PE20210040A1 - Moduladores de la via de estres integrada - Google Patents

Moduladores de la via de estres integrada

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Publication number
PE20210040A1
PE20210040A1 PE2020000461A PE2020000461A PE20210040A1 PE 20210040 A1 PE20210040 A1 PE 20210040A1 PE 2020000461 A PE2020000461 A PE 2020000461A PE 2020000461 A PE2020000461 A PE 2020000461A PE 20210040 A1 PE20210040 A1 PE 20210040A1
Authority
PE
Peru
Prior art keywords
independently
compound
integrated stress
octan
fluorophenoxy
Prior art date
Application number
PE2020000461A
Other languages
English (en)
Inventor
Kathleen Martin
Carmela Sidrauski
Marina A Pliushchev
Jennifer M Frost
Yunsong Tong
Lawrence A Black
Xiangdong Xu
Lei Shi
Qingwei I Zhang
Seungwon Chung
Zhaoming Xiong
Ramzi Farah Sweis
Michael J Dart
Brian S Brown
Kathleen Murauski
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 PE20210040A1 publication Critical patent/PE20210040A1/es

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    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/423—Oxazoles condensed with carbocyclic rings
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
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    • C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
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    • C07C255/26—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups, amino groups and singly-bound oxygen atoms bound to the carbon skeleton
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    • C07C255/37—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by etherified hydroxy groups
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Abstract

Se refiere a un compuesto de formula (l) o una de sus sales, solvatos, hidratos, tautomeros, esteres, N-oxidos o estereoisomeros, en donde D es un cicloalquilo biciclico en puente, heterociclilo biciclico en puente, entre otros; L1 y L2 son cada uno, de modo independiente, alquileno C1-C6, alquenileno C2-C6, entre otros; R1 y R2 son cada uno, de modo independiente, hidrogeno, alquilo C1-C6, entre otros; A y W son cada uno, de modo independiente, fenilo o heteroarilo de 5-6 miembros; t y s son cada uno, de modo independiente, 0 o 1. Son compuestos preferidos: N,N'-(biciclo[2,2,2]octan-1,4-diil)bis[2-(4-cloro-3-fluorofenoxi)acetamida], 2-(4-cloro-3-fluorofenoxi)-N-[4-(2-{[6-(trifluorometil)piridin-3-il]oxi}acetamido)biciclo[2,2,2]octan-1-il]acetamida, entre otros. Dicho compuesto modula eIF2B y atenua la via de senalizacion de la respuesta al estres integrada (ISR), siendo utiles en el tratamiento de enfermedades, trastornos y condiciones relacionados. Tambien se refiere a una composicion que comprende dicho compuesto
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