ARYL HYDROCARBON RECEPTOR ANTAGONISTS AND USES THEREOF

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) WIP0 I PCT °Ens °nolo mu DID Ho IIll IIII iflo oimIE (10) International Publication Number WO 2018/191476 Al (51) International Patent Classification: C07D 471/04 (2006.01) C12N 5/0789 (2010.01) CO7D 487/04 (2006.01) A61K 35/12 (2015.01) CO7D 519/00 (2006.01) (21) International Application Number: PCT/US2018/027265 (22) International Filing Date: 12 April 2018 (12.04.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/484,692 12 April 2017 (12.04.2017) US 62/613,382 03 January 2018 (03.01.2018) US 62/625,896 02 February 2018 (02.02.2018) US (71) Applicant: MAGENTA THERAPEUTICS, INC. [US/US]; 50 Hampshire Street, 8th Floor, Cambridge, Massachusetts 02139 (US). (72) Inventors: ROMERO, Arthur Glenn; 1201 Turn- berry Ridge Ct., Chesterfield, Missouri 63005 (US). GONCALVES, Kevin A.; 135 Clarendon Street, Apt. 14Z, Boston, Massachusetts 02116 (US). (74) Agent: ERLACHER, Heidi A. et al.; Cooley LLP, 1299 Pennsylvania Avenue, NW, Suite 700, Washington, District of Columbia 20004 (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, = (54) Title: ARYL HYDROCARBON RECEPTOR ANTAGONISTS AND USES THEREOF do ti us AhR Atitalgtiltst Atthilty. -4- D 11.4S0 Cpd 5 Opci 16 Gotnttritt non M): (57) : The disclosure relates to aryl hydrocarbon receptor antagonists, such as substituted imidazopyridines and imidazopy- razines, as well as methods of expanding hematopoietic stem cells by culturing hematopoietic stem or progenitor cells in the presence of these agents. Additionally, the disclosure provides methods of treating various pathologies in a patient by administration of expand- ed hemato poietic stem cells. The disclosure further provides methods of synthesizing aryl hydrocarbon receptor antagonists, such as substituted imidazopyridines and imidazopyrazines, as well as kits containing aryl hydrocarbon receptor antagonists that can be used for the expa