Identification of retinoic acid receptor β subtype specific agonists

Journal of Medicinal Chemistry

Volumn 39, Issue 26, 1996, Pages 5027-5030

  Johnson, Alan T ^a   Klein, Elliott S ^a   Wang, Liming ^a   Pino, Mary E ^a   Chandraratna, Roshantha A S ^a  

^a ALLERGAN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RETINOIC ACID DERIVATIVE; RETINOIC ACID RECEPTOR; RETINOID;

ARTICLE; DOSE RESPONSE; DRUG ACTIVITY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; STRUCTURE ANALYSIS;

ANIMALS; HUMANS; RECEPTORS, RETINOIC ACID; RETINOIDS;

EID: 5544263313     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960687r     Document Type: Article

References (43)

1. The Retinoids: Biology, Chemistry, and Medicine, 2nd ed.; Sporn, M. B., Roberts, A. B., Goodman, D. S., Eds.; Raven Press Ltd.: New York, 1994; Vols. 1-2.
2. Mangelsdorf, D. J.; Umesono, K.; Evans, R. M. The Retinoid Receptors. In The Retinoids: Biology, Chemistry, and Medicine, 2nd ed.; Sporn, M. B., Roberts, A. B., Goodman, D. S., Eds.; Raven Press, Ltd.: New York, 1994; pp 319-349.
3. (a) Petkovich, M.; Brand, N. J.; Krust, A.; Chambon, P. A Human Retinoic Acid Receptor Which Belongs to the Family of Nuclear Receptors. Nature 1987, 330, 444-450.
4. (b) Giguere, U.; Ong, E. S.; Segui, P.; Evans, R. M. Identification of a Receptor for the Morphogen Retinoic Acid. Nature 1987, 330, 624-629.
5. (c) Brand, N.; Petkovich, M.; Krust, A.; Chambon, P.; deThe, H.; Marchio, A.; Dejean, A. Identification of a Second Human Retinoic Acid Receptor. Nature 1988, 332, 850-853;
6. (d) Benbrook, D.; Lernhardt, E.; Pfahl, M. A New Retinoic Acid Receptor Identified from a Hepatocellular Carcinoma. Nature 1988, 333, 669-672.
7. (e) Krust, A.; Kastner, P.; Petkovich, M.; Zelent, A.; Chambon, P. A Third Human Retinoic Acid Receptor, hRARγ. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 5310-5314.
8. (a) Heyman, R. A.; Mangelsdorf, D. J.; Dyck, J. A.; Stein, R. B.; Eichele, G.; Evans, R. M.; Thaller, C. 9-cis-Retinoic Acid is a High Affinity Ligand for the Retinoid X Receptor. Cell 1992, 68, 397-406.
9. (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. 9-cis-Retinoic Acid Stereoisomer Binds and Activates the Nuclear Receptor RXRα. Nature 1992, 355, 359-361.
10. Esgleyes-Ribot, T.; Chandraratna, R. A. S.; Lew-Kaya, D. A.; Sefton, J.; Duvic, M. Response of Psoriasis to a New Topical Retinoid, AGN 190168. J. Am. Acad. Dermatol. 1994, 30, 581-590.
11. Retinoids: Present and Future. Proceedings of a Symposium Held at the 18th World Congress of Dermatology; Shalita, A. R., Fritsch, P. O., Eds.; Supplement to J. Am. Acad. Dermatol. 1992, 27, part 2.
12. (a) Tallman, M. S.; Wiernick, P. H. Retinoids in Cancer Treatment. J. Clin. Pharmacol. 1992, 32, 868-888.
13. (b) Zhang, X.-K.; Liu, Y.; Lee, M.-O. Retinoids Receptors in Human Lung Cancer and Breast Cancer. Mutat. Res. 1996, 350, 267-277.
14. Rees, J. The Molecular Biology of Retinoic Acid Receptors: Orphan from Good Family Seeks Home. Br. J. Dermatol. 1992, 126, 97-104.
15. Elder, J. T.; Fisher, G. J.; Zhang, Q.-Y.; Eisen, D.; Krust, A.; Kastner, P.; Chambon, P.; Voorhees, J. J. Retinoic Acid Receptor Gene Expression in Human Skin. J. Invest. Dermatol. 1991, 96, 425-433.
