Synthesis and Bioactivity of Non-Secosteroidal Ligand for Vitamin D Receptor
Letters in Organic Chemistry, 2011, Vol. 8, No. 1 47
Nakabayashi, M.; Masuno, H.; Udagawa, N.; DeLuca, H. F.; Ikura,
Sports, Sciences, and Technology, based on screening and
counseling by the Atomic Energy Commission, by a Grant-
in-Aid for Young Scientists (B) (21790018) from the
Ministry of Education, Science, Sports, and Culture of Japan,
and the Kurata Memorial Hitachi Science and Technology
Foundation.
T.; Ito, N. 2-Substituted-16-ene-22-thia-1ꢀ,25-dihydroxy-26,27-
dimethyl-19-norvitamin D3 analogs: Synthesis, biological
evaluation, and crystal structure. Bioorg. Med. Chem., 2008, 16,
6949-6964; (e) Inaba, U.; Yoshimoto, N.; Sakamaki, Y.;
Nakabayashi, M.; Ikura, T.; Tamamura, H.; Ito, N.; Shimizu, M.;
Yamamoto, K. A new class of vitamin D analogues that induce
structural rearrangement of the ligand-binding pocket of the
receptor. J. Med. Chem., 2009, 52, 1438-1449.
[6]
(a) Boehm, M. F.; Fitzgerald, P.; Zou, A.; Elgort, M. G.; Bischoff,
E. D.; Mere, L.; Mais, D. E.; Bissonnette, R. P.; Heyman, R. A.;
Nadzan, A. M.; Reichman, M.; Allegretto, E. A. Novel
REFERENCES
[1]
(a) Bouillon, R.; Okamura, W. H.; Norman, A. W. Structure-
function relationships in the vitamin D endocrine system. Endocr.
Rev., 1995, 16, 200-257; (b) Feldman, D.; Glorieux, F. H.; Pike, J.
W. Vitamin D, 2nd ed.; Elsevier Academic Press, New York, 2005.
(a) Ettinger R. A.; Deluca H. F. The vitamin D endocrine system
and its therapeutic potential. Adv. Drug. Res., 1996, 28, 269-312;
(b) Kubodera, N. Search for and development of active vitamin D3
analogs. Curr. Bioact. Comp., 2006, 2, 301-315.
nonsecosteroidal vitamin
D mimics exert VDR-modulating
activities with less calcium mobilization than 1,25-
dihydroxyvitamin D3. Chem. Biol., 1999, 6, 265-275; (b) Polek, T.
C.; Murthy, S.; Blutt, S. E.; Boehm, M. F.; Zou, A.; Weigel, N. L.;
Allegretto, E. A. Novel nonsecosteroidal vitamin D receptor
modulator inhibits the growth of LNCaP xenograft tumors in
athymic mice without increased serum calcium. The Prostate,
2001, 49, 224-233.
Hosoda, S.; Tanatani, A.; Wakabayashi, K.; Makishima, M.; Imai,
K.; Miyachi, H.; Nagasawa, K.; Hashimoto, Y. Ligands with a 3,3-
diphenylpentane skeleton for nuclear vitamin D and androgen
receptors: Dual activities and metabolic activation. Bioorg. Med.
Chem., 2006, 14, 5489-5502.
Hakamata, W.; Sato, Y.; Okuda, H.; Honzawa, S.; Saito, N.;
Kishimoto, S.; Yamashita, A.; Sugiura, T.; Kittaka, A.; Kurihara,
M. (2S,2ꢀR)-Analogue of LG190178 is a major active isomer.
Bioorg. Med. Chem. Lett., 2008, 18, 120-123.
Kakuda, S.; Okada, K.; Eguchi, H.; Takenouchi, K.; Hakamata, W.;
Kurihara, M.; Takimoto-Kamimura, M. Structure of the ligand-
binding domain of rat VDR in complex with the nonsecosteroidal
vitamin D3 analogue YR301. Acta Cryst., 2008, F64, 970-973.
Malloy, P. J.; Pike, J. W.; Feldman, D. The vitamin D receptor and
the syndrome of hereditary 1,25-dihydroxyvitamin D-resistant
rickets. Endocr. Rev., 1999, 20, 156-188.
[2]
[3]
[4]
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.
(a) Suhara, Y.; Kittaka, A.; Ono, K.; Kurihara, M.; Fujishima, T.;
Yoshida, A.; Takayama, H. Design and efficient synthesis of new
[7]
stable 1ꢀ,25-dihydroxy-19-norvitamin D3 analogues containing
amide bond. Bioorg. Med. Chem. Lett., 2002, 12, 3533-3536; (b)
Kittaka, A.; Kurihara, M.; Peleg, S.; Suhara, Y.; Takayama, H. 2ꢀ-
[8]
[9]
(3-Hydroxypropyl)-
and
2ꢀ-(3-hydroxypropoxy)-1ꢀ,25-
dihydroxyvitamin D3 accessible to vitamin D receptor mutant
related to hereditary vitamin D-resistant rickets. Chem. Pharm.
