COMPOUNDS FOR TREATING DENGUE VIRUS INFECTION AND OTHER VIRAL INFECTIONS

摘要

International Patent Classification: C07D 209/30 (2006.01) C07D 209/42 (2006.01) (21) International Application Number: PCT/US2018/032849 (22) International Filing Date: 15 May 2018 (15.05.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/506,588 15 May 2017 (15.05.2017) US (71) Applicants: DANA-FARBER CANCER INSTITUTE, INC. [US/US]; 450 Brookline Avenue, Boston, MA 02215 (US). PRESIDENT AND FELLOWS OF HARVARD COLLEGE [US/US]; 17 Quincy Street, Cambridge, MA 02138 (US). (72) Inventors: YANG, Priscilla, L.; 26 Greenview Avenue, Boston, MA 02130 (US). LIAN, Wenlong, L.; 155 Strath- more Road, Apt. #1, Boston, MA 02135 (US). GRAY, Nathanael, S.; 26 Greenview Avenue, Boston, MA 02130 (US). KWIATKOWSKI, Nicholas, Paul; 12 Kilsyth Road, #2, Brookline, MA 02445 (US). WANG, Jinhua; 103 Loring Avenue, Winchester, MA 01890 (US). JANG, Jaebong; 521 Heath Street, Brookline, MA 02467 (US). (74) Agent: ZHANG, Wei; Wolf, Greenfield & Sacks, P.C., 600 Atlantic Avenue, Boston, MA 02210-2206 (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, JO, 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, (54) Title: COMPOUNDS FOR TREATING DENGUE VIRUS INFECTION AND OTHER VIRAL INFECTIONS + compound, co- 0V2 NGC M01=1 Remove inoculum, wash and add Pre-incubation incubation fresh media 1 4 , 1 -45 min 0 1 h Figure 2A 6x113 5 4x10 5 .4 0ta DV2 NGC M01=1 E ▪ 2x10 5- -2 -1 0 log[K786-9730]/01 K786-0739 -2x10 5 RC Y Single-cycle yield by plaque formation assay 4 24 h 00 O O (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 22 November 2018 (22.11.2018) WIP01 PCT oimitia °nolo Holoffinonuno oimIE (10) International Publication Number WO 2018/213365 Al (57) : The present disclosure provides antiviral (e.g., anti -Dengue virus) agents, such as compounds of Formula (I). Also provided are pharmaceutical compositions and kits of the compounds of Formula (I). Further provided are methods and uses of the antiviral agents (e.g., the compounds of Formula (I); and compounds K786-9739, S4105, C200-5340, G199-0398, C200-9144, S7337, S1633, and C066-4182, and derivatives thereof) for treating or preventing a viral infection Dengue fever). The antiviral agents (e.g., may inhibit the entry of a virus into a cell by, e.g., inhibiting the fusion between the envelope of the virus and the membrane of the cell. [Continued on next page] WO 2018/213365 Al MIDEDIM011111 11111111E1010010E11111101111111101111111111111111111 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))