-CH3;, R21, R35, R36.

Tipo: Patente Internacional (Tratado de Cooperación de Patentes). Resumen de patente/invención. Número de Solicitud: PCT/EP2011/004451.

Solicitante: LEAD DISCOVERY CENTER GMBH.

Nacionalidad solicitante: Alemania.

Dirección: Otto-Hahn-Strasse 15 44227 Dortmund ALEMANIA.

Inventor/es: ULLRICH, AXEL, KLEBL, BERT, WOLF, ALEXANDER, CHOIDAS, AXEL, KOCH, UWE, SCHULTZ-FADEMRECHT,Carsten, EICKHOFF,JAN.

Fecha de Publicación: .

Clasificación Internacional de Patentes:

  • SECCION C — QUIMICA; METALURGIA > QUIMICA ORGANICA > COMPUESTOS HETEROCICLICOS (Compuestos macromoleculares... > Compuestos heterocíclicos que contienen dos o más... > C07D401/14 (que contienen tres o más heterociclos)
  • SECCION A — NECESIDADES CORRIENTES DE LA VIDA > CIENCIAS MEDICAS O VETERINARIAS; HIGIENE > ACTIVIDAD TERAPEUTICA ESPECIFICA DE COMPUESTOS QUIMICOS... > A61P35/00 (Agentes antineoplásicos)
  • SECCION C — QUIMICA; METALURGIA > QUIMICA ORGANICA > COMPUESTOS HETEROCICLICOS (Compuestos macromoleculares... > Compuestos heterocíclicos que contienen dos o más... > C07D401/12 (unidos por una cadena que contiene heteroátomos como enlaces de cadena)
  • SECCION C — QUIMICA; METALURGIA > QUIMICA ORGANICA > COMPUESTOS HETEROCICLICOS (Compuestos macromoleculares... > Compuestos heterocíclicos que contienen dos o más... > C07D417/12 (unidos por una cadena que contiene heteroátomos como enlaces de cadena)
  • SECCION C — QUIMICA; METALURGIA > QUIMICA ORGANICA > COMPUESTOS HETEROCICLICOS (Compuestos macromoleculares... > Compuestos heterocíclicos que contienen dos o más... > C07D413/14 (que contienen tres o más heterociclos)
  • SECCION C — QUIMICA; METALURGIA > QUIMICA ORGANICA > COMPUESTOS HETEROCICLICOS (Compuestos macromoleculares... > Compuestos heterocíclicos que contienen dos o más... > C07D417/14 (que contiene tres o más heterociclos)
  • SECCION A — NECESIDADES CORRIENTES DE LA VIDA > CIENCIAS MEDICAS O VETERINARIAS; HIGIENE > PREPARACIONES DE USO MEDICO, DENTAL O PARA EL ASEO... > Preparaciones medicinales que contienen ingredientes... > A61K31/4709 (Quinoleínas no condensadas conteniendo otros heterociclos)
  • SECCION C — QUIMICA; METALURGIA > QUIMICA ORGANICA > COMPUESTOS HETEROCICLICOS (Compuestos macromoleculares... > Compuestos heterocíclicos que contienen dos o más... > C07D413/12 (unidos por una cadena que contiene heteroátomos como enlaces de cadena)

PDF original: ES-2530492_T3.pdf

 

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Fragmento de la descripción:

El presente invento trata de compuestos nuevos que son inhibidores del receptor Axl de la subfamilia tirosina quinasa que incluye Axl, Mer y Tyro3. Estos compuestos son adecuados para el tratamiento o prevención de trastornos asociados a, en combinación con o causados por la hiperfunción de un receptor de la familia Axl. Los compuestos son adecuados para el tratamiento de trastornos hiperproliferativos, como el cáncer, en especial cáncer metastásico.

Los receptores tirosina quinasa (RTKs) son receptores de la superficie celular que emiten señales a partir del entorno extracelular para controlar el crecimiento, la diferenciación y la supervivencia de las células. La falta de regulación en la expresión de proteínas quinasas por medio de la eliminación de genes, se ha averiguado que la – mutación o –amplificación es importante para el inicio y –evolución de los tumores, como la proliferación, supervivencia, -motilidad e –invasividad de las células cancerígenas, así como la angiogénesis tumoral y la resistencia a la quimioterapia. Debido a lo avanzado de los conocimientos sobre la relevancia de su papel, las proteínas quinasas son un objetivo importante para las nuevas terapias, especialmente para el cáncer (Hananhan et al., 2000; Blume-Jensen et al., 2001) .

Axl es miembro de la familia TAM (Tyro-Axl-Mer) de los receptores de tirosina quinasas. Esta familia se caracteriza por un dominio extracelular, que consiste en dos dominios similares a la inmunoglobulina seguidos de dos dominios de fibronectina similares al tipo 3. La activación de la subfamilia Axl RTK se da por el ligando de la proteína afín, con una detención del crecimiento específico 6 (Gas6) . La afinidad de Gas6 es mayor para Axl, seguida de Tyro3 y por último Mer, y por lo tanto activa las tres proteínas a grados variables. Gas6 pertenece a la familia dependiente de la vitamina K y muestra una secuencia de identidad del 43 % y la misma organización de dominio que la proteína S, una proteína en suero (Hafizi et al., 2006) .

Axl se expresa de forma ubicua a niveles bajos y es detectable en varios órganos. El modelo de expresión de los otros dos miembros de la misma familia es diferente del de Axl. La expresión de Tyro3 se da fundamentalmente en el cerebro y el SNC (sistema nervioso central) , mientras que la expresión de Mer se da casi exclusivamente en el linaje de células monocito (Rescigno et al. 1991, Mark et al., 1994, Graham et al., 1994) .

Las RTKs de la familia TAM regulan una gran variedad de respuestas celulares, incluida la supervivencia, proliferación, migración y adhesión celular (Hafizi et al., 2006) . Se ha demostrado que la señalización de receptores TAM regula la homeostasis vascular de músculo liso (Korshunov et al., 2007) , la función plaquetaria, estabilización de trombos (Angelillo-Scherrer et al., 2001; Gould et al., 2005) , y eritropoyesis (Angelillo-Scherrer et al., 2008) . Además, los receptores TAM están implicados en el control de la supervivencia de células oligodendrogliales (Shankar et al., 2006) y la regulación de la función de los osteoclastos (Katagiri et al., 2001) . Los receptores TAM juegan un papel principal en la inmunidad innata (Lemke et al., 2008) y en la inflamación (Sharif et al., 2006; Rothlin et al., 2007) . La familia de los TAM promueve la fagocitosis de las células apoptóticas (Prasas et al., 2006) y estimula la diferenciación de las células asesinas naturales (Park et al., 2009; Caraux et al., 2006) . La activación de Axl está unida a muchas vías de transducción de señal, incluidas las Akt, quinasas MAP, NF-_B, vías de transducción de señal STAT y otras (Hafizi et al., 2006) .

Se observa un alto nivel de expresión de Axl en muchos tumores humanos (Berclaz et al., 2001; Craven et al., 1995; Shieh et al., 2005; Sun et al., 2004; Green et al., 2006; Ito et al., 1999) y se asocia con las fases y progresión de tumores de pacientes de cáncer (Gjerdrum et al., 2010; Sawabu et al., 2007; Green et al., 2006; Shieh et al., 2005; Sun et al., 2003) .

Es objeto del presente invento proporcionar compuestos y/o sales aceptadas en farmacia que pueden usarse como agentes farmacológicos activos, especialmente para el tratamiento de enfermedades proliferativas de las células como el cáncer, así como compuestos que comprendan como mínimo uno de estos compuestos y/o sales aceptadas en farmacia como ingredientes farmacológicos activos.

Los compuestos del presente invento son inhibidores eficaces de los elementos RTK de la familia TAM y, por lo tanto, son adecuados para el tratamiento de trastornos asociados con, asociados a y/o causados por la hiperfunción de los elementos RTK de la familia TAM, y por lo tanto tienen efecto sobre la supervivencia, proliferación, autofagia, homeostasis vascular de musculo liso, migración, adhesión, angiogénesis, agregación plaquetaria, estabilización de trombos, eritropoyesis, supervivencia de las células oligodendrogliales, función osteoclástica, inmunidad innata, inflamación, fagocitosis de células apoptóticas y/o la diferenciación de células asesinas naturales.

El invento proporciona inhibidores eficaces para la quinasa de receptor Axl que son adecuados para el tratamiento de trastornos hiperproliferativos asociados con, en combinación con y/o causados por la hiperfunción de Axl, especialmente los trastornos de receptores Axl de tirosina quinasa inducida. Los compuestos del invento pueden inhibir la proliferación celular y, por lo tanto, son adecuados para el tratamiento y/o prevención de trastornos

hiperproliferativos de receptores Axl receptor de la tirosina quinasa, especialmente en el grupo que incluye el cáncer y las metástasis tumorales primarias. En una de las mejores representaciones del invento, los trastornos de receptores Axl inducidos por tirosina quinasa se asocian con una sobre-expresión y/o hiperactividad de los receptores de Axl de receptores de tirosina quinasa, por ejemplo, el aumento de la autofosforilación en comparación con los tejidos normales. Los trastornos pueden ser cáncer de mama, de colon, de próstata, de pulmón, gástrico, de ovario, de endometrio, renal, hepatocelular, de tiroides, uterino, de esófago, de células escamosas, leucemia, osteosarcoma, melanoma, glioblastoma y neuroblastoma. En una de las mejores representaciones, los trastornos están entre cáncer de mama, glioblastoma, cáncer renal, cáncer de pulmón de células no microlíticas (NSCLC) , y melanoma. Los compuestos también son adecuados para la prevención y/o tratamiento de otros trastornos hiperproliferativos, especialmente en trastornos hiperproliferativos benignos como hiperplasia benigna de próstata.

