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WO 2016/040896 Al FIG. JO (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 2016/040896 Al 17 March 2016 (17.03.2016) P O P C T (51) International Patent Classification: (74) Agent: MILLER, Kimberly, J.; Knobbe, Martens, Olson A61K 31/105 (2006.01) A61P 35/00 (2006.01) & Bear LLP, 2040 Main Street 14th Floor, Irvine, CA A61K 31/122 (2006.01) 92614 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US20 15/04983 1 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) Date: International Filing BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 11 September 2015 ( 11.09.201 5) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (30) Priority Data: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 62/049,974 12 September 2014 (12.09.2014) US SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: PELLFICURE PHARMACEUTICALS, INC. [US/US]; 2325 Camino Del Collado, La Jolla, CA (84) Designated States (unless otherwise indicated, for every 92037 (US). kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (72) Inventors: BORGSTROM, Per; 2325 Camino Del Col TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, lado, La Jolla, CA 92037 (US). CHRASTINA, Adrian; TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, 2325 Camino Del Collado, La Jolla, CA 92037 (US). DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, BARON, Veronique, Therese; 2325 Camino Del Collado, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, La Jolla, CA 92037 (US). ABEDINPOUR, Parisa; 2325 SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Camino Del Collado, La Jolla, CA 92037 (US). GW, KM, ML, MR, NE, SN, TD, TG). [Continued on nextpage] (54) Title: COMPOSITIONS AND METHODS FOR TREATMENT OF PROSTATE CARCINOMA (57) Abstract: Disclosed herein are 1,4- naphthoquinone analogs, pharmaceutic 100 al compositions that include one or more of such 1,4-naphthoquinone ana 90.0 logs, and methods of treating and/or 80 0 ameliorating diseases and/or conditions 70.0 associated with a cancer, such as pro state cancer with such 1,4-naph 60.0 thoquinone analogs. Also included are 50.0 combination therapies wherein a 1,4- naphthoquinone analog disclosed 40.0 herein, and a hormone therapy agent are 30.0 provided to a subject suffering from a condition such as cancer. 20.0 10.0 .0 FIG. J O wo 2016/040896 Al III III II II III III I II II III III II III II I II Declarations under Rule 4.17: Published: — as to applicant's entitlement to apply for and be granted — with international search report (Art. 21(3)) a patent (Rule 4.1 7(H)) — before the expiration of the time limit for amending the — as to the applicant's entitlement to claim the priority of claims and to be republished in the event of receipt of the earlier application (Rule 4.17(Hi)) amendments (Rule 48.2(h)) COMPOSITIONS AND METHODS FOR TREATMENT OF PROSTATE CARCINOMA CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of priority to U.S. Provisional Application No. 62/049,974 filed September 12, 2014, the disclosure of which is hereby expressly incorporated by reference in its entirety. FIELD OF THE INVENTION [0002] Aspects of the present application relate to the fields of chemistry, biochemistry and medicine. More particularly, disclosed herein are novel 1,4- naphthoquinone analogs, pharmaceutical compositions that include one or more of such 1,4- naphthoquinone analogs, and methods of treating and/or ameliorating diseases and/or conditions associated with a cancer, such as prostate cancer with such 1,4-naphthoquinone analogs. Also included are combination therapies, wherein a 1,4-naphthoquinone analog disclosed herein, and a hormone therapy agent, such as a hormonal ablation compound, are provided to a subject having a cancer, such as a prostate cancer. BACKGROUND [0003] Prostate cancer develops in the prostate and is typically slow growing; however, some prostate cancers are aggressive. Prostate cancer cells are typically androgen/testosterone/DHT dependent and may metastasize from the prostate to other parts of the body, particularly the bones and lymph nodes. Treatment options for prostate cancer that remains within the prostate include watchful waiting/active surveillance, external beam radiation therapy, brachytherapy, cryosurgery, high-intensity focused ultrasound (HIFU), and surgery. Hormonal therapy and chemotherapy are often reserved for disease that has spread beyond the prostate. However, there are exceptions in that radiation therapy may be used for some advanced tumors, and hormonal therapy may be used for some early stage tumors. [0004] After one to three years of hormonal therapy, it is common that prostate cancer cells resume growth despite the androgen/testosterone/DHT blockade. Previously referred to as "hormone-refractory