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WO 2017/173206 Al 5 October 2017 (05.10.2017) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2017/173206 Al 5 October 2017 (05.10.2017) P O P C T (51) International Patent Classification: CA 94121 (US). HUBBARD, Robert; 7684 Marker Road, A61K 31/52 (2006.01) C07D 473/02 (2006.01) San Diego, CA 92087 (US). MIKOLON, David; 6140 A61K 31/505 (2006.01) C07D 473/26 (2006.01) Calle Empinada, San Diego, CA 92120 (US). RAYMON, A61K 31/519 (2006.01) C07D 473/32 (2006.01) Heather; 3520 Vista de la Orilla, San Diego, CA 921 17 (US). SHI, Tao; 4650 Tarantella Lane, San Diego, CA (21) International Application Number: 92130 (US). TRAN, Tam, M.; 8953 Libra Drive, San PCT/US20 17/025252 Diego, CA 92126 (US). TSUJI, Toshiya; 4171 Donald (22) International Filing Date: Court, San Diego, CA 921 17 (US). WONG, Lilly, L.; 871 3 1 March 2017 (3 1.03.2017) Viva Court, Solana Beach, CA 92075 (US). XU, Suichan; 9650 Deer Trail Place, San Diego, CA 92127 (US). ZHU, (25) Filing Language: English Dan; 4432 Calle Mar De Armonia, San Diego, CA 92130 (26) Publication Language: English (US). (30) Priority Data: (74) Agents: BRUNER, Michael, J. et al; Jones Day, 250 Ve- 62/3 17,412 1 April 2016 (01.04.2016) US sey Street, New York, NY 10281-1047 (US). (71) Applicant: SIGNAL PHARMACEUTICALS, LLC (81) Designated States (unless otherwise indicated, for every [US/US]; 10300 Campus Point Drive, Suite 100, San kind of national protection available): AE, AG, AL, AM, Diego, CA 92121 (US). AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, (72) Inventors: BOYLAN, John, F.; 10486 Harvest View DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, Way, San Diego, CA 92128 (US). BRAY, Gordon, L.; HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, 301 Main Street, Unit 8c, San Francisco, CA 94105 (US). KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, FILVAROFF, Ellen; 538 18th Avenue, San Francisco, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, [Continued on nextpage] (54) Title: SUBSTITUTED AMINOPURINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH (57) Abstract: Provided herein are methods for treating or preventing a cancer, including solid tumors and hematologic al cancers, comprising administering an effective amount of aminopurine compounds of formula (I), and compositions comprising an effective amount of such compounds. Ceie.»S; Ι W O 2017/173206 1lllll II Hill lllll Hill llll III III Hill lllll Hill Hill Hill llll llll llll llll NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). VN, ZA, ZM, ZW. Published: (84) Designated States (unless otherwise indicated, for every — with international search report (Art. 21(3)) kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, — before the expiration of the time limit for amending the TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, claims and to be republished in the event of receipt of TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, amendments (Rule 48.2(h)) DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ , LT, SUBSTITUTED AMINOPURINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Patent Application No. 62/317,412, filed April 1, 2016, which is incorporated herein by reference in its entirety and for all purposes. FIELD [0002] Provided herein are methods for treating or preventing a cancer, including solid tumors and hematological cancers, comprising administering an effective amount of certain aminopurine compounds described herein, and compositions comprising an effective amount of such compounds. BACKGROUND [0003] Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, or lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis). Clinical data and molecular biologic studies indicate that cancer is a multistep process that begins with minor preneoplastic changes, which may under certain conditions progress to neoplasia. The neoplastic lesion may evolve clonally and develop an increasing capacity for invasion, growth, metastasis, and heterogeneity, especially under conditions in which the neoplastic cells escape the host's immune surveillance (Roitt, L, Brostoff, J and Kale, D., Immunology, 17.1-17.12 (3rd ed., Mosby, St. Louis, Mo., 1993)). [0004] Cancers figure among the leading causes of death worldwide, accounting for 8.2 million deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades (See Cancer Fact sheet No 297, World Health Organization, February 2014, retrieved 10 June 2014 and Globocan 2012, IARC). [0005] The current drugs used in cancer treatment are highly toxic and often non-specific. Current anticancer therapy strategies