AR077664A2 - Compuestos como ligandos de receptores de canabinoides - Google Patents

Compuestos como ligandos de receptores de canabinoides

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Publication number
AR077664A2
AR077664A2 ARP100102555A ARP100102555A AR077664A2 AR 077664 A2 AR077664 A2 AR 077664A2 AR P100102555 A ARP100102555 A AR P100102555A AR P100102555 A ARP100102555 A AR P100102555A AR 077664 A2 AR077664 A2 AR 077664A2
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Argentina
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cr1cr1d
haloalkyl
alkyl
independently
instance
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ARP100102555A
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English (en)
Inventor
William A Carrol
Michael J Dart
Jennifer M Frost
Steven P Latshaw
Teodozyj Kolasa
Tongmei Li
Sridhar Peddi
Bo Liu
Arturo Perez-Medrano
Meena V Patel
Xeuqing Wang
Derek W Nelson
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Abbott Lab
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41210849&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR077664(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Abbott Lab filed Critical Abbott Lab
Publication of AR077664A2 publication Critical patent/AR077664A2/es

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Abstract

Se divulgan asimismo composiciones que comprenden dichos compuestos y métodos para el tratamiento de condiciones y trastornos usando dichos compuestos y composiciones para diabetes, trastornos cardiovasculares y del sistema nervioso central. Reivindicacion 1: Un compuesto caracterizado porque tiene la formula (1), o una sal, solvato, prodroga, o sal de prodroga farmacéuticamente aceptable o combinacion de los mismos donde X4 es O, S, S(O), S(O)2, o N(Rbx); donde Rbx es hidrogeno, alquilo, haloalquilo, alcoxialquilo, -C(O)O(alquilo), cicloalquilo monocíclico, -(CR1cR1d)q3-(cicloalquilo monocíclico), o haloalcoxialquilo; y A1 es -G1a-G1b, -(CR1aR1b)q1-G1c, -(CR1aR1b)q1-A2, -(CR1gR1h)q2-A4, -N(Rb)C(O)Ra, -N(Rb)C(O)ORd, -N(Rb)C(O)N(Rb)(Rc), -N(Rb)(Rc), o -N=C(Rp)Rq); o X4 y A1 juntos son N=N(Rcx); A2 es -C(O)Ra, -S(O)2Rd, -SRd, -C(O)ORa, -C(O)N(Rb)(Rc), -C(S)N(Rb)(Rc), -S(O)2N(Rb)(Rc), -C(=NORf)Ra, -CN, -N(Rc)C(O)Ra, -N(Rc)C(O)ORd, -N(Rc)S(O)2Rd, -N(Rc)C(O)N(Rb)(Rc), -N(Rc)S(O)2N(Rb)(Rc), -ORm, o -N(Rb)(Rn); A3 es C(O)Rh, -S(O)2Re, -C(O)N(Rh)2, -C(S)N(Rh)2, -S(O)2N(Rh)2, -C(=NORh)Rh, -N(Rh)C(O)Rh, -N(Rh)C(O)ORe, -N(Rh)S(O)2Re, -N(Rh)C(O)N(Rh)2, -N(Rh)S(O)2N(Rh1)2, -CN, -ORh, o -N(Rh)2; A4 es cicloalquilo, alcoxi, haloalcoxi, o N(R1m)2 donde cada instancia de R1m es en forma independiente hidrogeno o alquilo; cada instancia de Ra y Rc, es en forma independiente hidrogeno, alquilo, haloalquilo, -(CR1aR1b)q3-A3, G1d, o -(CR1aR1b)q3-G1d; Rb, en cada instancia, es en forma independiente hidrogeno, alquilo, haloalquilo, alcoxialquilo, cicloalquilo