ES2670394T3 - Inhibidores de ciclofilinas para utilizar en la prevención y/o el tratamiento de patologías virales o infecciones - Google Patents

Inhibidores de ciclofilinas para utilizar en la prevención y/o el tratamiento de patologías virales o infecciones Download PDF

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ES2670394T3
ES2670394T3 ES10798084.9T ES10798084T ES2670394T3 ES 2670394 T3 ES2670394 T3 ES 2670394T3 ES 10798084 T ES10798084 T ES 10798084T ES 2670394 T3 ES2670394 T3 ES 2670394T3
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aryl
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Jean-François GUICHOU
Lionel Colliandre
Hakim Ahmed-Belkacem
Jean-Michel Pawlotsky
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Centre National de la Recherche Scientifique CNRS
Universite de Montpellier I
Assistance Publique Hopitaux de Paris APHP
Institut National de la Sante et de la Recherche Medicale INSERM
Universite Paris Est Creteil Paris 12
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Centre National de la Recherche Scientifique CNRS
Universite de Montpellier I
Assistance Publique Hopitaux de Paris APHP
Institut National de la Sante et de la Recherche Medicale INSERM
Universite Paris Est Creteil Paris 12
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    • C07—ORGANIC CHEMISTRY
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    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
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    • C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
    • C07C275/20—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
    • C07C275/24—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
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    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
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    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
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    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

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Abstract

Compuesto de fórmula (I):**Fórmula** en la que: - n es 0, 1 o 2; - A es CH, o A es C y forma, junto con R1, R2 y CO, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido; - X es CO o CS, - R1 se selecciona del grupo que consiste en: H, grupos alquilo, y grupos aralquilo, estando dichos grupos alquilo o aralquilo posiblemente sustituidos, - R2 es un grupo de fórmula NR3R4 u OR5, en el que: · R3 y R4 se seleccionan cada uno independientemente de: H, ORa, grupos alquilo, grupos aralquilo, y grupos arilo, eligiendo Ra del grupo que consiste en: H, grupos alquilo, grupos arilo, y grupos aralquilo; en los que R3 y R4 pueden formar, junto con el átomo de nitrógeno que llevan, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido, · R5 se selecciona entre: grupos alquilo, grupos arilo, y grupos aralquilo, en el que R5 puede formar, junto con el átomo de oxígeno que lleva, un grupo heterociclilo de 5 a 20 átomos, posiblemente sustituido, - R6 es H o un grupo alquilo, o puede formar junto con R2 un grupo heterociclilo de 20 a 30 átomos de carbono, o puede formar junto con R1 un grupo heterociclilo de 10 a 30 átomos, - R7 se selecciona entre el grupo que consiste en: grupos arilo, grupos heteroarilo, -NHPh, grupos heterociclilo, y grupos alquilo; en el que cuando R7 es arilo, heteroarilo o heterociclilo, está sustituido con al menos un grupo NH2, o sus sales farmacéuticamente aceptables, hidratos o sales hidratadas o sus estructuras cristalinas polimórficas, racematos, diastereómeros o enantiómeros, para su uso en la prevención y/o el tratamiento de patologías virales o infecciones, en el que dicho compuesto tiene la fórmula (III):**Fórmula** en la que R4 y Ra son como se han definido anteriormente, o dicho compuesto tiene la fórmula (IV):**Fórmula** en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (V):**Fórmula** en la que R1 es como se ha definido anteriormente, y R3 y R4 forman junto con el átomo de nitrógeno que llevan un grupo que tiene la fórmula:**Fórmula** en la que n es 0, 1 o 2, y R es H o arilo, opcionalmente sustituido, o dicho compuesto tiene la fórmula (VI):**Fórmula** en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (VII):**Fórmula** en la que R3 y R4 son como se han definido anteriormente, y R8 es un grupo heteroarilo, o dicho compuesto tiene la fórmula (VIII):**Fórmula** en la que R11 y R12 