AR108395A1 - Moduladores de la vía de estrés integrada - Google Patents

Moduladores de la vía de estrés integrada

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Publication number
AR108395A1
AR108395A1 ARP170101184A ARP170101184A AR108395A1 AR 108395 A1 AR108395 A1 AR 108395A1 AR P170101184 A ARP170101184 A AR P170101184A AR P170101184 A ARP170101184 A AR P170101184A AR 108395 A1 AR108395 A1 AR 108395A1
Authority
AR
Argentina
Prior art keywords
alkyl
membered
halo
independently
nrbrc
Prior art date
Application number
ARP170101184A
Other languages
English (en)
Inventor
Michael J Dart
Seungwon Chung
Charles W Hutchins
Yunsong Tong
Qinwei I Zhang
Lei Shi
Ramzi Farah Sweis
Xiangdong Xu
Lawrence A Black
Jennifer M Frost
Marina Pliushchev
Carmela Sidrauski
Original Assignee
Calico Life Sciences Llc
Abbvie Inc
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 Calico Life Sciences Llc, Abbvie Inc filed Critical Calico Life Sciences Llc
Publication of AR108395A1 publication Critical patent/AR108395A1/es

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    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
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Abstract

Se proporcionan en la presente compuestos, composiciones y métodos de utilidad para modular la respuesta al estrés integrada (ISR) y para tratar enfermedades, trastornos y condiciones relacionados. Reivindicación 1: Un compuesto de la fórmula (1), o una de sus sales, solvatos, hidratos, tautómeros o estereoisómeros farmacéuticamente aceptables, en donde: D es un cicloalquilo monocíclico en puente, heterociclo monocíclico en puente o cubanilo, en donde cada cicloalquilo monocíclico en puente, heterociclo monocíclico en puente o cubanilo está opcionalmente sustituido con 1 - 4 RX; L¹ es alquileno C₁₋₆, alquenileno C₁₋₆ o heteroalquileno de 2 - 7 miembros, en donde cada alquileno C₁₋₆, alquenileno C₁₋₆ o heteroalquileno de 2 - 7 miembros está opcionalmente sustituido con 1 - 5 RX; R¹ y R² son cada uno, de modo independiente, hidrógeno, alquilo C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, hidroxi-alquilo C₁₋₆ o sililoxi-alquilo C₁₋₆; Q es C(O) o S(O)₂; A y W son cada uno, de modo independiente, fenilo o heteroarilo, en donde cada fenilo o heteroarilo está opcionalmente sustituido con 1 - 5 RY; cada RX se selecciona, de modo independiente, del grupo que consiste en alquilo C₁₋₆, hidroxi-alquilo C₁₋₆, halo-alquilo C₁₋₆, amino-alquilo C₁₋₆, ciano-alquilo C₁₋₆, oxo, halo, ciano, -ORA, -NRBRC, -NRBC(O)RD, -C(O)NRBRC, -C(O)RD, -C(O)OH, -C(O)ORD, -SRE, -S(O)RD y -S(O)₂RD; cada RY se selecciona, de modo independiente, del grupo que consiste en hidrógeno, alquenilo C₁₋₆, hidroxi-alquilo C₁₋₆, hidroxi-alquenilo C₁₋₆, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆, amino-alquilo C₁₋₆, amido-alquilo C₁₋₆, ciano-alquilo C₁₋₆, sililoxi-alcoxi C₁₋₆, hidroxil-alcoxi C₁₋₆, oxo, halo, ciano, -ORA, -NRBRC, -NRBC(O)RD, -C(O)NRBRC, -C(O)RD, -C(O)OH, -C(O)ORD, -S(RF)ₘ, -S(O)RD, -S(O)₂RD, S(O)NRBRC, -NRBS(O)₂RD, -OS(O)RD, -OS(O)₂RD, G¹ o alquilen C₁₋₆-G¹; o 2 grupos RY en átomos adyacentes, junto con los átomos a los que están unidos, forman un anillo cicloalquilo fusionado de 3 - 7 miembros, un anillo heterociclilo fusionado de 3 - 7 miembros o un anillo heteroarilo fusionado de 5 - 6 miembros, cada uno opcionalmente sustituido con 1 - 5 RX; cada G¹ es, de modo independiente, cicloalquilo de 3 - 7 miembros, heterociclilo de 4 - 7 miembros, arilo o heteroarilo de 5 - 6 miembros, en donde cada cicloalquilo de 3 - 7 miembros, heterociclilo de 4 - 7 miembros, arilo o heteroarilo de 5 - 6 miembros está opcionalmente sustituido con 1 - 6 RZ; cada RZ se selecciona, de modo independiente, del grupo que consiste en alquilo C₁₋₆, hidroxi-alquilo C₁₋₆, halo-alquilo C₁₋₆, halo, ciano, -ORA, -NRBRC, -NRBC(O)RD, -C(O)NRBRC, -C(O)RD, -C(O)OH, -C(O)ORD y S(O)₂RD; RA es en cada aparición, de modo independiente, hidrógeno, alquilo C₁₋₆, halo-alquilo C₁₋₆, -ORA¹, -C(O)NRBRC, -C(O)RD, -C(O)OH o -C(O)ORD; cada uno de RB y RC es, de modo independiente, hidrógeno, alquilo C₁₋₆, cicloalquilo de 3 - 7 miembros o heterociclilo de 4 - 7 miembros, en donde cada alquilo, cicloalquilo o heterociclilo está opcionalmente sustituido con 1 - 6 RZ; o RB y RC junto con el átomo al que están unidos forman un cicloalquilo de 3 - 7 miembros o anillo heterociclilo opcionalmente sustituido con 1 - 6 RZ; RD es en cada aparición, de modo independiente, alquilo C₁₋₆ o halo-alquilo C₁₋₆; cada RE es, de modo independiente, hidrógeno, alquilo C₁₋₆ o halo-alquilo C₁₋₆; cada RF es, de modo independiente, hidrógeno, alquilo C₁₋₆ o halo; cada RA¹ es hidrógeno, alquilo C₁₋₆, halo-alquilo C₁₋₆, cicloalquilo de 3 - 7 miembros o heterociclilo de 4 - 7 miembros, m es 1, 3 ó 5; y t es 0 ó 1.
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