Patent SG-11201407238V-A (SG)
Title: 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile and therapeutic uses thereof
Inventor: COLLINS IAN
IPC: A61P35/00
Filed: 2013-05-14
Abstract: (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 21 November 2013 (21.11.2013) WIPOIPCT (10) International Publication Number WO 2013/171470 A1 (51) International Patent Classification: C07D 401/12 (2006.01) A61P 35/00 (2006.01) A61K31/506 (2006.01) (21) International Application Number: PCT/GB2013/051233 (22) International Filing Date: 14 May 2013 (14.05.2013) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 61/647,200 15 May 2012 (15.05.2012) US (71) Applicant: CANCER RESEARCH TECHNOLOGY LIMITED [GB/GB]; Angel Building, 407 St John Street, London Greater London EC IV 4AD (GB). (72) Inventors: COLLINS, Ian; The Institute of Cancer Re­ search, 15 Cotswold Road, Sutton Surrey SM2 5NG (GB). MATTHEWS, Thomas Peter; The Institute of Cancer Re- search, 15 Cotswold Road, Sutton Surrey SM2 5NG (GB). FARIA DA FONSECA MCHARDY, Tatiana; The Insti- ~~ tute of Cancer Research, 15 Cotswold Road, Sutton Surrey = SM2 5NG (GB). OSBORNE, James; Biofocus, Chester- _ ford Research Park, Chesterford Park, Saffron Walden Es- sex CB10 1XL (GB). LAINCHBURY, Michael; Argenta Discovery 2009 Limited, 8-9 Spire Green Centre, Flex [Continued on next page] (54) Title: 5-[[4-[[MORPHOLIN-2-YL]METHYLAMINO]-5-(TRIFLUOROMETHYL)-2-PYRIDYL]AMINO]PYRAZINE-2- = CARBONITRILE AND THERAPEUTIC USES THEREOF (57) Abstract: The present invention pertains gen­ erally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4- [ [morpholin-2 -yljmethylamino] - - 5 (trifluoro - methyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as \"TFM com­ pounds\") which, inter alia, inhibit Checkpoint Kinase (CHK1) 1 kinase function. The present in­ vention also pertains to pharmaceutical composi­ tions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the in­ hibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., op­ tionally in combination with another agent, for ex­ ample, (a) DNA a topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or a thymidylate synthase (TS) inhibitor; (d) a mi­ crotubule targeted agent; (e) ionising radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme. CJ o & Meadow, Harlow Essex CM 19 5TR (GB). WALTON, Mi­ chael Ian; The Institute of Cancer Research, 15 Cotswold Road, Sutton Surrey SM2 5NG (GB). GARRETT, Michelle Dawn; The Institute of Cancer Research, 15 Cotswold Road, Sutton Surrey SM2 5NG (GB). (74) Agent: WYTENBURG, Wilhelmus; Mewburn Ellis LLP, 33 Gutter Lane, London Greater London EC2V 8AS (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, 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, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, WO 2013/171470 Al I lllll llllllll II llllll III lllll lllll lllll III III III lllll lllll lllll lllll llll lllllll llll llll llll TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Published: ML, MR, NE, SN, TD, TG). — -with international search report (Art. 21(3)) Declarations under Rule 4.17: — of inventorship (Rule 4.17 (iv))