son, independientemente uno del otro, seleccionados del grupo que consiste en: H, alquilo, alcoxi, arilo, y aralquilo, y A' es CH2 o NH, o dicho compuesto tiene la fórmula (IX):**Fórmula** en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (X):**Fórmula** en la que R3 y R4 son como se han definido anteriormente, en la que los sustituyentes en un grupo alquilo, heterociclilo, arilo, aralquilo o heteroarilo en cualquier átomo de dicho grupo se seleccionan del grupo que consiste en alquilo, alquenilo, alquinilo, alcoxi, halo, hidroxi, ciano, nitro, amino, SO3H, sulfato, fosfato, perfluoroalquilo, perfluoroalcoxi, metilendioxi, etilendioxi, carboxilo, oxo, tioxo, imino (alquilo, arilo, aralquilo), S(O)n alquilo, en el que n es 0-2, S(O)n arilo, en el que n es 0-2, S(O)n heteroarilo, en el que n es 0-2, S(O)n heterociclilo, en el que n es 0-2, amina, éster, amida, sulfonamida, arilo no sustituido, heteroarilo no sustituido, heterociclilo no sustituido, y cicloalquilo no sustituido, y en la que - arilo se refiere a un sistema anular de hidrocarburo monocíclico, bicíclico o tricíclico aromático, en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente, - heterociclilo se refiere a un sistema anular no aromático monocíclico de 3-10 miembros, bicíclico de 8-12 miembros, o tricíclico de 11-14 miembros que tiene 1-3 heteroátomos si es monocíclico, 1-6 heteroátomos si es bicíclico o 1-9 heteroátomos si es tricíclico, dichos heteroátomos seleccionados de O, N, o S, en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente, - heteroarilo se refiere a un sistema anular aromático monocíclico de 5-8 miembros, bicíclico de 8-12 miembros o tricíclico de 11-14 miembros que tiene 1-3 heteroátomos si es monocíclico, 1-6 heteroátomos si es bicíclico o 1-9 heteroátomos si es tricíclico, dichos heteroátomos seleccionados de O, N, o S, en el cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente.

Description

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DESCRIPCIÓN
Inhibidores de ciclofilinas para utilizar en la prevención y/o el tratamiento de patologías virales o infecciones
[0001] La presente invención se refiere a nuevos inhibidores de ciclofilinas, así como usos de los mismos.
[0002] Las ciclofilinas (o Cyp) son miembros de la clase de inmunofilina de proteínas, que comprenden, en particular, ciclofilina A (CypA), ciclofilina B (CypB) y ciclofilina D (CypD). Estas proteínas celulares ubicuas poseen actividades de cis-trans prolil isomerasa (PPIasa) (Fischer, G., H. Bang, y C. Mech. 1984. Determination of enzymatic catalysis for the cis-trans-isomerization of peptide binding in proline-containing peptides. Biomed Biochim Acta 43: 1101-1111) y se supone que están implicadas en el plegamiento de proteínas y funcionan como chaperones en el transporte intracelular (Snyder, S.H., y D.M. Sabatini 1995. Immunophilins and the nervous system. Nat Med. 1: 32-37). Las ciclofilinas también son conocidas por ser moléculas receptoras intracelulares para ciclosporinas (Handschumacher, R.E., M.W. Harding, J. Rice, R.J. Drugge, y D.W. Speicher 1984. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science 226: 544-546), una clase de undecapéptidos cíclicos producidos por Trichoderma polysporum (Dreyfuss, M., E. Harri, H. Hoffmann, H. Kobel, W. Pache, y H. Tscherter. 1976. Cyclosporin A y C. New metabolites from Trichoderma polysporum. Eur J. Appl Microbiol. 3: 125-133). La unión de las ciclosporinas a ciclofilinas conduce al bloqueo de la actividad de isomerasa.
[0003] Estos ciclofilinas se conocen como dianas de fármacos para un conjunto de enfermedades que incluyen la infección por VIH (J. Luban et al, Cell, 1993, 73, 1067-1078; Daelemans et al, Antiviral Res 24 Oct 2009), malaria (Bell et al., Int J Parasitol 2005) y la isquemia (Yang Y, Moir E, Kontopidis G, Taylor P, Wear MA, Malone K, Dunsmore CJ, Page AP, Turner NJ, Walkinshaw MD. Biochem Biophys Res Commun. 30 Nov 2007; 363 (4): 10139).
[0004] Entre los inhibidores de la ciclofilina conocidos, pueden mencionarse la [D-MeAla]3-[EtVal]4-ciclosporina (también conocida como Debio 025 - Debiopharm), así como NIM811 ([Melle]4-ciclosporina - Novartis). El compuesto Debio 025 es un undecapéptido cíclico y está, en particular, descrito por Wenger et al. en el documento WO 00/01715 (número de registro CAS 254435-95-5). El compuesto NIM811 es un undecapéptido cíclico y está, en particular, descrito por Ko et al. en el documento EP 0 484 281.
