THA T THEUS009796668B2 LULLULOITTI (12 ) United States Patent ( 10 ) Patent No. : US 9 ,796 ,668 B2 Anderson et al . ( 45 ) Date of Patent: Oct . 24 , 2017 ( 54 ) NATURAL PRODUCT ANALOGS (58 ) Field of Classification Search INCLUDING AN ANTI- INFLAMMATORY CPC . .. .. C07C 255 /46 ; C07C 2101 / 16 ; C07J CYANOENONE PHARMACORE AND 41 /0094 ; C07J 41 /0055 ; C07J 53 /001 ; METHODS OF USE C07J 71 /0005 ; C07J 21 /003 USPC .. .. .. 558 /426 ; 514 /520 See application file for complete search history . (71 ) Applicant: REATA PHARMACEUTICALS , INC ., Irving , TX (US ) ( 56 ) References Cited U . S . PATENT DOCUMENTS ( 72 ) Inventors : Eric Anderson , Southlake , TX (US ) ; 3 ,013 ,010 A 2 / 1957 Cardenas 2 , 875 , 201 A 2 / 1959 Johns Gary L . Bolton , Ann Arbor, MI (US ) ; 4 , 395 ,423 A 7 / 1983 Neumann Deborah A . Ferguson , Branchburg , NJ 4 , 808 ,614 A 2 / 1989 Hertel (US ) ; Xin Jiang , Coppell, TX (US ) ; 5 ,002 , 939 A 3 / 1991 Streber Robert M . 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No. : 14 / 950, 557 ( Continued ) ( 22 ) Filed : Nov . 24 , 2015 FOREIGN PATENT DOCUMENTS (65 ) Prior Publication Data CN 1687021 A 10 / 2005 CN 102070697 5 / 2010 US 2016 /0145200 A1 May 26 , 2016 ( Continued ) Related U . S . Application Data OTHER PUBLICATIONS (60 ) Division of application No . 13 / 552, 530 , filed on Jul. “ CDDO in treating patients with metastatic or unresectable solid 18 , 2012 , now Pat . No . 9 , 233 , 998 , which is a tumors or lymphoma, " www . clinicaltrials . gov / ct2 / show / continuation of application No. 12 /426 , 889 , filed on NCT00352040 ? term = CDDO & rank = 1 , Dec . 14 , 2008 . Apr. 20 , 2009 , now Pat. No. 8 , 258 , 329 . ( Continued ) Primary Examiner - Barbara P Badio ( 60 ) Provisional application No . 61/ 046 , 363 , filed on Apr. (74 ) Attorney, Agent , or Firm — Parker Highlander PLLC 18 , 2008 . (57 ) ABSTRACT (51 ) Int. Ci. This invention provides novel compounds comprising the A61K 31 /277 ( 2006 .01 ) following anti - inflammatory pharmacore : C07C 255 / 46 ( 2006 .01 ) CO7D 311 / 74 ( 2006 .01 ) C070 317 / 26 ( 2006 .01 ) CO7D 493 / 10 ( 2006 . 01 ) CO7F 7 / 18 ( 2006 .01 ) 2 C07 ) 21/ 00 ( 2006 . 01 ) C07J 41/ 00 ( 2006 . 01 ) mun C07 ) 53/ 00 ( 2006 .01 ) Ri R2 C07 ) 71 /00 ( 2006 .01 ) (52 ) U . S . CI. ??? . .. C07C 255 /46 ( 2013 . 01 ) ; C070 311/ 74 wherein X , R , and R , are defined herein . Also provided are (2013 . 01 ) ; C070 317 / 26 ( 2013 .01 ) ; C07D pharmaceutical compositions, kits and articles of manufac 493 / 10 ( 2013 .01 ) ; C07F 7 / 1856 (2013 .01 ) ; ture comprising such compounds, methods and intermedi C07 ) 21 /003 ( 2013 .01 ) ; C07J 41 /0055 ates useful for making the compounds , and methods ofusing (2013 . 01 ) ; C07J 41/ 0094 ( 2013 .01 ) ; C07 ) the compounds and compositions. 53/ 001 ( 2013 .01 ) ; C07J 71 /0005 ( 2013 .01 ) ; C07C 2601/ 16 ( 2017 .05 ) 7 Claims, 24 Drawing Sheets US 9 , 796 ,668 B2 Page 2 (56 ) References Cited 2009 / 0060873 A1 3 /2009 Sporn et al. 2009 / 0093447 Al 4 / 2009 Konopleva et al. U . S . 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