US009051320B1 (12) United States Patent (10) Patent No.: US 9,051,320 B1 Evans (45) Date of Patent: Jun. 9, 2015 (54) METHODS FOR THE TREATMENT OF 399:S A. 23.9 Shipschultz et al.t al. METABOLIC DSORDERS BY A SELECTIVE 2011 0110886 A1 5, 2011 Braddock SMALL MOLECULE AUTOTAXN 2011/O160148 A1 6, 2011 Parrill-baker et al. INHIBITOR 2011/0230471 A1 9, 2011 Staehle et al. 2011/0237583 A1 9/2011 Schiemann et al. (71) Applicant: Pharm Akea, Inc., San Diego, CA (US) 2012fOO15959 A1 1/2012 Staehle et al. O O 2012, OO15976 A1 1/2012 Schultz et al. (72) Inventor: Jillian Frances Evans, San Diego, CA 2012/005901.6 A1 3/2012 Schiemann et al. (US) 2012/0100592 A1 4/2012 Parrill-baker et al. 2012/0115852 A1 5, 2012 Schultz et al. (73) Assignee: PHARMAKEA, INC., San Diego, CA 2012fO190650 A1 T/2012 Gupte et al. (US) 2012/0202827 A1 8/2012 Schiemann et al. 2013, OO12505 A1 1/2013 Staehle et al. (*) Notice: Subject to any disclaimer, the term of this 2013,0029948 A1 1/2013 Roppe et al. patent is extended or adjusted under 35 2013/0150326 A1* 6/2013 Roppe et al. .................... 514,64 U.S.C. 154(b) by 0 days. 2013/0251728 A1 9/2013 Harp et al. 2014/0113953 A1 4/2014 Stoffel et al. (21) Appl. No.: 14/462,459 2014/0171361 A1 6/2014 Jonker et al. 1-1. 2014/0171403 A1 6/2014 Legrand et al. (22) Filed: Aug. 18, 2014 2014/0171404 A1 6/2014 Furminger et al. (51) Int. Cl. 2014/0200231 A1 T/2014 Beauchampe h tal. A6 IK3I/405 (2006.01) FOREIGN PATENT DOCUMENTS CO7D 47L/4 (2006.01) A6 IK3I/437 (2006.01) WO WO-2008-157361 12/2008 CO7D 403/04 (2006.01) WO WO-2009-046804 4/2009 A6 IK3I/4I55 (2006.01) WO WO-2009-046841 4/2009 CO7D 40/4 (2006.01) W: W3: 39. A6 IK3I/4439 (2006.01) WO WO-2010-040080 4/2010 CO7D 403/06 (2006.01) WO WO-2010-060532 6, 2010 A6 IK3I/4025 (2006.01) WO WO-2010-063352 6, 2010 WO WO-2010-112116 10, 2010 A6 IK 45/06 (2006.01) WO WO-2010-112124 10, 2010 (52) U.S. Cl. WO WO-2010-115491 10, 2010 CPC ............ C07D 471/14 (2013.01); A61K3I/437 WO WO-2010-132479 11, 2010 (2013.01); C07D 403/04 (2013.01); A61 K WO WO-2011-0O2918 1, 2011 31/4155 (2013.01); C07D401/14 (2013.01); W W39: 438: A6 IK3I/4439 (2013.01); C07D 403/06 WO WO-2011-053597 5, 2011 (2013.01); A61K 31/4025 (2013.01); A61 K WO WO-2011-1 16867 9, 2011 45/06 (2013.01); A6IK3I/405 (2013.01) WO WO-2012-02462O 2, 2012 (58) Field of Classification Search W: Wi: 1585 CPC ........ A61K 31/405: A61 K 45/06 WO WO-2013-0541.85 4/2013 See application file for complete search history. WO WO-2013-061297 5, 2013 WO WO-2013-1861.59 12/2013 (56) References Cited WO WO-2014-048865 4/2014 WO WO-2014-097151 6, 2014 U.S. PATENT DOCUMENTS OTHER PUBLICATIONS 5, 186,522 A 2/1993 Spencer 5,210,574 A 5, 1993 Kita Federico et al., Mol. Endocr. 26: 786-797, 2012.* 5,538,444 A 7, 1996 Strand et al. Boucher et al., Diabetologia 48: 569-577, 2005.* 5,564,676 A 10, 1996 Goloff et al. Zou et al., Vasc. 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