[0005] Estos inhibidores conocidos son moléculas con un peso molecular alto.
[0006] El objetivo de la presente invención es proporcionar nuevos inhibidores de las ciclofilinas, tales como ciclofilinas humanas A, B, y D, que tienen un perfil farmacológico mejorado.
[0007] El objetivo de la presente invención es proporcionar nuevos inhibidores de ciclofilinas que tienen un peso molecular bajo y que son adecuadas para la administración oral.
[0008] Otro objetivo de la presente invención es proporcionar inhibidores de ciclofilinas que tienen una actividad de inhibición selectiva para cada ciclofilina.
La presente invención se refiere a compuestos de fórmula (I):
imagen1
en la que:
- n es 0, 1 o 2;
- A es CH, o A es C y forma, junto con R1, R2 y CO, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido;
- X es CO, o CS,
- R1 se selecciona del grupo que consiste en: H, grupos alquilo, y grupos aralquilo, estando dichos grupos alquilo o aralquilo posiblemente sustituidos,
- R2 es un grupo de fórmula NR3R4 u OR5, en el que:
• R3 y R4 se seleccionan cada uno independientemente de: H, ORa, grupos alquilo, grupos aralquilo, y grupos arilo, eligiendo Ra del grupo que consiste en: H, grupos alquilo, grupos arilo, y grupos aralquilo;
en los que R3 y R4 pueden formar, junto con el átomo de nitrógeno que llevan, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido,
• R5 se selecciona entre: grupos alquilo, grupos arilo, y grupos aralquilo,
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en el que R5 puede formar, junto con el átomo de oxígeno que lleva, un grupo heterociclilo de 5 a 20 átomos, posiblemente sustituido,
- R6 es H o un grupo alquilo, o puede formar junto con R2 un grupo heterociclilo de 20 a 30 átomos de carbono, o puede formar junto con R1 un grupo heterociclilo de 10 a 30 átomos,
- R7 se selecciona entre el grupo que consiste en: grupos arilo, grupos heteroarilo, - NHPh, grupos heterociclilo, y grupos alquilo; en el que cuando R7 es arilo, heteroarilo o heterociclilo, está sustituido con al menos un grupo NH2,
o sus sales farmacéuticamente aceptables, hidratos o sales hidratadas o sus estructuras cristalinas polimórficas, racematos, diastereómeros o enantiómeros,
para su uso en la prevención y/o el tratamiento de patologías virales o infecciones, en los que dicho compuesto tiene la fórmula (III):
imagen2
en la que R4 y Ra son como se han definido anteriormente, o dicho compuesto tiene la fórmula (IV):
imagen3
en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (V):
imagen4
en la que R1 es como se ha definido anteriormente,
y R3 y R4 forman junto con el átomo de nitrógeno que llevan un grupo que tiene la fórmula:
R
imagen5
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en la que n es 0, 1 o 2, y R es H o arilo, opcionalmente sustituido, o dicho compuesto tiene la fórmula (VI):
imagen6
en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (VII):
imagen7
en la que R3 y R4 son como se han definido anteriormente, y R8 es un grupo heteroarilo, o dicho compuesto tiene la fórmula (VIII):
imagen8
en la que R11 y R12 son, independientemente uno del otro, seleccionados del grupo que consiste en: H, alquilo, alcoxi, arilo, y aralquilo, y A' es CH2 o NH, o dicho compuesto tiene la fórmula (IX):
imagen9
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en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (X):
imagen10
en la que R3 y R4 son como se han definido anteriormente, en la que
los sustituyentes en un grupo alquilo, heterociclilo, arilo, aralquilo o heteroarilo en cualquier átomo de dicho grupo se seleccionan del grupo que consiste en alquilo, alquenilo, alquinilo, alcoxi, halo, hidroxi, ciano, nitro, amino, SO3H, sulfato, fosfato, perfluoroalquilo, perfluoroalcoxi, metilendioxi, etilendioxi, carboxilo, oxo, tioxo, imino (alquilo, arilo, aralquilo), S(O)n alquilo, en el que n es 0-2, S(O)n arilo, en el que n es 0-2), S(O)n heteroarilo, en el que n es 0-2, S(O)n heterociclilo, en el que n es 0-2, amina, éster, amida, sulfonamida, arilo no sustituido, heteroarilo no sustituido, heterociclilo no sustituido, y cicloalquilo no sustituido, y en la que
- arilo se refiere a un sistema anular de hidrocarburo monocíclico, bicíclico o tricíclico aromático, en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente,
- heterociclilo se refiere a un sistema anular no aromático monocíclico de 3-10 miembros, bicíclico de 8-12 miembros, o tricíclico de 11-14 miembros que tiene 1-3 heteroátomos si es monocíclico, 1-6 heteroátomos si es bicíclico o 1-9 heteroátomos si es tricíclico, dichos heteroátomos seleccionados de O, N, o S, en el que cualquier átomo de anillo capaz de sustitución puede estar sustituido por un sustituyente,
- heteroarilo se refiere a un sistema anular aromático monocíclico de 5-8 miembros, bicíclico de 8-12 miembros o tricíclico de 11-14 miembros que tiene 1-3 heteroátomos si es monocíclico, 1-6 heteroátomos si es bicíclico o 1-9 heteroátomos si es tricíclico, dichos heteroátomos seleccionados de O, N, o S, en el cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente.
