Influence of various central moieties on the hypolipidemic properties of long hydrocarbon chain diols and diacids

Journal of Medicinal Chemistry

Volumn 49, Issue 1, 2006, Pages 334-348

  Oniciu, Daniela C ^a,c   Dasseux, Jean Louis H ^a   Yang, Jing ^b   Mueller, Ralf ^b   Pop, Emil ^b   Denysenko, Anna ^b   Duan, Caiming ^b   Huang, Tian Bao ^b   Zhang, Lianhao ^b   Krause, Brian R ^a   Drake, Sandra L ^a   Lalwani, Narendra ^a   Cramer, Clay T ^a   Goetz, Brian ^a   Pape, Michael E ^a   McKee, Andrew ^a   Fici, Gregory J ^a   Lutostanski, Janell M ^a   Brown, Stephen C ^a   Bisgaier, Charles L ^a  

^a Esperion Therapeutics Inc   (United States)

^b Alchem Laboratories Corporation   (United States)

^c University of Florida ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,13 DIHYDROXY 2,2,12,12 TETRAMETHYLTRIDECAN 7 ONE; CARBAMIC ACID; CARBENOID; CARBROMAL; ESTER; GLUCOSE; GLYCOL; HYDROCARBON; HYDROXYL GROUP; LIPID; UNCLASSIFIED DRUG; UREA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL CULTURE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; FEMALE; HYPERLIPIDEMIA; ISOTOPE LABELING; LIVER CELL; METABOLIC SYNDROME X; NONHUMAN; OBESITY; RAT; RAT STRAIN; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ADMINISTRATION, ORAL; ALCOHOLS; ANIMALS; ANTILIPEMIC AGENTS; DIABETES MELLITUS, EXPERIMENTAL; DICARBOXYLIC ACIDS; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG TOLERANCE; FEMALE; HEPATOCYTES; HYDROCARBONS; HYPERLIPIDEMIAS; LIPIDS; MOLECULAR STRUCTURE; RATS; RATS, ZUCKER; STRUCTURE-ACTIVITY RELATIONSHIP; TIME FACTORS;

EID: 30444451316     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050650j     Document Type: Article

References (41)

