AR125309A2 - Moduladores de prodroga de la vía de estrés integrada - Google Patents

Moduladores de prodroga de la vía de estrés integrada

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Publication number
AR125309A2
AR125309A2 ARP220100871A ARP220100871A AR125309A2 AR 125309 A2 AR125309 A2 AR 125309A2 AR P220100871 A ARP220100871 A AR P220100871A AR P220100871 A ARP220100871 A AR P220100871A AR 125309 A2 AR125309 A2 AR 125309A2
Authority
AR
Argentina
Prior art keywords
alkylene
phenylene
disease
5alkylene
methylene
Prior art date
Application number
ARP220100871A
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 AR125309A2 publication Critical patent/AR125309A2/es

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    • C07C235/02—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
    • 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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    • C07C235/02—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
    • 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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    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/221—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
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    • A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
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    • C07C271/06—Esters of carbamic acids
    • C07C271/32—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C271/34—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
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    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/34—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfuric acids
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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
    • C07D213/60—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 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 ring carbon atoms
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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
    • C07D213/60—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 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 ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
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    • C07F9/576—Six-membered rings
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  • Chemical & Material Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
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  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Engineering & Computer Science (AREA)
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  • Diabetes (AREA)
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  • Urology & Nephrology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Biomedical Technology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Optical Modulation, Optical Deflection, Nonlinear Optics, Optical Demodulation, Optical Logic Elements (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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 representado por la fórmula (1); o una de sus sales, cocristales, solvatos, hidratos, tautómeros, ésteres, N-óxidos o estereoisómeros farmacéuticamente aceptables, en donde: R¹ se selecciona del grupo que consiste en -C(O)-alquilo C₁₋₄, -C(O)-O-alquilo C₁₋₄, -C(O)-N(Rᵃ)-alquilo C₁₋₄, -C(O)-alquilen C₁₋₄-alcoxi C₁₋₄, -C(O)-alquilen C₁₋₄-O-alquilen C₁₋₄-alcoxi C₁₋₄, -metilen-O-P(O)(OH)₂, -C(O)-alquilen C₁₋₅-O-P(O)(OH)₂, -C(O)-O-alquilen C₁₋₅-OP(O)(OH)₂, -C(O)-N(Rᵃ)-alquilen C₁₋₅-O-P(O)(OH)₂, -C(O)-alquilen C₁₋₅-P(O)(OH)₂, -C(O)-alquilen C₁₋₅-fenilen-O-P(O)(OH)₂, -C(O)-alquilen C₁₋₅-fenilen-(O-P(O)(OH)₂)₂, -C(O)-alquilen C₁₋₅-fenilen-(OP(O)(OH)₂)(O-alquilen C₁₋₅-P(O)(OH)₂), -metilen-O-C(O)alquilen C₁₋₅-fenilen-O-P(O)(OH)₂ o -metilen-O-C(O)alquilen C₁₋₅-fenilen-(OP(O)(OH)₂)₂, -C(O)-O-alquilen C₁₋₅-O-C(O)alquilen C₁₋₅-fenilen-OP(O)(OH)₂, -C(O)-N(Rᵃ)-heteroarilen-alquilen C₁₋₂-O-P(O)(OH)₂, -P(O)(OH)₂, -SO₃H, -SO₂NRᵃRᵇ, -C(O)-heteroarilo, -C(O)-alquilen C₁₋₅-Oalquilen C₁₋₅-fenilo y metilen-alcóxido C₁₋₅; en donde -C(O)-alquilo C₁₋₄ está sustituido con uno o dos sustituyentes seleccionados cada uno, de modo independiente, del grupo que consiste en -NRᵃRᵇ y -CO₂H; y en donde -C(O)-O-alquilo C₁₋₄, -C(O)-N(Rᵃ)-alquilo C₁₋₄, -C(O)-alquilen C₁₋₄-alcoxi C₁₋₄, -C(O)-alquilen C₁₋₄-O-alquilen C₁₋₄-alcoxi C₁₋₄, metilen-O-P(O)(OH)₂, -C(O)-alquilen C₁₋₅-O-P(O)(OH)₂, -C(O)-O-alquilen C₁₋₅-O-P(O)(OH)₂, -C(O)-N(Rᵃ)-alquilen C₁₋₅-O-P(O)(OH)₂, -C(O)-alquilen C₁₋₅-P(O)(OH)₂, -C(O)-alquilen C₁₋₅-fenilen-O-P(O)(OH)₂, -C(O)-alquilen C₁₋₅-fenilen-(OP(O)(OH)₂)₂, -C(O)-alquilen C₁₋₅-fenilen-(O-P(O)(OH)₂)(O-alquilen C₁₋₅-P(O)(OH)₂), -metilen-O-C(O)alquilen C₁₋₅-fenilen-O-P(O)(OH)₂ o -metilen-O-C(O)alquilen C₁₋₅-fenilen-(O-P(O)(OH)₂)₂, -C(O)-O-alquilen C₁₋₅-O-C(O)alquilen C₁₋₅-fenilen-O-P(O)(OH)₂, -C(O)-heteroarilo, -C(O)-alquilen C₁₋₅-O-alquilen C₁₋₅-fenilo y -C(O)-N(Rᵃ)-heteroarilenalquilen C₁₋₂-O-P(O)(OH)₂ pueden estar opcionalmente sustituidos con uno, dos, tres o cuatro sustituyentes seleccionados cada uno, de modo independiente, del grupo que consiste en halógeno, -CO₂H, -NRᵃRᵇ y alquilo C₁₋₂ (opcionalmente sustituido con uno, dos o tres flúor) y arilo; y Rᵃ y Rᵇ se seleccionan de modo independiente, para cada aparición, del grupo que consiste en hidrógeno y alquilo C₁₋₃. Reivindicación 38: Un método de tratamiento de una enfermedad neurodegenerativa, una leucodistrofia, un cáncer, una enfermedad inflamatoria, una enfermedad autoinmune, una infección viral, una enfermedad cutánea, una enfermedad fibrótica, una enfermedad de hemoglobina, una enfermedad renal, una condición de pérdida de la audición, una enfermedad ocular, una enfermedad musculoesquelética, una enfermedad metabólica, o una enfermedad mitocondrial en un paciente que lo necesita, que comprende la administración al paciente de una cantidad eficaz de compuesto de acuerdo con cualquiera de las reivindicaciones 1 - 35. Reivindicación 58: Un método de tratamiento de una enfermedad relacionada con una modulación de la actividad o niveles de eIF2B, la actividad o niveles de eIF2a, o la actividad o niveles de un componente de la vía de eIF2 o la vía de ISR en un paciente que lo necesita, que comprende la administración al paciente de una cantidad eficaz de un compuesto de acuerdo con cualquiera de las reivindicaciones 1 - 35. Reivindicación 61: Un método de tratamiento de un cáncer en un paciente que lo necesita, que comprende la administración al paciente de un compuesto de acuerdo con cualquiera de las reivindicaciones 1 - 35 en combinación con un agente inmunoterapéutico.
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