monocíclico, -(CR1cR1d)q3-(cicloalquilo monocíclico), o haloalcoxialquilo; Rd, en cada instancia, es en forma independiente alquilo, haloalquilo, -(CR1aR1b)q3-A3, G1d, o -(CR1aR1b)q3-G1d; Rcx es alquilo, haloalquilo, -(CR1aR1b)q3-A3, G1d, o -(CR1aR1b)q3-G1d; Rm es hidrogeno, -(CR1aR1b)q3-A3, G1d, o -(CR1aR1b)q3-G1d; Rn es haloalquilo, -(CR1aR1b)q3-A3, G1d, o -(CR1aR1b)q3-G1d; Rp es hidrogeno, alquilo, haloalquilo, -(CR1aR1b)q3-A3, -C(O)ORd, -C(O)Rd, G1d, o -(CR1aR1b)q3-G1d; Rq es hidrogeno, alquilo, haloalquilo, -N(Rb)(Rc), -(CR1aR1b)q3-A3, G1d, o -(CR1aR1b)q3-G1d; o Rp y Rq, junto con el átomo de carbono al cual están unidos, forman un anillo monocíclico de 5, 6, 7 u 8 miembros, opcionalmente sustituido con 1, 2, 3, 4, o 5 sustituyentes seleccionados en forma independiente entre el grupo que consiste en oxo, alquilo, haloalquilo, y halogeno; A5 representa la formula (a), (b), (c), (d), o (e), G1a y G1b son en forma independiente cicloalquilo, cicloalquenilo, heterociclo, arilo, o heteroarilo; G1c es cicloalquenilo, heterociclo, arilo, o heteroarilo; el anillo representado por G1a está opcionalmente sustituido con 1, 2, 3, 4, o 5 sustituyentes seleccionados en forma independiente entre el grupo que consiste en alquilo, alquenilo, alquinilo, halogeno, haloalquilo, =N-CN, =N-ORf, -CN, oxo, -ORf, -OC(O)Rf, -OC(O)N(Rf)2, -S(O)2Re, -S(O)2N(Rf)2, -C(O)Rf, -C(O)ORf, -C(O)N(Rf)2, -N(Rf)2, -N(Rf)C(O)Rf, -N(Rf)S(O)2Re, -N(Rf)C(O)O(Re), -N(Rf)C(O)N(Rf)2, -(CR1cR1d)q3-ORf, -(CR1cR1d)q3-OC(O)Rf, -(CR1cR1d)q3-OC(O)N(Rf)2, -(CR1cR1d)q3-S(O)2Re, -(CR1cR1d)q3-S(O)2N(Rf)2, -(CR1cR1d)q3-C(O)Rf, -(CR1cR1d)q3-C(O)ORf, -(CR1cR1d)q3-C(O)N(Rf)2, -(CR1cR1d)q3-N(Rf)2, -(CR1cR1d)q3-N(Rf)C(O)Rf, -(CR1cR1d)q3-N(Rf)S(O)2Re, -(CR1cR1d)q3-N(Rf)C(O)O(Re), -(CR1cR1d)q3-N(Rf)C(O)N(Rf)2, y -(CR1cR1d)q3-CN; los anillos representados por G1b, G1c, y el cicloalquilo de A4 están opcionalmente sustituidos en cada caso con 1, 2, 3, 4, o 5 sustituyentes seleccionados en forma independiente entre el grupo que consiste G1d, alquilo, alquenilo, alquinilo, halogeno, haloalquilo, =N-CN, =N-ORf, -CN, oxo, -ORf, -OC(O)Rf -OC(O)N(Rf)2, -S(O)2Re, -S(O)2N(Rf)2, -C(O)Rf, -C(O)ORf, -C(O)N(Rf)2, -N(Rf)2, -N(Rf)C(O)Rf, -N(Rf)S(O)2Re, -N(Rf)C(O)O(Re), -N(Rf)C(O)N(Rf)2, -(CR1cR1d)q3-G1d, -(CR1cR1d)q3-ORf, -(CR1cR1d)q3-OC(O)Rf, -(CR1cR1d)q3-OC(O)N(Rf)2, -(CR1cR1d)q3-S(O)2Re, -(CR1cR1d)q3-S(O)2N(Rf)2, -(CR1cR1d)q3-C(O)Rf, -(CR1cR1d)q3-C(O)ORf, -(CR1cR1d)q3-C(O)N(Rf)2, -(CR1cR1d)q3-N(Rf)2, -(CR1cR1d)q3-N(Rf)C(O)Rf, -(CR1cR1d)q3-N(Rf)S(O)2Re, -(CR1cR1d)q3-N(Rf)C(O)O(Re), -(CR1cR1d)q3-N(Rf)C(O)N(Rf)2 y -(CR1cR1d)q3-CN; G1d, en cada instancia, es en forma independiente un heterociclo monocíclico, un heteroarilo monocíclico, un fenilo, un cicloalquilo monocíclico, o un cicloalquenilo monocíclico; donde G1d está opcionalmente sustituido con 1, 2, 3, o 4 