16. Reczek, P. R.; Ostrowski, J.; Yu, K.-L.; Chen, S.; Hammer, L.; Roalsvig, T.; Starrett, J. E., Jr.; Driscoll, J. P.; Whiting, G.; Spinazze, P. G.; Tramposch, K. M.; Mansuri, M. M. Role of Retinoic Acid Receptor Gamma in the Rhino Mouse and Rabbit Irritation Models of Retinoid Activity. Skin Pharmacol. 1995, 8, 292-299.
17. (a) Dolle, P.; Ruberte, E.; Kastner, P.; Petkovich, M.; Stoner, C. M.; Gudas, L. J.; Chambon, P.; Differential Expression of Genes Encoding α, β and γ Retinoic Acid Receptors and CRABP in Developing Limbs of the Mouse. Nature 1989, 342, 702-705.
18. (b) Ruberte, E.; Dolle', P.; Krust, A.; Zelent, A.; Morris-Kay, G.; Chambon, P. Specific Spatial and Temporal Distribution of Retinoic Acid Receptor Gamma Transcripts During Mouse Embryogenesis. Development 1990, 108, 213-222.
19. (a) Chandraratna, R. A. S.; Gillett, S. J.; Song, T. K.; Attard, J.; Vuligonda, S.; Garst, M. E.; Arefieg, T.; Gil, D. W.; Wheeler, L. Synthesis and Pharmacological Activity of Conformationally Restricted, Acetylenic Retinoid Analogs. Bioorg. Med. Chem. Lett. 1995, 5, 523-527.
20. (b) Beard, R. L.; Gil, D. W.; Marier, D. K.; Henry, E.; Colon, D. F.; Gillett, S. J.; Arefieg, T.; Breen, T. S.; Krauss, H.; Davies, P. J. A.; Chandraratna, R. A. S. Structural Basis for the Differential RXR & RAR Activity of Stilbene Retinoid Analogs. Bioorg. Med. Chem. Lett. 1994, 4, 1447-1452.
21. (c) Lehmann, J. M.; Jong, L.; Fanjul, A.; Cameron, J. F.; Lu, X. P.; Haefner, P.; Dawson, M. I.; Pfahl, M. Retinoids Selective for Retinoid X Receptor Response Pathways. Science 1992, 258, 1944-1946.
22. (d) Boehm, M. F.; Zhang, L.; Badea, B. A.; White, S. K.; Mais, D. E.; Berger, E.; Suto, C. M.; Goldman, M. E.; Heyman, R. A. Synthesis and Structure-Activity Relationships of Novel Retinod X Receptor-Selective Retinoids. J. Med. Chem. 1994, 37, 2930-2941.
23. (a) Teng, M.; Duong, T. T.; Klein, E. S.; Pino, M. E.; Chandraratna, R. A. S. Identification of a Retinoic Acid Receptor α Subtype Specific Agonist. J. Med. Chem. 1996, 39, 3035-3038.
24. (b) Charpentier, B.; Bernardon, J.-M.; Eustache, J.; Millois, C.; Martin, B.; Michel, S.; Shroot, B. Synthesis, Structure-Activity Relationships, and Biological Activities of Ligands Binding to Retinoic Acid Receptor Subtypes. J. Med. Chem. 1995, 38, 4993-5006.
25. (c) Yu, K.-L.; Spinazze, P.; Ostrowski, J.; Currier, S. J.; Pack, E. J.; Hammer, L.; Roalsvig, T.; Honeyman, J. A.; Tortolani, D. R.; Reczek, P. R.; Mansuri, M. M.; Starrett, J. E., Jr. Retinoic Acid Receptor β, γ-Selective Ligands: Synthesis and Biolgical Activity of 6-Substituted 2-Naphthoic Acid Retinoids. J. Med Chem. 1996, 39, 2411-2421.
26. (d) Lehmann, J. M.; Dawson, M. I.; Hobbs, P. D.; Husmann. M.; Pfahl, M. Identification of Retinoids with Nuclear Receptor Subtype-selective Activities. Cancer Res. 1991, 51, 4804-4809.
27. (e) Kagechika, H.; Kawachi, E.; Hashimoto, Y.; Himi, T.; Shudo, K. Retinobenzoic Acids. 1. Structure-Activity Relationships of Aromatic Amides with Retinoidal Activity. J. Med. Chem. 1988, 31, 182.
28. (a) Johnson, A. T.; Klein, E. S.; Gillett, S. J.; Wang, L.; Song, T. K.; Pino, M. E.; Chandraratna. R. A. S. Synthesis and Characterization of a Highly Potent and Effective Antagonist of Retinoic Acid Receptors. J. Med. Chem. 1995, 38, 4764-4767.
29. (b) Eyrolles, L.; Kagechiko, H.; Kawachi, E.; Fukasawa, H.; Iijima, T.; Matsushima, Y.; Hashimoto, Y.; Shudo, K. Retinobenzoic Acids. 6. Retinoid Antagonists with a Heterocyclic Ring. J. Med. Chem. 1994, 37, 1508-1517.
