US009630959B2 (12) United States Patent (10) Patent No.: US 9,630,959 B2 Ando et al. (45) Date of Patent: Apr. 25, 2017 (54) TRPV1 ANTAGONISTS INCLUDING 4,797.419 A 1/1989 Moos et al. DHYDROXY SUBSTITUENT AND USES 5,059,595 A 10/1991 Le Grazie THEREOF 5,073,543 A 12/1991 Marshall 5, 120,548 A 6/1992 McClelland et al. (71) Applicants:pp.11canus: Purdue Phnarma L.P., SlamStamford, Iord, CT 5,138,058 A 8, 1992 Geisen et al. (US); Shionogi & Co., Ltd., Osaka-shi (Continued) (JP) FOREIGN PATENT DOCUMENTS (72) Inventors: Shigeru Ando, Toyonaka (JP); CA 2114178 1, 1994 Noriyuki Kurose, Toyonaka (JP); EP 1388538 T 2003 Laykea Tafesse, Robbinsville, NJ (US) (Continued) (73) Assignees: Purdue Pharma L.P., Stamford, CT (US); Shionogi & Co., Ltd., Osaka (JP) OTHER PUBLICATIONS c Russian Office Action for Russian patent application No. (*) Notice: Subject to any disclaimer, the term of this 201410 1255 dated Nov. 10, 2015. patent is extended or adjusted under 35 Continued U.S.C. 154(b) by 0 days. (Continued) (21) Appl. No.: 15/018,493 Primary Examiner — Nizal Chandrakumar 9 (74) Attorney, Agent, or Firm — Dechert LLP (22) Filed: Feb. 8, 2016 (57) ABSTRACT (65) Prior Publication Data The disclosure relates to Compounds of Formula (I) US 2016/02220O2 A1 Aug. 4, 2016 Related U.S. Application Data OH (I) (63) Continuation of application No. 14/127,903, filed as application No. PCT/IB2012/001252 on Jun. 21, HO R4 2012, now Pat. No. 9,273,043. (60) Provisional application No. 61/499,989, filed on Jun. N 22, 2011. 2N (51) Int. Cl. R CO7D 403/00 (2006.01) N CO7D 417/4 (2006.01) N A6 IK 3/428 (2006.01) VVV (CH), C07D 417/12 (2006.01) - A6 IK 3/496 (2006.01) C07C 57/15 (2006.01) 1. C07C 59/255 (2006.01) O NH C07C 309/29 (2006.01) 4. C07C 309/30 (2006.01) % Ns (52) U.S. Cl. CPC .......... C07D 417/14 (2013.01); A61K 31/428 (2013.01); A61 K3I/496 (2013.01); C07C 57/15 (2013.01); C07C 59/255 (2013.01); C07C309/29 (2013.01); C07C309/30 (2013.01); C07D 417/12 (2013.01) Rs Ro (58) Field of Classification Search CPC .................................................... CO7D 417/14 and pharmaceutically acceptable derivatives thereof, where USPC . 544/364 R. R. Rs. Ro, and m are as defined herein, compositions See application file for complete search history. comprising an effective amount of a Compound of Formula (56) References Cited (I) or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition Such as pain, U.S. PATENT DOCUMENTS pain associated with osteoarthritis, osteoarthritis, UI, an ulcer, IBD, and IBS, comprising administering to an animal 3. A g 1929 RSig in need thereof an effective amount of a Compound of 384 5,770 A 11, 1974 fE. et al. Formula (I) or a pharmaceutically acceptable derivative 3,916,899 A 1 1/1975 Theeuwes et al. thereof. 4,008,719 A 2f1977 Theeuwes et al. 4.409,229 A 10/1983. Ong et al. 34 Claims, 3 Drawing Sheets US 9,630,959 B2 Page 2 (56) References Cited 8,604,037 B2 12/2013 Sun et al. 8,642,634 B2 2/2014 Pasteris et al. U.S. PATENT DOCUMENTS s: R: 1 58 urOSet et al.1 5,354,556. A 10/1994 Sparks et al. 9.434,721 B2 9/2016 Sun et al. 5,399,574 A 3, 1995 Robertson et al. 2003. O153568 A1 8/2003 Cusack et al. 5,442,064 A 8/1995 Pieper et al. 2003/0186994 A1 10/2003 Mylari 5,529.998 A 6, 1996 Haebich et al. 2003/0232996 A1 12/2003 Brown et al. 5,591,767 A 1/1997 Mohr et al. 2004.0034061 A1 2/2004 Nakazato et al. 5,639,476 A 6, 1997 OShlack et al. 2004/0038982 A1 22004 Bondinell et al. 5,674,533 A 10, 1997 Santus et al. 2004.0102450 A1 5/2004 Ewing et al. 5,698,155 A 12/1997 Grosswald et al. 2004/O152690 A1 8, 2004 Balan et al. 5,728,704 A 3/1998 Mylari et al. 2004/O186111 A1 9, 2004 Sun et al. 5,733,566 A 3, 1998 Lewis et al. 2004/02599 12 A1 12/2004 