Patent SG-11201408271V-A (SG)
Title: Substituted pyrrolidines as factor xia inhibitors for the treatment thromboembolic diseases
Inventor: IMAGAWA AKIRA
IPC: A61K31/454
Filed: 2013-05-23
Abstract: (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 28 November 2013 (28.11.2013) WIPOIPCT (10) International Publication Number WO 2013/174937 A1 (51) International Patent Classification: C07D 401/14 (2006.01) C07D 413/14 (2006.01) C07D 401/04 (2006.01) C07D 403/04 (2006.01) C07D 403/14 (2006.01) C07D 413/04 (2006.01) A61K31/496 (2006.01) A61K 31/5377 (2006.01) A61K31/4025 (2006.01) A61K31/454 (2006.01) A61K 31/41 (2006.01) A61P9/00 (2006.01) (21) International Application Number: (22) International Filing Date: (25) Filing Language: (26) Publication Language: PCT/EP2013/060650 23 May 2013 (23.05.2013) English English (30) Priority Data: 1209138.5 24 May 2012 (24.05.2012) GB (71) Applicant (for all designated States except US): ONO PHARMACEUTICAL CO., LTD [JP/JP]; 1-5, Doshomachi 2-chome, Chuo-ku, Osaka-shi, Osaka 541 - 8526 (JP). (72) Inventors; and (71) Applicants (for US only): IMAGAWA, Akira [JP/JP]; Ono Pharmaceutical Co., Ltd, 1-5, Doshomachi 2-chome, Chuo-ku, Osaka-shi, Osaka 541-8526 (JP). KONDO, Takashi [JP/JP]; Ono Pharmaceutical Co., Ltd, 1-5, Doshomachi 2-chome, Chuo-ku, Osaka-shi, Osaka 541 - 8526 (JP). NISHIYAMA, Taihei [JP/JP]; Ono Pharma­ ceutical Co., Ltd, 1-5, Doshomachi 2-chome, Chuo-ku, Osaka-shi, Osaka 541-8526 (JP). COURTNEY, Steve [GB/GB]; Evotec (UK) Ltd, 114 Milton Park, Abingdon Oxfordshire OX14 4SA (GB). YARNOLD, Chris [GB/GB]; Evotec (UK) Ltd, 114 Milton Park, Abingdon Oxfordshire OX14 4SA (GB). ICHIHARA, Osamu [JP/GB]; Evotec (UK) Ltd, 114 Milton Park, Abingdon Oxfordshire OX14 4SA (GB). FLANAGAN, Stuart [GB/GB]; Evotec (UK) Ltd, 114 Milton Park, Abingdon Oxfordshire OX14 4SA (GB). (74) Agent: MCCLUSKIE, Gail Wilson; 14 South Square, Gray's Inn, London Greater London WC1R 5JJ (GB). (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, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, 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, [Continued on next page] (54) Title: SUBSTITUTED PYRROLIDINES AS FACTOR XIA INHIBITORS FOR THE TREATMENT THROMBOEMBOLIC DISEASES /-~V < (Ri) (cycA) (57) Abstract: The present invention provides compounds of the general formula (I), their salts and N- oxides, and solv­ ates and prodrugs thereof (wherein the substituents are as defined in the description). The compounds of the general formula (I) are inhibitors of factor XIa, and are useful in the prevention of and/or therapy for thromboembolic diseases. %/ R4 (i) l> m o\ •t i> M R V-^( )~ R2 ^Cyc^ ( R3 >„ WO 2013/174937 A11 lllll llllllll II llllll III lllll lllll lllll III III III lllll lllll lllll lllll llll lllllll llll llll llll RW, 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, 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, FT, 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, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3))