sustituyentes seleccionados en forma independiente entre el grupo que consiste en -N(Rh)2, -CN, oxo, alquilo, haloalquilo, alcoxi, haloalcoxi, halogeno, y OH; Re, en cada instancia, es en forma independiente alquilo C1-4, haloalquilo C1-4, cicloalquilo monocíclico, heterociclo monocíclico, o -(CR1cR1d)q3-(cicloalquilo monocíclico); Rf, en cada instancia, es en forma independiente hidrogeno, alquilo C1-4, haloalquilo C1-4, -(CR1cR1d)q3-ORh, heterociclo monocíclico, cicloalquilo monocíclico, o -(CR1cR1d)q3-(cicloalquilo monocíclico); Rh, en cada instancia, es en forma independiente hidrogeno, alquilo C1-4, haloalquilo C1-4, cicloalquilo monocíclico, o -(CR1cR1d)q3-(cicloalquilo monocíclico); R21, R22, R23, R24, y R25 es en forma independiente alquilo, alquenilo, alquinilo, haloalquilo, -(CR2aR2b)q4-OH, -(CR2aR2b)q4-O-aIquilo, -(CR2aR2b)q4-O-haloalquilo, -(CR2aR2b)q4-O-G2a, -(CR2aR2b)q4-O-(CR2cR2d)q3-G2a, -(CR2aR2b)q5-C(O)-Ra, -(CR2aR2b)q5-C(=N-ORf)Ra, -(CR2aR2b)q5-SO2-Rd, -(CR2aR2b)q5-G2b, -(CR2aR2b)q5-C(O)N(Rb)(Rc), o -(CR2aR2b)q5-CN; cada instancia de G2a es en forma independiente cicloalquilo, heterociclo, arilo, o heteroarilo; G2b es un anillo monocíclico seleccionado entre el grupo que consiste en cicloalquilo, cicloalquenilo, tienilo, fenilo, furanilo, oxazolilo, isoxazolilo, oxadiazolilo, y heterociclo; donde el heterociclo contiene 0 o 1 doble enlace, 1 o 2 oxígenos, y 0 o 1 nitrogeno como átomos del anillo; dos átomos no adyacentes de dicho anillo heterociclo pueden estar opcionalmente unidos por medio de un puente alquenileno de 2, 3, o 4 átomos de carbono, u opcionalmente unidos por un puente alquileno de 1, 2, 3, o 4 átomos de carbono; cada anillo G2b está opcionalmente fusionado con un anillo monocíclico seleccionado entre el grupo que consiste en benzo, cicloalquilo, cicloalquenilo, heterociclo y heteroarilo; cada instancia de G2a y G2b en forma independiente no está sustituida o está sustituida con 1, 2, 3, 4, 5, o 6 sustituyentes seleccionados en forma independiente entre el grupo que consiste en oxo, alquilo, halogeno, -OH, alcoxi, haloalcoxi, y haloalquilo; X1 es O o S; X2 es O, S, o N(R10) donde R10 es alquilo, alcoxialquilo, haloalcoxialquilo, o haloalquilo; X3 es O o S; R3, R4, R5, R6, R7, R8, R9, R11, y R12 es en forma independiente G3, hidrogeno, alquilo, alquenilo, alquinilo, -NO2, -CN, halogeno, -ORh, N(Rh)2, - C(O)Rh, -C(O)O(Rh), haloalquilo, -(CR3aR3b)q6-ORh, -(CR3aR3b)q6-N(Rh)2, -(CR3aR3b)q6-C(O)Rh, o -(CR3aR3b)q6-C(O)O(Rh); R13 y R14 es en forma independiente G3, hidrogeno, alquilo, haloalquilo, o -(CR3aR3b)q6-ORh; o R13 y R14 tomados junto con el átomo de carbono al cual están unidos forman un anillo heterociclo monocíclico o un anillo cicloalquilo monocíclico, donde cada uno de los cuales en forma independiente no está sustituido o está sustituido con 1, 2, 3, o 4 sustituyentes seleccionados