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~S H ~~ US008.003636B2 (12) United States Patent (10) Patent No.: US 8,003,636 B2 Wollmann et al. (45) Date of Patent: Aug. 23, 2011 (54) CERTAIN CRYSTALLINE 7,407,938 B2 8, 2008 Jaehne et al. 7488,829 B2 2/2009 Glombik et al. DIPHENYLAZETIDINONE HYDRATES, 7,579,339 B2 8, 2009 Jaehne et al. PHARMACEUTICAL COMPOSITIONS 7,671,047 B2 3/2010 Jaehne et al. THEREOF AND METHODS FOR THEIR USE 2003/0212070 A1 11/2003 Schwink et al. 2004/OO77623 A1 4/2004 Jaehne et al. 2004/0082561 A1 4/2004 Jaehne et al. (75) Inventors: Theodor Andreas Wollmann, 2005/0239766 A1 10, 2005 Starke et al. Hattersheim (DE); Regina Duffy, 2005/0267038 A1 12/2005 Glombik et al. Hattersheim (DE); Frank Cullmann, 2007/O1495O1 A1 6/2007 Jendralla et al. Eschborn (DE) 2007/O197498 A1 8, 2007 Jaehne et al. 2008/0274947 A1* 11/2008 Jaehne et al. ................. 540,200 (73) Assignee: Sanofi-Aventis Deutschland GmbH 2008/0281092 A1 11/2008 Glombik et al. 2008/0319218 A1 12/2008 Haubrich et al. (DE) 2008/0319221 A1 12/2008 Junker et al. 2010, 0160282 A1 6, 2010 Glombik et al. *) Notice: Subject to anyy disclaimer, the term of this patent is extended or adjusted under 35 FOREIGN PATENT DOCUMENTS U.S.C. 154(b) by 350 days. CA 2 136893 6, 2002 EP O 462.884 12/1991 (21) Appl. No.: 12/269,802 EP O 656 3.54 6, 1995 WO WO97, 16455 A1 5, 1997 WO WO 97.26265 A1 7/1997 (22) Filed: Nov. 12, 2008 WO WO 97/41097 A2 11/1997 WO WO 97.454.06 A1 12/1997 (65) Prior Publication Data WO WO 98.08871 A1 3, 1998 US 2009/O2O3578 A1 Aug. 13, 2009 WO WO99.03861 A1 1, 1999 (Continued) Related U.S. Application Data OTHER PUBLICATIONS (60) Provisional application No. 60/990,225, filed on Nov. Copending U.S. Appl. No. 1 1/155,109, filed Jun. 17, 2005, Glombik 26, 2007. et al. Copending U.S. Appl. No. 1 1/767.284, filed Jun. 22, 2007. Haubrich et al. (30) Foreign Application Priority Data Copending U.S. Appl. No. 12/219,196, filed Jul. 17, 2008, Glombik et al. Nov. 13, 2007 (DE) ......................... 10 2007 O54 497 Copending U.S. Appl. No. 12/271.236, filed Nov. 13, 2008, Junker et al. (51) Int. Cl. Castaher, R. M., et al., “EZetimbe, Hypolipidemic Cholesterol CO7D 205/08 (2006.01) Absorption Inhibitor SCH-58235.” Drugs of the Future 2000, A 6LX3/397 (2006.01) 25(7):679-685. (52) U.S. Cl. ................................... 514/210.02:540/200 (Continued) (58) Field of Classification Search .................. 540/200; 514/210.02 Primary Examiner — Mark Berch See application file for complete search history. (74) Attorney, Agent, or Firm — Finnegan, Henderson, Farabow, Garrett & Dunner, LLP (56) References Cited (57) ABSTRACT U.S. PATENT DOCUMENTS Provided are certain crystalline hydrates of the formula I 4,596,789 A 6, 1986 Dutta et al. 5, 190,923 A 3, 1993 Vincent et al. O 5,656,624 A 8, 1997 Vaccaro et al. 5,756,470 A 5, 1998 Yumibe et al. 5,846,966 A 12/1998 Rosenblum