Procaspase-activating compounds and compositions
View Patent ↗The invention provides compounds and compositions useful for the modulation of certain enzymes. The compounds and compositions can induce of cell death, particularly cancer cell death. The invention also provides methods for the synthesis and use of the compounds and compositions, including the use of compounds and compositions in therapy for the treatment of cancer and selective induction of apoptosis in cells.
1. A compound that directly activates procaspase-3 upon contacting procaspase-3, wherein the compound is a novel compound of Formula I:
wherein
R 1 is a substituted (aryl)methylene, or (aryl)methine wherein the methine carbon is optionally substituted with phenyl;
n is 2;
each R 2 is methyl, ethyl or t-butyl or two R 2 groups form an ortho-fused benzo group; and
wherein R 1 is substituted (aryl)methylene, the (aryl)methylene substitution comprises one or more nitro, sulfonamide, azidomethylene, phenoxy, phenyl, trifluoromethyl, trifluoromethoxy, phenylsulfonylmethylene, benzoyl, or a combination thereof;
or a pharmaceutically acceptable salt or solvate thereof.
2. The compound of claim 1 wherein each R 2 is t-butyl.
3. The compound of claim 1 wherein R 1 is (aryl)methine wherein the methine carbon is substituted with phenyl.
4. The compound of claim 1 wherein R 1 is:
5. The compound of claim 1 wherein the compound induces death of cancer cells in culture.
6. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable diluent, excipient, or carrier.
7. The compound:
8. A pharmaceutical composition comprising a compound of claim 7 and a pharmaceutically acceptable diluent, excipient, or carrier, wherein the compound is:
or a pharmaceutically acceptable salt or solvate thereof.