SG11201908679QA - Isomerically pure 18f-labelled tetrahydrofolates - Google Patents

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 27 September 2018 (27.09.2018) WIP0 I PCT omit VIII °nolo olo X111011101011 0 101111111 ow (10) International Publication Number WO 2018/172243 Al (51) International Patent Classification: CO7D 475/04 (2006.01) CO7B 59/00 (2006.01) A61K 31/519 (2006.01) (21) International Application Number: PCT/EP2018/056806 (22) International Filing Date: 19 March 2018 (19.03.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 17161884.6 20 March 2017 (20.03.2017) EP (71) Applicant: MERCK PATENT GMBH [DE/DE]; Frank- furter Strasse 250, 64293 Darmstadt (DE). (72) Inventors: MOSER, Rudolf; Lahnhalde 11, 8200 SCHAFFHAUSEN (CH). GROEHN, Viola; Bahnhofs- trasse 2, 8447 DACHSEN (CH). MUELLER, Cristi- na; Haldenstrasse 24, 5415 NUSSBAUMEN (CH). SCHIBLI, Roger; Schartenrainstrasse 42, 8093 BADEN (CH). AMETAMEY, Simon; Uetlibergstrasse 308, 8045 ZUERICH (CH). BOSS, Silvan; Rosentrasse 1, 2562 PORT (CH). (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, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: ' 6 E-4 with international search report (Art. 21(3)) 71' N (54) Title: ISOMERICALLY PURE 18F-LABELLED TETRAHYDROFOLATES 1-1 (57) : The present invention is directed towards isomerically pure 18 F-labelled (6S)-or (6R)-5-methyltetrahydrofolate radio- pharmaceuticals, wherein the phenyl group within the folate structure, has been replaced by an F-labelled N-heterocycle, for use in 18 \" diagnostic imaging of a cell or population of cells expressing a folate-receptor in vitro or in vivo or for use in monitoring of cancer or 0 inflammatory and autoimmune diseases and therapy thereof.