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PE20190348A1 - Moduladores de la via de estres integrada - Google Patents

Moduladores de la via de estres integrada

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Publication number
PE20190348A1
PE20190348A1 PE2018002316A PE2018002316A PE20190348A1 PE 20190348 A1 PE20190348 A1 PE 20190348A1 PE 2018002316 A PE2018002316 A PE 2018002316A PE 2018002316 A PE2018002316 A PE 2018002316A PE 20190348 A1 PE20190348 A1 PE 20190348A1
Authority
PE
Peru
Prior art keywords
modulators
independently
compounds
integrated stress
isr
Prior art date
Application number
PE2018002316A
Other languages
English (en)
Inventor
Carmela Sidrauski
Marina Pliushchev
Jennifer M Frost
Lawrence A Black
Xiangdong Xu
Ramzi Farath Sweis
Lei Shi
Qinwei I Zhang
Yunsong Tong
Charles W Hutchins
Seungwon Chung
Michael J Dart
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 PE20190348A1 publication Critical patent/PE20190348A1/es

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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—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
    • A61K31/33—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
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D213/62—Oxygen or sulfur atoms
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    • C07D213/65—One oxygen atom attached in position 3 or 5
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Abstract

Referido a compuestos de Formula I o sus sales, solvatos, hidratos, tautomeros o estereoisomeros farmaceuticamente aceptables, los cuales son moduladores de la via de estres integrada (ISR). Estos compuestos de formula (I) se caracterizan porque: D es un cicloalquilo, monociclico en puente, heterociclo monociclico en puente o cubanilo, entre otros; L1 y L2 son independientemente, alquileno C1-C6, alquenileno C2-C6, entre otros; R1 y R2 son independientemente, H, alquilo C1-C6, alcoxi C1-C6, entre otros; A y W son independientemente fenilo, o heteroarilo de 5-6 miembros; t es 0 o 1. Entre los compuestos preferidos tenemos: 2-(4-cloro-3-fluorofenoxi)-N-{(2S)-4-[2-(4-clorofenoxi)acetamido]-2-hidroxibiciclo[2.2.2]octan-1-il}acetamida; 2-(3,4-dicloro-3-fluorofenoxi)-N-{3-[2-(piridin-2-il)acetamido]biciclo[1.1.1]pentan-1-il}acetamida; entre otros. Tambien se refiere a composiciones, metodos de produccion y su uso para modular la ISR y para tratar enfermedades, trastornos y afecciones relacionados como enfermedad neurodegenerativa, leucodistrofia, cancer, entre otros.
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