[0009] Se describen compuestos que tienen fórmula (I):
imagen11
en la que:
- n es 0, 1,2 o 3;
- A es CH o N, o A es C y forma, junto con R1, R2 y CO, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido;
- X es CO, SO2 o CS,
- R1 se selecciona del grupo que consiste en: H, grupos alquilo, y grupos aralquilo, estando dichos grupos alquilo o aralquilo posiblemente sustituidos,
- R2 es un grupo de fórmula NR3R4 u OR5, en el que:
• R3 y R4 se seleccionan cada uno independientemente de: H, ORa, grupos alquilo, grupos aralquilo, y grupos
arilo, eligiendo Ra del grupo que consiste en: H, grupos alquilo, grupos arilo, y grupos aralquilo; en los que R3 y R4 pueden formar, junto con el átomo de nitrógeno que llevan, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido,
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• R5 se selecciona entre: grupos alquilo, grupos arilo, y grupos aralquilo,
en el que R5 puede formar, junto con el átomo de oxígeno que lleva, un grupo heterociclilo de 5 a 20 átomos, posiblemente sustituido,
- R6 es H o un grupo alquilo, o puede formar junto con R2 un grupo heterociclilo de 20 a 30 átomos de carbono, preferiblemente de 25 a 30 átomos, o puede formar junto con R1 un grupo heterociclilo de 10 a 30 átomos,
- R7 se selecciona entre el grupo que consiste en: grupos arilo, grupos heteroarilo, -NHPh, grupos heterociclilo, y grupos alquilo; en el que cuando R7 es arilo, heteroarilo o heterociclilo, está sustituido con al menos un grupo NH2, en los que, cuando A es N, R1 y R2 pueden formar, junto con A y CO, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido,
o sus sales farmacéuticamente aceptables, hidratos o sales hidratadas o sus estructuras cristalinas polimórficas, racematos, diastereómeros o enantiómeros,
para su uso en la prevención y/o el tratamiento de patologías virales o infecciones.
[0010] El término "alquilo" (o "Alq") significa un grupo hidrocarburo alifático saturado o insaturado que puede ser lineal o ramificado que tiene de 1 a 12 átomos de carbono en la cadena. Los grupos alquilo preferidos tienen de 1 a 6 átomos de carbono en la cadena. "Ramificado" significa que uno o grupos alquilo inferior, tales como metilo, etilo o propilo están unidos a una cadena de alquilo lineal. "Alquilo inferior" significa de 1 a 4 átomos de carbono en la cadena que puede ser lineal o ramificada. Se describe que el alquilo puede estar sustituido con uno o más "sustituyentes de grupo alquilo", que pueden ser iguales o diferentes, e incluyen, por ejemplo, halo, cicloalquilo, hidroxi, alcoxi, amino, acilamino, aroilamino, carboxi.
[0011] El término "halo" (o "Hal") se refiere a los átomos del grupo 17 de la tabla periódica (halógenos) e incluye, en particular, átomo de flúor, cloro, bromo y yodo.
[0012] Los términos "arilalquilo" o "aralquilo" se refieren a un resto alquilo en el que un átomo de hidrógeno del alquilo es reemplazado por un grupo arilo (posiblemente sustituido). Ejemplos de "arilalquilo" o "aralquilo" incluyen grupos bencilo y 9-fluorenilo.
