Practical synthesis and evaluation of the biological activities of 1α,25-dihydroxyvitamin D3 antagonists, 1α,25- dihydroxyvitamin D3-26,23-lactams. Designed on the basis of the helix 12-folding inhibition hypothesis

Journal of Medicinal Chemistry

Volumn 49, Issue 8, 2006, Pages 2398-2406

  Nakano, Yusuke ^a   Kato, Yuko ^a,b   Imai, Keisuke ^c   Ochiai, Eiji ^b   Namekawa, Jun Ichi ^b   Ishizuka, Seiichi ^b   Takenouchi, Kazuya ^b   Tanatani, Aya ^a   Hashimoto, Yuichi ^a   Nagasawa, Kazuo ^d  

^a UNIVERSITY OF TOKYO   (Japan)

^b TEIJIN LTD   (Japan)

^c ASTELLAS PHARMA INC   (Japan)

^d TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1ALPHA,25 DIHYDROXYVITAMIN D 3 26,23 LACTAM DERIVATIVE; CALCITRIOL ANTAGONIST; ERGOCALCIFEROL; RECEPTOR ANTIBODY; TEI 9647; UNCLASSIFIED DRUG; ZK 168281;

ANIMAL CELL; ARTICLE; CELL DIFFERENTIATION; CELL STRAIN HL 60; CONTROLLED STUDY; CYCLOADDITION; DRUG ACTIVITY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NONHUMAN; RAT; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BINDING SITES; CALCITRIOL; CELL DIFFERENTIATION; CERCOPITHECUS AETHIOPS; COMPUTATIONAL BIOLOGY; COS CELLS; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; HL-60 CELLS; HUMANS; LACTAMS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PROTEIN STRUCTURE, SECONDARY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; VITAMIN D;

EID: 33646117039     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050738x     Document Type: Article

References (53)