Entre los ejemplos de trastornos asociados con, en combinación con y/o provocados por la hiperfunción de Hiperfunción de Axl se encuentran: leucemia linfoblástica aguda, leucemia mieloide aguda, carcinoma adrenocortical, cánceres relacionados con el sida, linfoma relacionado con el sida, cáncer anal, cáncer de apéndice, astrocitomas, tumor teratoideo/rabdoide atípico, carcinoma de células basales, cáncer de conducto biliar, de vejiga, de huesos, osteosarcoma e histiocitoma fibroso maligno, glioma de tronco encefálico, tumor cerebral, tumor atípico teratoide/rabdoide del sistema nervioso central, astrocitomas, craneofaringioma, ependimoblastoma, ependimoma, meduloblastoma, meduloepitelioma, tumores parenquimales pineales de diferenciación intermedia, tumores y pineoblastoma primitivos supratentoriales, tumores cerebrales y de la médula espinal, cáncer de mama, tumores bronquiales, linfoma de Burkitt, tumor carcinoide, cáncer gastrointestinal, linfoma del sistema nervioso central (SNC) , cáncer cervical, cordoma, leucemia linfocítica crónica, leucemia mielógena crónica, trastornos mieloproliferativos... [Seguir leyendo]

 


Reivindicaciones:

1. Los compuestos que tienen la fórmula general (I)

donde

A representa C-R10, N; B representa C-R11, N; 10 D representa uno de los siguientes heterociclos R1, R4, R88, R92, R100 se seleccionan de forma mutuamente independiente a partir de -H, -F, -Cl, -Br, -I, -OH, -NH2, -NHR19, -NR19R20, -OCH3, -OC2H5, -OC3H7, -OCH (CH3) 2, -OC (CH3) 3, -OC4H9, -NO2, -CHO, -COCH3, 20 COC2H5, -Ociclo-C3H5, -OCH2-ciclo-C3H5, -O-C2H4-ciclo-C3H5, -OPh, -COC3H7, -COCH (CH3) 2, -COC (CH3) 3, -COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH (CH3) 2, -COOC (CH3) 3, -OOC-CH3, -OOC-C2H5, -OOC-C3H7, -OOC-CH (CH3) 2, -OOC-C (CH3) 3, -NHCH3, -NHC2H5, -NHC3H7, -NHCH (CH3) 2, -NHC (CH3) 3, -N (CH3) 2, N (C2H5) 2, -N (C3H7) 2, -N[CH (CH3) 2]2, -N[C (CH3) 3]2, -OCF3, -OC2F5, -CH2F, -CHF2, -CF3, -CH2Cl, -CH2Br, -CH2I, -CH2-CH2F, -CH2-CHF2, -CH2-CF3, -CH2-CH2Cl, -CH2-CH2Br, -CH2-CH2I, ciclo-C3H5, -CH2-ciclo-C3H5,

CH3, -C2H5, -C3H7, -CH (CH3) 2, -C4H9, -CH2-CH (CH3) 2, -CH (CH3) -C2H5, -C (CH3) 3, -C5H11, -CH (CH3) -C3H7, CH2-CH (CH3) -C2H5, -CH (CH3) -CH (CH3) 2, -C (CH3) 2-C2H5, -CH2-C (CH3) 3, -CH (C2H5) 2, -C2H4-CH (CH3) 2, -C6H13, -C3H6-CH (CH3) 2, -C2H4-CH (CH3) -C2H5, -CH (CH3) -C4H9, -CH2-CH (CH3) -C3H7, -CH (CH3) -CH2CH (CH3) 2, -CH (CH3) -CH (CH3) -C2H5, -CH2-CH (CH3) -CH (CH3) 2, -CH2-C (CH3) 2-C2H5, -C (CH3) 2-C3H7, C (CH3) 2-CH (CH3) 2, -C2H4-C (CH3) 3, -CH (CH3) -C (CH3) 3, -CH=CH2, -CH2-CH=CH2, -C (CH3) =CH2, -CH=CH-CH3, -C2H4-CH=CH2, -CH2-CH=CH-CH3, -CH=CH-C2H5, -CH2-C (CH3) =CH2, -CH (CH3) -CH=CH, -CH=C (CH3) 2, C (CH3) =CH-CH3, -CH=CH-CH=CH2, -C3H6-CH=CH2, -C2H4-CH=CH-CH3, -CH2-CH=CH-C2H5, -CH=CH-C3H7, -CH2-CH=CH-CH=CH2, -CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH2, -C (CH3) =CH-CH=CH2, -CH=C (CH3) -CH=CH2, -CH=CH-C (CH3) =CH2, -C2H4-C (CH3) =CH2, -CH2-CH (CH3) -CH=CH2, -CH (CH3) -CH2-CH=CH2, -CH2CH=C (CH3) 2, -CH2-C (CH3) =CH-CH3, -CH (CH3) -CH=CH-CH3, -CH=CH-CH (CH3) 2, -CH=C (CH3) -C2H5, C (CH3) =CH-C2H5, -C (CH3) =C (CH3) 2, -C (CH3) 2-CH=CH2, -CH (CH3) -C (CH3) =CH2, -C (CH3) =CH-CH=CH2, -CH=C (CH3) -CH=CH2, -CH=CHC (CH3) =CH2, -C4H8-CH=CH2, -C3H6-CH=CH-CH3, -C2H4-CH=CH-C2H5, -CH2-CH=CH-C3H7, -CH=CH-C4H9, -C3H6-C (CH3) =CH2, -C2H4-CH (CH3) -CH=CH2, -CH2-CH (CH3) -CH2-CH=CH2, -CH (CH3) -C2H4-CH=CH2, -C2H4-CH=C (CH3) 2, -C2H4-C (CH3) =CH-CH3, -CH2-CH (CH3) -CH=CH-CH3, -CH (CH3) -CH2-CH=CH-CH3, -CH2-CH=CH-CH (CH3) 2, -CH2-CH=C (CH3) -C2H5, -CH2-C (CH3) =CH-C2H5, -CH (CH3) -CH=CH-C2H5, -CH=CH-CH2-CH (CH3) 2, -CH=CH-CH (CH3) -C2H5, -CH=C (CH3) -C3H7, -C (CH3) =CH-C3H7, -CH2-CH (CH3) -C (CH3) =CH2, -CH (CH3) -CH2-C (CH3) =CH2, -CH (CH3) -CH (CH3) -CH=CH2, -CH2-C (CH3) 2-CH=CH2, C (CH3) 2-CH2-CH=CH2, -CH2-C (CH3) =C (CH3) 2, -CH (CH3) -CH=C (CH3) 2, -C (CH3) 2-CH=CH-CH3, -CH (CH3) C (CH3) =CH-CH3, -CH=C (CH3) -CH (CH3) 2, -C (CH3) =CH-CH (CH3) 2, -C (CH3) =C (CH3) -C2H5, -CH=CH-C (CH3) 3, C (CH3) 2-C (CH3) =CH2, -CH (C2H5) -C (CH3) =CH2, -C (CH3) (C2H5) -CH=CH2, -CH (CH3) -C (C2H5) =CH2, -CH2C (C3H7) =CH2, -CH2-C (C2H5) =CH-CH3, -CH (C2H5) -CH=CH-CH3, -C (C4H9) =CH2, -C (C3H7) =CH-CH3, C (C2H5) =CH-C2H5, -C (C2H5) =C (CH3) 2, -C[C (CH3) 3]=CH2, -C[CH (CH3) (C2H5) ]=CH2, -C[CH2-CH (CH3) 2]=CH2, C2H4-CH=CH-CH=CH2, -CH2-CH=CHCH2-CH=CH2, -CH=CH-C2H4-CH=CH2, -CH2-CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH-CH3, -CH=CH CH=CH-C2H5, -CH2-CH=CH-C (CH3) =CH2, -CH2-CH=C (CH3) -CH=CH2, -CH2-C (CH3) =CH-CH=CH2, -CH (CH3) -CH=CH-CH=CH2, -CH=CH-CH2-C (CH3) =CH2, -CH=CH-CH (CH3) -CH=CH2, -CH=C (CH3) -CH2-CH=CH2, -C (CH3) =CH-CH2-CH=CH2, -CH=CH-CH=C (CH3) 2, -CH=CH-C (CH3) =CH-CH3, -CH=C (CH3) -CH=CH-CH3, -C (CH3) =CH-CH=CH-CH3, -CH=C (CH3) -C (CH3) =CH2, -C (CH3) =CH-C (CH3) =CH2, C (CH3) =C (CH3) -CH=CH2, -CH=CH-CH=CH-CH=CH2, -C≡CH, -C≡C-CH3, -CH2-C≡-CH, -C2H4-C≡CH, -CH2-C≡C-CH3, -C≡C-C2H5, -C3H6-C≡CH, -C2H4-C≡C-CH3, -CH2-C≡C-C2H5, -C≡C-C3H7, -CH (CH3) -C≡CH, -CH2-CH (CH3) -C≡CH, -CH (CH3) -CH2-C≡CH, -CH (CH3) -C≡C-CH3, -C4H8-C≡CH, -C3H6-C≡C-CH3, -C2H4-C≡C-C2H5, CH2-C≡C-C3H7, -C≡C-C4H9, -C2H4-CH (CH3) -C≡CH, -CH2-CH (CH3) -CH2-C≡CH, -CH (CH3) -C2H4-C≡CH, -CH2-CH (CH3) -C≡C-CH3, -CH (CH3) -CH2-C≡C-CH3, -CH (CH3) -C≡C-C2H5, -CH2-C≡CCH (CH3) 2, -C≡C-CH (CH3) -C2H5, -C≡C-CH2-CH (CH3) 2, -C≡C-C (CH3) 3, -CH (C2H5) -C≡C-CH3, -C (CH3) 2-C≡CCH3, -CH (C2H5) -CH2-C≡CH, -CH2-CH (C2H5) -C≡CH, -C (CH3) 2-CH2-C≡CH, -CH2-C (CH3) 2-C≡CH, -CH (CH3) -CH (CH3) -C≡CH, -CH (C3H7) -C≡CH, -C (CH3) (C2H5) -C≡CH, -C≡C-C≡CH, -CH2-C≡C-C≡CH, -C≡CC≡C-CH3, -CH (C≡CH) 2, -C2H4-C≡C-C≡CH, -CH2-C≡C-CH2-C≡CH, -C≡C-C2H4-C≡CH, -CH2-C≡C-C≡C-CH3, -C≡C-CH2-C≡C-CH3, -C≡C-C≡C-C2H5, -C≡C-CH (CH3) -C≡CH, -CH (CH3) -C≡C-C≡CH, -CH (C≡CH) -CH2-C≡CH, -C (C≡CH) 2-CH3, -CH2-CH (C≡CH) 2, -CH (C≡CH) C≡C-CH3;, R21, R35, R36; R2 y R3 se seleccionan de forma mutuamente independiente a partir de -R88, -R37, -R38, -R54, -O-R54, -R55, -O-R55 , -R56, -OR56, -R57, -O-R57, donde los grupos C1-6alquil, C2-6alquenil, C2-6alquinil o C1-6alcoxi representados por R88 se mono o polisustituyen opcionalmente por -OH, -F, -Cl, -Br, -I, -O-R71, R72, -R138, -COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH (CH3) 2, -COOC (CH3) 3, - (C=O) -NR16R17, -SO2-NR16R17, -SOm-R16R17, -CR16R17H, -NR16R17;