[0013] El término "cicloalquilo" tal como se emplea en el presente documento incluye grupos hidrocarburo saturados cíclicos, bicíclicos, tricíclicos o policíclicos que tienen de 3 a 12 carbonos, en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente. Los ejemplos de restos cicloalquilo incluyen, pero no se limitan a, ciclohexilo y adamantilo.
[0014] El término "arilo" se refiere a un sistema anular de hidrocarburo aromático monocíclico, bicíclico o tricíclico, en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente. Los ejemplos de restos arilo incluyen, pero no se limitan a, fenilo, naftilo, y antracenilo.
[0015] El término "heterociclilo" se refiere a un sistema anular no aromático monocíclcio de 3-10 miembros, bicíclico de 8-12 miembros o tricíclico de 11-14 miembros que tiene 1-3 heteroátomos si es monocíclico, 1-6 heteroátomos si es bicíclico, o 1-9 heteroátomos si es tricíclico, dichos heteroátomos seleccionados de O, N, o S (por ejemplo, átomos de carbono y 1-3, 1-6, o 1-9 heteroátomos de N, O o S si es monocíclico, bicíclico, o tricíclico, respectivamente), en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente.
[0016] El término "heteroarilo" se refiere a un sistema anular aromático monocíclico de 5-8 miembros, bicíclico de 812 miembros o tricíclico de 11-14 miembros que tiene de 1-3 heteroátomos si es monocíclico, 1-6 heteroátomos si es bicíclico o 1-9 heteroátomos si es tricíclico, dichos heteroátomos seleccionados de O, N, o S (por ejemplo, átomos de carbono y 1-3, 1-6, o 1-9 heteroátomos de N, O, o S si es monocíclico, bicíclico, o tricíclico, respectivamente), en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente.
[0017] Como grupos (hetero)arilo o (hetero)ciclilo, se pueden mencionar los siguientes:

Claims (4)

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    1. Compuesto de fórmula (I):
    imagen1
    en la que:
    - n es 0, 1 o 2;
    - A es CH, o A es C y forma, junto con R1, R2 y CO, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido;
    - X es CO o CS,
    - R1 se selecciona del grupo que consiste en: H, grupos alquilo, y grupos aralquilo, estando dichos grupos alquilo o aralquilo posiblemente sustituidos,
    - R2 es un grupo de fórmula NR3R4 u OR5, en el que:
    • R3 y R4 se seleccionan cada uno independientemente de: H, ORa, grupos alquilo, grupos aralquilo, y grupos arilo, eligiendo Ra del grupo que consiste en: H, grupos alquilo, grupos arilo, y grupos aralquilo;
    en los que R3 y R4 pueden formar, junto con el átomo de nitrógeno que llevan, un grupo heterociclilo que comprende de 5 a 20 átomos, posiblemente sustituido,
    • R5 se selecciona entre: grupos alquilo, grupos arilo, y grupos aralquilo,
    en el que R5 puede formar, junto con el átomo de oxígeno que lleva, un grupo heterociclilo de 5 a 20 átomos, posiblemente sustituido,
    - R6 es H o un grupo alquilo, o puede formar junto con R2 un grupo heterociclilo de 20 a 30 átomos de carbono, o puede formar junto con R1 un grupo heterociclilo de 10 a 30 átomos,
    - R7 se selecciona entre el grupo que consiste en: grupos arilo, grupos heteroarilo, -NHPh, grupos heterociclilo, y grupos alquilo; en el que cuando R7 es arilo, heteroarilo o heterociclilo, está sustituido con al menos un grupo NH2,
    o sus sales farmacéuticamente aceptables, hidratos o sales hidratadas o sus estructuras cristalinas polimórficas, racematos, diastereómeros o enantiómeros,
    para su uso en la prevención y/o el tratamiento de patologías virales o infecciones, en el que dicho compuesto tiene la fórmula (III):
    imagen2
    en la que R4 y Ra son como se han definido anteriormente, o dicho compuesto tiene la fórmula (IV):
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    imagen3
    en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (V):
    imagen4
    en la que R1 es como se ha definido anteriormente,
    y R3 y R4 forman junto con el átomo de nitrógeno que llevan un grupo que tiene la fórmula:
    imagen5
