DRG-MDM2-4 for use as a novel mouse double minute 2 (MDM2) inhibitor
The invention relates to compounds according to formula (I) and pharmaceutically acceptable derivatives thereof for use as novel inhibitors of Mouse Double Minute 2 (MDM2) activity by inhibiting interactions between MDM2 and its natural negative regulator, p53. Pharmaceutical compositions containing a compound of Formula (I), or a derivative thereof, including compositions that also contain one or more additional antiproliferative agents, can be used in methods of treating proliferative diseases, including various cancers.
1 . A pharmaceutical composition comprising a compound of Formula I,
or a hydrate, a solvate, a stereoisomer, a salt, or a tautomer thereof, and at least one pharmaceutically acceptable excipient.
2 . A pharmaceutical composition comprising a compound of Formula I,
or a hydrate, a solvate, a stereoisomer, a salt, or a tautomer thereof, and one or more anti-proliferative agents.
3 . The pharmaceutical composition of claim 2 , wherein the anti-proliferative agents are selected from the group consisting of alkylating agents, anthracyclines, taxanes or cytoskeletal disruptors, epothilones, histone deacetylase inhibitors, inhibitors of topoisomerase I, inhibitors of topoisomerase II, kinase inhibitors, tyrosine kinase inhibitors, nucleotide analogs and precursor analogs, peptide antibiotics, platinum-based agents, retinoids, vinca alkaloids, and derivatives thereof.
4 . The pharmaceutical composition of claim 2 , wherein the anti-proliferative agents are selected from the group consisting of methotrexate, pemetrexed, pralatrexate, raltitrexed, etoposide, teniposide, abiraterone, bicalutamide, cyproterone, degarelix, exemestane, fiilvestrant, goserelin, histrelin, leuprolide, mifepristone, triptorelin, lenalidomide, pomalidomide, thalidomide, everolimus, temsirolimus, anagrelide, ceritinib, dabrafenib, idelalisib, ibrutinib, palbociclib, vemurafenib, bleomycin, dactinomycin, eribulin, estramustine, ixabepilone, mitomycin, procarbazine, alectinib, fluoxymesterone, iobenguane, imiquimod, interferon, ixazomib, lanreotide, lentinan, octreotide, omacetaxine, tegafur, gimeracil, oteracil, uracil, and combretastatin.
5 . A method of treating breast or colon cancer in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of a compound of Formula I,
or a hydrate, a solvate, a stereoisomer, a salt, or a tautomer thereof.
6 . A method of treating breast or colon cancer in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 1 .
7 . A method of treating breast or colon cancer in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 2 .