TANI MUU ATA MATERIAUS009834545B2 NA MAMA NA MAMA NA MTOTO (12 ) United States Patent ( 10 ) Patent No. : US 9 , 834 ,545 B2 Chen et al. ( 45 ) Date of Patent: Dec. 5 , 2017 ( 54 ) MODULATORS OF CHEMOKINE ( 58 ) Field of Classification Search RECEPTORS None See application file for complete search history. ( 71) Applicant : CHEMOCENTRYX , INC . , Mountain View , CA (US ) ( 56 ) References Cited (72 ) Inventors : Xi Chen , E . Palo Alto , CA (US ); Dean U . S . PATENT DOCUMENTS R . Dragoli , Los Altos, CA ( US ) ; Junfa 6 , 166 ,050 A 12 /2000 Lombardo et al. Fan , Palo Alto , CA (US ); Jaroslaw 2003 /0204085 A1 10 / 2003 Taveras et al. Kalisiak , Mountain View , CA (US ) ; 2004 / 0097547 AL 5 / 2004 Taveras et al . Antoni Krasinski, Sunnyvale , CA 2004 /0106794 Al 6 / 2004 Taveras et al. (US ) ; Manmohan Reddy Leleti, San 2004 /0147559 Al 7 / 2004 Taveras et al. 2004 /0209946 Al 10 / 2004 Yin et al . Jose , CA (US ) ; Venkat Mali, 2008 / 0261917 A1 10 / 2008 Willems et al . 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WO 02 /057230 AL 7 / 2002 WO 02 / 067919 AL 9 / 2002 WO 02 / 076926 AL 10 / 2002 ( 21 ) Appl. No .: 15 / 353, 889 WO 02 / 083624 Al 10 / 2002 WO 03 /080053 AL 10 / 2003 ( 22 ) Filed : Nov . 17 , 2016 WO 2004 /011418 AL 2 /2004 wo 2005 /075447 AL 8 / 2005 (65 ) Prior Publication Data Wo 2006 /021544 AL 3 /2006 US 2017 /0144997 A1 May 25, 2017 ( Continued ) OTHER PUBLICATIONS Related U . S . Application Data Aki, Cynthia et al. , “ Diaminocyclobutenediones as potent and orally (60 ) Provisional application No . 62/ 257 , 389, filed on Nov. available CXCR2 receptor antagonists : SAR in the phenolic amide 19 , 2015 , provisional application No . 62/ 277 ,711 , region , " Bioorganic & Medicinal Chemistry Letters (available filed on Jan . 12 , 2016 . online May 18 , 2009 ) ; 19 :4446 - 4449 . (Continued ) (51 ) Int. Cl. C07D 405 / 14 ( 2006 . 01 ) Primary Examiner — Brian J Davis A61K 31 / 506 ( 2006 .01 ) ( 74 ) Attorney , Agent, or Firm — Mintz Levin Cohn Ferris A61K 31 /4155 ( 2006 .01 ) Glovsky and Popeo PC A61K 31 /4439 ( 2006 .01 ) A61K 31 / 454 ( 2006 .01 ) (57 ) ABSTRACT A61K 31 /341 ( 2006 .01 ) Compounds are provided as chemokine inhibitors having A61K 31 / 4035 ( 2006 .01 ) the structure : A61K 45 / 06 ( 2006 . 01 ) C07D 209 /46 (2006 .01 ) C07D 307 / 52 ( 2006 . 01 ) C07D 405 / 12 ( 2006 .01 ) RSa R56 A61K 31/ 4725 ( 2006 .01 ) (52 ) U . S . CI. 7 CPC .. .. .. .. C07D 405 / 14 (2013 .01 ) ; A61K 31 /341 N Jo ( 2013 .01 ) ; A61K 31/ 4035 ( 2013 .01 ) ; A61K ROS 31/ 4155 (2013 . 01 ) ; A61K 31 /4439 ( 2013 .01 ) ; A61K 31/ 454 (2013 . 01 ) ; A61K 31/ 4725 ROA ( 2013 .01 ) ; A61K 31/ 506 ( 2013 .01 ) ; A61K 45 / 06 ( 2013 .01 ) ; C07D 209 / 46 ( 2013 . 01 ) ; C07D 307 / 52 (2013 . 01 ) ; CO7D 405 / 12 ( 2013 .01 ) 33 Claims, 38 Drawing Sheets US 9 ,834 ,545 B2 Page 2 (56 ) References Cited Gunda, Shravan Kumar et al. , “ Structural investigations of CXCR2 receptor antagonists by COMFA , COMSIA and flexible docking FOREIGN PATENT DOCUMENTS studies , ” Acta Pharm ( Jul. 17 , 2012 ) ; 62 : 287 - 304 . 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ChemoCentryx , Inc. , Mountain View , CA (May 12 , 2016 ) ; 2 pages. Am . Chem . Soc . ( Jan . 16 , 1998 ) ; 120: 829- 830 . U . S . Patent Dec . 5 , 2017 Sheet 1 of 38 US 9 ,834 , 545 B2 FIGURE 1A CCR6 IC50 CXCR2 IC50 O . 1 . 000 +to +uffin + ++ + ToCOHCOH 0 0 1 . 001 + + + * * * 1 .002 Nto + + + + + + -???