(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/041040 Al 9 March 2017 (09.03.2017) P O PCT (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C07D 215/38 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/US20 16/050270 KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (22) International Filing Date: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 2 September 2016 (02.09.2016) PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 62/214,613 4 September 2015 (04.09.2015) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: CITY OF HOPE [US/US]; 1500 E. Duarte TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, Road, Duarte, CA 91010-3000 (US). DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (72) Inventors: JONES, Jeremy; 3235 Las Lunas Street, Pas SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, adena, CA 9 1107 (US). PAL, Sumanta, Kumar; 2496 W. GW, KM, ML, MR, NE, SN, TD, TG). Kern River Lane, Brea, CA 92821 (US). Published: (74) Agents: TERRANOVA, Zachary, L. et al; Mintz Levin Cohn Ferris Glovsky And Popeo, P.C., 3580 Carmel — with international search report (Art. 21(3)) Mountain Road, Suite 300, San Diego, CA 92 130-6768 — with sequence listing part of description (Rule 5.2(a)) (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (54) Title: ANDROGEN RECEPTOR ANTAGONISTS 22Rvl xenograft o o o Castrate control COHP24 o (57) Abstract: Disclosed herein are compositions and methods for modulating the androgen receptor. o ANDROGEN RECEPTOR ANTAGONISTS CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No. 62/214,613, filed September 4, 20 5, which is incorporated herein by reference in its entirety for all purposes. REFERENCE TO A "SEQUENCE LISTING," A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED AS AN ASCII FILE [0002] The Sequence Listing written in file 48440-546001WO_ST25.TXT, created September 2, 2016, 55,151 bytes, machine format IBM-PC, MS-Windows operating system, is hereby incorporated by reference. BACKGROUND [0003] Androgen receptor (A l ) is a member of the nuclear hormone receptor family activated by androgens, such as dihydrotestosterone (DHT). AR is a prime therapeutic target for treating prostate cancer. Several compounds have been developed as chemotherapy for prostate cancer. [0004] Androgen receptor competitive antagonists (antiandrogens) are drugs used to treat hormonal-based syndromes and prostate cancer. Current drugs for prostate cancer include flutamide, bicaiutamide, nilutamide, enzalutaraide and ARN-509. Each of these inhibitors binds to the hormone-binding pocket (HBP) of the androgen receptor. This is the same site that the natural physiological steroids testosterone (TES) and dihydrotestosterone (DHT) bind. The drugs work by competing with the natural hormones for binding to the pocket and, as a result, lessening activation of the receptor. Androgen receptor antagonists with different mechanisms of action and/or different binding sites would be complementary to the current commercially available antagonists. [0005] Disclosed herein are solutions to these and other problems in the art. BRIEF SUMMARY 0006] In an aspect is provided a compound, or a pharmaceutically acceptable salt thereof, having the formula: 0007] R is hydrogen or substituted or unsubstituted pyrid-2-yi. R is independently a 2 2 , 2 10 8 8 hydrogen, halogen, -CX 3, -CHX -CH 2X , -CN, -S 2 R , -SO 2 NR R , -NHNR R , 8 8 8 9 -ONR R , M IC (}} !i\ ---NH ( (0 ) R R , -N(0) RA2 , -NR R , -C(0)R , 9 7 8 10 ~ 9 9 9 -C(0)~OR , -C(0)NR R , -OR , -NR SO2R , -N C (0)R , -NR C(0)-QR , -NR OR , 2 -OCX 3, -OCHX 2, -O substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkvl, substituted or unsubstituted cvcloalkyl, substituted or unsubstituted heterocycloalkvl, substituted or unsubstituted aryf, or substituted or unsubstituted heteroaryl. R3 3 14 12 is independently a hydrogen, halogen, -CX , -CHX 2, -CH2X , -CN, -SQ„ R , -SO NR R , 12 ~ -NHNH 2, -ONR R , NHC=(0)NHNH 2, 2 2 13 1 -NHC=(0)NR R , -N(0) FFI3 , -NR R , -C(0)R , -C(0)OR , O -OR 14, -NR S0 R14, -NR C= (O)R 13, -NR C(0)-OR 13, -NR OR 13, 3 -OCX , -OCHX 2, OCH X , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkvl, substituted or unsubstituted cvcloalkyl, substituted