    en la que n es 0, 1 o 2, y R es H o arilo, opcionalmente sustituido, o dicho compuesto tiene la fórmula (VI):
    imagen6
    en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (VII):
    5
    10
    15
    20
    25
    30
    35
    40
    45
    50
    55
    60
    65
    imagen7
    en la que R3 y R4 son como se han definido anteriormente, y Rs es un grupo heteroarilo, o dicho compuesto tiene la fórmula (VIII):
    imagen8
    en la que R11 y R12 son, independientemente uno del otro, seleccionados del grupo que consiste en: H, alquilo, alcoxi, arilo, y aralquilo, y A' es CH2 o NH, o dicho compuesto tiene la fórmula (IX):
    imagen9
    en la que R3 y R4 son como se han definido anteriormente, o dicho compuesto tiene la fórmula (X):
    imagen10
    5
    10
    15
    20
    25
    30
    35
    40
    45
    50
    55
    60
    65
    en la que R3 y R4 son como se han definido anteriormente, en la que
    los sustituyentes en un grupo alquilo, heterociclilo, arilo, aralquilo o heteroarilo en cualquier átomo de dicho grupo se seleccionan del grupo que consiste en alquilo, alquenilo, alquinilo, alcoxi, halo, hidroxi, ciano, nitro, amino, SO3H, sulfato, fosfato, perfluoroalquilo, perfluoroalcoxi, metilendioxi, etilendioxi, carboxilo, oxo, tioxo, imino (alquilo, arilo, aralquilo), S(O)n alquilo, en el que n es 0-2, S(O)n arilo, en el que n es 0-2, S(O)n heteroarilo, en el que n es 0-2, S(O)n heterociclilo, en el que n es 0-2, amina, éster, amida, sulfonamida, arilo no sustituido, heteroarilo no sustituido, heterociclilo no sustituido, y cicloalquilo no sustituido, y en la que
    - arilo se refiere a un sistema anular de hidrocarburo monocíclico, bicíclico o tricíclico aromático, en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente,
    - heterociclilo se refiere a un sistema anular no aromático monocíclico de 3-10 miembros, bicíclico de 8-12 miembros, o tricíclico de 11-14 miembros que tiene 1-3 heteroátomos si es monocíclico, 1-6 heteroátomos si es bicíclico o 1-9 heteroátomos si es tricíclico, dichos heteroátomos seleccionados de O, N, o S, en el que cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente,
    - heteroarilo se refiere a un sistema anular aromático monocíclico de 5-8 miembros, bicíclico de 8-12 miembros o tricíclico de 11-14 miembros que tiene 1-3 heteroátomos si es monocíclico, 1-6 heteroátomos si es bicíclico o 1-9 heteroátomos si es tricíclico, dichos heteroátomos seleccionados de O, N, o S, en el cualquier átomo del anillo capaz de sustitución puede estar sustituido por un sustituyente.
  2. 2. Compuesto que tiene la fórmula (I-ter-1):
    imagen11
    en la que R1, A, y R6 son como se han definido en la reivindicación 1,
    y R2 es un grupo de fórmula NR3R4 con R3 y R4 formando junto con el átomo de nitrógeno que llevan un grupo que tiene la fórmula:
    imagen12
    en la que n es 0, 1 o 2, y R es H o arilo, opcionalmente sustituido
    en cualquier átomo por un sustituyente seleccionado del grupo que consiste en alquilo, alquenilo, alquinilo, alcoxi, halo, hidroxi, ciano, nitro, amino, SO3H, sulfato, fosfato, perfluoroalquilo, perfluoroalcoxi, metilendioxi, etilendioxi, carboxilo, oxo, tioxo, imino (alquilo, arilo, aralquilo), S(O)n alquilo, en el que n es 0-2, S(O)n arilo, en el que n es 0-2, S(O)n heteroarilo, en el que n es 0-2, S(O)n heterociclilo, en el que n es 0-2, amina, éster, amida, sulfonamida, arilo no sustituido, heteroarilo no sustituido, heterociclilo no sustituido, y cicloalquilo no sustituido,
    o sus sales farmacéuticamente aceptables, hidratos o sales hidratadas o sus estructuras cristalinas polimórficas, racematos, diastereómeros o enantiómeros.
  3. 3. Compuesto, según la reivindicación 2, que tiene una de las siguientes fórmulas:
    imagen13
  4. 4. Composición farmacéutica que comprende el compuesto, según la reivindicación 2 o 3, en asociación con un vehículo farmacéuticamente aceptable.
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