et al. OH 5,889,002 A 3, 1999 Nielsen et al. 6,221,633 B1 4/2001 Ertlet al. 6,221,897 B1 4/2001 Fricket al. 6,225,310 B1 5, 2001 Nielsen et al. 6,245,744 B1 6, 2001 Fricket al. 6,268,343 B1 7/2001 Knudsen et al. 6,342,512 B1 1/2002 Kirsch et al. 6,380.230 B1 4/2002 Brodin et al. 6,498,156 B2 12/2002 Glombik et al. O OH OH onH2O 6,525,083 B2 2/2003 Acton, III et al. 6,589,984 B1 7/2003 Naniwa et al. N 6,624,185 B2 9, 2003 Glombik et al. ~s H ~~" 6,861444 B2 3/2005 Ikuta et al. OH OH 6,884,812 B2 4/2005 Glombik et al. 6,992,067 B2 1/2006 Glombik et al. 7,067,689 B1 6, 2006 Renze et al. in which n has a value of from 0.5 to 1.8. The compound may 7,205.290 B2 4/2007 Jaehne et al. be suitable, for example, as a hypolipidemic. 7.388,004 B2 6, 2008 Jaehne et al. 7,390,790 B2 6, 2008 Jaehne et al. 16 Claims, 3 Drawing Sheets US 8,003,636 B2 Page 2 FOREIGN PATENT DOCUMENTS Office Action for U.S. Appl. No. 1 1/155,109 mailed on Dec. 3, 2008, WO WO 99/15525 4f1999 9 pages. WO WO99/46262 9, 1999 Notice of Allowance for U.S. Appl. No. 1 1/177,410 (issued patent WO WOOO,34331 6, 2000 7,067,689), mailed on Mar. 31, 2006, 4 pages. WO WOOOf 40569 T 2000 Office Action for U.S. Appl. No. 1 1/767,298, mailed Aug. 15, 2008, WO WOOOf 63703 A1 10, 2000 5 pages. WO WOOOf 64876 11, 2000 Office Action for U.S. Appl. No. 1 1/797.720 (issued patent WO WOOO64888 11, 2000 7488,829), mailed on Nov. 16, 2007, 6 pages. WO WOOOf71549 11, 2000 Final Office Action for U.S. Appl. No. 1 1/797,720 (issued patent WO WOOOf 78312 12/2000 7488,829), mailed on Apr. 21, 2008, 8 pages. WO WOO1/04156 1, 2001 Notice of Allowance for U.S. Appl. No. 1 1/797,720 (issued patent WO WOO1,09111 2, 2001 7488,829), mailed on Oct. 2, 2008, 6 pages. WO WOO1/62266 8, 2001 Asakawa, A. et al., Cocaine-Amphetamine-Regulated Transcript WO WOO1/83451 11, 2001 Influences Energy Metabolism, Anxiety and Gastric Emptying in WO WOO1.85695 11, 2001 Mice, Hormone and Metabolic Research, 2001, vol. 33, No. 9, pp. WO WOO1,90094 11, 2001 554-558. WO WO O2/44.150 6, 2002 Barf, T. et al., Arylsulfonamidothiazoles as a New Class of Potential WO WOO2,50027 6, 2002 Antidiabetic Drugs, Discovery of Potent and Selective Inhibitors of WO WOO3,O15769 2, 2003 the 11 B-Hydroxysteroid DehydrogenaseType 1, Journal of Medici WO WO 2009 112203 A1 * 9, 2009 nal Chemistry, 2002, vol. 45, No. 18, pp. 3813-3815. OTHER PUBLICATIONS Chaudhary, A. et al., CO. Offgas as a Mechanistic Probe and Scale Up Tool in N-Acylations. Using Mixed Anhydrides from Amino Goodman and Gilman's The Pharmacological Basis of Therapeutics, Acids and Isobutyl Chloroformate, Organic Process Research and 10th Ed., 2001, p. 54. Development, 2003, vol. 7, pp. 888-895. Kosoglou, T., et al., "Coadministration of Simvastatin and Ezetimibe Greene, T. et al., Protective Groups in Organic Synthesis, John Wiley Leads to Significant Reduction in LDL-Cholesterol.” Proceedings of and