AR075402A1 - Derivados heterociclicos oxigenados y/o nitrogenados de tetrahidronaftaleno, medicamentos que los contienen y uso de los mismos en el tratamiento de trastornos metabolicos, tales como obesidad,entre otros. - Google Patents

Derivados heterociclicos oxigenados y/o nitrogenados de tetrahidronaftaleno, medicamentos que los contienen y uso de los mismos en el tratamiento de trastornos metabolicos, tales como obesidad,entre otros.

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Publication number
AR075402A1
AR075402A1 ARP100100387A ARP100100387A AR075402A1 AR 075402 A1 AR075402 A1 AR 075402A1 AR P100100387 A ARP100100387 A AR P100100387A AR P100100387 A ARP100100387 A AR P100100387A AR 075402 A1 AR075402 A1 AR 075402A1
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AR
Argentina
Prior art keywords
alkyl
independently
nitrogen atom
group
alkoxy
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ARP100100387A
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English (en)
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Sanofi Aventis
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Publication of AR075402A1 publication Critical patent/AR075402A1/es

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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
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Abstract

Uso de los tetrahidronaftalenos sustituidos de la invencion y a derivados de los mismos como antagonistas de MCH. Reivindicacion 1: Un compuesto de la formula (1) en la que R1 es H, alquilo C1-8, alcoxi C1-4-alquilo C1-4, alquenilo C3-8, alquinilo C3-8, CO(R9), (C(R10)(R11))q-R12, CO(C(R13)(R14))r-R15, CO-O-alquilo C1-8 o CO(C(R13)(R14))r-N(R16)(R17); R2 es H, alquilo C1-8, alcoxi C1-4-alquilo C1-4, alquenilo C3-8, alquinilo C3-8, CO(R9), (C(R10)(R11))q-R12, CO(C(R13)(R14))r-R15, CO-O-alquilo C1-8 o CO(C(R13)(R14))r-N(R16)(R17); R1 y R2, junto con el átomo de nitrogeno al que están unidos, forman un anillo mono-, bi- o espirocíclico de 4 a 10 miembros que, además del átomo de nitrogeno, puede incluir de 0 a 3 heteroátomos adicionales seleccionados entre el grupo de oxígeno, nitrogeno y azufre, donde el sistema de anillo heterocíclico puede estar sustituido adicionalmente con F, CI, Br, CF3, CN, alquilo C1-6, cicloalquilo C3-8, O-alquilo C1-8, alcoxi C1-4-alquilo C1-4, hidroxi-alquilo C1-6, oxo, CO(R18), CON(R19)(R20), hidroxilo, COO(R21), N(R22)CO-alquilo C1-6, N(R23)(R24) o SO2-alquilo C1-6; cada uno de R10 y R11 es independientemente H, alquilo C1-6, hidroxi-alquilo C1-2, F o OH; cada uno de R9, R13, R14, R16, R17, R18, R19, R20, R21, R22, R23 y R24 es independientemente H o alquilo C1-6; o R16 y R17, R23 y R24 forma independientemente, opcionalmente junto con el átomo de nitrogeno al que está unido, un anillo de 5-6 miembros que, además del átomo de nitrogeno, también puede incluir 0-1 heteroátomos adicionales del grupo de NH, N-alquilo C1-6, oxígeno y azufre; cada uno de q y r es independientemente 0, 1, 2, 3, 4, 5 o 6; cada uno de R12 y R15 es independientemente H, OH, F, O-alquilo C1-6, S-alquilo C1-6, CN, COO(R25), N(R26)CO-alquilo C1-6, N(R27)(R28), CON(R29)(R30), SO2-alquilo C1-6, un anillo mono-, bi- o espirocíclico de 3-12 miembros que puede contener de uno a cuatro heteroátomos del grupo de N, O y S y el anillo de 3-12 miembros puede contener sustituyentes