USOO9000041B2 (12) United States Patent (10) Patent No.: US 9,000,041 B2 Dasseux et al. (45) Date of Patent: Apr. 7, 2015 (54) HYDROXYL COMPOUNDS AND (52) U.S. Cl. COMPOSITIONS FOR CHOLESTEROL CPC ............... C07C 59/245 (2013.01); C07C31/20 MANAGEMENT AND RELATED USES (2013.01); C07C31/22 (2013.01); C07C3I/24 (2013.01); C07C 59/11 (2013.01); C07C (71) Applicants: Jean-Louis Henri Dasseux, Toulouse 59/285 (2013.01); C07C 59/29 (2013.01); Toulouse (FR) C07C 59/54 (2013.01); C07C 62/02 (2013.01); C07C 62/06 (2013.01); C07C 65/17 (2013.01); (72) Inventors: Jean-Louis Henri Dasseux, Toulouse C07C 69/757 (2013.01); C07D 213/80 (FR): Carmen Daniela Oniciu, (2013.01); C07D 309/10 (2013.01); C07D Toulouse (FR) 309/12 (2013.01); C07D405/12 (2013.01); C07F 9/093 (2013.01); C07F 9/094 (2013.01); (73) Assignee: Esperion Therapeutics, Inc., Ann C07F 9/117 (2013.01); C07F 9/2425 Arbor, MI (US) (2013.01); C07F 9/4423 (2013.01); C07C 2101/02 (2013.01); C07C 2101/04 (2013.01); (*) Notice: Subject to any disclaimer, the term of this C07C 2101/08 (2013.01) patent is extended or adjusted under 35 (58) Field of Classification Search U.S.C. 154(b) by 0 days. NoneSee application file for complete search history. (21) Appl. No.: 13/925,818 (56) References Cited (22) Filed: Jun. 24, 2013 U.S. PATENT DOCUMENTS (65) Prior Publication Data S.E.I k A 1919: E.C. C. a. al. US 2013/02891 17 A1 Oct. 31, 2013 (Continued) Related U.S. Application Data FOREIGN PATENT DOCUMENTS (60) Continuation of application No. 13/470,825, filed on EP O 284 108 9, 1987 May 14, 2012, now Pat. No. 8,497.301, which is a FR 1545 224 A 11, 1968 continuation of application No. 12/870,184, filed on (Continued) Aug. 27, 2010, now abandoned, which is a division of OTHER PUBLICATIONS application No. 1 1/680,105, filed on Feb. 28, 2007, now Pat. No. 7,812,199, which is a division of Ackerley, et al., A Novel Approach to Dual-Acting Thromboxane application No. 10/743,470, filed on Dec. 23, 2003, Receptor Antagonist/Synthase Inhibitors Based on the link of 1.3- now Pat. No. 7,335,799. dioxane-thrombaxane receptor antagonists and -thromboxane (60) Provisional application No. 60/441,795, filed on Jan. synthase inhibitors, J. Med. 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Primary Examiner — Sudhakar Katakam A6 IK3I/20 (2006.01) (74) Attorney, Agent, or Firm — Goodwin Procter LLP C07C 59/245 (2006.01) (57) ABSTRACT C07C3L/20 (2006.01) C07C3L/22 (2006.01) The present invention relates to novel hydroxyl compounds, C07C3L/24 (2006.01) compositions comprising hydroxyl compounds, and methods C07C 59/11 (2006.01) useful for treating and preventing a variety of diseases and C07C 59/285 (2006.01) conditions Such as, but not limited tO aging, Alzheimer's C07C 59/29 (2006.01) Disease, cancer, cardiovascular disease, diabetic nephropa CD7C 59/246 (2006.01) thy, diabetic retinopathy, a disorder of glucose metabolism, C07C 59/48 (2006.01) dyslipidemia, dyslipoproteinemia, hypertension, impotence, C07C 59/54 (2006.01) inflammation, insulin resistance, lipid elimination in bile, CD7C 62/02 (2006.01) obesity, oxysterol elimination 1. bile, pancreatitis, pancreat CD7C 62/06 (2006.01) t1uS, Parkinson's disease, a perox1some proliferator activated C07C 65/17 (2006.01) receptor-associated disorder, phospholipid elimination 1. C07C 69/757 (2006.01) bile, renal disease, septicemia, metabolic syndrome disorders CO7D 23/80 (2006.01) (e.g., Syndrome X), thrombotic disorder. Compounds and C07D 309/10 (2006.01) methods of the invention can also be used to modulate C C07D 309/12 (2006.01) reactive protein or enhance bile production in a patient. In CO7D 405/2 (2006.01) Certa1n embodiments, the compounds, compositions, and C07F 9/09 (2006.01) methods of the invention are useful in combination therapy C07F 9/11 7 (2006.01) with other therapeutics, Such as hypocholesterolemic and C07F 9/24 (2006.01) hypoglycemic agents. C07F 9/44 (2006.01) 27 Claims, No Drawings US 9,000,041 B2 Page 2 (56) References Cited FOREIGN PATENT DOCUMENTS U.S. PATENT DOCUMENTS GB 1196594 7, 1970 GB 1196595 7, 1970 3,773,946 A 1 1/1973 Creger GB 1196596 7, 1970 3,930,024. A 12/1975 Creger GB 1196597 7, 1970 4,287,200 A 9/1981 Kawamatsu et al. GB 1196598 7, 1970 4.584,321. A 4/1986 Manghisi et al. WO WO96,30328 10, 1996 4,613,593. 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