Heterocyclic inhibitors of necroptosis
AssigneesPresident and Fellows of Harvard College, Tufts University, The Brigham and Women's Hospital, Inc., Trustees of Boston University
InventorsGregory D. CUNY, Xin TENG, Junying YUAN, Alexei DEGTEREV, John A. PORCO, JR.
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Abstract
The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I) and (Ia)-(Ie) and are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring the compounds of the invention. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.
Claims21
1-19. (canceled)
A compound having a structure according to Formula (I-c)
- wherein:
- R1 is selected from H, halogen, optionally substituted C1-6 lower alkyl, or optionally substituted C1-6 cycloalkyl, or optionally substituted aryl;
- R2 is selected from H or optionally substituted C1-6 lower alkyl;
- R4A and R4B are selected, independently, from hydrogen, halogen, carboxamido, nitro, and cyano;
- R5 is H or optionally substituted C1-6 lower alkyl;
- R7 is H or optionally substituted C1-6 lower alkyl;
- each of R8, R9, R10, R11, and R12 is selected, independently, from H, lower C1-6 alkyl, halogen, amino, amido, alkoxy, nitro, and cyano, wherein at least one of R8, R9, R10, R11, and R12 is not hydrogen;
- or any pharmaceutically acceptable salt or solvate thereof, or stereoisomer thereof.
Dependencies are inferred from the claim text.