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AR037621A1 - Antagonistas de la hormona concentradora de melanina (mch), composiciones farmaceuticas, un proceso para elaborar una composicion farmaceutica y el uso de dichos compuestos, solos o en combinacion para la fabricacion de un medicamento para el tratamiento de la obesidad - Google Patents

Antagonistas de la hormona concentradora de melanina (mch), composiciones farmaceuticas, un proceso para elaborar una composicion farmaceutica y el uso de dichos compuestos, solos o en combinacion para la fabricacion de un medicamento para el tratamiento de la obesidad

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Publication number
AR037621A1
AR037621A1 ARP020104668A ARP020104668A AR037621A1 AR 037621 A1 AR037621 A1 AR 037621A1 AR P020104668 A ARP020104668 A AR P020104668A AR P020104668 A ARP020104668 A AR P020104668A AR 037621 A1 AR037621 A1 AR 037621A1
Authority
AR
Argentina
Prior art keywords
alkyl
aryl
group
groups
heteroaryl
Prior art date
Application number
ARP020104668A
Other languages
English (en)
Original Assignee
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Corp filed Critical Schering Corp
Publication of AR037621A1 publication Critical patent/AR037621A1/es

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    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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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    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract

Antagonista de la hormona concentradora de melanina (MCH) representado por la fórmula estructural (1); o una sal o solvato aceptable para uso farmacéutico de dicho compuesto, isómero o mezcla racémica, en la cual Ar1 es arilo, heteroarilo, arilo sustituido con (R7)p o heteroarilo sustituido con (R7)p, en donde p es un número entero de 1 a 3 y cuando p es mayor a 1, cada R7 puede ser igual o diferente y se selecciona independientemente del grupo que consiste en alquilo, cicloalquilo, halo, -CN, alcoxi, -CF3, -OCF3, -C(O)N(R8)2, -N(R9)2, (C1-6)alquilenoN(R9)2-S-alquilo, -S(O)-alquilo, -S(O2)-alquilo, -S(O2)N(R8)2, -N(R8)C(O)R5, (C1-6)alquiloN(R8)C(O)R5, NO2, -C(O)alquilo, C(O2)R8, C(R8)2OR8, C=NOR8 y una porción cíclica seleccionada del grupo que está compuesto por el grupo de fórmulas (2); en donde dicha porción cíclica, junto con Ar1, opcionalmente puede formar una porción aromática fusionada tal como indol, indolona, benzimidazol, benzoxazol, benztiazol, benzisoxazol, o benztriazol; y además en donde si dos grupos R7 son adyacentes, dichas porciones R7 adyacentes pueden estar opcionalmente unidas para formar una porción metilandioxi o etilendioxi, Ar2 es arilo, heteroarilo, arilo sustituido con (R7)p o heteroarilo sustituido con (R7)p, en donde p es un número entero de 1 a 3 y cuando p es mayor a 1, cada R7 puede ser igual o diferente y se selecciona independientemente del grupo que consiste en alquilo, cicloalquilo, halo, -CN, alcoxi, -CF3, -OCF3, -C(O)N(R8)2, -N(R9), alquileno (C1-6)-N(R9)2-alquilo, -S(O)-alquilo, -S(O2)-alquilo, -S(O2)N(R8)2, -N(R8)C(O)R5, (C1-6)N(R8)C(O)R5, NO2, -C(O)alquilo, C(O2)R8, C(R8)2OR8, C=NOR8 y una porción cíclica seleccionada del grupo que está integrado por el grupo de fórmulas (2) en donde dicha porción cíclica, junto con Ar1, opcionalmente puede formar una porción aromática fusionada tal como indol, indolona, benzoimidazol, benzoxazol, benzotiazol, benzoisoxazol, o benzotriazol; y además en donde si dos grupos R7 son adyacentes, dichas porciones R7 adyacentes pueden estar opcionalmente unidas para