adicionales tales como F, CI, Br, OH, CF3, NO2, CN, OCF3, oxo, O-alquilo C1-6, alcoxi C1-4-alquilo C1-4, S-alquilo C1-6, alquilo C1-6, alquenilo C2-6, cicloalquilo C3-8, O-cicloalquilo C3-8, cicloalquenilo C3-8, O-cicloalquenilo C3-8, alquinilo C2-6, N(R31)(R32), COO(R33), SO2-alquilo C1-4 y COOH; cada uno de R25, R26, R27, R28, R29, R30, R31, R32 y R33 es independientemente H o alquilo C1-6; o cada uno de R27 y R28, R29 y R30, R31 y R32 forma independientemente, opcionalmente junto con el átomo de nitrogeno al que está unido, un anillo de 5-6 miembros que, además del átomo de nitrogeno, también puede incluir 0-1 heteroátomos adicionales del grupo de NH, N-alquilo C1-6, oxígeno y azufre; L1 es C(R34)(R35), C(R36)(R37)C(R38)(R39) o cicloalquilo C3-6; R1 puede unirse opcionalmente a uno de los radicales R34, R35, R36, R37, R38 o R39, para formar un anillo de 5-6 miembros opcionalmente sustituido en la cadena de carbono con alquilo C1-4; cada uno de R34, R35, R36, R37, R38 y R39 es independientemente H o alquilo C1-6; cada uno de R3, R4 y R5 es independientemente H, F, CI, Br, I, OH, CF3, NO2, CN, OCF3, O-alquilo C1-6, S-alquilo C1-6, O-alcoxi C1-4-alquilo C1-4, alquilo C1-6, CON(R40)(R41) o CO(R42); cada uno de R40, R41 y R42 es independientemente H o alquilo C1-6; o cada uno de R40 y R41 forma, opcionalmente junto con el átomo de nitrogeno al que está unido, un anillo de 5-6 miembros que, además del átomo de nitrogeno, también puede incluir 0-1 heteroátomos adicionales del grupo de NH, N-alquilo C1-6, oxígeno y azufre; X es C(R7'')(R7'''); cada uno de R6, R6', R7, R7', R7'' y R7''' es independientemente H, F, alquilo C1-6, OH u O-alquilo C1-6; R8 es H o alquilo C1-6; A es un anillo aromático de 5-6 miembros que puede incluir hasta 2 heteroátomos seleccionados entre el grupo de nitrogeno, oxígeno y azufre, y puede estar sustituido con uno o más de los sustituyentes H, F, CI, Br, I, OH, CF3, NO2, CN, OCF3, O-alquilo C1-6, O-alcoxi C1-4-alquilo C1-4, alquilo C1-6, N(R43)(R44), SO2-CH3, CON(R45)(R46), N(R47)CO(R48) y CO(R49); cada uno de R43, R44, R45, R46, R47, R48, R49 es independientemente H o alquilo C1-6; o cada uno de R43 y R44, R45 y R46 forma independientemente, opcionalmente junto con el átomo de nitrogeno al que está unido, un anillo de 5-6 miembros que, además del átomo de nitrogeno, también puede incluir 0-1 heteroátomos adicionales del grupo de NH, N-alquilo C1-4, oxígeno y azufre; L2 es un enlace o un enlazador que tiene de 1 a 4 miembros, donde los miembros se seleccionan entre el grupo que consiste en O, S, SO2, N(R50), CO, C(R51)(R52) y C?C, para dar un radical químicamente viable, y el enlazador no tiene ningun grupo O-CO o COO; B es alquilo C1-4, CF3, alcoxi C1-4-alquilo C1-4, hidroxi-alquilo C1-6, un anillo cicloalquilo mono-, bi- o espirocíclico, de 3 a 10 miembros, donde el sistema de anillo puede estar sustituido adicionalmente con uno o más de los siguientes sustituyentes: F, CF3, alquilo C1-6, O-alquilo C1-8, alcoxi C1-4-alquilo C1-4, hidroxi-alquilo C1-4, oxo, CO(R53) e hidroxilo; cada uno de R50, R51, R52 y R53 es independientemente H o alquilo C1-6; y las sales fisiologicamente compatibles del mismo, excluyendo el compuesto 4-(1-hidroxiciclobutilmetoxi)-N-((S)-6-pirrolidin-1-ilmetil-1,2,3,4-tetrahidronaftalen-2-il)benzamida.
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