N-(2-benzoylphenyl)-L-tyrosine PPARγ agonists. 2. Structure-activity relationship and optimization of the phenyl alkyl ether moiety

Journal of Medicinal Chemistry

Volumn 41, Issue 25, 1998, Pages 5037-5054

  Collins, Jon L ^a   Blanchard, Steven G ^a   Boswell, G Evan ^a   Charifson, Paul S ^a,b   Cobb, Jeff E ^a   Henke, Brad R ^a   Hull Ryde, Emily A ^a   Kazmierski, Wieslaw M ^a   Lake, Debra H ^a   Leesnitzer, Lisa M ^a   Lehmann, Jürgen ^a   Lenhard, James M ^a   Orband Miller, Lisa A ^a   Gray Nunez, Yolanda ^a   Parks, Derek J ^a   Plunkett, Kelli D ^a   Tong, Wei Qin ^a  

^a GLAXOSMITHKLINE   (United States)

^b VERTEX PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

[(2 BENZOYLPHENYL)AMINO] 3 [4 [2 (5 METHYL 2 PHENYLOXAZOL 4 YL)ETHOXY]PHENYL]PROPANOIC ACID; [(2 BENZOYLPHENYL)AMINO] 3 [4 [2 (5 METHYL 2 PYRIDIN 4 YLOXAZOL 4 YL)ETHOXY]PHENYL]PROPIONIC ACID; [(2 BENZOYLPHENYL)AMINO] 3 [4 [2 [5 METHYL 2 (4 METHYLPIPERAZIN 1 YL)THIAZOL 4 YL]ETHOXY]PHENYL]PROPIONIC ACID; ANTIDIABETIC AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; DRUG EFFECT; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; GLUCOSE METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; STRUCTURE ACTIVITY RELATION;

ADIPOCYTES; ANIMALS; ANTILIPEMIC AGENTS; CELL DIFFERENTIATION; CELL LINE; DNA-BINDING PROTEINS; HUMANS; HYPOGLYCEMIC AGENTS; LIGANDS; LIPIDS; MICE; OXAZOLES; PROPIONIC ACIDS; RADIOLIGAND ASSAY; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECOMBINANT FUSION PROTEINS; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; TRANSCRIPTION FACTORS; TRANSFECTION; TYROSINE;

EID: 7844226652     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980413z     Document Type: Article

References (30)

