PE20211277A1 - Moduladores de profarmacos de la via de estres integrada - Google Patents

Moduladores de profarmacos de la via de estres integrada

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Publication number
PE20211277A1
PE20211277A1 PE2021000488A PE2021000488A PE20211277A1 PE 20211277 A1 PE20211277 A1 PE 20211277A1 PE 2021000488 A PE2021000488 A PE 2021000488A PE 2021000488 A PE2021000488 A PE 2021000488A PE 20211277 A1 PE20211277 A1 PE 20211277A1
Authority
PE
Peru
Prior art keywords
prodrug
modulators
4alkyl
compound
integrated stress
Prior art date
Application number
PE2021000488A
Other languages
English (en)
Inventor
Kathleen Ann Martin
Carmela Sidrauski
Michael J Dart
Jennifer M Frost
Yunsong Tong
Xiangdong Xu
Lei Shi
Kathleen Murauski
Marina Pliushchev
Brian S Brown
Eric Voight
John T Randolph
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 PE20211277A1 publication Critical patent/PE20211277A1/es

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    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/14—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
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    • C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C235/36—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
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Abstract

La presente invencion se refiere a un compuesto de formula (I); en donde R1 se selecciona de -C(O)-alquiloC1-4, -C(O)-O-alquiloC1-4, -C(O)-N(Ra )-alquiloC1-4, -C(O)-alquilenoC1-4-alcoxi C1-4, -C(O)-alquilenoC1-4-O-alquilenoC1-4-alcoxiC1-4, -metileno-O-P(O)(OH)2, entre otros; Ra y Rb se seleccionan independientemente en hidrogeno y alquilo C1-3. Dichos compuestos son utiles como moduladores de eIF2B (factor del inicio de la traduccion) y en la atenuacion de la via de senalizacion de ISR (respuesta de estres integrada); en algunas modalidades es un profarmaco del compuesto de formula (II). Un compuesto seleccionado es acetato de (2S)-1,4-bis[2-(4-cloro-3-fluorofenoxi)acetamido]biciclo[2.2.2]octan-2-ilo. Tambien refiere una composicion farmaceutica que lo comprende; siendo util para tratar una enfermedad neurodegenerativa, una leucodistrofia, un cancer, una enfermedad inflamatoria, una enfermedad autoinmune, una infeccion viral, entre otras.
PE2021000488A 2018-10-11 2019-10-11 Moduladores de profarmacos de la via de estres integrada PE20211277A1 (es)

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US201862744293P 2018-10-11 2018-10-11
PCT/US2019/055850 WO2020077217A1 (en) 2018-10-11 2019-10-11 Prodrug modulators of the integrated stress pathway

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CA3100715A1 (en) 2018-06-05 2019-12-12 Praxis Biotech LLC Inhibitors of integrated stress response pathway
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