1. (a) Mueller, R.; Yang, J.; Duan, C.; Pop, E.; Zhang, L. H.; Huang, T.-B.; Denisenko, A.; Denisko, O. V.; Oniciu, D. C.; Bisgaier, C. L.; Pape, M. E.; Freiman, C. D.; Goetz, B.; Cramer, C. T.; Hopson, K. L.; Dasseux, J.-L. H. Long Hydrocarbon Chain Ether Diols and Diacids that Favorably Alter Lipid Disorders in Vivo. J. Med. Chem. 2004, 47, 5183-5197.
2. (b) Dasseux, J.-L. H.; Oniciu, D. C. Methods for synthesizing Ether Compounds and Intermediates Therefor. US Patent 6,410,802, 2002.
3. (c) Dasseux, J.-L. H.; Oniciu, D. C. Ether Compounds. US Patent 6,459,003, 2002.
4. (d) Dasseux, J.-L. H.; Oniciu, D. C. Ether Compounds and Compositions for Cholesterol Management and Related Uses. US Patent 6,713,597 B2, 2004.
5. Mueller, R.; Yang, J.; Duan, C.; Pop, E.; Geoffroy, O. J.; Zhang, L. H.; Huang, T.-B.; Denisenko, S.; McCosar, B. H.; Oniciu, D. C.; Bisgaier, C. L.; Pape, M. E.; Freiman, C. D.; Goetz, B.; Cramer, C. T.; Hopson, K. L.; Dasseux, J.-L. H. Long Hydrocarbon Chain Keto Diols and Diacids that Favorably Alter Lipid Disorders in Vivo. J. Med. Chem. 2004, 47, 6082-6099.
6. (a) Bell, R. P. L.; Verdijk, D.; Relou, M.; Smith, D.; Regeling, H.; Leemhuis, F. M. C.; Oniciu, D. C., Cramer, C. T.; Goetz, B.; Pape, M. E.; Krause, B. R.; Dasseux, J.-L. H. α-Cycloalkyl-substituted oi-Keto-dicarboxylic Acids as Regulators of Lipid Metabolism. Bioorg. Med. Chem. 2005, 13, 223-236.
7. (b) Dasseux, J.-L. H.; Oniciu, D. C. Cycloalkyl-Hydroxyl Compounds and Compositions for Cholesterol Management and Related Uses. US Pat. Appl. 10/743,109, December 23, 2003.
8. Cramer, C.; Goetz, B.; Hopson, K.; Fiel, G.; Ackermann, R.; Brown, S.; Bisgaier, C.; Rajeswaran, W. G.; Oniciu, D. C.; Pape, M. E. Effects of a Novel Dual Lipid Synthesis Inhibitor and Its Potential Utility in Treating Dyslipidemia and Metabolic Syndrome. J. Lipid Res. 2004, 45, 1289-1301.
9. Elokdah, H.; Sulkowski, T. S.; Abou-Gharbia, M.; Butera, J. A.; Chai, S.-Y.; McFarlane, G. R.; McKean, M.-L.; Babiak, J. L.; Adelman, S. J.; Quinet, E. M. Design, Synthesis, and Biological Evaluation of Thio-Containing Compounds with HDL-Cholesterol-Elevating Properties. J. Med. Chem. 2004, 47, 681-695.
10. Bisgaier, C. L.; Essenburg, A. D.; Barnett, B. C.; Auerbach, B. J.; Haubenwallner, S.; Leff, T.; White, A. D.; Creger, P.; Pape, M. E.; Rea, T. J.; Newton, R. S. A novel compound that elevates high-density lipoprotein and activates the peroxisome proliferator activated receptor. J. Lipid Res. 1998, 39, 17-30.
11. Bisgaier, C. L.; Creger, P. L.; Saltiel, A. R.; Tafuri, S. R. Carboxy-alkyl ethers, formulations, and treatment of vascular diseases, US Patent 5,756,544, May 26, 1998.
12. Bays, H. E.; McKenney, J. M.; Dujovne, C. A.; Schrott, H. G.; Zema, M. J.; Nyberg, J.; MacDougall, D. E. Effectiveness and Tolerability of a New Lipid-Altering Agent, Gemcabene, in Patients With Low Levels of High-Density Lipoprotein Cholesterol. Am. J. Cardiol. 2003, 92, 538-543.
13. Dasseux, J.-L. H.; Oniciu, D. C. Sulfide and Disulfide Compounds and Compositions for Cholesterol Management and Related Uses. US Patent 6,703,422, 2004.
14. Dasseux, J.-L. H.; Oniciu, D. C. Sulfoxide and Bis-Sulfoxide Compounds and Compositions for Cholesterol Management and Related Uses. US Patent 6,673,780, 2004.
15. Dasseux, J.-L. H.; Oniciu, D. C. Hydroxyl Compounds and Compositions for Cholesterol Management and Related Uses. US Pat. Appl. 10/743,470, December 23, 2003.
16. Dasseux, J.-L. H.; Oniciu, D. C. Dihydroxyl Compounds and Compositions for Cholesterol Management and Related Uses. US Pat. Appl. 10/743,287, December 23, 2003.
17. Dasseux, J.-L. H.; Oniciu, D. C. Ketone Compounds and Compositions for Cholesterol Management and Related Uses. US Pat. Appl. 10/743,952, December 24, 2003.
18. Dasseux, J.-L. H.; Oniciu, D. C. Functionalized Long Chain Derivatives as Acyl Coenzyme-A Mimics, Compositions Thereof, And Methods of Cholesterol Management and Related Uses. US Pat. Appl. 10/410,262, April 10, 2003.
