Stereoselective synthesis and receptor activity of conformationally defined retinoid X receptor selective ligands

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 4, 1999, Pages 589-594

  Vuligonda, Vidyasagar ^a   Garst, Michael E ^a   Chandraratna, Roshantha A S ^a  

^a ALLERGAN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALITRETINOIN; LIGAND; RETINOIC ACID DERIVATIVE; RETINOID X RECEPTOR;

ARTICLE; BINDING AFFINITY; DRUG CONFORMATION; DRUG SYNTHESIS; LIGAND BINDING; NON INSULIN DEPENDENT DIABETES MELLITUS; STEREOCHEMISTRY; STRUCTURE ANALYSIS;

BINDING SITES; LIGANDS; PROTEIN CONFORMATION; RECEPTORS, RETINOIC ACID; RETINOID X RECEPTORS; RETINOIDS; STEREOISOMERISM; TRANSCRIPTION FACTORS;

EID: 0033593863     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00048-7     Document Type: Article

References (27)

1. nd ed.; Sporn, M. B., Roberts, A. B.; Goodman, D. S., Eds.; Raven: New York 1994.
2. (b) Orfanos, C. E.; Ehlert, R.; Gollnick, H. Drugs 1987, 34, 459.
3. (c) Nagpal, S.; Chandraratna, R. A. S. Curr. Pharmaceut. Design 1996, 2, 295.
4. 2. (a) See ref 1a: Mangelsdorf, D. J.; Umesono, K.; Evans, R. M. The Retinoid Receptors, p319.
5. (b) Leid, M.; Kastner, P.; Chambon, P. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 3559.
6. 3. Mangelsdorf, D. J.; Borgmeyer, U.; Heyman, R. A.; Zhou, Y. U.; Ong, E. S.; Oro, A. E.; Kakizuka, A.; Evans, R. M. Genes Dev. 1992, 6, 329.
7. 4. Zhang, X.-K.; Lehmann, J. M.; Hoffmann, B.; Dawson, M. I.; Cameron, J.; Graupner, G.; Hermann, T.; Tran, P.; Pfahl, M. Nature 1992, 358, 587.
8. 5. (a) Yu, V. C.; Delsert, C.; Anderson, B.; Holoway, J. M.; Devaary, O. V.; Naar, A. M.; Kim, S. Y.; Boutin, J. M.; Glass, C. K.; Rosenfeld, M. G. Cell 1991, 67, 1251.
9. (b) Isseman, I.; Prince, R. A.; Tugwood, J. D.; Green, S. Biochemie 1993, 75, 251.
10. 6. (a) Giguere, V.; Ong, E. S.; Segui, P.; Evans, R. M. Nature 1987, 330, 624.
11. (b) Petrovich, M.; Brand, N. J.; Krust, A.; Chambon, P. Nature 1987, 330, 444.
12. 7. (a) Heyman, R. A.; Mangelsdorf, D. J.; Dyck, J. A.; Stein, R. B.; Eichele, G.; Evans, R. M.; Thaller, C. Cell 1992, 68, 397.
13. (b) Levin, A. A.; Sturzenbecker, L. J.; Kazmer, S.; Bosakowski, T.; Huselton, C.; Allenby, G.; Speck, J.; Kratzeisen, C.; Rosenberger, M.; Lovey, A.; Grippo, J. F. Nature 1992, 355, 359.
14. 8. (a) Jong, L.; Fanjul, A.; Cameron, J. F.; Lu, X. P.; Haefner, P.; Dawson, M. I.; Pfahl, M. Science 1992, 258, 194.
15. (b) Boehm, M. F.; McClurg, M. R.; Pathirana, C.; Mangelsdorf, D.; White, S.; Hebert, J.; Winn, D.; Goldman, M. E.; Heyman, R. A. J. Med. Chem. 1994, 37, 408.
16. (c) Beard, R. L.; Chandraratna, R. A. S.; Colon, D. F.; Gillett, S. J.; Henry, E.; Marler, D. K.; Song, T.; Denys, L.; Garst, M. E.; Arefieg, T.; Klein, E.; Gil, D. W.; Wheeler, L.; Kochar, D. M.; Davies, P. J. A. J. Med. Chem. 1995, 38, 2820.
17. (d) Apfel, C. M.; Kamber, M.; Klaus, M.; Mohr, P.; Keidel, S.; LeMotte, P. K. J. Biol. Chem. 1995, 270, 30765.
18. (e) Vuligonda, V.; Lin, Y.; Chandraratna, R. A. S. Bioorg. Med. Chem. Lett. 1996, 6, 213.
19. 9. Wong, M. F.; Repa, J. J.; Clagett-Dame, M.; Curley, R. W. Jr. Bioorg. Med. Chem. Lett. 1997, 7, 2313.
20. 10. Ernst, L.; Hopf, H.; Krause, N. J. Org. Chem. 1987, 52, 398.
21. 11. Corey, E. J.; Erickson, B. W. J. Org. Chem. 1974, 39, 821.
22. 12. Hudlicky, T.; Fan, R.; Reed, J. P.; Gadamasetti, K.G. Org. React. 1994, 41, 1.
23. 13. Baldwin, J. E.; Ullenius, C. J. Amer. Chem. Soc. 1974, 96, 1542.
24. 14. Williams, D. H.; Faulkner, F. H. Tetrahedron 1992, 52, 4245.
25. 15. (a) Christensen, K.; Estes, P. A.; Onate, S. A.; Beck, C. A.; DeMarzo, A. Mol. Endocrinol. 1991, 5, 1755.
26. (b) Cheng, Y. C.; Prussof, W. H. Biochem. Pharm. 1973, 22, 3099.
27. 16. Compounds 5 and 6 are full agonists at all three RXRs tested in the cotransfection assay performed as described in reference 8e above. The potencies of the compounds in the transactivation assays are consistent with the observed binding affinities.