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(12) United States Patent (10) Patent No.: US 8,853,266 B2 Dalton Et Al

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(12) United States Patent (10) Patent No.: US 8,853,266 B2 Dalton Et Al 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. 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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. 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(trifluoromethyl)-propionanilide and the Determination of the Abso 2010.0022641 A1 1/2010 Dalton et al.
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