19. Dasseux, J.-L. H.; Oniciu, D. C. Mimics of Acyl Coenzyme-A Comprising Pantolactone and Pantothenic Acid Derivatives, Compositions Thereof, and Methods of Cholesterol Management and Related Uses. US Pat. Appl. 10/410,444, April 10, 2003.
20. Dasseux, J.-L. H.; Oniciu, D. C. Urea and Thiourea Compounds and Preparations for Cholesterol Management and Related Uses. US Pat. Appl. 10/743,282, December 23, 2003.
21. Schwetlick, K.; et al. Organikum. Organisch-Chemisches Grund-praktikum, 15th ed.; VEB Deutscher Verlag Der Wissenschaften: Berlin, 1984; p 261.
22. Vogel, A. I. Vogel's Textbook of practical organic chemistry, 5th ed.; John Wiley and Sons; New York, 1989; p 552.
23. Katsura, Y.; Inoue, Y.; Tomoi, M.; Takasugi, H, Studies on Antiulcer Drugs. V. Synthesis and Antiulcer Activity of Aralkylbenzazoles. Chem. Pharm. Bull. 1992, 40, 2062-2074.
24. Hinsberg, O. Über das Verhalten von Phenylsulfid gegen Hydroperoxyd. Ber. Dtsch. Chem. Ges. 1910, 43, 289-290.
25. Barlin, G. B.; Brown, W. V. Some Oxidation, Reduction, and Replacement Reactions of the Methylsulphinyl Group in Substituted Six-membered Nitrogen Heterocycles. J. Chem. Soc. C 1969, 921.
26. Reid, E. E.; Ruhoff, J. R. Pelargonic Acid. In Organic Syntheses, Collective Volume 2; Blatt, A. H., Ed.; John Wiley and Sons: New York 1943; pp 474-475.
27. Rubottom, G. M.; Kim, C.-W. Preparation of Methyl Ketones by the Sequential Treatment of Carboxylic Acids with Methyllithium and Chlorotrimethylsilane. J. Org. Chem. 1983, 48, 1550-1552.
28. Isele, G.; Martinez, J. A.; Schill, G. Synthese von vielgliedrigen W-Tosylazacycloalkanen durch Alkylierung von p-Toluolsulfonsäureamid mit Dihalogenoalkanen unter Zweiphasen-Katalyse. Synthesis 1981, 455-457.
29. Bergeron, R. J.; Müller, R.; Bussenius, J.; McManis, J. S.; Merriman, R. L.; Smith, R. S.; Yao, H.; Weimar, W. R. Synthesis and Evaluation of Hydroxylated Polyamine Analogues as Antiproliferatives. J. Med. Chem. 2000, 43, 224-235.
30. Biloski, A. J.; Ganem, B. Improved Oxidation of Amines with Dibenzoyl Peroxide. Synthesis 1983, 537-538.
31. (a) Sheehan, J. C.; Bolhofer, W. A. An Improved Procedure for the Condensation of Potassium Phthalimide with Organic Halides. J. Am. Chem. Soc. 1950, 72, 2786-2788.
32. (b) Sasse, A.; Kiec-Kononowicz, K.; Stark, H.; Motyl, M.; Reidemeister, S.; Ganellin, C. R.; Ligneau, X.; Schwartz, J.-C.; Schunack, W. Development of Chiral N-Alkylcarbamates as New Leads for Potent and Selective H3-Receptor Antagonists: Synthesis, Capillary Electrophoresis, and in Vitro and Oral in Vivo Activity. J. Med. Chem. 1999, 42, 593-600.
33. Schwetlick, K. et al. Organikum. Organisch-Chemisches Grund-praktikum, 15th ed.; VEB Deutscher Verlag Der Wissenschaften: Berlin, 1984; p 533.
34. Jasys, V. J.; Kelbaugh, P. R.; Nason, D. M.; Phillips, D.; Rosnack, K. J.; Forman, J. T.; Saccomano, N. A.; Stroh, J. G.; Volkmann, R. A. Novel Quarternary Ammonium Salt-Containing Polyamines from the Agelenopsis aperta Funnel-Web Spider. J. Org. Chem. 1992, 57, 1814-1820.
35. Nelson, T. D.; Meyers, A. I. A Rapid Total Synthesis of an Ellagitannin. J. Org. Chem. 1994, 39, 2577-2580.
36. Bernady, K. F.; Floyd, M. B.; Poletto, J. F.; Weiss, M. J. Prostaglandins and Congeners. 20. Synthesis of Prostaglandins via Conjugate Addition of Lithium trans-1-Alkenyltrialkylalanate Reagents. A Novel Reagent for Conjugate 1,4-Additions. J. Org. Chem. 1979, 44, 1438.
37. (a) Sasse, K. In Methoden der Organischen Chemie (Houben-Weyl); Müller, E., Ed.; Georg Thieme Verlag: Stuttgart 1964; Band XII/2, Teil 2, pp 239-240.
38. (b) Moss, R. A.; Ragunathan, K. G. An unusually reactive phosphodiester. Tetrahedron Lett. 2000, 41, 3275-3278.
39. Ren, T.; Zhang, G.; Liu, D. Synthesis of bifunctional cationic compound for gene delivery. Tetrahedron Lett. 2001, 42, 1007-1010.
40. Seglen, P. O. Hepatocyte suspensions and cultures as tools in experimental carcinogenesis. J. Toxicol. Environ. Health 1979, 5, 551-560.
41. Kieft, K. A.; Bocan, T. M.; Krause, B. R. Rapid on-line determination of cholesterol distribution among plasma lipoproteins after high-performance gel filtration chromatography. J. Lipid Res. 1991, 32, 859-866.