USOO8853266B2 (12) United States Patent (10) Patent No.: US 8,853,266 B2 Dalton et al. (45) Date of Patent: *Oct. 7, 2014 (54) SELECTIVE ANDROGEN RECEPTOR 3,875,229 A 4, 1975 Gold MODULATORS FOR TREATING DABETES 4,036.979 A 7, 1977 Asato 4,139,638 A 2f1979 Neri et al. 4,191,775 A 3, 1980 Glen (75) Inventors: James T. Dalton, Upper Arlington, OH 4,239,776 A 12/1980 Glen et al. (US): Duane D. Miller, Germantown, 4,282,218 A 8, 1981 Glen et al. TN (US) 4,386,080 A 5/1983 Crossley et al. 4411,890 A 10/1983 Momany et al. (73) Assignee: University of Tennessee Research 4,465,507 A 8/1984 Konno et al. F dati Kn ille, TN (US) 4,636,505 A 1/1987 Tucker Oundation, Knoxv1lle, 4,880,839 A 1 1/1989 Tucker 4,977,288 A 12/1990 Kassis et al. (*) Notice: Subject to any disclaimer, the term of this 5,162,504 A 11/1992 Horoszewicz patent is extended or adjusted under 35 5,179,080 A 1/1993 Rothkopfet al. U.S.C. 154(b) by 992 days. 5,441,868 A 8, 1995 Lin et al. 5,547.933 A 8, 1996 Lin et al. This patent is Subject to a terminal dis- 5,609,849 A 3/1997 Kung claimer. 5,612,359 A 3/1997 Murugesan et al. 5,618,698 A 4/1997 Lin et al. 5,621,080 A 4/1997 Lin et al. (21) Appl. No.: 11/785,064 5,656,651 A 8/1997 Sovak et al. 6,019,957 A 2/2000 Miller et al. (22) Filed: Apr. 13, 2007 6,043,265 A 3/2000 Murugesan et al. 6,071,957 A 6/2000 Miller et al. (65) Prior Publication Data 6, 160,011 A 12/2000 Miller et al. 6,482,861 B2 11/2002 Miller et al. US 2007/O281906 A1 Dec. 6, 2007 6,492,554 B2 12/2002 Dalton et al. 6,548,529 B1 4/2003 Roblet al. O O 6,569,896 B2 5/2003 Dalton et al. Related U.S. Application Data 6,777.427 B2 8/2004 Miyakawa et al. (63) Continuation-in-part of application No. 1 1/634,380, 8. E: S. She s al filed on Dec. 6, 2006, which is a continuation-in-part w--/ of application No. 11/510,844, filed on Aug. 28, 2006, (Continued) which is a continuation-in-part of application No. 1 1/505.363, filed on Aug. 17, 2006, now abandoned, FOREIGN PATENT DOCUMENTS and a continuation-in-part of application No. AU 2002364949 6, 2003 1 1/505.499, filed on Aug. 17, 2006, now Pat. No. AU 2003216,174 9, 2003 7,645,898, which is a continuation-in-part of (Continued) application No. 1 1/355,187, filed on Feb. 16, 2006, now Pat. No. 7,919,647, which is a OTHER PUBLICATIONS continuation-in-part of application No. 1 1/220,414, filed on Sep. 7, 2005, now Pat. No. 7,855.229, which is U.S. Appl. No. 09/935,044, filed Aug. 23, 2001, Dalton et al. a continuation-in-part of application No. 1 1/146,427, U.S. Appl. No. 09/935.045, filed Aug. 23, 2001, Dalton et al. filed on Jun. 7, 2005, now Pat. No. 7,622,503, which is U.S. Appl. No. 10/298,229, filed Nov. 28, 2002, Miller et al. inn-in- U.S. Appl. No. 10/270,232, filed Oct. 15, 2002, Dalton et al. a continuation-in-part of application No. 10/961.380, U.S. Appl. No. 10/277,108, filed Oct. 23, 2002, Dalton et al. filed on Oct. 12, 2004, now abandoned. U.S. Appl. No. 10/270,233, filed Oct. 15, 2002, Dalton et al. U.S. Appl. No. 10/270,732, filed Oct. 15, 2002, Dalton et al. (51) Int. Cl. U.S. Appl. No. 10/310,150, filed Dec. 5, 2002, Steiner et al. AOIN 37/34 (2006.01) Howard Tucker and Glynne J. Chesterson, J. Med Chem. 1988, 31. A 6LX3L/275 (2006.01) pp. 885-887, “Resolution of the Nonsteroidal Antiandrogen 4'- AOIN37/2 (2006.01) Cyano-3-(4-fluorophenyl)sulfonyl-2-hydroxy-2-methyl-3'- AOIN 37/44 (2006.01) AOIN37/18 (2006.01) (Continued) A6 IK3I/65 (2006.01) C07C 255/00 (2006.01) Primary Examiner — Uma Ramachandran (52) U.S. Cl. (74) Attorney, Agent, or Firm — Mark S. Cohen: Pearl USPC ........... 514/522:514/521: 514/524; 514/563: Cohen Zedek Latzer Baratz LLP 514/619; 514/620; 558/414 (58) Field of Classification Search (57) ABSTRACT USPC ........... 