o R2 y/o R3 se seleccionan de forma mutuamente independiente a partir de -O-R18 , -O-CR73R74-R18 , -OCR73R74 -CR75R76-R18

, -O-CR73R74-CR75R76-CR77R78-R18 , -O-CR73R74-CR75R76-CR77R78-CR79R80-R18 , -O-CR73R74-CR75R76 -CR77R78-CR79R80-CR81R82-R18, -OCR73R74-CR75-R76-CR77-R78-CR79R80-CR81R82-CR83R84-R18 , R73 -R84 de forma mutuamente independiente representan -H, -OH, -F, -Cl, -Br, -I, -R85; R18 representa -H, -OH, -F, -Cl, -Br, -I, -O-R86, -R87, -COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH (CH3) 2, -COOC (CH3) 3, - (C=O) -NR16R17, -SO2-NR16R17, -SOm-R16R17, -CR16R17H, -NR16R17; m = 0, 1, 2; R5 y R6, que podrían ser iguales o diferentes, representan -H; -OH, -F, -Cl, -Br, -I, -CN, -NO2, -CH3, -C2H5, -C3H7, -CH (CH3) 2, -C4H9, CH2-CH (CH3) 2, ciclo-C3H5, -CH2-ciclo-C3H5, -CH (CH3) -C2H5, -C (CH3) 3, -C5H11, -CH (CH3) -C3H7, -CH2-CH (CH3) -C2H5, -CH (CH3) -CH (CH3) 2, -C (CH3) 2-C2H5, -CH2-C (CH3) 3, -CH (C2H5) 2, -C2H4-CH (CH3) 2, -C6H13, -C3H6-CH (CH3) 2, -C2H4-CH (CH3) -C2H5, -CH (CH3) -C4H9, -CH2-CH (CH3) -C3H7, -CH (CH3) -CH2-CH (CH3) 2. -CH (CH3) -CH (CH3) -C2H5, -CH2-CH (CH3) -CH (CH3) 2, -CH2-C (CH3) 2-C2H5, -C (CH3) 2-C3H7, -C (CH3) 2-CH (CH3) 2, -C2H4-C (CH3) 3, -CH (CH3) -C (CH3) 3, -CH=CH2, -CH2-CH=CH2, -C (CH3) =CH2, -CH=CH-CH3, -C2H4-CH=CH2, -CH2-CH=CH-CH3, -CH=CH-C2H5, -CH2-C (CH3) =CH2, -CH (CH3) -CH=CH, -CH=C (CH3) 2, -C (CH3) =CH-CH3, -CH=CH-CH=CH2, -C3H6-CH=CH2, -C2H4-CH=CH-CH3, -CH2-CH=CH-C2H5, -CH=CH-C3H7, -CH2-CH=CH-CH=CH2, -CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH2, -C (CH3) =CH-CH=CH2, -CH=C (CH3) -CH=CH2, -CH=CHC (CH3) =CH2, -C2H4-C (CH3) =CH2, -CH2-CH (CH3) -CH=CH2, -CH (CH3) -CH2-CH=CH2, -CH2-CH=C (CH3) 2, -CH2C (CH3) =CH-CH3, -CH (CH3) -CH=CH-CH3, -CH=CH-CH (CH3) 2, -CH=C (CH3) -C2H5, -C (CH3) =CH-C2H5, C (CH3) =C (CH3) 2, -C (CH3) 2-CH=CH2, -CH (CH3) -C (CH3) =CH2, -C (CH3) =CH-CH=CH2, -CH=C (CH3) -CH=CH2, -CH=CHC (CH3) =CH2, -C4H8-CH=CH2, -C3H6-CH=CH-CH3, -C2H4-CH=CH-C2H5, -CH2-CH=CH-C3H7, -CH=CH-C4H9, -C3H6-C (CH3) =CH2, -C2H4-CH (CH3) -CH=CH2, -CH2-CH (CH3) -CH2-CH=CH2, -CH (CH3) -C2H4-CH=CH2, -C2H4-CH=C (CH3) 2, -C2H4-C (CH3) =CH-CH3, -CH2-CH (CH3) -CH=CH-CH3, -CH (CH3) -CH2-CH=CH-CH3, -CH2CH=CH-CH (CH3) 2, -CH2-CH=C (CH3) -C2H5, -CH2-C (CH3) =CH-C2H5, -CH (CH3) -CH=CH-C2H5, -CH=CH-CH2CH (CH3) 2, -CH=CH-CH (CH3) -C2H5, -CH=C (CH3) -C3H7, -C (CH3) =CH-C3H7, -CH2-CH (CH3) -C (CH3) =CH2, -CH (CH3) -CH2-C (CH3) =CH2, -CH (CH3) -CH (CH3) -CH=CH2, -CH2-C (CH3) 2-CH=CH2, -C (CH3) 2-CH2-CH=CH2, CH2-C (CH3) =C (CH3) 2, -CH (CH3) -CH=C (CH3) 2, -C (CH3) 2-CH=CH-CH3, -CH (CH3) -C (CH3) =CH-CH3, CH=C (CH3) -CH (CH3) 2, -C (CH3) =CH-CH (CH3) 2, -C (CH3) =C (CH3) -C2H5, -CH=CH-C (CH3) 3, -C (CH3) 2C (CH3) =CH2, -CH (C2H5) -C (CH3) =CH2, -C (CH3) (C2H5) -CH=CH2, -CH (CH3) -C (C2H5) =CH2, -CH2-C (C3H7) =CH2, -CH2-C (C2H5) =CH-CH3, -CH (C2H5) -CH=CH-CH3, -C (C4H9) =CH2, -C (C3H7) =CH-CH3, -C (C2H5) =CH-C2H5, C (C2H5) =C (CH3) 2, -C[C (CH3) 3]=CH2, -C[CH (CH3) (C2H5) ]=CH2, -C[CH2-CH (CH3) 2]=CH2, -C2H4-CH=CH-CH=CH2, -CH2-CH=CHCH2-CH=CH2, -CH=CH-C2H4-CH=CH2, -CH2-CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH-CH3, -CH=CHCH=CH-C2H5, -CH2-CH=CH-C (CH3) =CH2, -CH2-CH=C (CH3) -CH=CH2, -CH2-C (CH3) =CH-CH=CH2, -CH (CH3) -CH=CH-CH=CH2, -CH=CH-CH2-C (CH3) =CH2, -CH=CH-CH (CH3) -CH=CH2, -CH=C (CH3) -CH2-CH=CH2, -C (CH3) =CH-CH2-CH=CH2, -CH=CH-CH=C (CH3) 2, -CH=CH-C (CH3) =CH-CH3, -CH=C (CH3) -CH=CH-CH3, -C (CH3) =CH-CH=CH-CH3, -CH=C (CH3) -C (CH3) =CH2, -C (CH3) =CH-C (CH3) =CH2, C (CH3) =C (CH3) -CH=CH2, -CH=CH-CH=CH-CH=CH2, -C≡CH, -C≡C-CH3, -CH2-C=CH, -C2H4-C=CH, -CH2-C≡C-CH3, -C≡C-C2H5, -C3H6-C≡CH, -C2H4-C≡C-CH3, -CH2-C≡C-C2H5, -C≡C-C3H7, -CH (CH3) -C≡CH, -CH2-CH (CH3) -C≡CH, -CH (CH3) -CH2-C≡CH, -CH (CH3) -C≡C-CH3, -C4H8-C≡CH, -C3H6-C≡C-CH3, -C2H4-C≡C-C2H5, CH2-C≡C-C3H7, -C≡C-C4H9, -C2H4-CH (CH3) -C≡CH, -CH2-CH (CH3) -CH2-C≡CH, -CH (CH3) -C2H4-C≡CH, -CH2-CH (CH3) -C≡C-CH3, -CH (CH3) -CH2-C≡C-CH3, -CH (CH3) -C≡C-C2H5, -CH2-C≡CCH (CH3) 2, -C≡C-CH (CH3) -C2H5, -C≡C-CH2-CH (CH3) 2, -C≡C-C (CH3) 3, -CH (C2H5) -C≡C-CH3, -C (CH3) 2-C≡CCH3, -CH (C2H5) -CH2-C≡CH, -CH2-CH (C2H5) -C≡CH, -C (CH3) 2-CH2-C≡CH, -CH2-C (CH3) 2-C≡CH, -CH (CH3) -CH (CH3) -C≡CH, -CH (C3H7) -C≡CH, -C (CH3) (C2H5) -C≡CH, -C≡C-C≡CH, -CH2-C≡C-C≡CH, -C≡CC≡C-CH3, -CH (C≡CH) 2, -C2H4-C≡C-C≡CH, -CH2-C≡C-CH2-C≡CH, -C≡C-C2H4-C≡CH, -CH2-C≡C-C≡C-CH3, -C≡C-CH2-C≡C-CH3, -C≡C-C≡C-C2H5, -C≡C-CH (CH3) -C≡CH, -CH (CH3) -C≡C-C≡CH, -CH (C≡CH) -CH2-C≡CH, -C (C≡CH) 2-CH3, -CH2-CH (C≡CH) 2, -CH (C≡CH) C≡C-CH3, -O-R89; R7, R8, R10 y R11, que podrían ser iguales o diferentes, representan -H, -F, -Cl, -Br, -I, -CN, -NO2, -CH3, -C2H5, -C3H7, -CH (CH3) 2, cydo-C3H5, -CH2-ciclo-C3H5, -C4H9, -CH2-CH (CH3) 2, -CH (CH3) -C2H5, -C (CH3) 3, -C5H11, -CH (CH3) -C3H7, -CH2-CH (CH3) -C2H5, -CH (CH3) -CH (CH3) 2, -C (CH3) 2-C2H5, -CH2-C (CH3) 3, -CH (C2H5) 2, -C2H4-CH (CH3) 2, -C6H13, -C3H6-CH (CH3) 2, -C2H4-CH (CH3) -C2H5, -CH (CH3) -C4H9, -CH2-CH (CH3) -C3H7, CH (CH3) -CH2-CH (CH3) 2, -CH (CH3) -CH (CH3) -C2H5, -CH27-CH (CH3) -CH (CH3) 2, -CH2-C (CH3) 2-C2H5, -C (CH3) 2-C3H7, -C (CH3) 2-CH (CH3) 2, -C2H4-C (CH3) 3, -CH (CH3) -C (CH3) 3, -CH=CH2, -CH2-CH=CH2, -C (CH3) =CH2, -CH=CH-CH3, -C2H4-CH=CH2, -CH2-CH=CH-CH3, -CH=CH-C2H5, -CH2-C (CH3) =CH2, -CH (CH3) -CH=CH, CH=C (CH3) 2, -C (CH3) =CH-CH3, -CH=CH-CH=CH2, -C3H6-CH=CH2, -C2H4-CH=CH-CH3, -CH2-CH=CH-C2H5, -CH=CH-C3H7, -CH2-CH=CH-CH=CH2, -CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH2, -C (CH3) =CH-CH=CH2, -CH=C (CH3) -CH=CH2, -CH=CH-C (CH3) =CH2, -C2H4-C (CH3) =CH2, -CH2-CH (CH3) -CH=CH2, -CH (CH3) -CH2-CH=CH2, -CH2-CH=C (CH3) 2, -CH2-C (CH3) =CH-CH3, -CH (CH3) -CH=CH-CH3, -CH=CH-CH (CH3) 2, -CH=C (CH3) -C2H5, -C (CH3) =CH-C2H5, -C (CH3) =C (CH3) 2, -C (CH3) 2-CH=CH2, -CH (CH3) -C (CH3) =CH2, -C (CH3) =CH-CH=CH2, -CH=C (CH3) -CH=CH2, -CH=CHC (CH3) =CH2, -C4H8-CH=CH2, -C3H6-CH=CH-CH3, -C2H4-CH=CH-C2H5, -CH2-CH=CH-C3H7, -CH=CH-C4H9, -C3H6-C (CH3) =CH2, -C2H4-CH (CH3) -CH=CH2, -CH2-CH (CH3) -CH2-CH=CH2, -CH (CH3) -C2H4-CH=CH2, -C2H4-CH=C (CH3) 2, -C2H4-C (CH3) =CH-CH3, -CH2-CH (CH3) -CH=CH-CH3, -CH (CH3) -CH2-CH=CH-CH3, -CH2-CH=CH-CH (CH3) 2, -CH2-CH=C (CH3) -C2H5, -CH2-C (CH3) =CH-C2H5, -CH (CH3) -CH=CH-C2H5, -CH=CH-CH2-CH (CH3) 2, -CH=CH-CH (CH3) -C2H5, -CH=C (CH3) -C3H7, -C (CH3) =CH-C3H7, -CH2-CH (CH3) -C (CH3) =CH2, -CH (CH3) -CH2-C (CH3) =CH2, -CH (CH3) -CH (CH3) -CH=CH2, -CH2-C (CH3) 2-CH=CH2, -C (CH3) 2-CH2-CH=CH2, -CH2-C (CH3) =C (CH3) 2, -CH (CH3) -CH=C (CH3) 2, -C (CH3) 2-CH=CH-CH3, -CH (CH3) -C (CH3) =CH-CH3, -CH=C (CH3) -CH (CH3) 2, -C (CH3) =CH-CH (CH3) 2, -C (CH3) =C (CH3) -C2H5, -CH=CHC (CH3) 3, -C (CH3) 2-C (CH3) =CH2, -CH (C2H5) -C (CH3) =CH2, -C (CH3) (C2H5) -CH=CH2, -CH (CH3) -C (C2H5) =CH2, -CH2-C (C3H7) =CH2, -CH2-C (C2H5) =CH-CH3, -CH (C2H5) -CH=CH-CH3, -C (C4H9) =CH2, -C (C3H7) =CH-CH3, C (C2H5) =CH-C2H5, -C (C2H5) =C (CH3) 2, -C[C (CH3) 3]=CH2, -C[CH (CH3) (C2H5) ]=CH2, -C[CH2-CH (CH3) 2]=CH2, C2H4-CH=CH-CH=CH2, -CH2-CH=CHCH2-CH=CH2, -CH=CH-C2H4-CH=CH2, -CH2-CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH-CH3, -CH=CHCH=CH-C2H5, -CH2-CH=CH-C (CH3) =CH2, -CH2-CH=C (CH3) -CH=CH2, -CH2C (CH3) =CH-CH=CH2, -CH (CH3) -CH=CH-CH=CH2, -CH=CH-CH2-C (CH3) =CH2, -CH=CH-CH (CH3) -CH=CH2, -CH=C (CH3) -CH2-CH=CH2, -C (CH3) =CH-CH2-CH=CH2, -CH=CH-CH=C (CH3) 2, -CH=CH-C (CH3) =CH-CH3, -CH=C (CH3) -CH=CH-CH3, -C (CH3) =CH-CH=CH-CH3, -CH=C (CH3) -C (CH3) =CH2, -C (CH3) =CH-C (CH3) =CH2, C (CH3) =C (CH3) -CH=CH2, -CH=CH-CH=CH-CH=CH2, -C≡CH, -C≡C-CH3, -CH2-C≡CH, -C2H4-C≡CH, -CH2-C≡C-CH3, -C≡C-C2H5, -C3H6-C≡CH, -C2H4-C≡C-CH3, -CH2-C≡C-C2H5, -C≡C-C3H7, -CH (CH3) -C≡CH, -CH2-CH (CH3) -C≡CH, -CH (CH3) -CH2-C≡CH, -CH (CH3) -C≡C-CH3, -C4H8-C≡CH, -C3H6-C≡C-CH3, -C2H4-C≡C-C2H5, CH2-C≡C-C3H7, -C≡C-C4H9, -C2H4-CH (CH3) -C≡CH, -CH2-CH (CH3) -CH2-C≡CH, -CH (CH3) -C2H4-C≡CH, -CH2-CH (CH3) -C≡C-CH3, -CH (CH3) -CH2-C≡C-CH3, -CH (CH3) -C≡C-C2H5, -CH2-C≡CCH (CH3) 2, -C≡C-CH (CH3) -C2H5, -C≡C-CH2-CH (CH3) 2, -C≡C-C (CH3) 3, -CH (C2H5) -C≡C-CH3, -C (CH3) 2-C≡CCH3, -CH (C2H5) -CH2-C≡CH, -CH2-CH (C2H5) -C≡CH, -C (CH3) 2-CH2-C≡CH, -CH2-C (CH3) 2-C≡CH, -CH (CH3) -CH (CH3) -C≡CH, -CH (C3H7) -C≡CH, -C (CH3) (C2H5) -C≡CH, -C≡C-C≡CH, -CH2-C≡C-C≡CH, -C≡CC≡-C2H4-C≡C-C≡CH, -CH2

C-CH3, -CH (C≡CH) 2, C≡C-CH2-C≡CH, -C≡C-C2H4-C≡CH, -CH2-C≡C-C≡C-CH3, -C≡C-CH2-C≡C-CH3, -C≡C-C≡C-C2H5, -C≡C-CH (CH3) -C≡CH, -CH (CH3) -C≡C-C≡CH, -CH (C≡CH) -CH2-C≡CH, -C (C≡CH) 2-CH3, -CH2-CH (C≡CH) 2, -CH (C≡CH) C≡C-CH3, -O-R90, -O-R110, -O-R111, donde los grupos C1-6alquil, C2-6alquenil, C2-6alquinil y C1-6alcoxi se mono o polisustituyen opcionalmente por -OH, -F, -Cl, -Br, -I, ; R9 representa -H, -R91; R12 representa -R92, -CN, -R93, -R94, -OR94, fenil, naftalinil, donde los grupos C1-6alquil, C2-6alquenil, C2-6alquinil o C1-6alcoxi representados por R92 se mono o polisustituyen opcionalmente por -OH, -F, -Cl, -Br, -I, -O-R95, R96, -COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH (CH3) 2, -COOC (CH3) 3, - (C=O) -NR16R17, -SO2-NR16R17, -SOm-R16R17, -CR16R17H, -NR16R17; y donde los sistemas de anillo carbocíclico o heterocíclico saturado o insaturado de entre tres y doce miembros representado por R137 se mono o polisustituyen opcionalmente por -OH, -F, -Cl, -Br, -I, -R96;