1. (a) Vitamin D Physiology, Molecular Biology, and Clinical, Applications. Holick, M. F., Ed.; Humana Press: Totowa, NJ, 1999.
2. (b) Bouillon, R.; Okamura, W. H.; Norman, A. W. Structure-Function- Relationships in the Vitamin-D Endocrine System. Endocr. Rev. 1995, 16, 200-257.
3. (a) Mangelsdorf, D. J.; Thummel, C.; Beato, M.; Herrlich, P.; Schutz, G.; Umesono, K.; Blumgerg, B.; Kastner, P.; Mark, M.; Chambon, P.; Evans, R. M. The Nuclear Receptor Superfamily - The 2nd Decade. Cell 1995, 83, 835-839.
4. (b) Björklund, S.; Almouzni, G.; Davidson, I.; Nightingale, K. P. Global Transcription Regulators of Eukaryotes. Cell 1999, 96, 759-767.
5. Moras, D.; Gronemeyer, H. The Nuclear Receptor Ligand-Binding Domain: Structure and Function. Curr. Opin. Cell. Biol. 1998, 10, 384-391.
6. (a) Brzozowski, A. M.; Pike, C. W.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engström, O.; Öhman, L.; Greene, G. L.; Gustafsson, J.-A.; Carlquist, M. Molecular Basis of Agonism and Antagonism in the Oestrogen Receptor. Nature 1997, 389, 753-758.
7. (b) Carlberg, C. Molecular Basis of the Selective Activity of Vitamin D Analogues. J. Cell. Biochem. 2003, 88, 274-281.
8. 3 Signaling. Nature 1992, 355, 446-449.
9. (a) Carlberg, C. Ligand-Mediated Conformational Changes of the VDR are Required for Gene Transactivation. J. Steroid Biochem. Mol. Biol. 2004, 89-90, 227-232.
10. (b) Christakos, S.; Dhawan, P.; Liu, Y.; Peng, X.; Porta, A. New Insights into the Mechanisms of Vitamin D Action. J. Cell. Biochem. 2003, 88, 695-705.
11. (c) Gonzalez, M. M.; Samenfeld, P.; Peräkylä, M.; Carlberg, C. Corepressor Excess Shifts the Two-Side Chain Vitamin D Analogue Gemini from an Agonist to an Inverse Agonist of the Vitamin D Receptor. Mol. Endocrinol 2003, 17, 2028-2038.
12. 3 Hypersensitivity of Osteoclast Precursors from Patients with Paget's Disease. J. Bone Miner. Res. 2000, 15, 228-236.
13. (b) Kurihara, N.; Reddy, S. V.; Menaa, C.; Anderson, D.; Roodman, G. D. Osteoclasts Expressing the Measles Virus Nucleocapsid Gene Display a Pagetic Phenotype. J. Clin. Invest. 2000, 105, 607-614.
14. (c) Leach, R. J.; Roodman, G. D. Genetics of Endocrine Disease -The Genetics of Paget's Disease of the Bone. J. Clin. Endocrinol. Metab. 2001, 86, 24-28.
15. (d) Reddy, S. V.; Kurihara, N.; Menaa, C.; Landucci, G.; Forthal, D.; Koop, B. A.; Windle, J. J.; Roodman, G. D. Osteoclasts Formed by Measles Virus-Infected Osteoclast Precursors from hCD46 Transgenic Mice Express Characteristics of Pagetic Osteoclasts. Endocrinology 2001, 142, 2898-2905.
16. (e) Friedrichs, W. E.; Reddy, S. V.; Bruder, J. M.; Cundy, T.; Cornish, J.; Singer, F. R.; Roodman, G. D. Sequence Analysis of Measles Virus Nucleocapsid Transcripts in Patients with Paget's Disease. J. Bone Miner. Res. 2002, 17, 145-151.
17. (f) Kurihara, N.; Ishizuka, S.; Demulder, A.; Menaa, C.; Roodman, G. D. Paget's Disease - A VDR Coactivator Disease? J. Steroid Biochem. Mol. Biol. 2004, 89-90, 321-325.
18. 3 from Pagetic Bone Marrow Cells. J. Steroid Biochem. Mol. Biol. 2004, 89-90, 331-334.
19. (h) Kurihara, N.; Reddy, S. V.; Araki, N.; Ishizuka, S.; Ozono, K.; Cornish, J.; Cundy, T.; Singer, F. R.; Roodman, G. D. Role of TAF (II)-17, a VDR Binding Protein, in the Increased Osteoclast Formation in Paget's Disease. J. Bone Miner. Res. 2004, 19, 1154-1164.
20. 3-26, 23-Lactone, a Vitamin D Receptor Antagonist that Inhibits Osteoclast Formation and Bone Resorption in Bone Marrow Cultures from Patients with Paget's Disease. Endocrinology 2005, 146, 2023-2030.
21. 3 Show Cell-Specific Actions. Chem. Biol. 2000, 7, 885-894.
22. 3 Receptor. Mol. Pharmacol. 2000, 58, 1067-1074.
23. 3 Receptor Antagonists. Mol. Pharmacol. 2001, 59, 1478-1485.
24. 3 Receptor for the Partial Agonism of Carboxylic Ester Antagonists. J. Mol. Biol. 2002, 315, 229-238.
25. 3. J. Biol. Chem. 1999, 274, 16392-16399.
26. 3 Analogue Toward Vitamin D Receptor Function. J. Biol. Chem. 1999, 274, 32376-32381.
27. 3-,26,23S-Lactone Antagonizes the Nuclear Vitamin D Receptor by Mediating a Unique Noncovalent Conformational Change. Mol. Endocrinol. 2000, 11, 1788-1796.