entre el grupo que consiste en alquilo, OH, alcoxi, haloalcoxi, haloalquilo, y oxo; R15 y R16 es en forma independiente G3, hidrogeno, alquilo, haloalquilo, o -(CR3aR3b)q6-ORh; o R5 y R16 tomados junto con el átomo de carbono al cual están unidos forman un anillo cicloalquilo monocíclico o un anillo heterociclo monocíclico; donde cada uno de los cuales en forma independiente no está sustituido o está sustituido con 1, 2, 3, o 4 sustituyentes seleccionados entre el grupo que consiste en alquilo, OH, alcoxi, haloalcoxi, haloalquilo, y oxo; G3, en cada instancia, es en forma independiente cicloalquilo, cicloalquenilo, arilo, heterociclo, o heteroarilo, donde cada G3 en forma independiente no está sustituida o está sustituida con 1, 2, 3 o 4 sustituyentes seleccionados entre el grupo que consiste en alquilo C1-4, alquenilo C2-4, alquinilo C2-4, halogeno, haloalquilo C1-4, =N-CN, =N-ORh, -CN, oxo, -ORh, -OC(O)Rh, -OC(O)N(Rh)2, -S(O)2Re, -S(O)2N(Rh)2, -C(O)Rh, -C(O)Orh, -C(O)N(Rh)2, -N(Rh)2, -N(Rh)C(O)Rh, -N(Rh)S(O)2Re, -N(Rh)C(O)O(Re), y -N(Rh)C(O)N(Rh)2; R1a en cada instancia, es en forma independiente hidrogeno, halogeno, alquilo C1-4 o haloalquilo C1-4; R1b en cada instancia, es en forma independiente hidrogeno, halogeno, alquilo C1-4, alquenilo C2-4, haloalquilo C1-4, -ORh, -N(Rh)2, -N(Rh)C(O)Rh, -N(Rh)C(O)ORe, o -N(Rh)S(O)2Re; R1g en cada instancia, es en forma independiente hidrogeno, halogeno, alquilo C1-4, haloalquilo C1-4, -ORh, -N(Rh)2, -N(Rh)C(O)Rh, -N(Rh)C(O)ORe, o -N(Rh)S(O)2Re; con la condicion de que al menos una instancia de R1g es halogeno, haloalquilo C1-4, -ORh, -N(Rh)2, -N(Rh)C(O)Rh, -N(Rh)C(O)ORe, o -N(Rh)S(O)2Re; R1h, en cada instancia, es en forma independiente hidrogeno, halogeno, alquilo C1-4, o haloalquilo C1-4; R1c, R1d, R2a, R2b, R2c, R2d, R3a y R3b, en cada instancia, es en forma independiente hidrogeno, halogeno, alquilo C1-4, o haloalquilo C1-4; Rx en cada instancia, es en forma independiente G1d, alquilo C1-4, alquenilo C2-4, alquinilo C2-4, halogeno, haloalquilo C1-4, NO2, -CN, -ORf, -OC(O)Rf, -OC(O)N(Rf)2, S(O)2Re, -S(O)2N(Rf)2, -C(O)Rf, -C(O)ORf, -C(O)N(Rf)2, -N(Rf)2, -N(Rf)C(O)Rf, -N(Rf)S(O)2Re, -N(Rf)C(O)O(Re), -N(Rf)C(O)N(Rf)2, -(CR1cR1d)q3-ORf, -(CR1cR1d)q3-OC(O)Rf, -(CR1cR1d)q3-OC(O)N(Rf)2, -(CR1cR1d)q3-S(O)2Re, -(CR1cR1d)q3-S(O)2N(Rf)2, -(CR1cR1d)q3-C(O)Rf, -(CR1cR1d)q3-C(O)ORf, -(CR1cR1d)q3-C(O)N(Rf)2, -(CR1cR1d)q3-N(Rf)2, -(CR1cR1d)q3-N(Rf)C(O)Rf, -(CR1cR1d)q3-N(Rf)S(O)2Re, -(CR1cR1d)q3-N(Rf)C(O)O(Re), -(CR1cR1d)q3-N(Rf)C(O)N(Rf)2, o -(CR1cR1d)q3-CN; q1, en cada instancia, es en forma independiente 1, 2, 3, o 4; q2 y q4, en cada instancia, son en forma independiente 2, 3, 4, o 5; q3, en cada instancia, es 1, 2 o 3; q5 y q6, en cada instanc
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US20100069348A1 (en) 2010-03-18
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