Bull., 2003, 51, 357-358; (c) Honzawa, S.; Suhara, Y.; Nihei, K.;
Saito, N.; Kishimoto, S.; Fujishima, T.; Kurihara, M.; Sugiura, T.;
Waku, K.; Takayama, H.; Kittaka, A. Concise synthesis and
biological activities of 2ꢀ-alkyl- and 2ꢀ-(ꢁ-hydroxyalkyl)-20-epi-
1ꢀ,25-dihydroxyvitamin D3. Bioorg. Med. Chem. Lett., 2003, 13,
3503-3506; (d) Saito, N.; Suhara, Y.; Kurihara, M.; Fujishima, T.;
Honzawa, S.; Takayanagi, H.; Kozono, T.; Matsumoto, M.;
Ohmori, M.; Miyata, N.; Takayama, H.; Kittaka, A. Design and
[10]
[11]
Kristjansson, K.; Rut, A. R.; Hewison, M.; O’Riordan, J. L;
Hughes, M. R. Specificity of T cells invading the skin during acute
graft-vs.-host disease after semiallogeneic bone marrow
transplantation. J. Clin. Invest., 1993, 92, 12-20.
(a) Swann, S. L.; Bergh, J. J.; Farach-Carson, M. C.; Koh, J. T.
Rational design of vitamin D3 analogues which selectively restore
activity to a vitamin D receptor mutant associated with rickets.
Org. Lett., 2002, 4, 3863-3866; (b) Honzawa, S.; Yamamoto, Y.;
Yamashita, A.; Sugiura, T.; Kurihara, M.; Arai, M.; Kato, S.;
efficient
synthesis
of
2ꢀ-(ꢁ-hydroxyalkoxy)-1ꢀ,25-
[12]
dihydroxyvitamin D3 analogues, including 2-epi-ED-71 and their
20-epimers with HL-60 cell differentiation activity. J. Org. Chem.,
2004, 69, 7463-7471; (e) Honzawa, S.; Hirasaka, K.; Yamamoto,
Y.; Peleg, S.; Fujishima, T.; Kurihara, M.; Saito, N.; Kishimoto, S.;
Sugiura, T.; Waku, K.; Takayama, H.; Kittaka, A. Design,
Kittaka, A. The 2ꢀ-(3-hydroxypropyl) group as an active motif in
vitamin D3 analogues as agonists of the mutant vitamin D receptor
(Arg274Leu). Bioorg. Med. Chem., 2008, 16, 3002-3024.
Swan, S. L.; Bergh, J. L.; Farach-Carson, M. C.; Ocasio, C. A.;
Koh, J. T. Structure-based design of selective agonists for a rickets-
associated mutant of the vitamin D receptor. J. Am. Chem. Soc.,
2002, 124, 13795-13805.
(a) Corey, E. J.; Bakshi, R. K.; Shibata, S. Highly enantioselective
borane reduction of ketones catalyzed by chiral oxazaborolidines.
Mechanism and synthetic implications. J. Am. Chem. Soc., 1987,
109, 5551-5553. (b) Cho, B. T.; Kang, S. K.; Shin, S. H.
Application of optically active 1,2-diol monotosylates for synthesis
of ꢂ-azido and ꢂ-amino alcohols with very high enantiomeric
purity. Synthesis of enantiopure (R)-octopamine, (R)-tembamide
and (R)-aegeline. Tetrahedron Asymmetry, 2002, 13, 1209-1217.
synthesis and biological evaluation of novel 1ꢀ,25-
dihydroxyvitamin D3 analogues possessing aromatic ring on 2ꢀ-
position. Tetrahedron, 2005, 61, 11253-11263.
[13]
[14]
[5]
(a) Perakyla, M.; Malinen, M.; Herzig, K. H.; Carlberg, C. Gene
regulatory potential of nonsteroidal vitamin D receptor ligands.
Mol. Endocrinol., 2005, 19, 2060-2073; (b) Hosoda, S.; Tanatani,
A.; Wakabayashi, K.; Nakano, Y.; Miyachi, H.; Nagasawa, K.;
Hashimoto, Y. Ligands with dual vitamin D3-agonistic and
androgen-antagonistic activities. Bioorg. Med. Chem. Lett., 2005,
15, 4327-4331; (c) Ma, Y.; Khalifa, B.; Yee, Y. K.; Lu, J.;
Memezawa, A.; Savkur, R. S.; Yamamoto, Y.; Chintalacharuvu, S.
R.; Yamaoka, K.; Stayrook, K. R.; Bramlett, K. S.; Zeng, Q. Q.;
Chandrasekhar, S.; Yu, X. P.; Linebarger, J. H.; Iturria, S. J.;
Burris, T. P.; Kato, S.; Chin, W. W.; Nagpal, S. Identification and
characterization of noncalcemic, tissue-selective, nonsecosteroidal
vitamin D receptor modulators. J. Clin. Invest., 2006, 116, 892-
904; (d) Shimizu, M.; Miyamoto, Y.; Takaku, H.; Matsuo, M.;