SG11201909513QA - Prodrugs of 2-pmpa for healthy tissue protection during psma-targeted cancer imaging or radiotherapy - Google Patents

Abstract

TrisPOC--PMPA LP - 1144 2-PMPA (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 18 October 2018 (18.10.2018) W I PO I PCT omitia °nolo mu ollionmomoilloo# (10) International Publication Number WO 2018/191376 A3 (51) International Patent Classification: A61K 51/04 (2006.01) A61P 35/00 (2006.01) A61K 31/663 (2006.01) (21) International Application Number: PCT/US2018/027106 (22) International Filing Date: 11 April 2018 (11.04.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/484,219 11 April 2017 (11.04.2017) US (71) Applicants: THE JOHNS HOPKINS UNIVERSITY [US/US]; 3400 N. Charles Street, Baltimore, Maryland 21218 (US). HEIDELBERG UNIVERSITY [DE/DE]; Grabengasse 1, 69117 Heidelberg (DE). (72) Inventors: SLUSHER, Barbara; 7424 Longfield Dri- ve, Kingsville, Maryland 21087 (US). NEDELCOVYCH, Michael; 3000 S. Randolph Street, Apt. 621, Arlington, Vir- ginia 22206 (US). RAIS, Rana; 12905 Vistaview Drive, West Friendship, Maryland 21794 (US). KRATOCHWIL, Clemens; Gartenstr. 9, 6949 Hirschberg (DE). (74) Agent: CHILDERS, Jeffrey, W.; Casimir Jones, S.C., 2275 Deming Way, Suite 310, Middleton, WI 53562 (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, (54) Title: PRODRUGS OF 2-PMPA FOR HEALTHY TISSUE PROTECTION DURING PSMA-TARGETED CANCER IMAGING = OR RADIOTHERAPY 2-PMPA 2-PMPA Prod rugs Cr) N 00 O O LTP144 Tris-P0C-2-PMPA 200000 150000 100000 a. 2 a. 50000 Kidney Fig. 1 (57) : The use of a class of prodrugs of 2-PMPA that alter tissue distribution of 2-PMPA to non-prostate tissues is disclosed. The presently disclosed prodrugs preferentially distribute to healthy tissues including the kidney, lacrimal glands, and salivary glands, which represent sites of off-target binding and toxicity for PSMA-targeted prostate cancer imaging agents and therapies. Accordingly, the 2-PMPA prodrugs can be used to pretreat, bind to, and shield the kidney and salivary glands from PSMA-targeted cytotoxic or radiotherapy. [Continued on next page] WO 2018/191376 A3 MIDEDIMOMOIDEIREIO I 3 HHOEMEROMEEN 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)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) (88) Date of publication of the international search report: 27 December 2018 (27.12.2018)