US009963446B2 (12 ) United States Patent ( 10 ) Patent No. : US 9 ,963 , 446 B2 Burch et al. ( 45) Date of Patent: * May 8 , 2018 ( 54 ) OXEPAN - 2 - YL - PYRAZOL - 4 - YL 6 ,395 , 916 B1 5 /2002 Buchwald et al . HETEROCYCLYL - CARBOXAMIDE 6 , 946, 560 B2 9 / 2005 Buchwald et al. 7 , 026 , 498 B2 4 /2006 Buchwald et al . COMPOUNDS AND METHODS OF USE 7 , 223 , 879 B2 5 / 2007 Buchwald et al . 7 ,247 , 731 B2 7 / 2007 Buchwald et al . ( 71 ) Applicant: Genentech , Inc. , South San Francisco , 7 , 329, 758 B1 2 / 2008 Grubbs et al. CA (US ) 7 ,560 , 582 B2 . 7 / 2009 Buchwald et al. 7 , 858 ,784 B2 12 / 2010 Buchwald et al . (72 ) Inventors : Jason Burch , Pointe - Claire (CA ) ; 8 , 318 ,723 B2 * 11/ 2012 Mao CO7D 213/ 74 Huifen Chen , Burlingame, CA (US ) ; 514 /217 . 05 9 , 328 , 106 B2 * 5 / 2016 Burch .. .. .. .. .. .. .. C07D 417 / 14 Xiaojing Wang, Foster City , CA (US ) 2012 / 0225062 A1 9 / 2012 Burger et al . ( 73 ) Assignee: Genentech , Inc. , South San Francisco , 2013 /0079321 A1 3 /2013 Hodges et al . CA (US ) FOREIGN PATENT DOCUMENTS ( * ) Notice : Subject to any disclaimer, the term of this Wo 1996 /015111 Al 5 / 1996 patent is extended or adjusted under 35 WO 2007 / 044515 AL 4 / 2007 U . S .C . 154 ( b ) by 0 days . days . WO 2007 /099326 AL 9 /2007 WO 2011 / 124580 A 10 / 2011 This patent is subject to a terminal dis wo 2012 /004217 AL 1 / 2012 claimer . ( Continued ) (21 ) Appl. No. : 15 /266 , 243 OTHER PUBLICATIONS International Search Report issued in International Application No . ( 22) Filed : Sep . 15 , 2016 PCT/ EP2015 / 055596 , dated May 27, 2015 , in 4 pages. Written Opinion of the International Searching Authority issued in (65 ) Prior Publication Data International Application No. PCT/ EP2015 /055596 , dated May 27 , US 2017 /0001997 A1 Jan . 5 , 2017 2015 , in 7 pages. ( Author Not Identified ) Beilsteins Handbuch Der Organischen Related U . S . 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A61K 31/ 427 ( 2006 . 01 ) (Continued ) A61K 31 /4439 ( 2006 .01 ) A61K 31 /4709 ( 2006 . 01 ) Primary Examiner — Yevgeny Valenrod A61K 31/ 497 ( 2006 .01 ) (74 ) Attorney , Agent, or Firm — Brian L . Buckwalter A61K 31/ 4985 ( 2006 . 01 ) (57 ) ABSTRACT A61K 31 /06 ( 2006 .01 ) Oxepan - 2 - yl pyrazol- 4 - yl- heterocyclyl - carboxamide com CO7D 487 /04 ( 2006 . 01 ) pounds of Formula 1 , including stereoisomers , geometric isomers , tautomers , and pharmaceutically acceptable salts A61K 45 / 06 ( 2006 . 01) thereof, wherein X is thiazolyl, pyrazinyl , pyridinyl, or (52 ) U . S . CI. pyrimidinyl, are useful for inhibiting Pim kinase , and for CPC . .. .. .. C07 417 / 14 (2013 .01 ) ; A61K 31 /427 treating disorders such as cancer mediated by Pim kinase . ( 2013 .01 ) ; A61K 31 /4439 ( 2013 . 01 ) ; A61K Methods of using compounds of Formula I for in vitro , in 31/ 4709 ( 2013 .01 ) ; A61K 31/ 497 ( 2013 .01 ) ; situ , and in vivo diagnosis , prevention or treatment of such A61K 31/ 4985 ( 2013 .01 ) ; A61K 45 / 06 disorders in mammalian cells , or associated pathological (2013 .01 ); C07D 487/ 04 ( 2013 .01 ) conditions, are disclosed . (58 ) Field of Classification Search CPC . .. .. .. .. .. A61K 31/ 427 ; A61K 31 /4439 ; A61K 31/ 4709 ; A61K 31 /497 ; A61K 31 / 4985 ; A61K 45 /06 ; CO7D 417 / 14 ; C07D 487 / 04 USPC . .. .. .. .. .. .. .. .. 514 / 249 RI See application file for complete search history . ( 56 ) References Cited U . S . 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