R13

se selecciona a partir de -H, -OH, -F, -Cl, -Br, -I, -NO2, -CH3, -C2H5, -C3H7, -CH (CH3) 2, -C4H9, -CH2CH (CH3) 2, -CH (CH3) -C2H5, -C (CH3) 3, -C5H11, -CH (CH3) -C3H7, -CH2-CH (CH3) -C2H5, -CH (CH3) -CH (CH3) 2, C (CH3) 2-C2H5, -CH2-C (CH3) 3, -CH (C2H5) 2, -C2H4-CH (CH3) 2, -C6H13, -C3H6-CH (CH3) 2, -C2H4-CH (CH3) -C2H5, -CH (CH3) -C4H9, -CH2-CH (CH3) -C3H7, -CH (CH3) -CH2-CH (CH3) 2, -CH (CH3) -CH (CH3) -C2H5, -CH2CH (CH3) -CH (CH3) 2, -CH2-C (CH3) 2-C2H5, -C (CH3) 2-C3H7, -C (CH3) 2-CH (CH3) 2, -C2H4-C (CH3) 3, -CH (CH3) C (CH3) 3, -CH=CH2, -CH2-CH=CH2, -C (CH3) =CH2, -CH=CHCH3, -C2H4-CH=CH2, -CH2-CH=CH-CH3, -CH=CH-C2H5, -CH2-C (CH3) =CH2, -CH (CH3) -CH=CH, -CH=C (CH3) 2, -C (CH3) =CH-CH3, -CH=CH-CH=CH2, -C3H6-CH=CH2, -C2H4-CH=CH-CH3, -CH2-CH=CHC2H5, -CH=CH-C3H7, -CH2-CH=CH-CH=CH2, -CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH2, -C (CH3) =CHCH=CH2, -CH=C (CH3) -CH=CH2, -CH=CH-C (CH3) =CH2, -C2H4C (CH3) =CH2, -CH2-CH (CH3) -CH=CH2, -CH (CH3) -CH2-CH=CH2, -CH2-CH=C (CH3) 2, -CH2-C (CH3) =CH-CH3, -CH (CH3) -CH=CH-CH3, -CH=CHCH (CH3) 2, -CH=C (CH3) -C2H5, -C (CH3) =CH-C2H5, -C (CH3) =C (CH3) 2, -C (CH3) 2-CH=CH2, -CH (CH3) -C (CH3) =CH2, -C (CH3) =CH-CH=CH2, -CH=C (CH3) -CH=CH2, -CH=CH-C (CH3) =CH2, -C4H8-CH=CH2, -C3H6-CH=CH-CH3, -C2H4-CH=CH-C2H5, -CH2-CH=CH-C3H7, -CH=CH-C4H9, -C3H6-C (CH3) =CH2, C2H4-CH (CH3) -CH=CH2, -CH2-CH (CH3) -CH2-CH=CH2, -CH (CH3) -C2H4-CH=CH2, -C2H4-CH=C (CH3) 2, -C2H4C (CH3) =CH-CH3, -CH2-CH (CH3) -CH=CH-CH3, -CH (CH3) -CH2-CH=CH-CH3, -CH2-CH=CH-CH (CH3) 2, -CH2-CH=C (CH3) -C2H5, -CH2-C (CH3) =CH-C2H5, -CH (CH3) -CH=CH-C2H5, -CH=CH-CH2-CH (CH3) 2, -CH=CH-CH (CH3) -C2H5, -CH=C (CH3) -C3H7, -C (CH3) =CH-C3H7, -CH2-CH (CH3) -C (CH3) =CH2, -CH (CH3) -CH2C (CH3) =CH2, -CH (CH3) -CH (CH3) -CH=CH2, -CH2-C (CH3) 2-CH=CH2, -C (CH3) 2-CH2-CH=CH2, -CH2C (CH3) =C (CH3) 2, -CH (CH3) -CH=C (CH3) 2, -C (CH3) 2-CH=CH-CH3, -CH (CH3) -C (CH3) =CH-CH3, -CH=C (CH3) CH (CH3) 2, -C (CH3) =CH-CH (CH3) 2, -C (CH3) =C (CH3) -C2H5, -CH=CH-C (CH3) 3, -C (CH3) 2-C (CH3) =CH2, -CH (C2H5) -C (CH3) =CH2, -C (CH3) (C2H5) -CH=CH2, -CH (CH3) -C (C2H5) =CH2, -CH2-C (C3H7) =CH2, -CH2C (C2H5) =CH-CH3, -CH (C2H5) -CH=CH-CH3, -C (C4H9) =CH2, -C (C3H7) =CH-CH3, -C (C2H5) =CH-C2H5, C (C2H5) =C (CH3) 2, -C[C (CH3) 3]=CH2, -C[CH (CH3) (C2H5) ]=CH2, -C[CH2-CH (CH3) 2]=CH2, -C2H4-CH=CH-CH=CH2, -CH2-CH=CHCH2-CH=CH2, -CH=CH-C2H4-CH=CH2, -CH2-CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH-CH3, -CH=CHCH=CH-C2H5, -CH2-CH=CH-C (CH3) =CH2, -CH2-CH=C (CH3) -CH=CH2, -CH2-C (CH3) =CH-CH=CH2, -CH (CH3) -CH=CH-CH=CH2, -CH=CH-CH2-C (CH3) =CH2, -CH=CH-CH (CH3) -CH=CH2, -CH=C (CH3) -CH2-CH=CH2, -C (CH3) =CH-CH2-CH=CH2, -CH=CH-CH=C (CH3) 2, -CH=CH-C (CH3) =CH-CH3, -CH=C (CH3) -CH=CH-CH3, -C (CH3) =CH-CH=CH-CH3, -CH=C (CH3) -C (CH3) =CH2, -C (CH3) =CH-C (CH3) =CH2, C (CH3) =C (CH3) -CH=CH2, -CH=CH-CH=CH-CH=CH2, -C≡CH, -C≡C-CH3, -CH2-C≡CH, -C2H4-C≡CH, -CH2-C≡C-CH3, -C≡C-C2H5, -C3H6-C≡CH, -C2H4-C≡C-CH3, -CH2-C≡C-C2H5, -C≡C-C3H7, -CH (CH3) -C≡CH, -CH2-CH (CH3) -C≡CH, -CH (CH3) -CH2-C≡CH, -CH (CH3) -C≡C-CH3, -C4H8-C≡CH, -C3H6-C≡C-CH3, -C2H4-C≡C-C2H5, CH2-C≡C-C3H7, -C≡C-C4H9, -C2H4-CH (CH3) -C≡CH, -CH2-CH (CH3) -CH2-C≡CH, -CH (CH3) -C2H4-C≡CH, -CH2-CH (CH3) -C≡C-CH3, -CH (CH3) -CH2-C≡C-CH3, -CH (CH3) -C≡C-C2H5, -CH2-C≡CCH (CH3) 2, -C≡C-CH (CH3) -C2H5, -C≡C-CH2-CH (CH3) 2, -C≡C-C (CH3) 3, -CH (C2H5) -C≡C-CH3, -C (CH3) 2-C≡CCH3, -CH (C2H5) -CH2-C≡CH, -CH2-CH (C2H5) -C≡CH, -CH2-C (CH3) 2-C≡CH, -CH (CH3) -CH (CH3) -C≡CH, -CH (C3H7) -C≡CH, -C (CH3) (C2H5) -C≡CH, -C=C-C=CH, -CH2-C=C-C≡CH, -C≡C-C≡C-CH3, -CH (C≡CH) 2, -C2H4-C≡C-C≡CH, -CH2-C≡C-CH2-C≡CH, -C≡C-C2H4-C≡CH, -CH2-C≡C-C≡C-CH3, -C≡C-CH2-C≡C-CH3, -C≡C-C≡C-C2H5, -C≡C-CH (CH3) -C≡CH, -CH (CH3) -C≡C-C≡CH, -CH (C≡CH) -CH2-C≡CH, -C (C≡CH) 2-CH3, -CH2-CH (C≡CH) 2, -CH (C≡CH) -C≡C-CH3, ciclo-C3H5, -O-R97 , -R98, -R99; donde R12 y R13 representan los grupos de alquenilene, R12 y R13 podrían combinarse para formar un anillo aromático condensado junto con los átomos del residuo D a los que están unidos R12 y R13 para formar un grupo bicíclico con residuo D;

R14

representa

(i) - H, -OH, -F, -Cl, -Br, -I, -NO2, -CN, -NH2;

, -R101 , -R102 , -R103

(ii) - R100 , -O-R102 , -O-R103 , -R136, donde los grupos C1-6alquil, C2-6alquenil, C2-6alquinil y C16alcoxi representados por R100 y los grupos de éter representados por -R136 se mono o polisustituyen opcionalmente

-R105

por -OH, -F, -Cl, -Br, -I, -O-R104 , , -COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH (CH3) 2, -COOC (CH3) 3, - (C=O) -NR16R17, -SO2-NR16R17, -SOm-R16R17, -CR16R17H, -NR16R17;

(iii) -R113, donde el sistema de anillo carbocíclico o heterocíclico saturado o insaturado de entre tres y doce miembros representado por -R113 se mono o polisustituyen opcionalmente por -F, -Cl, -Br, -I, -OH, -NO2, -NH2, -C2H4