prostate cancer" or "androgen-independent prostate cancer," the term castration-resistant prostate cancer (CRPC) is now commonly used. Chemotherapeutic agents and immunotherapy have been shown to prolong survival after CRPC but the survival benefit is limited. Despite the efforts of many, the need for more cancer treatments, in particular prostate cancer treatments, is manifest. SUMMARY [0005] Some alternatives disclosed herein relate to a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Some alternatives disclosed herein relate to a compound of Formula (II) or a pharmaceutically acceptable salt thereof. Some alternatives disclosed herein relate to a compound of Formula (III) or a pharmaceutically acceptable salt thereof. Some alternatives disclosed herein relate to a compound of Formula (IV) or a pharmaceutically acceptable salt thereof. [0006] Some alternatives disclosed herein relate to a pharmaceutical composition containing a compound of Formula (I), (II), (III), or (IV), or a pharmaceutically acceptable salt of Formula (I), (II), (III), or (IV), and a hormone therapy agent. The pharmaceutical composition can be used for inhibiting and/or delaying prostate cancer cell growth and/or the onset of castration-resistant prostate cancer (CRPC) and/or for inhibiting or delaying progression of stage I prostate cancer to stage II prostate cancer and/or for inhibiting or delaying progression of stage II prostate cancer to stage III prostate cancer, and/or for inhibiting or delaying progression of stage III prostate cancer to stage IV prostate cancer and/or for inhibiting or delaying progression of stage IV prostate cancer and/or for inhibiting or delaying the onset of metastasis after the onset of prostate cancer. The pharmaceutical composition can be used for decreasing prostate tumor size. The hormone therapy agent can be selected from cyproterone acetate, abiraterone, finasteride, flutamide, nilutamide, bicalutamide, diethylstilbestrol (DES), megestrol acetate, fosfestrol, estamustine phosphate, leuprolide, triptorelin, goserelin, histrelin, buserelin, abarelix, degarelix, orteronel, VT-464, enzalutamide, ARN-509, vinclozolin, galeterone, ketoconazole, L-39, aminoglutethimide, prochloraz, dutasteride, izonsteride, turosteride, epristeride, genisterin, gossypol, equol, 18B- glycyrrhetinic acid, altraric acid, N-butylbenzene-sulfonamide, 3,3'-diindolylmethane, deslorelin, nafarelin, cetrorelix, and ganirelix. In some alternatives, the hormone therapy agent is an agent that reduces the production of testosterone. In some alternatives, the hormone therapy agent inhibits the conversion of testosterone to DHT. In some alternatives, the hormone therapy agent is an agent that reduces the production of testosterone and/or inhibits the conversion of testosterone to DHT. In some alternatives, the hormone therapy agent is not an androgen receptor antagonist. In some alternatives, the hormone therapy agent can be selected from abiraterone, finasteride, diethylstilbestrol (DES), megestrol acetate, fosfestrol, leuprolide, triptorelin, goserelin, histrelin, buserelin, abarelix, degarelix, orteronel, VT-464, ketoconazole, L-39, aminoglutethimide, prochloraz, dutasteride, izonsteride, turosteride, epristeride, equol, deslorelin, nafarelin, cetrorelix, and ganirelix. [0007] Some alternatives disclosed herein relate to a method of inhibiting or delaying the growth of prostate cancer, and/or inhibiting or delaying the onset of castration- resistant prostate cancer (CRPC) and/or for inhibiting or delaying progression of stage I prostate cancer to stage II prostate cancer and/or for inhibiting or delaying progression of stage II prostate cancer to stage III prostate cancer, and/or for inhibiting or delaying progression of stage III prostate cancer to stage IV prostate cancer and/or for inhibiting or delaying progression of stage IV prostate cancer and/or for inhibiting or delaying the onset of metastasis after the onset of prostate cancer by providing a subject having prostate cancer with a therapeutically effective amount of a compound of Formula (I), (II), (III), or (IV), or a pharmaceutically acceptable salt of Formula (I), (II), (III), or (IV), and, optionally, identifying or selecting the subject prior to administration as a subject having prostate cancer or CRPC or stage I, stage II, stage II, or stage IV prostate cancer, and, optionally, determining the inhibition, amelioration, or remission of prostate cancer or CRPC or stage I, stage II, stage III, or stage IV prostate cancer during or after administration. The compound of Formula (I), (II), (III), or (IV), or pharmaceutically acceptable salt thereof, can be administered to the subject in combination with an androgen deprivation therapy.
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