1. Amos, A. F.; McCarty, D. J.; Zimmet, P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabetic Med. 1997, 14 (Suppl. 5), S1-S85.
2. DeFronzo, R. A. Lilly Lecture 1987. The triumvarate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 1988, 37, 667-687.
3. U.K. Prospective Diabetes Study Group. U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes 1995, 44, 1249-1258.
4. Molander, A.; Bitzén, P.-O.; Faber, O.; Groop, L. Sulphonylurea Antidiabetic Drugs-An Update of Their Clinical Pharmacology and Rational Therapeutic Use. Drugs 1989, 37, 58-72.
5. Harrower, A. D. B. Comparison of Efficacy, Secondary Failure Rate, and Complications of Sulfonylureas. J. Diab. Compd. 1994, 8, 201-203.
6. Depres, J. P.; Lamarcha, B.; Mauriège, P.; Cantin, B.; Dagenais, G. R.; Moorjani, S.; Lupien, P.-J. Hyperinsulinemia as an Independent Risk Factor for Ischemic Heart Disease. N. Engl. J. Med. 1996, 334, 952-957.
7. Saltiel, A. R.; Olefsky, J. M. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 1996, 45, 1661-1669.
8. Hulin, B.; McCarthy, P. A.; Gibbs, E. M. The glitazone family of antidiabetic agents. Curr. Pharm. Des. 1996, 2, 85-102.
9. Henry, R. R. Thiazolidinediones. Endocrinol. Metab. Clin. North Am. 1997, 26, 553-573.
10. Maggs, D. G.; Buchanan, T. A.; Burant, C. F.; Cline, G.; Gumbiner, B.; Hsueh, W. A.; Inzucchi, S.; Kelly, D.; Nolan, J.; Olefsky, J. M.; Polonksy, K. S.; Silver, D.; Valiquett, T. R.; Shulman, G. I. Metabolic Effects of Troglitazone Monotherapy in Type 2 Diabetes Mellitus. Ann. Int. Med. 1998, 128, 176-185.
11. Kumar, S.; Boulton, A. J. M.; Beck-Nielsen, H.; Berthezene, F.; Muggeo, M.; Persson, B.; Spinas, G. A.; Donoghue, S.; Lettis, S.; Stewart-Long, P. Troglitazone, an Insulin Action Enhancer, Improves Metabolic Control in NIDDM Patients. Diabetologia 1996, 39, 701-709.
12. Lehmann, J. M.; Moore, L. B.; Smith-Oliver, T. A.; Wilkison, W. O.; Willson, T. M.; Kliewer, S. A. An Antidiabetic Thiazolidinedione is a High Affinity Ligand for Peroxisome Proliferator-Activated Receptor γ (PPARγ). J. Biol. Chem. 1995, 270, 12953-12956.
13. Willson, T. M.; Cobb, J. E.; Cowan, D. J.; Wiethe, R. W.; Correa, I. D.; Prakash, S. R.; Beck, K. D.; Moore, L. B.; Kliewer, S. A.; Lehmann, J. M. The Structure-Activity Relationship between Peroxisome Proliferator-Activated Receptor γ Agonism and the Antihyperglycemic Activity of Thiazolidinediones. J. Med. Chem. 1996, 39, 665-668.
14. Spiegelman, B. M. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 1998, 47, 507-514.
15. Brun, R. P.; Kim, J. B.; Hu, E.; Spiegelman, B. M. Peroxisome proliferator-activated receptor gamma and the control of adipogenesis. Curr. Opin. Lipidol. 1997, 8, 212-218.
16. Henke, B. R.; Blanchard, S. G.; Brackeen, M. F.; Brown, K. K.; Cobb, J. E.; Collins, J. L.; Harrington, W. W.; Hashim, M. A.; Hull-Ryde, E. A.; Kaldor, I.; Kliewer, S. A.; Lake, D. H.; Leesnitzer, L. M.; Lehmann, J. M.; Lenhard, J. M.; Orband-Miller, L. A.; Miller, J.; Mook, R. A; Noble, S. A.; Oliver, W.; Parks, D. J.; Plunket, K. D.; Szewczyk, J. R.; Willson, T. M. N-(2-Benzoylphenyl)-L-tyrosine PPARγ Agonists. 1. Discovery of a Novel Series of Potent Antihyperglycemic and Antihyperlipidemic Agents. J. Med. Chem. 1998, 41, 5020-5036.
17. Mack, R. A.; Zazulak, W. I.; Radov, L. A.; Baer, J. E.; Stewart, J. D.; Elzer, P. H.; Kinsolving, C. R.; Georgiev, V. S. Drug-induced modifications of the immune response. 12, 4,5-Dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids and derivatives as novel antiallergic agents. J. Med. Chem. 1988, 32, 1910-1918.
18. Kashima, C.; Harada, Y.; Hosomi, A. Preparation of Sterically More Crowded 1,5-Disubstituted Imidazoles by the Regioselective N-Alkylation. Heterocycles 1993, 35, 433-439.
19. Francis, J. E.; Gorczyca, L. A.; Mazzenga, G. C.; Meckler, H. A convenient synthesis of 3,5-disubstituted-1,2,4-triazoles. Tetrahedron Lett. 1987, 28, 5133-5136.
20. Hulin, B.; Clark, D. A.; Goldstein, S. W.; McDermott, R. E.; Dambek, P. J.; Kappeler, W. H.; Lamphere, C. H.; Lewis, D. M.; Rizzi, J. P. Novel Thiazolidine-2,4-diones as Potent Euglycemic Agents. J. Med. Chem. 1992, 35, 1853-1864.
21. Nielsen, J.; Jensen, F. R. Solid-phase synthesis of small molecule libraries using double combinatorial chemistry. Tetrahedron Lett. 1997, 38, 2011-2014.
22. Rano, T. A.; Chapman, K. T. Solid-phase synthesis of aryl ethers via the Mitsunobu reaction. Tetrahedron Lett. 1995, 36, 3789-3792.
23. Krchnák, V.; Flegelová, Z.; Weichsel, A. S.; Lebl, M. Polymer-Supported Mitsunobu Formation and its Use in Combinatorial Chemistry. Tetrahedron Lett. 1995, 36, 6193-6196.
24. Richter, L. S.; Gadek, T. R. A Surprising Observation about Mitsunobu Reactions in Solid-Phase Synthesis. Tetrahedron Lett. 1994, 35, 4705-4706.
25. Wang, S.-S.; Gisin, B. F.; Winter, D. R; Makofske, R.; Kulesha, I. D.; Tzougraki, C.; Meienhofer, J. Facile Synthesis of amino acid and peptide esters under mild conditions via cesium salts. J. Org. Chem. 1977, 42, 1286-1290.
26. Navia, M. A.; Chaturvedi, P. R. Design principles for orally bioavailable drugs. Drug Discovery Today 1996, 1, 179-189.
27. Sohda, T.; Mizuno, K.; Momose, Y.; Ikeda, H.; Fujita, T.; Meguro, K. Studies on Antidiabetic Agents. 11. Novel Thiazolidinedione Derivatives as Potent Hypoglycemic and Hypolipidemic agents. J. Med. Chem. 1992, 35, 2617-2626.
28. Glass, C. K.; Rose, D. W.; Rosenfield, M. G. Nuclear Receptor Coactivators. Curr. Opin. Cell Biol. 1997, 9, 222-232.
29. Johnson, M. E.; Moore, L. M.; Ylvisaker, D. Minimax and maximin distance designs. J. Stat. Plan. Infer. 1990, 26, 131-148.
30. Mike Milburn, unpublished results from these laboratories. A detailed description will be published soon.