Patent SG-11201807834W-A (SG)
Title: Bridged bicyclic inhibitors of menin-mll and methods of use
Inventor: WU TAO
IPC: C07D401/12
Filed: 2017-03-15
Abstract: WO 17 / 16 100 2 Al (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 2017/161002 Al 21 September 2017 (21.09.2017) WIPO I PCT (51) International Patent Classification: A61K 31/445 (2006.01) C07D 401/12 (2006.01) (21) International Application Number: PCT/US2017/022535 (22) International Filing Date: 15 March 2017 (15.03.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/309,362 16 March 2016 (16.03.2016) US 62/431,387 7 December 2016 (07.12.2016) US (71) Applicants: KURA ONCOLOGY, INC. [US/US]; 11119 North Torrey Pines Road, Suite 125, La Jolla, CA 92037 (US). THE REGENTS OF THE UNIVERSITY OF MICHIGAN [US/US]; 1600 Huron Parkway, 2nd Floor, Ann Arbor, MI 48109 (US). (72) Inventors: WU, Tao; 2355 Terraza Guitara, Carlsbad, CA 92009 (US). LI, Liansheng; 13569 Arroyo Dale Lane, San Diego, CA 92130 (US). WANG, Yi; 7556 Charmant Drive, Apartment 1732, San Diego, CA 92122 (US). REN, Pingda; 5534 Havenridge Way, San Diego, CA 92130 (US). GREMBECKA, Jolanta; 1600 Huron Parkway, 2nd Floor, Ann Arbor, MI 48109 (US). CIERPICKI, To- masz; 1600 Huron Parkway, 2nd Floor, Ann Arbor, MI 48109 (US). KLOSSOWSKI, Szymon; 1600 Huron Park- way, 2nd Floor, Ann Arbor, MI 48109 (US). POLLOCK, Jonathan; 1600 Huron Parkway, 2nd Floor, Ann Arbor, MI 48109 (US). BORKIN, Dmitry; 1600 Huron Parkway, 2nd Floor, Ann Arbor, MI 48109 (US). (74) Agents: CHANG, Andrew L. et al.; Wilson Sonsini Goodrich & Rosati, 650 Page Mill Road, Palo Alto, CA 94304-1050 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, 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, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 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, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, 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, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3)) (54) Title: BRIDGED BICYCLIC INHIBITORS OF MENIN-MLL AND METHODS OF USE FIG. 4 Efficacy in MV4;11 sc. model --vehicle Control Compound A -e- 150 mg/kg/bid, Po Treatment period 0 12 15 18 (day) (57) : The present disclosure provides methods of inhibiting the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins. The methods are useful for the treatment of leukemia, solid cancers, diabetes and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin. Compositions for use in these methods are also provided. 1111111111111101110101011111010111110 011111111010111111101011111111111110111111 Mean tu mor v o lume (rnm 3 ) + SEM 2000 1800 1600 1400 1200 1000 800 600 400 200 0