Patent SG-11201809559U-A (SG)
Title: Substituted pyridines as inhibitors of dnmt1
Inventor: ADAMS NICHOLAS DAVID
IPC: C07D213/74
Filed: 2017-06-13
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 1 MEM 0 11101 HOE 010 1111 1 0 013 011110011111010 1111 1111011110111111 Organization International Bureau (10) International Publication Number (43) International Publication Date ......0\"\" WO 2017/216727 Al 21 December 2017 (21.12.2017) WIP0 I PCT (51) International Patent Classification: Road, Collegeville, Pennsylvania 19426 (US). BUTLIN, CO7D 213/73 (2006.01) A61K 31/4412 (2006.01) Roger J.; Wilmslow Road, Manchester Greater Manches- CO7D 213/74 (2006.01) A61P 37/00 (2006.01) ter M20 4BX (GB). GOLDBERG, Kristen M.; Wilmslow (21) International Application Number: Road, Manchester Greater Manchester M20 4BX (GB). PCT/IB2017/053511 JORDAN, Allan M.; Wilmslow Road, Manchester Greater Manchester M20 4BX (GB). KERSHAW, Christopher S.; (22) International Filing Date: Wilmslow Road, Manchester Greater Manchester M20 4BX 13 June 2017 (13.06.2017) (GB). RAOOF, Ali; Wilmslow Road, Manchester Greater (25) Filing Language: English Manchester M20 4BX (GB). WASZKOWYCS, Bohdan; Wilmslow Road, Manchester Greater Manchester M20 4BX (26) Publication Language: English (GB). (30) Priority Data: (81) Designated States (unless otherwise indicated, for every 62/349,227 13 June 2016 (13.06.2016) US kind of national protection available): AE, AG, AL, AM, 62/393,256 12 September 2016 (12.09.2016) US AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/412,343 25 October 2016 (25.10.2016) US 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, (71) Applicants: GLAXOSMITHKLINE INTELLECTUAL HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, PROPERTY DEVELOPMENT LIMITED [GB/GB]; KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 980 Great West Road, Brentford Middlesex TW89GS MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (GB). CANCER RESEARCH TECHNOLOGY LTD. OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, [GB/GB]; Sardinia House, Sardinia Street, London Greater SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, London WC2A 3NL (GB). TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. = _ (72) Inventors: ADAMS, Nicholas David; 1250 South Col-(84) Designated States (unless otherwise indicated, for every legeville Road, Collegeville, Pennsylvania 19426 (US). kind of regional protection available): ARIPO (BW, GH, BENOWITZ, Andrew B.; 1250 South Collegeville GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, = _ Road, Collegeville, Pennsylvania 19426 (US). RUEDA UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, BENEDE, Maria Lourdes; 1250 South Collegeville Road, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Collegeville, Pennsylvania 19426 (US). EVANS, Karen EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, Anderson; 1250 South Collegeville Road, Collegeville, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Pennsylvania 19426 (US). FOSBENNER, David T.; 1250 TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, South Collegeville Road, Collegeville, Pennsylvania 19426 KM, ML, MR, NE, SN, TD, TG). (US). KING, Bryan Wayne; 1250 South Collegeville _ — = = = _ = Road, Collegeville, Pennsylvania 19426 (US). LI, Mei; Published: 1250 South Collegeville Road, Collegeville, Pennsylva- — = = = 21(3)) 19426 LUENGO, Juan Ignacio; 1250 South with international search report (Art. nia (US). Collegeville Road, Collegeville, Pennsylvania 19426 (US). = = MILLER, William Henry; 1250 South Collegeville Road, Collegeville, Pennsylvania 19426 (US). REIF, Alexan- = der Joseph; 1250 South Collegeville Road, Collegeville, Pennsylvania 19426 (US). ROMERIL, Stuart Paul; 1250 = = — South Collegeville Road, Collegeville, Pennsylvania 19426 = (US). SCHMIDT, Stanley J.; 1250 South Collegeville = (54) Title: SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1 11 R lar (57) : The invention is directed to substituted pyridine derivatives. Specifically, the invention .4 N ei arR2ar * 3. , is directed to compounds according to Formula (Iar): (Iar) wherein Y ar , Xlar, x2ar, Rear, R 2ar , R 3ar , R oar R R5'r N ya r R oar and R 5 ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds IN of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre- 1-1 (Iar) cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and ei beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further IN directed to pharmaceutical compositions comprising a compound of the invention. The invention is 1-1 still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated 0 ei therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. O