or unsubstituted heterocycloalkvl, substituted or unsubstituted aryi, or substituted or unsubstituted heteroaryl. R 7, R8, R9, R 10 , R 11, R 2 , R 13, and R 1 are independently hydrogen, halogen, -CX3, -CHX2, -CH 2X , -OCX3, -OCHX2, -OCH 2X , -CN, -OH, -NH 2, -COOH, -CONH2 , -N0 2, -Si , -S0 H , -SO4H, -S N -NHNH 2, -ONH 2, M IC (0 X W W () N H2, -NHS0 2H , ~\ (0)H, -NHC(0)-OH, -NHOH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkvl, substituted or unsubstituted cvcloalkyl, substituted or unsubstituted heterocycloalkvl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R7 and R8 substituents bonded to the same nitrogen atom may optionally bejoined to form a substituted or unsubstituted heterocvcloalkyl or substituted or unsubstituted heteroaryl; R and R 2 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryi. R4 is independently 4 4 hydrogen, a -CX , -CHX 2, -CH2X , -CN, -C(G)H, -C(0)OH, -C(0)NH 2, substituted or unsubstituted a ky , substituted or unsubstituted heteroalkyl, substituted or unsubstituted cvcloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryi. R5 is independently a hydrogen, 5 halogen, X -CHX , -CH X , -CN, -C(0)H, -0 , 0 ! , -C(0)NH 2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cvcloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted and, or substituted or unsubstituted heteroaryi. R6 is independently a hydrogen, halogen, -CX , -C¾X 6, -CN, -C(0)H, -C(0)OH, -C(0)N¾, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cvcloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryi. L is independently a bond, substituted or unsubstituted aikyiene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkvnylene, substituted or unsubstituted heteroalkyl ene, substituted or unsubstituted heteroalkenylene, or substituted or unsubstituted heteroalkynylene. The symbols ml, m3, v2, and v3 are independently 1 or 2 . The symbols n2 and n3 are independently an integer from 0 to 4 . X, X2, X3, X4, X5, and X6 are independently -CI, -Br, -I, or -F. [0008] In another aspect is provided a pharmaceutical composition including a pharmaceutically acceptable excipient and a compound, or pharmaceutically acceptable salt thereof, as described herein. ] In another aspect is provided a method of treating a nuclear receptor activity-associated disease in a subject in need of such treatment, the method including administering a compound, or a pharmaceutically acceptable salt thereof, as described herein. [0010] In another aspect is provided a method of treating cancer in a subject in need of such treatment, the method including administering a compound, or a pharmaceutically acceptable salt thereof, as described herein. [0011] In another aspect is provided a method of inhibiting androgen receptor activity in a subject in need thereof, including administering to the subject a compound as described herein, or a pharmaceutically acceptable salt thereof. [0012] In another aspect is provided a method of inhibiting androgen receptor activity, the method including contacting an androgen receptor with an effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof. BRIEF DESCRIPTION OF THE DRAWINGS [0013] FIG. 1. Inhibition of AR activity in LNCaP cells. LNCaP cells were transfected with PSA-luciferase and a reniila control plasmid. The following day, quadruplicate wells were treated with 0.3nM DHT and increasing concentrations of the indicated compound, or vehicle. Luciferase activity was assayed 24 hours later, and the renilla-normalized PSA-luciferase activity s shown. [0014] FIG. 2 . LNCaP prostate cancer cells were grown for 7 days in the presence of the indicated compound (BiC = bicalutamide) and relative growth was assayed by D PI staining of fixed ceils and fluorescence measurement on a plate reader. Bars represent the standard error of conditions tested in quadruplicate [0015] FIG. 3 . Luciferase assay IC 0 determination and synergy with bicalutamide. See Example 2 . [0016] FIGS. 4A-4B. Activity against AR splice variants. FIG. 4A: AR-V7; FIG. 4B: A -V & es. See Example 3 . [0017] FIG. 5. Inhibition of xenograft growth in vivo; Y-axis: relative growth with respect to initial tumor size. Assay conditions (left to right): control, castrate, COHP7, and COHP24.