Anticancer compounds selective for ER-positive cancers
AssigneeThe Board of Trustees of the University of Illinois Urbana, Illinois
InventorsPaul J. Hergenrother, Matthew Boudreau
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Abstract
Small molecule ERα biomodulators that kill therapy-resistant ERa positive breast, ovarian, and endometrial cancer cells are disclosed. In one embodiment, the small molecule biomodulator has increased therapeutic utility because of an increased ability to kill therapy-resistant cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen, and fulvestrant/ICI). The small molecule biomodulators not only inhibit proliferation of the cancer cells but kills them, which prevents reactivation of tumors years later. Compounds of the invention, such as ErSO-DFP, are effective for treating ERa positive cancers such as breast cancer, ovarian cancer, uterine cancer, cervical carcinoma, endometrial cancer, and the like.
Claims22
A compound of Formula I:
- wherein
- X is O, S, or NRA,
- Y is NRA, O, or S;
- each RA is independently H or alkyl;
- R1 is alkyl, cycloalkyl, halo, —ORB, —SRB, or —N(RB)2, wherein alkyl and cycloalkyl of R1 is optionally substituted with one or more substituents;
- R2, R3 and R4 are each independently H, trifluoromethyl, alkyl, cycloalkyl, heterocycle, aryl, heteroaryl, halo, —ORB, —SRB, or —N(RB)2;
- each RB is independently H, trifluoromethyl, or alkyl;
- each RX is independently OH, halo, alkyl, —ORC, —SRC, —S(═O)2RC;
- each RC is independently H, trifluoromethyl, or alkyl;
- n is 1, 2, 3, 4, 5, or 0;
- and
- Z is a 6-, 5-, 4-, 7-, or 8-membered nitrogen-containing heterocycle, wherein a nitrogen atom of the nitrogen-containing heterocycle is bonded to the benzylic carbon atom of Formula I and is substituted with one or more substituents;
- or a salt thereof.
The compound ErSO-DFP ((R)-2):
Dependencies are inferred from the claim text.