30. (c) Yoshimura, H.; Nagai, M.; Hibi, S.; Kikuchi, K.; Abe, S.; Hida, T.; Higashi, S.; Hishinumura, I.; Yamanaka, T. A Novel Type of Retinoic Acid Receptor Antagonist: Synthesis and Structure-Activity Relationships of Heterocyclic Ring-Containing Benzoic Acid Derivatives. J. Med. Chem. 1995, 38, 3163-3173.
31. (d) Lee, M.-O.; Dawson, M. I.; Picard, N.; Hobbs, P. D.; Pfahl, M. A Novel Class of Retinoid Antagonist and Their Mechanism of Action. J. Biol. Chem. 1996, 271, 11897-11903.
32. (e) Apfel, C.; Bauer, F.; Crettaz, M.; Forni, L.; Kamber, M.; Kaufmann, F.; LeMotte, P.; Pirson, W.; Klaus, M. A Retinoic Acid Receptor α Antagonist Selectively Counteracts Retinoic Acid Effects. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7129-7133.
33. Recently Chen et al. reported on the biological activity of two RARβ specific agonists. Unfortunately the structures of these compounds were not disclosed. As a result, a valid comparison of their findings with those in this communication cannot be made at this time. Ghen, J.-Y.; Penco, S.; Ostrowski, J.; Balaguer, P.; Pons, M.; Starrett, J. E., Jr.; Reczek, P.; Chambon, P.; Gronemeyer, H. RAR-specific Agonisist / Antagonists which Dissociate Transactivation and AP1 Transrepression Inhibit Anchorage-independent Cell Proliferation. EMBO J. 1995, 14, 1187-1197.
34. Johnson, A. T.; Klein, E. S.; Gillett, S. J.; Wang, L.; Song, T. K.; Pino, M. E.; Chandraratna, R. A. S. Synthesis and Characterization of a Highly Potent and Effective Antagonist of Retinoic Acid Receptors. J. Med. Chem. 1995, 38, 4764-4767.
35. Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.; Pietroni, B. The Palladium-Catalyzed Cross Coupling of Vinyl and Aryl Triflates with 2-Furylzinc Chloride: An Efficient Route to 2-Vinyl-and 2-Arylfurans. Synlett 1990, 47-48.
36. Holt, D. A.; Levy, M. A.; Ladd, D. L.; Oh, H.-J.; Erb, J. M.; Heaslip, J. I.; Brandt, M.; Metcalf, B. W. Steroidal A Ring Aryl Carboxylic Acids: A New Class Of Steroid 5α-Reductase Inhibitors. J. Med. Chem. 1990, 33, 937-942.
37. Comins, D. L.; Dehghani, A. Pyridine-Derived Triflating Reagents: An Improved Preparation of Vinyl Triflates from Metallo Enolates. Tetrahedron Lett. 1992, 33, 6299-6302.
38. (a) Heyman, R. A.; Mangelsdorf, D. J.; Dyck, J. A.; Stein, R. B.; Eichele, G.; Evans, R. M.; Thaller, C. 9-Cis Retinoic Acid is a High Affinity Ligand for the Retinoid X Receptor. Cell 1992, 68, 397-406.
39. (b) Christensen, K.; Estes, P. A.; Onate, S. A.; Beck, C. A.; DeMarzo, A.; et al. Characterization and Functional Properties of the A and B Forms of Human Progesterone Receptors Synthesized in a Baculovirus System. Mol. Endocrinol. 1991, 5, 1755-1770.
40. 50) of an Enzymatic Reaction. Biochem. Pharmcol. 1973, 22, 3099-3108.
41. Klein, E. S.; Pino, M. E.; Johnson, A. T.; Davies, P. J. A.; Nagpal, S.; Thacher, S. M.; Krasinski, G.; Chandraratna, R. A. S. Identification and Functional Separation of Retinoic Acid Receptor Neutral Antagonists and Inverse Agonists. J. Biol. Chem. 1996, 271, 22692-22696.
42. Umesono, K.; Giguere, V.; Glass, C. K.; Rosenfeld, M. G.; Evans, R. M. Retinoic Acid and Thyroid Hormone Induce Gene Expression Through a Common Responsive Element. Nature 1988, 336, 262-265.
43. We have also found the C8 phenyl analog of compound 1 to exhibit the same profile as 1 in the RAR transactivation assay, though the efficacy at RARβ is somewhat lower.