28. 3. Endcrinology 2001, 142, 59-67.
29. 3 Receptor Antagonists. Mol. Pharmacol. 2001, 59, 1478-1485.
30. 3 Antagonists. J. Steroid Biochem. Mol. Biol. 2004, 89-90, 31-34.
31. 3-26,23-lactones and their 2α-functionalized analogues as highly potent VDR antagonists. Tetrahedron 2004, 60, 7951-7961.
32. Calverley, M. J. Synthesis of MC-903, A Biologically-Active Vitamin D Metabolite Analog. Tetrahedron 1987, 43, 4609-4619.
33. 3-26,23-Lactam. Molecules 2003, 8, 488-499.
34. 3 Antagonist. Bioorg. Med. Chem. Lett. 2004, 14, 2579-2583.
35. Ishioka, T.; Tanatani, A.; Nagasawa, K.; Hashimoto, Y. Anti-Androgens with Full Antagonistic Activity Toward Human Prostate Tumor LNCaP Cells with Mutated Androgen Receptor. Bioorg. Med. Chem. Lett. 2003, 13, 2655-2658.
36. Rochel, N.; Wurtz, J. M.; Mitschler, A.; Klaholz, B.; Moras, D. The Crystal Structure of the Nuclear Receptor for Vitamin D Bound to its Natural Ligand. Mol. Cell 2000, 5, 173-179.
37. Tocchini-Valentini, G.; Rochel, N.; Wurts, J. M.; Mitschler, A.; Moras, D. Crystal Structures of the Vitamin D Receptor Complexed to Superagonist 20-epi Ligands. Proc. Natl Acad. Sci. U.S.A. 2001, 98, 5491-5496.
38. Tocchini-Valentini, G.; Rochel, N.; Wurts, J. M.; Mitschler, A.; Moras, D. Crystal Structures of the Vitamin D Nuclear Receptor Liganded with the Vitamin D Side Chain Analogues Calcipotriol and Seocalcitol, Receptor Agonists of Clinical Importance. Insights into a Structural Basis for the Switching of Calcipotriol to a Receptor Antagonist by Further Side Chain Modification. J. Med. Chem. 2004, 47, 1956-1961.
39. Eelen, G.; Verlinden, L.; Rochel, N.; Claessens, F.; DeClercq, P.; Vandewalle, M.; Tocchini-Valentini, G.; Moras, D. Superagonistic Action of 14-epi-Analogs of 1,25-Dihydroxyvitamin D Explained by Vitamin D Receptor-Coactivator Interaction. Mol. Pharmacol. 2005, 67, 1566-1573.
40. Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.CHARMM: A Program for Macromolecular Energy, Minimization, and Dynamics Calculations. J. Comput. Chem. 1983, 4, 187-217.
41. Trost, B. M.; Dumas, J.; Villa, M. New Strategies for the Synthesis of Vitamin D Metabolites via Pd-Catalyzed Reactions. J. Am. Chem. Soc. 1992, 114, 9836-9845.
42. 2 (Calciferol). J. Org. Chem. 1986, 51, 4819-4828.
43. (a) Wovkulich, P. M.; Barcelos, F.; Batcho, A. D.; Sereno, J. F.; Baggiolini, E. G.; Hennessy, B. M.; Uskokovic, M. R. Stereoselective Total Synthesis of 1α,25S,26-Trihydroxychoiecalciferol. Tetrahedron 1984, 40, 2283-2296.
44. (b) Baggiolini, E. G.; Iacobelli, J. A.; Hennessy, B. M.; Batcho, A. D.; Sereno, J. F.; Uskokovic, M. R. Stereocontrolled Total Synthesis of 1α,25-Dihydroxycholecalciferol and 1α,25-Dihydroxyergocalciferol. J. Org. Chem. 1986, 51, 3098-3108.
45. Cicchi, S.; Goti, A.; Brandi, A.; Guarna, A.; De Sarlo, F. 1,3-Aminoalcohols by Reductive Cleavage of Isoxazolidines with Molybdenium Hexacarbonyl. Tetrahedron Lett. 1990, 31, 3351-3354.
46. 3 II. Specific Binding of 1α,24-Dihydroxyvitamin 63 to Chick Intestinal Receptor. Steroids 1981, 37, 33-43.
47. 3-26, 23-Lactone. Arch. Biochem. Biophys. 1985, 242, 82-89.
48. 3-Induced Differentiation in a Human Promyelocytic Leukemia Cell Line (HL-60): Receptor-Mediated Maturation to Macrophage-Like Cells. J. Cell Biol. 1984, 98, 391-398.
49. Collins, S. J.; Ruscetti, F. W.; Gallagher, R. E.; Gallo, R. C. Normal Functional Characteristics of Cultured Human Promyelocytic Leukemia Cells (HL-60) After Induction of Differentiation by Dimethylsulfoxide. J. Exp. Med. 1979, 149, 969-974.
50. 10b
51. 3 24-Hydroxylase Gene Promoter and Identification of 2 Vitamin Responsive Elements. Biochim. Biophys. Acta 1995, 1263, 1-9.
52. (a) Peräkylä, M.; Molnar, F.; Carlberg, C. A Structural Basis for the Species-Specific Antagonism of 26,23-Lactones on Vitamin D Signaling. Chem. Biol. 2004, 11, 1147-1156.
53. 3-26,23-Lactone Depends on the Primary Structure of the Carboxyl-Terminal Region of the Vitamin D Receptor. Mol. Endocrinol. 2005, 19, 1147-1157.