Necrosis Inhibitors
AssigneeNational Institute of Biological Sciences, Beijing
InventorsZhiyuan Zhang, Xiaodong Wang, Xiaoguang Lei, Yaning Su, Sudan He, Hanying Ruan, Liming Sun
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Abstract
The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.
Claims20
An amide compound that is an inhibitor of cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), of formula:
- wherein:
- R1 is a C3-C14 cyclic or hetero-cyclic moiety, particularly substituted or unsubstituted, 0-3 heteroatom C3-C9 cycloalkyl, cycloalkenyl, or cycloalkynyl;
- or substituted or unsubstituted, 0-3 heteroatom C5-C14 aryl;
- R2-R4 are independently:
- H, substituted or unsubstituted heteroatom, substituted or unsubstituted, 0-3 heteroatom C1-C9 alkyl, substituted or unsubstituted, 0-3 heteroatom C2-C9 alkenyl, substituted or unsubstituted, 0-3 heteroatom C2-C9 alkynyl, and substituted or unsubstituted, 0-3 heteroatom C5-C14 aryl, wherein each heteroatom is independently oxygen, phosphorus, sulfur or nitrogen;
- or
- a corresponding sulfonamide of the amide compound, or
- a pharmaceutically acceptable salt, hydride or stereoisomer the compound;
- with the proviso that if R1 is phenyl, R3 is H, and R4 is 1,1-dimethylpropyl, then R2 is other than H, preferably substituted or unsubstituted heteroatom, substituted or unsubstituted, 0-3 heteroatom C1-C9 alkyl, substituted or unsubstituted, 0-3 heteroatom C2-C9 alkenyl, substituted or unsubstituted, 0-3 heteroatom C2-C9 alkynyl, and substituted or unsubstituted, 0-3 heteroatom C5-C14 aryl, wherein each heteroatom is independently oxygen, phosphorus, sulfur or nitrogen.
Dependencies are inferred from the claim text.