, -R106 , -R108

N (CH3) 2, -CN, -CF3, =O, -R16 , -R17 , -O-R107 , -R109, un grupo carbocíclico o heterocíclico saturado o insaturado de entre tres y ocho miembros, donde los grupos de C1-6alquil representados por R106, los grupos de C16alquenil representados por R108, los grupos de C2-6alquinil representados por R109, los grupos de C1-6alcoxi representados por -O-R107 se mono o polisustituyen opcionalmente por -OH, -F, -Cl, -Br, -I, -O-R104, -R105, -COOH, -COOCH3, -COOC2H5, =COOC3H7, -COOCH (CH3) 2, -COOC (CH3) 3, - (C=O) -NR16R17, -SO2-NR16R17, -SOm-R16R17 , -CR16R17H, -NR16R17;

R16 y R17, que podrían ser iguales o diferentes, representan -H, -R112, sustituidos opcionalmente por -OH, -F, -Cl, -Br, -I, -NH2, -CN; o, de forma alternativa, R16 y R17 podrían combinarse con el átomo de nitrógeno al que están unidos, formando un grupo heterocíclico saturado o insaturado de entre cinco y ocho miembros seleccionado a partir de -R114; que es

-R117 -R118 -R120

opcionalmente mono o polisustituido por -OH, =O, -R116 , , , -O-R119 , , o un sistema de anillo carbocíclico o heterocíclico saturado o insaturado de entre tres y doce miembros seleccionados a partir de -R115; donde el grupo de C1-6alquil representado por R116, el grupo de C2-6alquenil representado por R117, el grupo de C26alquinil representado por R118 se sustituyen, opcionalmente, con -OH, -R122, o por un sistema de anillo carbocíclico

o heterocíclico saturado o insaturado de entre tres y doce miembros seleccionados a partir de -R121; un grupo de amino en el que uno o dos átomos de hidrógeno del grupo de amino se pueden sustituir por -R123 , o un sistema de anillo carbocíclico o heterocíclico saturado o insaturado de entre tres y doce miembros seleccionados a partir de -R124, y el grupo de C1-6alquil representado por R123 se puede sustituir por -OH, -R125, o un sistema de anillo carbocíclico o heterocíclico saturado o insaturado de entre tres y doce miembros seleccionado a partir de -R126;

o un sistema de anillo carbocíclico saturado o insaturado de entre tres y doce miembros seleccionados a partir de

-R129 -R130 -R132

R127; pueden sustituirse por -OH, =O, -R128 , , , -O-R131 , , o un sistema de anillo carbocíclico o heterocíclico saturado o insaturado de entre tres y doce miembros seleccionados a partir de -R133, donde el grupo e C1-6alquil representado por R128, grupo de C2-6alquenil representado por R129 y grupo de C2-6alquinil representado por R130 se pueden sustituir por -OH, -R134, o un sistema de anillo carbocíclico o heterocíclico saturado o insaturado de entre tres y doce miembros seleccionados a partir de -R135; cuando el grupo carbocíclico o heterocíclico se sustituye por grupos de C1-6alquil, dos grupos de alquil podrían combinarse conjuntamente para formar una cadena de alquileno; y el grupo carbocíclico o heterocíclico podría condensarse con otro grupo carbocíclico o heterocíclico saturado o insaturado de entre cinco y siete miembros para formar un grupo bicíclico; R19, R20, R71, R85, R86, R89, R90, R91, R95, R97, R104, R106, R107, R110, R111, R112, R116, R119 R122, R123, R125, R128, R131 y R134 representan, de forma mutuamente independiente -CH3, -H, -CF3, -Ph, -CH2-Ph, -C2H5, -C3H7, -CH (CH3) 2, -C4H9, -CH2-CH (CH3) 2, -CH (CH3) -C2H5, -C (CH3) 3, -C5H11, -CH (CH3) -C3H7, -CH2-CH (CH3) -C2H5, -CH (CH3) CH (CH3) 2, -C (CH3) 2-C2H5, -CH2-C (CH3) 3, -CH (C2H5) 2, -C2H4-CH (CH3) 2, -C6H13, -C3H6-CH (CH3) 2, -C2H4-CH (CH3) C2H5, -CH (CH3) -C4H9, -CH2-CH (CH3) -C3H7, -CH (CH3) -CH2-CH (CH3) 2, -CH (CH3) -CH (CH3) -C2H5, CH2-CH (CH3) -CH (CH3) 2, -CH2-C (CH3) 2-C2H5, -C (CH3) 2-C3H7, -C (CH3) 2-CH (CH3) 2, -C2H4-C (CH3) 3, CH (CH3) -C (CH3) 3;

R21 y R98 representa de forma mutuamente independiente -CR22R23R24 , -CR23R24-CR25R26R22 , -CR23R24-CR25R26 -

CR27R28R22

, -CR23R24-CR25R26-CR27R28-CR29R30R22 , -CR23R24-CR25R26-CR27R28-CR29R30-CR31R32R22 -CR23R24 CR25R26-CR27R28-CR29R30-CR31R32-CR33R34R22;

R22

-R34 representan de forma mutuamente independiente -H, -F, -Cl, -Br, -I, -CH3, -CF3, -OCH3, -OCF3, -C2H5, -

R35 R99

C3H7; y representan de forma mutuamente independiente -O-CR22R23R24 , -O-CR23R24-CR25R26R22 , OCR23R24-CR25R26-CR27R28R22 , -O-CR23R24-CR25R26-CR27R28-CR29R30R22 , -O-CR23R24-CR25R26-CR27R28-CR29R30 -CR31R32R22, -O-CR23R24-CR25R26-CR27R28-CR29R30-CR31R32-CR33R34R22;

R36 R72 R87 R96 R105 R120 R132 y R136

, , , , , , representan de forma mutuamente independiente -CR23R24-XH, -XCR22R23R24 , -X-CR23R24-CR25R26R22 , -CR23R24-X-CR25R26R22 , -CR23R24-CR25R26-XH, -XCR23R24-CR27R26 -

CR27R28R22

, -CR23R24-X-CR25R26-CR27R28R22 , -CR23R24-CR25R26 -X-CR27R28R22 , -CR23R24-CR25R26-CR27R28-XH, -XCR23R24-CR25R26-CR27R28-CR29R30R22 , -CR23R24-XCR25R26CR27R28-CR29R30R22 , -CR23R24-CR25R26-X-CR27R28 -

CR29R30R22

, -CR23R24-CR25R26-CR27R28-XCR29R30R22 , -CR23R24-CR25R26-CR27R28-CR29R30-XH, -X-CR23R24-CR25R26 CR27R28-CR29R30-CR31R32R22 , -CR23R24-X-CR25R26-CR27R28-CR29R30-CR31R32R22 , -CR23R24-CR25R26-X-CR27R28 CR29R30-CR31R32R22 , -CR23R24-CR25R26-CR27R28-X-CR29R30-CR31R32R22 , -CR23R24-CR25R26-CR27R28-CR29R30-X-

CR31R32R22

, -CR23R24-CR25R26-CR27R28-CR29R30-CR31R32-XH, -X-CR23R24-CR25R26-CR27R28-CR29R30-CR31R32 -

CR33R34R22

, -CR23R24-X-CR2SR26-CR27R28-CR29R30-CR31R32-CR33R34R22 , -CR23R24-CR25R26-X-CR27R28-CR29R30 CR31R32-CR33R34R22 , -CR23R24-CR25R26-CR27R28-X-CR29R30-CR31R32-CR33R34R22 , -CR23R24-CR25R26-CR27R28 CR29R30-X-CR31R32-CR33R34R22 , -CR23R24-CR25R26-CR27R28-CR29R30-CR31R32-X-CR33R34R22 , -CR23R24-CR25R26 CR27R28-CR29R30-CR31R32-CR33R34-XH; X representa -O-, -CO-, -O-CO-

R37 R38 R93

, , y R101 representan de forma mutuamente independiente -CR40R41-YH, -Y-CR39R40R41 , -YCR40R41 -

CR42R43R39

, -CR40R41-Y-CR42R43R39 , -CR40R41-CR42R43-YH, -Y-CR40R41-CR42R43-CR44R45R39 , -CR40R41-Y-CR42R43 -

CR44R45R39

, -CR40R41-CR42R43-Y-CR44R45R39 , -CR40R41-CR42R43-CR44R45-YH, -YCR40R41-CR42R43-CR44R45 -CR46R47R39, -CR40R41-Y-CR42R43-CR44R45-CR46R47R39, -CR40R41-CR42R43-Y-CR44R45-CR46R47R39, -CR40R41-CR42R43 CR44R45-Y-CR46R46R39 , -CR40R42-CR42R43-CR44R45-CR46R47-YH, -Y-CR40R41-CR42R43-CR44R45-CR46R47-CR48R49R39 , -CR40R41-Y-CR42R43-CR44R45-CR46R47-CR48R49R39 , -CR40R41-CR42R43-Y-CR44R45-CR46R47-CR48R49R39 , -CR40R41 CR42R43-CR44R45-YCR46R47-CR48R49R39 -CR40R41-CR42R43-CR44R45-CR46R47-Y-CR48R49R39 , -CR40R41-CR42R43 CR44R45-CR46R47-CR48R49-YH, -Y-CR40R41-CR42R43-CR44R45-CR46R47-CR48R49-CR50R51R39 , -CR40R41-YCR42R43 CR44R45-CR46R47-CR48R49-CR50R51R39, -CR40R41-CR42R43-Y-CR44R45-CR46R47-CR48R49-CR50R51R39 , -CR40R41 CR42R43-CR44R45-Y-CR46R47-CR48R49-CR50R51R39 , -CR40R41-CR42R43-CR44R45-CR46R47-Y-CR48R49-R50R51R39 , CR40R41-CR42R43-CR44R45-CR46R47-CR48R49-Y-CR50R51R39 , -CR40R41-CR42R43-CR44R45-CR46R47-CR48R49-CR50R51 -YH; R39 -R53 representan de forma mutuamente independiente -H, -CH3, -C2H5, -C3H7; Y representa -NR52-CO-, -CO-NR53-; R54, R55 y R102 representan de forma mutuamente independiente R56 R57 R94 R103

