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AR065932A1 - Derivados de imidazolidinacarboxamida como inhibidores de lipasas y fosfolipasas - Google Patents

Derivados de imidazolidinacarboxamida como inhibidores de lipasas y fosfolipasas

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Publication number
AR065932A1
AR065932A1 ARP080101389A ARP080101389A AR065932A1 AR 065932 A1 AR065932 A1 AR 065932A1 AR P080101389 A ARP080101389 A AR P080101389A AR P080101389 A ARP080101389 A AR P080101389A AR 065932 A1 AR065932 A1 AR 065932A1
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Argentina
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alkyl
alkylene
cycloalkyl
aryl
different way
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ARP080101389A
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Anesini Claudia
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Abstract

Su uso como medicamentos y composiciones farmacéuticas. Reivindicacion 1: Un compuesto de la formula (1) en la que: X, Y de igual o diferente modo -C(R3)(R4)-, -(C=O)-, -(C=S), en la que al menos uno de X o Y es -(C=O)- o -(C=S)-; pero ambos nopueden ser simultáneamente -(C=O)- o -(C=S)-; o X e Y juntos son C(R3)=C(R3); R hidrogeno, alquilo (C1-8), halogenoalquilo (C1-5), (CR5R6)m-O(R7), alquiloxi(C1-3)-alquileno(C1-3, arilo, heterociclo, alquilen(C1-4)-arilo, alquilen(C1-4)-heteroarilo,alquilen(C1-4)-cicloalquilo (C5-12), en los que el cicloalquilo, arilo, heterociclo o heteroarilo pueden estar sustituidos una más veces con F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O-alquilo(C1-6), O-alcoxi(C1-4)-alquilo(C1-4), S-alquilo(C1-6),alquilo (C1-6), halogenoalquilo (C2-4), O-halogenoalquilo(C2-4), alquenilo (C2-6), cicloalquilo (C3-8), O-cicloalquilo(C3-8), alquinilo (C2-6), alquilen(C0-8)-arilo, O-alquilen(C0-8)-arilo, S-arilo, alquilen(C0-8)-heteroarilo, N-(R5)(R6), SO2-CH3,SO2-NH2, SF5, COOH, COO-alquilo(C1-6), CON(R5)(R6), N(R5)CO(R6), N(R5)SO2(R6), CO(R5), (CR5R6)m'-O(R7), O-CO-N(R5)(R6), O-CO-alquilen(C1-6)-CO-O-alquilo(C1-6), O-CO-alquilen(C1-6)-CO-OH, O-CO-alquilen(C1-6)-CO-N(R5)(R6), en los que el arilo yheteroarilo pueden estar a su vez sustituidos una o más veces con F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O-alquilo(C1-6), O-alcoxi(C1-4)-alquilo(C1-4), S-alquilo(C1-6), alquilo (C1-6), alquenilo (C2-6), cicloalquilo (C3-8), O-cicloalquilo(C3-8),alquinilo (C2-6), N(R8)(R9), SO2-CH3, SF5, COOH, COO-alquilo(C1-6), CON(R8)(R9), N(R8)CO(R9), N(R8SO2(R9), CO(R8), (CR8R9)m''-O(R10), O-CO-N(R8)(R9), O-CO-alquilen(C1-6)-CO-O-alquilo(C1-6), O-CO-alquilen(C1-6)-CO-OH, O-CO-alquilen(C1-6)-CO-N(R8)(R9); m, m', m'' 0, 1, 2, 3, 4, 5, 6; R5, R6, R7, R8, R9, R10 de igual o diferente modo hidrogeno, alquilo (C1-8); o -(C=O)-NR1aR2a; o -(C=O)-O-R1b; o Ry X para X = -C(R3)(R4)- forman un sistema anular monocíclico, de 4 a 7 miembros, saturadoso parcialmente insaturado o un sistema anular bibíblico, de 8 a 14 miembros, saturado o parcialmente insaturado, cuyos miembros individuales de los sistemas anulares se pueden sustituir por uno a tres átomos o grupos de átomos de la serie -CHR11-, -CR11R12-, -(C=R11)-, =C(R11)-, -NR11-, -C(=O)-, -O-, -S-, -SO-, -SO2-, con la condicion de que dos unidades de la serie -O-, -S-, -SO-, -SO2- no pueden ser adyacentes; R11, R12 de igual o diferente modo hidrogeno, alquilo (C1-6), arilo, cicloalquilo(C3-12), alquilen(C1-4)-arilo, alquilen(C1-3)-cicloalquilo(C3-12); en los que el arilo o cicloalquilo pueden estar sustituidos con F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O-alquilo(C1-6), O-alcoxi(C1-4)-alquilo(C1-4), S-alquilo(C1-6), alquilo (C1-6),halogenoalquilo(C2-4), O-halogenoalquilo(C2-4), alquenilo (C2-6), alquinilo (C2-6), N(R13)(R14), SO2-CH3, SO2-NH2, SF5, COOH, COO-alquilo(C1-6), CON(R13)(R14), N(R13)CO(R14), N(R13)SO2(R14), CO(R13), (CR13R14)n-O(R15), O-CO-N(R13)(R14), O-CO-alquilen(C1-6)-CO-O-alquilo(C1-6), O-CO-alquilen(C1-6)-CO-OH, O-CO-alquilen(C1-6)-CO-N(R13)(R14); n 