Sons, Inc., 1999, 3 Ed., pp. 1, 4-5, 372-374,383-387,415-419, the 3rd International Congress on Coronary Artery Disease. From 701-702, 705-707, and 728-731. Ishihara, K. et al., 3,4,5-Trifluorobenzeneboronic Acid as an Prevention to Intervention, 2000, p. 275. Extremely Active Amidation Catalyst, Journal of Organic Chemistry, Vaccaro, W. D., et al., “Sugar-Substituted 2-AZetidinone. As Choles 1996, vol. 61, pp. 4196-4197. terol Absorption Inhibitors.” Biorganic & Medicinal Chemistry Let Klausner, Y. et al., Coupling Reagents' in Peptide Synthesis, Synthe ters 8(1998):35-40. sis, 1972, No. 9, pp. 453-463. Vaccaro, W. D., et al., “Sugar-Substituted 2-AZetidinone Cholesterol Kunishima, M. et al., 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4- Absorption Inhibitors: Enhanced Potency by Modification of the methyl-morpholiniurn Chloride: An Efficient Condensing Agent Sugar,” Biorganic & Medicinal Chemistry Letters 8(1998):313-318. Leading to the Formation of Amides and Esters, Tetrahedron, 1999, van Heek, M., et al., “Comparison of the activity and disposition of vol. 55, pp. 13159-13170. the novel cholesterol absorption inhibitor, SCH58235, and its Larock, R., Interconversion of Nitriles, Carboxylic Acids and Deriva glucuronide, SCH60663.” British Journal of Pharmacology tives, Comprehensive Organic Transformations: A Guide to Func 129: 1748-1754 (2000). tional Group Preparations, VCHPublishers, NewYork, 1999, 2" Ed., Zaks, A., et al., “Enzymatic Glucuronidation of a Novel Cholesterol pp. 1929-1930. Absorption Inhibitor, SCH58235. Applied Biochemistry and Lee, D. et al., Leptin Agonists as a Potential Approach to the Treat Biotechnology, 73:205-214 (1998). ment of Obesity, Drugs of the Future, 2001, vol. 26, No. 9, pp. Non-Final Office Action for U.S. Appl. No. 10/021.502 (issued 873-881. patent 6,992,067), mailed on Sep. 10, 2003, 4 pages. Okada, H. et al., Synthesis and Antitumor Activities of Prodrugs of Final Office Action for U.S. Appl. No. 10/021.502 (issued patent Benzoylphenylureas, Chemical and Pharmaceutical Bulletin, 1994, 6,992,067), mailed on Apr. 16, 2004. 11 pages. vol. 42, No. 1, pp. 57-61. Non-Final Office Action for U.S. Appl. No. 10/021.502 (issued Prata, C. et al., Charge-Reversal Amphiphiles for Gene Delivery, patent 6,992,067), mailed on Aug. 25, 2004, 5 pages. Journal of the American Chemical Society, 2004, vol. 126, pp. 12196 Non-Final Office Action for U.S. Appl. No. 10/021.502 (issued 12197 patent 6,992,067), mailed on Feb. 8, 2005, 9 pages. Prata, C. et al., Supporting Information for Charge Reversal Notice of Allowance for U.S. Appl. No. 10/021.502 (issued patent Amphiphiles for Gene Delivery, Journal of the American Chemical 6,992,067), mailed on Jul. 12, 2005, 4 pages. Society, 2004, vol. 126, pp. S1-S8. Office Action for U.S. Appl. No. 10/813,954 (issued patent Saitoh, M.
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