Matsumoto et al. 5,837,716 A 11/1998 Hough 2005.0009841 A1 1/2005 Zheng et al. 5,854.245 A 12/1998 Duggan et al. 2005, 0107384 A1 5/2005 Angibaud et al. 5,891,889 A 4/1999 Anthony et al. 2005/O119251 A1 6/2005 Fu et al. 5.948,786 A 9/1999 Fujiwara et al. 2005/0222410 A1 10, 2005 Stokes et al. 5.990,107 A 11/1999 Egbertson et al. 2006, OOO9459 A1 1/2006 Chakka et al. 6,051,712 A 4/2000 Binggeli et al. 2006, OO524.03 A1 3/2006 Isobe et al. 6,136,839 A 10/2000 Isakson et al. 2006/0116368 A1 6/2006 Calvo et al. 6,150,129 A 11/2000 Cook et al. 2006/O128717 A1 6/2006 Sun et al. 6,239,267 B1 5, 2001 Duckworth et al. 2006/O128755 A1 6/2006 Nakagawa et al. 6,248,756 B1 6/2001 Anthony et al. 2006, O148844 A1 7/2006 Nakade et al. 6,335, 180 B1 1/2002 Julius et al. 2006, O1998O2 A1 9, 2006 Abreo et al. 6,406,908 B1 6/2002 Mcintyre et al. 2006, O199824 A1 9/2006 Sun et al. 6,414,149 B1 7/2002 Chu-Moyer et al. 2006/0223849 A1 10/2006 Malli et al. 6,482.479 B1 1 1/2002 Dubal et al. 2006/0235004 A1 10, 2006 Geneste et al. 6,544.998 B2 4/2003 Mylari 2006/0293308 A1 12/2006 Abreo et al. 6,602,875 B2 8/2003 Chu-Moyer et al. 2007/O155707 A1 7/2007 Dasse et al. 6,673,799 B1 1/2004 Taniguchi et al. 2007/0208001 A1 9/2007 Zhuo et al. 6,723,730 B2 4/2004 Bakthavatchalam et al. 2007/0244088 Al 10/2007 Brickmann et al. 6,812,236 B2 11/2004 Gibson et al. 2008, OO15230 A1 1/2008 Kambojet al. 6,852,732 B2 2/2005 Nakazato et al. 2008, OO396.29 A1 2/2008 Ramesh et al. 6,887,870 B1 5, 2005 Ahmad et al. 2008/0076924 A1 3/2008 Betschmannet al. 6,963,000 B2 11/2005 Alanine et al. 2008, 0096895 A1 4/2008 Kambojet al. 6,974,818 B2 12/2005 Kyle et al. 2008O153835 A1 62008 Kyle et al. 7,060,331 B2 6, 2006 Kirsch et al. 2008.0167321 A1 7/2008 Kambojet al. 7,071,335 B2 7/2006 Kyle et al. 2008. O182851 A1 7/2008 Thomas et al. 7,129,235 B2 10/2006 Zheng et al. 2008, 0200472 A1 8 2008 Kyle et al. 7,157.462 B2 1/2007 Sun et al. 2008/028091.6 A1 11/2008 Bilich et al. 7,193,113 B2 3/2007 Ishihara et al. 2008/0293733 A1 11/2008 BearSS et al. 7,223,788 B2 5, 2007 Schwink et al. 2009.0062345 A1 3/2009 Vasudevan et al. 7,256,193 B2 8/2007 Kyle et al. 2009/0093497 A1 4/2009 Bolin et al. 7,262,194 B2 8/2007 Kyle et al. 2009/O105271 A1 4/2009 Martinborough et al. 7,279,493 B2 10/2007 Kyle et al. 2009, O131447 A1 5/2009 Kambojet al. 7.312,246 B2 12/2007 Hamilton et al. 2009.0143302 A1 6/2009 Yen et al. 7,332.495 B2 2/2008 Li et al. 2009/0170867 A1 7/2009 Kurose 7,335,658 B2 2/2008 Chakka et al. 2009,0170868 A1 7/2009 Tafesse 7,342,017 B2 3/2008 Kyle et al. 2009/0176796 A1 7/2009 Ta?esse 7,355,045 B2 4/2008 Dey et al. 2010.00225.30 A1 1/2010 Schiemann et al. 7,390,813 B1 6/2008 Gray-Keller et al. 2010/0261723 A1 10/2010 Finlay 7,452,555 B2 11/2008 Childs 2010/0331369 A1 12/2010 Sun et al. 7,456,180 B2 11/2008 Sviridov et al. 2011 0071192 A1 3f2011 Sun et al. 7,514,436 B2 4/2009 Gschwend et al. 2011 0104301 A1 5, 2011 Ahern et al. 7,528,134 B2 5, 2009 Bhatia et al. 2011 O152324 A1 6/2011 Kyle et al. 7,538,121 B2 5, 2009 MacDonald et al. 2012,0065.197 A1 3/2012 Christau et al. 7,569,583 B2 8, 2009 Schwink et al. 2012/0114600 A1 5, 2012 McKinnell et al. 7,572,812 B2 8, 2009 Sun et al. 2012/0202794 A1 8/2012 Sofia et al. 7,572,815 B2 8/2009 Nakagawa et al. 2013,0210800 A1 8, 2013 Nair et al. 7,582,635 B2 9, 2009 Sun et al. 2014,0004155 A1 1/2014 Jiang et al. 7,592,343 B2 9/2009 Kambojet al. 2014/O155419 A1 6/2014 Baloglu et al. 7,632,950 B2 12/2009 Kuwabara et al. 2014/O187554 A1 7/2014 Kamenecka et al. 7,683,063 B2 3/2010 Kyle et al. 2015,0018366 A1 1/2015 Tafesse 7,696,207 B2 4/2010 Kyle et al. 7,737,148 B2 6/2010 Sun et al. FOREIGN PATENT DOCUMENTS 7,767,677 B2 8/2010 Kambojet al. 7,776,861 B2 8, 2010 Sun et al.