Compounds, compositions, and methods for treatment of androgen-mediated disease
AssigneesThe Regents of the University of California, Ohio State Innovation Foundation
InventorsAllen C. Gao, Pui-Kai Li
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Abstract
Provided herein are steroid sulfatase inhibitor compounds and androgen receptor inhibitor compounds that can be useful in, for example, the treatment of cancers such as prostate cancer and breast cancer. Pharmaceutical compositions and kits including the compounds are described, as well as methods for the treatment of cancer such as prostate cancer and breast cancer.
Claims20
A compound according to Formula III:
- or pharmaceutically acceptable salt thereof, wherein:
- R1 and R2 are each independently hydrogen or C1-6 alkyl;
- R3, R4, and R5 are each independently hydrogen, halogen, —OH, C1-6 alkyl, or C1-6 alkoxy;
- R6, R7, R8, R9, and R10 are each independently hydrogen, halogen, —OH, —NH3, —NO2, —CN, C1-6haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy;
- R11 is a bond, C1-6 alkylene, NR12, or O;
- and
- R12 is hydrogen or C1-6 alkyl.
A pharmaceutical composition comprising:
- (i) an antiandrogen drug;
- and
- (ii-a) a compound according to Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is —X(SO2)Y—;
- X is O and Y is NH, or X is NH and Y is O;
- and
- R1 is combined with two carbons of the phenyl group to which it is attached to form an oxathiazolidine dioxide;
- or
- (ii-b) a compound according to Formula II:
- or a pharmaceutically acceptable salt thereof, wherein:
- the dashed line represents a single bond or a double bond;
- R20 is —O(SO2)NR23R24—, which is combined with two carbons of the phenyl group to which it is attached to form a 4- to 10-membered heterocycle, or
- R20 is —O(SO2)NR23R25;
- R21, R22, R23, and R25 are each independently hydrogen or C1-6 alkyl;
- and
- R24 is a bond, C1-6 alkylene, or C1-6 alkenylene.
The method of 15, wherein the cancer is selected from the group consisting of an androgen-independent cancer, a metastatic cancer, a castrate-resistant cancer, a castration recurrent cancer, a hormone-resistant cancer, a metastatic castrate-resistant cancer, and combinations thereof.
Dependencies are inferred from the claim text.