Patent SG-11201809982R-A (SG)
Title: Chemical conjugates of evans blue derivatives and their use as radiotherapy and imaging agents
Inventor: CHEN XIAOYUAN
IPC: A61K51/04
Filed: 2017-05-09
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 111111101111 Organization 0 11101 HOE 010 1111 1 0 I 1111111111H11011101111111111011110111111 International Bureau (10) International Publication Number (43) International Publication Date .....0\"\" WO 2017/196806 Al 16 November 2017 (16.11.2017) WIPO I PCT (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 207/444 (2006.01) A61K 51/04 (2006.01) kind of national protection available): AE, AG, AL, AM, (21) International Application Number: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, PCT/US2017/031696 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, (22) International Filing Date: HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, 09 May 2017 (09.05.2017) 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, (25) Filing Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (26) Publication Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (30) Priority Data: TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 62/333,427 09 May 2016 (09.05.2016) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: THE UNITED STATES OF AMERICA, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, AS REPRESENTED BY THE SECRETARY, DE- UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, PARTMENT OF HEALTH AND HUMAN SERVICES TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, [US/US]; National Institutes of Health Office of Technol-EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, ogy Transfer, 6011 Executive Boulevard, Suite 325, MSC MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, 7660, Bethesda, Maryland 20892-7660 (US). TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (72) Inventors: CHEN, Xiaoyuan; 10901 Lamplighter Lane, KM, ML, MR, NE, SN, TD, TG). Potomac, Maryland 20854 (US). WEISS, Orit Jacobson; _ 11525 Soward Dr., Silver Spring, Maryland 20902 (US). Declarations under Rule 4.17: = — as to applicant's entitlement to apply for and be granted a = (74) Agent: GARABEDIAN, Todd E.; CANTOR COLBURN patent (Rule 4.17(ii)) LLP, 20 Church Street, 22nd Floor, Hartford, Connecticut — as to the applicant's entitlement to claim the priority of the —_ 06103 (US). earlier application (Rule 4.17(iii)) = = (54) Title: CHEMICAL CONJUGATES OF EVANS BLUE DERIVATIVES AND THEIR USE AS RADIOTHERAPY AND AGENTS = IMAGING (57) : The present invention is directed to a compound of =_ — Formula I or Formula III or a pharmaceutically acceptable ester, \"H OH R, R3R ' R L,—N amide, solvate, or salt thereof, or a salt of such an ester or amide = = \"°' 0* i 110. L R,, o or a solvate of such an ester amide or salt: wherein the definitions L, • 8 • of R1 Hogs nl. Formula I -R13 and L1-L4 are provided in the disclosure, and wherein = S-4--FlIa R14 is a peptide. The compounds of Formula I may be covalently = N •H R, R,iR bonded to a peptide via a linker to provide a compound of Formula 2 = H S 40 ap * L I R L, III and thereby extend the half-life of the therapeutic compound. 0 The invention is also directed to pharmaceutical compositions of = ‘1,13 HO S the disclosed compounds, as well as their use in the diagnosis or = treatment of diseases. = = 1-1 AN bintliva © fficimoistifies Raker GC .m, cm 11 N Fig. I 1—I © awikearforkhotin. ei C [Continued on next page] WO 2017/196806 Al MIDEDIM01101 DIDIRMEM111111111111111H11111111111101111111111111111111 Published: — with international search report (Art. 21(3))