, , y representan, de forma mutuamente independiente -CR58R16R17 , -CR58R59R60 , -CR16R17 -

CR61R62R58

, -CR59R60-CR61R62R58 , -CR59R60-CR16R17R58 , -CR16R17-CR61R62-CR63R64R58 , -CR59R60-CR61R62 -CR63R64R58, -CR59R60-CR16R17-CR63R64R58, -CR59R60-CR61R62-CR16R17R58, -CR16R17-CR61R62-CR63R64-CR65R66R58 , CR59R60-CR61R62-CR63R64-CR65R66R58 , -CR59R60-CR16R17-CR63R64-CR66R67R58 , -CR59R60-CR61R62-CR16R17 -

CR65R66R58

, -CR59R60-CR61R62-CR63R64-CR16R17R58 , -CR16R17-CR61R62-CR63R64-CR65R66-CR67R68R58 , -CR59R60 CR61R62-CR63R64-CR65R66-CR67R68R58 , -CR59R60-CR16R17-CR63R64-CR65R66-CR67R68R58 , -CR59R60--CR61R62 CR16R17-CR65R66-CR67R68R69, -CR59R60-CR61R62-CR63R64-CR16R17-CR67R68R58, -CR59R60-CR61R62-CR63R64-CR65R66 -

CR16R17R58

, -CR16R17-CR61R62-CR63R64-CR65R66-CR67R68-CR69R70R58 , -CR59R60-CR16R17-CR63R64-CR65R66-CR67R68-CR69R70R58 , -CR59R60-CR61R62-CR16R17-CR65R66-CR67R68-CR69R70R58 , -CR59R60-CR61R62-CR63R64-CR16R17-CR67R68-CR69R70R58 , -CR59R60-CR61R62-CR63R64-CR65R66-CR16R17-CR69R70R58 , -CR59R60-CR61R62-CR63R64-CR65R66-CR67R68-CR16R17R58; R58 -R70 representan, de forma mutuamente independiente, -H, -NH2, -OH, -F, -Cl, -Br, -I, -R71, -O-R71, -R72, -O-R95 , -R96, -O-R104, -R105, -COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH (CH3) 2, -COOC (CH3) 3, - (C=O) -NR16R17 , -SO2-NR16R17, -SOm-R16R17, -CR16R17H, -NR16R17 , R108, R117 y R129 representan, de forma mutuamente independiente, -CH=CH2, -CH2-CH=CH2, -H, -C (CH3) =CH2, -CH=CH-CH3, -C2H4-CH=CH2, -CH2-CH=CH-CH3, -CH=CH-C2H5, -CH2-C (CH3) =CH2, -CH (CH3) -CH=CH, CH=C (CH3) 2, -C (CH3) =CH-CH3, -CH=CH-CH=CH2, -C3H6-CH=CH2, -C2H4-CH=CH-CH3, -CH2-CH=CHC2H5, -CH=CH-C3H7, -CH2-CH=CH-CH=CH2, -CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH2, -C (CH3) =CHCH=CH2, -CH=C (CH3) -CH=CH2, -CH=CH-C (CH3) =CH2, -C2H4-C (CH3) =CH2, -CH2-CH (CH3) -CH=CH2, -CH (CH3) -CH2-CH=CH2, -CH2-CH=C (CH3) 2, -CH2-C (CH3) =CH-CH3, -CH (CH3) -CH=CH-CH3, -CH=CHCH (CH3) 2, -CH=C (CH3) -C2H5, -C (CH3) =CH-C2H5, -C (CH3) =C (CH3) 2, -C (CH3) 2-CH=CH2, -CH (CH3) -C (CH3) =CH2, -C (CH3) =CH-CH=CH2, -CH=C (CH3) -CH=CH2, -CH=CH-C (CH3) =CH2, -C4H8-CH=CH2, -C3H6-CH=CH-CH3, -C2H4-CH=CH-C2H5, -CH2-CH=CH-C3H7, -CH=CH-C4H9, -C3H6-C (CH3) =CH2, -C2H4-CH (CH3) -CH=CH2, -CH2-CH (CH3) -CH2-CH=CH2. -CH (CH3) -C2H4-CH=CH2, -C2H4-CH=C (CH3) 2, -C2H4-C (CH3) =CH-CH3, -CH2-CH (CH3) -CH=CH-CH3. -CH (CH3) -CH2-CH=CH-CH3, -CH2-CH=CH-CH (CH3) 2, -CH2-CH=C (CH3) -C2H5, -CH2-C (CH3) =CH-C2H5, -CH (CH3) -CH=CH-C2H5, -CH=CH-CH2-CH (CH3) 2, -CH=CH-CH (CH3) -C2H5, -CH=C (CH3) -C3H7, -C (CH3) =CH

C3H7, -CH2-CH (CH3) -C (CH3) =CH2, -CH (CH3) -CH2-C (CH3) =CH2, -CH (CH3) -CH (CH3) -CH=CH2, -CH2-C (CH3) 2-CH=CH2, -C (CH3) 2-CH2-CH=CH2, -CH2-C (CH3) =C (CH3) 2, -CH (CH3) -CH=C (CH3) 2, -C (CH3) 2-CH=CH-CH3, -CH (CH3) -C (CH3) =CH-CH3, -CH=C (CH3) -CH (CH3) 2, -C (CH3) =CH-CH (CH3) 2, -C (CH3) =C (CH3) -C2H5, -CH=CHC (CH3) 3, -C (CH3) 2-C (CH3) =CH2, -CH (C2H5) -C (CH3) =CH2, -C (CH3) (C2H5) -CH=CH2, -CH (CH3) -C (C2H5) =CH2, 5 CH2-C (C3H7) =CH2, -CH2-C (C2H5) =CH-CH3, -CH (C2H5) -CH=CH-CH3, -C (C4H9) =CH2, -C (C3H7) =CH-CH3, C (C2H5) =CH-C2H5, -C (C2H5) =C (CH3) 2, -C[C (CH3) 3]=CH2, -C[CH (CH3) (C2H5) ]=CH2, -C[CH2-CH (CH3) 2]=CH2, C2H4-CH=CH-CH=CH2, -CH2-CH=CHCH2-CH=CH2, -CH=CH-C2H4-CH=CH2, -CH2-CH=CH-CH=CH-CH3, -CH=CH-CH2-CH=CH-CH3, -CH=CHCH=CH-C2H5, -CH2-CH=CH-C (CH3) =CH2, -CH2-CH=C (CH3) -CH=CH2, -CH2C (CH3) =CH-CH=CH2, -CH (CH3) -CH=CH-CH=CH2, -CH=CH-CH2-C (CH3) =CH2, -CH=CH-CH (CH3) -CH=CH2,

CH=C (CH3) -CH2-CH=CH2, -C (CH3) =CH-CH2-CH=CH2, -CH=CH-CH=C (CH3) 2, -CH=CH-C (CH3) =CH-CH3, -CH=C (CH3) -CH=CH-CH3, - (CH3) =CH-CH=CH-CH3, -CH=C (CH3) -C (CH3) =CH2, -C (CH3) =CH-C (CH3) =CH2, C (CH3) =C (CH3) -CH=CH2, -CH=CH-CH=CH-CH=CH2; R109, R118 y R130 representan, de forma mutuamente independiente, -H, -C≡CH, -C≡C-CH3, -CH2-C≡CH, -C2H4-C≡CH, -CH2-C≡C-CH3, -C≡C-C2H5, -C3H6-C≡CH, -C2H4-C≡C-CH3, -CH2-C≡C-C2H5, -C≡C-C3H7, -CH (CH3)

C≡CH, -CH2-CH (CH3) -C≡CH, -CH (CH3) -CH2-C≡CH, -CH (CH3) -C≡C-CH3, -C4H8-C≡CH, -C3H6-C≡C-CH3, -C2H4C≡C-C2H5, -CH2-C≡C-C3H7, -C≡C-C4H9, -C2H4-CH (CH3) -C≡CH, -CH2-CH (CH3) -CH2-C≡CH, -CH (CH3) -C2H4-C=CH, -CH2-CH (CH3) -C≡C-CH3, -CH (CH3) CH2-C=C≡CH3, -CH (CH3) -C≡C-C2H5, -CH2-C≡CCH (CH3) 2, -C≡C-CH (CH3) -C2H5, -C≡C-CH2-CH (CH3) 2, -C≡C-C (CH3) 3, -CH (C2H5) -C≡C-CH3, -C (CH3) 2-C≡CCH3, -CH (C2H5) CH2-C≡CH, -CH2-CH (C2H5) -C≡CH, -C (CH3) 2-CH2-C≡CH, -CH2-C (CH3) 2-C≡CH, -CH (CH3) -CH (CH3) -C≡CH,

CH (C3H7) -C≡CH, -C (CH3) (C2H5) -C≡CH, -C≡C-C≡CH, -CH2-C≡C-C≡CH, -C≡CC≡C-CH3, -CH (C≡CH) 2, -C2H4-C≡C-C≡CH, -CH2-C≡C-CH2-C≡CH, -C≡C-C2H4-C≡CH, -CH2-C≡C-C≡C-CH3, -C≡C-CH2-C≡C-CH3, -C≡C-C≡C-C2H5, -C≡C-CH (CH3) -C≡CH, -CH (CH3) -C≡C-C≡CH, -CH (C≡CH) -CH2-C≡CH, -C (C≡CH) 2-CH3, -CH2-CH (C≡CH) 2, -CH (C≡CH) -C≡C-CH3; R113, R115, R121, R124, R126, R127, R133, R135, R137 y R138 representan de forma mutuamente independiente

R114

representa y enantiómeros, formas estereoisoméricas, mezclas de enantiómeros, diastereómeros, mezclas de diastereómeros, hidratos, solvatos, formas de sales ácidas, tautómeros, óxidos de N y racematos de los compuestos anteriormente mencionados y sales de los anteriores aceptables farmacológicamente.