are typically focused on rapid proliferating cells, which can shrink primary and metastatic tumors, but such effects are usually transient and tumor relapse of most metastatic cancers frequently occur. One possible reason for failure is the existence of cancer stem cells. Unlike most cells within the tumor, cancer stem cells are resistant to well- defined chemotherapy, and after treatment, they can regenerate all the cell types in the tumor through their stem cell-like behavior of largely quiescent nature and their abundant expression of drug transporters. [0006] There is an enormous variety of cancers which are described in detail in the medical literature. The incidence of cancer continues to climb as the general population ages, as new cancers develop, and as susceptible populations (e.g., people infected with AIDS or excessively exposed to sunlight) grow. However, options for the treatment of cancer are limited. A tremendous demand therefore exists for new methods and compositions that can be used to treat patients with cancer [0007] Citation or identification of any reference in Section of this application is not to be construed as an admission that the reference is prior art to the present application. SUMMARY [0008] Provided herein are Aminopurine Compounds, including compositions (e.g. pharmaceutical compositions) comprising such Aminopurine Compounds, that can be used in the methods provided herein. [0009] Provided herein are methods of treating a cancer, in particular a solid tumor or a hematological cancer. The Aminopurine Compound provided herein can be used in the methods for treating or preventing a cancer, in particular a solid tumor or a hematological cancer, as described herein. The methods comprise administering to a subject in need thereof an effective amount of Aminopurine Compound 1. Also provided herein are methods for treating and preventing cancer metastasis, comprising administering to a subject in need thereof an effective amount of an Aminopurine Compound as provided herein. The Aminopurine Compound provided herein can be used in the methods for treating and preventing cancer metastasis. Additionally, provided herein are methods of eradicating cancer stem cells in a subject, comprising administering to a subject in need thereof an effective amount of an Aminopurine Compound as provided herein. The Aminopurine Compound provided herein can be used in the methods of eradicating cancer stem cells in a subject. Also provided are methods of inducing differentiation in cancer stem cells in a subject, comprising administering to a subject in need thereof an effective amount of an Aminopurine Compound as provided herein. The Aminopurine Compound provided herein can be used in the methods of inducing differentiation in cancer stem cells in a subject. In another aspect, provided are methods of inducing cancer stem cell death in a subject, comprising administering to a subject in need thereof an effective amount of an Aminopurine Compound as provided herein. The Aminopurine Compound provided herein can be used in the methods of inducing cancer stem cell death in a subject. [0010] Provided herein are methods of treating a cancer, in particular a solid tumor or a hematological cancer using a pharmaceutical composition that includes an Aminopurine Compound described herein. The Aminopurine Compound pharmaceutical composition provided herein can be used in the methods for treating or preventing a cancer, in particular a solid tumor or a hematological cancer, as described herein. The methods comprise administering to a subject in need thereof an effective amount of a pharmaceutical composition that includes Aminopurine Compound 1. Also provided herein are methods for treating and preventing cancer metastasis, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition that includes an Aminopurine Compound as provided herein. The Aminopurine Compound pharmaceutical composition provided herein can be used in the methods for treating and preventing cancer metastasis. Additionally, provided herein are methods of eradicating cancer stem cells in a subject, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition that includes an Aminopurine Compound as provided herein. The Aminopurine Compound pharmaceutical composition provided herein can be used in the methods of eradicating cancer stem cells in a subject. Also provided are methods of inducing differentiation in cancer stem cells in a subject, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition that includes an Aminopurine Compound as provided herein.
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