0, 1, 2, 3, 4, 5, 6; R13, R14, R15 de igual o diferente modo hidrogeno, alquilo (C1-8); R1, R1a, R1b de igual o diferente modo alquilo (C5-16), CH2-arilo, alquilen(C1-2)-heteroarilo, CH2-cicloalquilo(C5-12), en los que el arilo, heteroarilo o cicloalquilo pueden estar sustituidos una o más veces con F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O-alquilo(C1-6), O-alcoxi(C1-4)-alquilo(C1-4), S-alquilo(C1-6), alquilo (C1-6), halogenoalquilo (C2-4), O-halogenoalquilo(C2-4), alquenilo (C2-6), cicloalquilo (C3-8), O-cicloalquilo(C3-8), alquinilo (C2-6), alquilen(C0-8)-arilo, O-alquilen(0-8)-arilo, S-arilo, alquilen(C0-8)-heteroarilo,N(R16)(R17), SO2-CH3, SO2-NH2, SF5, COOH, COO-alquilo(C1-6), CON(R16)(R17), N(R16)CO(R17), N(R16)SO2(R17), CO(R16), (CR16R17)o-O(R18), O-CO-N(R16)(R17), O-CO-alquilen(C1-6)-CO-O-alquilo(C1-6), O-CO-alquilen(C1-6)-CO-OH, O-CO-alquilen(C1-6)-CO-N(R16)(R17), en los que el arilo o heteroarilo a su vez pueden estar sustituidos una o más veces con F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O-alquilo(C1-6), O-alcoxi(C1-4)-alquilo(C1-4), S-alquilo(C1-6), alquilo (C1-6), alquenilo (C2-6), cicloalquilo(C3-8), O-cicloalquilo(C3-8), alquinilo (C2-6), N(R19)(R20), SO2-CH3, SF5, COOH, COO-alquilo(C1-6), CON(R19)(R20), N(R19)CO(R20), N(R19)SO2(R20), CO(R19), (CR19R20)o'-O(R21), O-CO-N(R19)(R20), O-CO-alquilen(C1-6)-CO-O-alquilo(C1-6), O-CO-alquilen(C1-6)-CO-OH, O-CO-alquilen(C1-6)-CO-N(R19)(R20); o, o' 0, 1, 2, 3, 4, 5, 6; R16, R17, R18, R19, R20, R21 de igual o diferente modo hidrogeno, alquilo (C1-8); o un radical de formula (2), con W -C(R28)(R29)-, -C(R28)(R29)-C(R28a)(R29a)-, -C(R28)(R29)-O-; R22, R23, R24, R25, R26, R27, R28, R29, R28a, R29a de igual o diferente modo hidrogeno, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, SF5, O-alquilo(C1-6), O-alcoxi(C1-4)-alquilo(C1-4), S-alquilo(C1-6), alquilo (C1-6), halogenoalquilo (C2-4), O-halogenoalquilo(C2-4), alquenilo (C2-6), cicloalquilo (C3-8), O-cicloalquilo(C3-8), cicloalquenilo (C3-8), alquinilo (C2-6), N(R30)(R31), SO2-CH3, COOH, COO-alquilo(C1-6), CON(R30)(R31), N(R30)CO(R31), N(R30)SO2(R31), CO(R30), (CR30R31)p-O(R32), O-CO-N(R30)(R31), O-CO-alquilen(C1-6)-CO-O-alquilo(C1-6), O-CO-alquilen(C1-6)-CO-OH, O-CO-alquilen(C1-6)-CO-N(R30)(R31); p 0, 1, 2, 3, 4, 5, 6; R30, R31, R32 de igual o diferente modo hidrogeno, alquilo (C1-6); o R22 y R28 o R23 y R29 junto con losátomos de carbono que los llevan forman un sistema anular monocíclico, de 5 o 6 miembros, saturado, parcialmente insaturado o aromático, cuyos miembros individuales se pueden sustituir por -CHR33-, -CR33R34-, =(C-R33)-; o R24 y R26 o R25 y R27 juntocon los átomos de carbono que los llevan forman un sistema anular monocíclico, de 5 o 6 miembros, saturado, parcialmente insaturado o aromático, cuyos miembros individuales se pueden sustituir por -CHR33-, -CR33R34-, =(C-R33)-; R33, R34 de igual odiferente modo F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, SF5, O-alquilo(C1-6), O-alcoxi(C1-4)-alquilo(C1-4), S-alquilo(C1-6), alquilo (C1-6), halogenoalquilo (C2-4)-, O-halogenoalquilo(C2-4), alquenilo (C2-6), cicloalquilo (C3-8), O-cicloalquilo (C3-8),alquinilo (C2-6), N-(R35)(R36), SO2-CH3, COOH, COO-alquilo(C1-6), CON(R35)(R36), N(R35)CO(R36), N(R35)SO2(R36), CO(R35), CR35R36)q-O(R37), O-CO-N(R35)(R36), O-CO-alquilen(C1-6)-CO-O-alquilo(C1-6), O-CO-alquilen(C1-6)-CO-OH, O-CO-alquilen(C1-6)-CO-N(R35)(R36); q 0, 1, 2, 3, 4, 5, 6; R35, R36, R37 de igual o diferente modo hidrogeno, alquilo (C1-6); R2, R2a de igual o diferente modo hidrogeno, alquilo (C1-8); R3, R4 de igual o diferente modo hidrogeno, alquilo (C1-6), bencilo; las formastautomeras del compuesto y las sales fisiologicamente toleradas del mismo; con la condicion de que R1 no es pentilo, CH2-fenilo, -CH2-(2-Cl-fenilo), cilohexilo, -(2-metilciclohexilo) si X = CH2, Y = CO, R = metilo, R2 = H.
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