2. Los compuestos preparados de acuerdo con la reivindicación 1, en los que el residuo D representa uno de los siguientes heterociclos,

y los sustituyentes R12 -R14 tienen los significados definidos en la fórmula (I) .

3. Los compuestos preparados de acuerdo con cualquiera de las reivindicaciones 1 y 2, en los que R1, R4, R5 y R6 se seleccionan a partir de hidrógeno o C1-6alquil, especialmente a partir del hidrógeno.

4. Los compuestos preparados de acuerdo con cualquiera de las reivindicaciones entre la 1 y la 3, que tienen la fórmula general (Ia)

5. Los compuestos preparados con cualquiera de las reivindicaciones entre la 1 y la 4, que tienen la fórmula general (Ib) o la fórmula general (Ic)

6. Los compuestos preparados de acuerdo con cualquiera de las reivindicaciones entre la 1 y la 5, donde R9 es un

átomo de hidrógeno. 10

7. El compuesto preparado de acuerdo con cualquiera de las reivindicaciones entre la 1 y la 6, donde el compuesto se selecciona a partir del grupo de compuestos que comprende: N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1, 5-dimetilo-pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-2-[4- (trifluorometilo) fenil]tiazole-4-carboxamida 4-bromo-N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1-metilo-pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1-metilo-pirazol-3-carboxamida 1-tert-butilo-N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-5-metilo-pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]tiazole-2-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-2-metilo-tiazole-4-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1-metilo-indazole-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-5-metilo-isoxazole-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-2-fenil-tiazole-4-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1-metilo-imidazole-2-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1-metilo-imidazole-4-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1-propil-pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1-[3- (1-piperidil) propil]pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1- (2, 2, 2-trifluoroetoximetilo) pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-4-etoxi-1- (4-fluorofenil) pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1- (4-fluorofenil) -4-metoxi-pirazol-3-carboxamida 4- ( (ciclopropilmetoxi) -N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1- (4-fluorofenil) pirazol-3carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-4- (2-dimetiloaminoetoxi) -1- (4-fluorofenil) pirazol3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-4- (2-dimetiloaminoetoxi) -1-4-fluorofenil) pirazol-3

carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1- (4-fluorofenil) -4-isopropoxi-pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-4-etoxi-1- (4-fluoro-2-metilo-fenil) pirazol-3-carboxamida 1- ( (2-cloro-4-fluoro-fenil) -N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-4-etoxi-pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]fenil]-4-etoxi-1- (4-fluorofenil) pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]fenil]-1- (4-fluorofenil) -4-isopropoxi-pirazol-3-carboxamida 4- ( (ciclopropilmetoxi) -N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]fenil]-1- (4-fluorofenil) pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]fenil]-4-etoxi-1- (4-fluoro-2-metilo-fenil) pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-metilo-fenil]-4-etoxi-1- (4-fluorofenil) pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-metilo-fenil]-1- (4-fluorofenil) -4-isopropoxi-pirazol-3-carboxamida 4- ( (ciclopropilmetoxi) -N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-metilo-fenil]-1- (4-fluorofenil) pirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-metilo-fenil]-4-etoxi-1- (4-fluoro-2-metilo-fenil) pirazol-3-carboxamida N-[3-cloro-4-[ (6, 7-dimetoxi-4-quinolil) oxi]fenil]-4-etoxi-1- (4-fluorofenil) pirazol-3-carboxamida N-[3-cloro-4-[ (6, 7-dimetoxi-4-quinolil) oxi]fenil]-1- (4-fluorofenil) -4-isopropoxi-pirazol-3-carboxamida N-[3-cloro-4-[ (6, 7-dimetoxi-4-quinolil) oxi]fenil]-4- (ciclopropilmetoxi) -1- (4-fluorofenil) pirazol-3-carboxamida N-[3-cloro-4-[ (6, 7-dimetoxi-4-quinolil) oxi]fenil]-4-etoxi-1- (4-fluoro-2-metilo-fenil) pirazol-3-carboxamida N- (4- ( (6, 7-dimetoxiquinolina-4-il) oxi) -3-fluorofenil) -4- (2- (dimetiloamino) etilo) -1- (4-fluorofenil) -1Hpirazol-3-carboxamida N-[4-[ (6, 7-dimetoxi-4-quinolil) oxi]-3-fluoro-fenil]-1-[2- (2-dimetiloaminoetilo) -4-fluoro-fenil]-4-etoxipirazol-3carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-2-fenil-tiazole-4-carboxamida 4-bromo-N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1-metilo-pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1-metilo-pirazol-3-carboxamida 1-tert-butil-N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-5-metilo-pirazol-3-Carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1, 5-dimetilo-pirazol-3-carboxamida 4-etoxi-N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluoro-2-metilo-fenil) pirazol-3carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-metoxi-pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-isopropoxipirazol-3-carboxamida 4- ( (ciclopropilmetoxi) -N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3carboxamida 1- ( (2-cloro-4-fluoro-fenil) -4-etoxi-N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]pirazol-3carboxamida 4- ( (2-dimetiloaminoetoxi) -N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3carboxamida 1- ( (2-bromo-4-fluoro-fenil) -4-etoxi-N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]pirazol-3carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4- (2-metoxietoxi) pirazol-3carboxamida 4-benziloxi-N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-nitro-pirazol-3-carboxamida 4-amino-N-[3-fluoro-4-[[6-metoxi-7- (3-morfolinopropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3-carboxamida N-[4-[[7- (3-aminopropoxi) -6-metoxi-4-quinolil]oxi]-3-fluoro-fenil]-4-etoxi-1- (4-fluorofenil) pirazol-3-carboxamida N-[4-[[7- (3-aminopropoxi) -6-metoxi-4-quinolil]oxi]-3-fluoro-fenil]-4-etoxi-1- (4-fluoro-2-metilo-fenil) pirazol-3carboxamida N-[4-[[7- (3-aminopropoxi) -6-metoxi-4-quinolil]oxi]-3-fluoro-fenil]-5-etoxi-2- (4-fluorofenil) oxazole-4-carboxamida 4-etoxi-N-[3-fluoro-4-[[6-metoxi-7-[3- (4-metilopiperazin-1-il) propoxi]-4-quinolil]oxi]fenil]-1- (4-fluoro-2-metilofenil) pirazol-3-carboxamida 4-etoxi-N-[3-fluoro-4-[[6-metoxi-7-[3- (4-metilopiperazin-1-il) propoxi]-4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3carboxamida N-[3-fluoro-4-[[6-metoxi-7-[3- (4-metilopiperazin-1-il) propoxi]-4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-metoxi-pirazol-3carboxamida 1- ( (2-cloro-4-fluoro-fenil) -4-etoxi-N-[3-fluoro-4-[[6-metoxi-7-[3-{4-metilopiperazin-1-il) propoxi]-4quinolil]oxi]fenil]pirazol-3-carboxamida 4- ( (ciclopropilmetoxi) -N-[3-fluoro-4-[[6-metoxi-7-[3- (4-metilopiperazin-1-il) propoxi]-4-quinolil]oxi]fenil]-1- (4fluorofenil) pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7-[3- (4-metilopiperazin-1-il) propoxi]-4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-isopropoxi-pirazol-3carboxamida 5-etoxi-N-[3-fluoro-4-[[6-metoxi-7-[3- (4-metilopiperazin-1-il) propoxi]-4-quinolil]oxi]fenil]-2- (4-fluorofenil) oxazole-4carboxamida 4- ( (ciclopropilmetoxi) -N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3carboxamida sal de ácido trifluoroacético 4-etoxi-N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-metoxipirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-isopropoxipirazol-3carboxamida 1- ( (2-cloro-4-fluoro-fenil) -4-etoxi-N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]pirazol-3carboxamida 4-etoxi-N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]-1- (4-fluoro-2-metilofenil) pirazol-3carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4- (2-metoxietoxi) pirazol-3carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-[ (1-metilopirrolidin-3il) metoxi]pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (3-piperazin-1-ilpropoxi) -4-quinolil]oxi]fenil]-2-fenil-tiazole-4-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-metoxi-pirazol-3-carboxamida 4-etoxi-N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-1- (4-fluoro-2-metilo-fenil) pirazol-3carboxamida 4- ( (ciclopropilmetoxi) -N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3carboxamida 4-bromo-N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-1- (4-fluorofenil) -4-[ (4-fluorofenil) metoxi]pirazol-3carboxamida 1-tert-butil-N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-5-metilo-pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-4-nitro-1-[3- (1-piperidil) propil]pirazol-3-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-5-metilo-2-fenil-oxazole-4-carboxamida N-[3-fluoro-4-[[6-metoxi-7- (4-piperidilmetoxi) -4-quinolil]oxi]fenil]-2-fenil-tiazole-4-carboxamida 4-etoxi-N-[4-[[7-[ (1-etilo-4-piperidil) metoxi]-6-metoxi-4-quinolil]oxi]-3-fluoro-fenil]-1- (4-fluoro-2-metilo-fenil) pirazol-3carboxamida 4-etoxi-N-[3-fluoro-4-[[7-[ (1-isobutil-4-piperidil) metoxi]-6-metoxi-4-quinolil]oxi]fenil]-1- (4-fluoro-2-metilo-fenil) pirazol-3carboxamida N-[5-[ (6, 7-dimetoxi-4-quinolil) oxi]-2-piridil]-4-etoxi-1- (4-fluorofenil) pirazol-3-carboxamida N-[5-[ (6, 7-dimetoxi-4-quinolil) oxi]-2-piridil]-4-etoxi-1- (4-fluoro-2-metilo-fenil) pirazol-3-carboxamida 1- ( (2-cloro-4-fluoro-fenil) -N-[5-[ (6, 7-dimetoxi-4-quinolil) oxi]-2-piridil]-4-etoxi-pirazol-3-carboxamida N-[5-