formar una porción metilendioxi o etilendioxi, X es O, S o N-(CN); Y es un enlace simple o un grupo alquileno; Z es un cicloalquileno C4-8 o heterocicloalquileno C4-8 en donde cada uno de dichos grupos cicloalquileno C4-8 o heterocicloalquileno C4-8 contiene opcionalmente uno o dos enlaces dobles dentro del anillo cíclico y está opcionalmente sustituido con 1 a 4 grupos R6 en el anillo en donde cada R6 está independientemente seleccionado del grupo que consiste de alquilo, cicloalquilo, -OH, -N(R9)2, -NR9COalquilo, alcoxi y -OC(O)-alquilo, con la condición de que cuando R6 es -OH o -N(R9)2, R6 no está unido a un carbono adyacente a un nitrógeno y cuando dos grupos R6 son -OH, ningún R6 está en el mismo carbono en Z y además que dos grupos R6 pueden estar opcionalmente unidos de modo que Z y dichos dos grupos R6 juntos formen un grupo bicicloalquileno o bicicloheteroalquileno que contiene de 5 a 12 átomos; R1 es como se muestra en la fórmula (3), arilo, heteroarilo, o como se muestra en las fórmula (4) ó (5), donde s y q independientemente son de 0 a 6, la suma de s y q es 2 a 6 y r es de 0 a 3; o como se muestra en el grupo de fórmulas (6), o R1 es -N(R3)2, -N(H)C(O)alquilenN(R3)2, -C(O)N(H)alquilenN(R3)2, -C(O)N(alquil)alquilenN(R3)2, -alquilenC(H)(OH)alquilenN(R3)2, -N(alquil)alquilenN(R3)2, -N(H)alquilenC(O)R5, -N(alquil)alquilenN(alquil)S(O2)R5 o -N(alquil)alquilenC(O)N(R3)2, R2 es hidrógeno o alquilo; cada R3 es independientemente hidrógeno, alquilo, cicloalquilo, cicloalquilalquilo, alcoxialquileno-, arilo, aralquilo, heteroarilo, heterociclilo, heteroaralquilo, -S(O2)alquilo, -S(O2)arilo, -S(O2)N(H)alquilo, -S(O2)N(alquilo)2, -S(O2)alquilo, -S(O2)heterocicloalquilo, -C(O)alquilo, -C(O)arilo, -C(O)heteroarilo, -C(O)heterocicloalquilo, -C(O)N(H)alquilo, -C(O)N(alquilo)2, -C(O)N(H)arilo, -C(O)Oarilo, o alquileno-C(O)Oalquilo, en donde cada uno de dichos grupos alquilo, alquileno, alcoxi, aralquilo, arilo, heteroarilo, heteroaralquilo, o cicloalquilo pueden estar independientemente no sustituido halo sustituidos o hidroxi sustituido; R4 es R3, alcoxi o -N(R3)2, con la condición de que cuando R4 está unido a un átomo de azufre entonces R4 no es hidrógeno; R5 es H, -N(R3)2, alquilo, cicloalquilo, cicloalquilalquilo, arilo, aralquilo, heteroaralquilo, alcoxi, o alcoxialquileno-, en donde cada uno de dichos grupos alquilo, alquileno, alcoxi, aralquilo, arilo, heteroaralquilo o cicloalquilo pueden estar independientemente no sustituidos, halo sustituidos o hidroxi sustituidos; R8 es H, alquilo o cicloalquilo; R9 es H, -C(O)alquilo o -S(O2)alquilo; R10 es R5 o halógeno; con las siguientes condiciones: que cada R3 de -N(R3)2 pueden ser iguales o diferentes y se seleccionan independientemente entre sí; que cada R8 y R9 de -C(O)N(R8)2, -N(R9)2 y -S(O2)N(R8)2 pueden ser iguales o diferentes y se seleccionan independientemente entre sí, y que en las fórmulas químicas anteriores, cada R3 y R4 pueden ser iguales o diferentes y se seleccionan independientemente entre sí; composiciones farmacéuticas, un proceso para elaborar una composición farmacéutica y el uso de dichos compuestos, solos o en combinación para la fabricación de un medicamento para el tratamiento de la obesidad.
ARP020104668A 2001-12-04 2002-12-03 Antagonistas de la hormona concentradora de melanina (mch), composiciones farmaceuticas, un proceso para elaborar una composicion farmaceutica y el uso de dichos compuestos, solos o en combinacion para la fabricacion de un medicamento para el tratamiento de la obesidad AR037621A1 (es)

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