514/80, 493, 184, 312, 419,521, 522, 514/524,529, 619, 620; 558/414 This invention provides use of a SARM compound or a com See application file for complete search history. position comprising the same in treating a variety of diseases or conditions in a Subject, including, inter-alia, a diabetes (56) References Cited disease, and/or disorder Such as cardiovascular disease, ath erosclerosis, cerebrovascular conditions, diabetic nephropa U.S. PATENT DOCUMENTS thy, diabetic neuropathy and diabetic retinopathy. 3,239,345 A 3/1966 Hodge 3,865,801 A 2f1975 Chiba et al. 5 Claims, 26 Drawing Sheets US 8,853,266 B2 Page 2 (56) References Cited EP 668351 8, 1995 EP 1221439 T 2002 U.S. PATENT DOCUMENTS EP 1401801 11, 2006 EP 1801140 6, 2007 6,960,474 B2 11/2005 Salvati et al. GB 136001 3, 1970 6,995,284 B2 2/2006 Dalton et al. GB 1360001 3, 1970 6,998,500 B2 2/2006 Dalton et al. JP 52-128329 1Of 1977 7,022,870 B2 4/2006 Dalton et al. JP 54-63047 12, 1980 7,026,500 B2 4/2006 Dalton et al. JP 59-033,250 2, 1984 7,041,844 B2 5/2006 Miller et al. WO WO 89/07110 8, 1989 7,205,437 B2 4/2007 Dalton et al. WO WO 89/07111 8, 1989 7,214,693 B2 5/2007 Dalton et al. WO WO91,05867 5, 1991 7,344,700 B2 3/2008 Dalton et al. WO WO93/04081 3, 1993 7,518,013 B2 4/2009 Dalton et al. WO 95/1977O 7, 1995 7,547,728 B2 6/2009 Steiner et al. WO WO95/1977O 7, 1995 7.622,503 B2 11/2009 Dalton et al. WO 98 05962 2, 1998 7,645,898 B2 1/2010 Dalton et al. WO WO 98.05962 2, 1998 7,705, 182 B2 4/2010 Dalton et al. WO 98/53826 12/1998 7,759,520 B2 7/2010 Dalton et al. WO 98/55153 12/1998 7,772.433 B2 8/2010 Dalton et al. WO WO 98.53826 12/1998 2001/0012839 A1 8, 2001 Miller et al. WO WO98,55153 12/1998 2002/0173445 A1 11/2002 Salvati et al. WO WOOO/O1389 1, 2000 2003/0162761 A1 8/2003 Steiner et al. WO O127622 4/2001 2003/0232792 A1 12, 2003 Dalton et al. WO O128990 4/2001 2004/00 14975 A1 1/2004 Dalton et al. WO WOO1,27086 4/2001 2004/0029913 A1 2/2004 Dalton et al. WO WO/O1/27086 4/2001 2004.0053897 A1 3, 2004 Dalton et al. WO WOO1,27622 4/2001 2004/OO87557 A1 5, 2004 Steiner et al. WO WOO1,28990 4/2001 2004/0087810 A1 5/2004 Dalton et al. WO O134563 5, 2001 2004/014.7489 A1 7/2004 Dalton et al. WO WOO1/34563 5, 2001 2004/O197928 A1 10, 2004 Dalton et al. WO WOO1? 68603 9, 2001 2004/0214790 A1 10/2004 Borgens et al. WO O2 OO617 1, 2002 2004/0224979 A1* 11/2004 Dalton et al. ................. 514/312 WO WO O2/OO617 1, 2002 2004/0260092 A1 12, 2004 Miller et al. WO 02/16310 2, 2002 2004/0260108 A1 12/2004 Dalton et al. WO WO O2, 16310 2, 2002 2004/02659 16 A1 12/2004 Dalton et al. WO WOO2,22585 3, 2002 2005/0033074 A1 2/2005 Dalton et al. WO WO?O2.22585 3, 2002 2005/003811.0 A1 2/2005 Steiner et al. WO WOO3,O11302 2, 2003 2005, 0137172 A1 6, 2005 Dalton et al. WO WO 03/049675 6, 2003 2005. O154043 A1 7, 2005 Zhai et al. WO WOO3,065992 8, 2003 2006/0004.042 A1 1/2006 Dalton et al. WO WOO3,O74449 9, 2003 2006/00 19931 A1 1/2006 Dalton et al. WO WOO3,O77919 9, 2003 2006.0035965 A1 2/2006 Dalton et al. WO WO?O3,O77919 9, 2003 2006/011 1441 A1 5/2006 Dalton et al. WO WO 2004/O34978 4/2004 2006/0183931 A1 8/2006 Dalton et al. W. W9299.935 4294 2006/0229362 A1 10, 2006 Dalton et al. WO WO 2004034978 4/2004 2006/0287349 A1 12/2006 Meissner et al. WO WO 2005/OOOT94 1, 2005 2007/0066568 A1 3, 2007 Dalton etal WO WO 2005/0372O1 A2 4, 2005 WO WO 2005/060647 7/2005 2007/O123563 A1 5, 2007 Dalton et al. WO WO 2005/120483 8, 2006 2007, 0161608 A1 7, 2007 Dalton et al. WO WO 2008/OO8433 1, 2008 2007/0281906 A1 12, 2007 Dalton et al. 2008/0076828 A1 3f2008 Dalton et al. OTHER PUBLICATIONS 2009/0088480 A1 4/2009 Dalton et al. 2009,0264534 A1 10, 2009 Dalton et al. (trifluoromethyl)-propionanilide and the Determination of the Abso 2010.0022641 A1 1/2010 Dalton et al.