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Progress in Chemistry 2016, Vol. 28 Issue (6): 839-859 DOI: 10.7536/PC151226 Previous Articles   Next Articles

• Review and comments •

Synthesis and Structure-Activity Relationship of Active Vitamin D3 Analogues

Hu Daihua, Chen Wang, Wang Yongji*   

  1. Vitamin D Research Institute, Shaanxi University of Technology, Hanzhong 723000, China
  • Received: Revised: Online: Published:
  • Supported by:
    The work was supported by the Natural Science Foundation of Shaanxi Province (No.2014JQ2083),the Key Project of Scientific and Technological Innovation Group of Shaanxi Province(No.2012KCT-29),the 2011 Project of Qinling-Bashan Mountains Bioresources Comprehensive Development C.I.C of Shaanxi Province(No.QBXT-Z(P)-15-15).
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1α,25-Dihydroxyvitamin D3(1α,25-(OH)2-D3, 125D)is the most active metabolite of vitamin D3, but the therapeutic application of 125D is limited by induction of hypercalcemia. The need for vitamin D compounds with selective biological profiles has stimulated the synthesis of more than three thousand analogues of 125D. This article reviews the recent progress of vitamin D research in the design and synthesis of the structural modifications in the A ring (including modification in the C2-, and C3-substitued, aromatic A ring and seco-A ring analogues), side chain, CD ring, seco-B ring, and non-secosteroidal vitamin D3 analogs, and the relation between the structure and the biological activities.

Contents
1 Introduction
2 Structure-activity relationship of analogues modified in the A ring
2.1 Analogues modification of C-2-substitued
2.2 Aromatic A-ring 125D analogues
2.3 Ring-A-seco-19-nor analogues
2.4 C-3-subtitued-25-hydroxy analogues
3 Structure-activity relationship of analogues modified in the side chains
3.1 26-Desmethyl-2-methylene-22-ene-19-nor-analogues
3.2 C-22-oxa-analogues
3.3 Analogues with aromatic side chains attached at C-17
3.4 C-2 substituted analogues having ringed side chains
3.5 Analogues of combination of triple bond and adamantane ring on the side chain
4 Structure-activity relationship of analogues modified in CD-ring
4.1 13α-Substituted-des-C-ring-19-nor-125D analogues
4.2 Analogues with α-hydroxyalkyl substituents at C12
4.3 9-Alkylidene-19-nor-125D analogues with unnatural triene system
5 Structure-activity relation of analogues modified substituted in seco-B ring
5.1 6-Substituted analogues of 125D
5.2 C-7-methyl-19-nor-125D analogues
6 Structure-activity relationship of non-secosteroidal vitamin D analogues
6.1 Bis- and tris-aromatic analogues
6.2 p-Carborane-based non-secosteroidal vitamin D analogues
7 Conclusion and outlook

Key words: 1α,25-dihydroxyvitamin D3, analogues, structure-activity relationship, chemical synthesis, biological activities

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[1] DeLuca H F, Plum L A, Clagett-Dame M. J. Steroid Biochem. Mol. Biol., 2007, 103: 263.
[2] Cai Z Y, DeLuca H F. Chin. J. Org. Chem., 2014, 34: 1582.
[3] (a) Cai Z Y. Chin. J. Org. Chem., 2013, 33: 2244.;(b) Wang Y H, Song W Q, Liu M, Wen P, Lu Q. West China J. Pharma. Sci., 2014, 455.;(c) Wen P, Zhao L, Wu J, Lu Q. West China J. Pharma. Sci., 2011, 26:87.; (d) Yu Y F, Liu Z P. Chin. J. Med. Chem., 2006, 16:311.; (e) Posner G H, Kahraman M. Eur. J. Org. Chem., 2003, 2003: 3889.
[4] Fujishima T, Nozaki T, Suenaga T. Bioorg. Med. Chem., 2013, 21: 5209.
[5] Matsuo M, Hasegawa A, Takano M, Saito H, Kakuda S, Chida T, Takagi K I, Ochiai E, Horie K, Harada Y. ACS Med. Chem. Lett., 2013, 4: 671.
[6] Honzawa S,Hirasaka K,Yamamoto Y,Peleg S,Fujishima T,Kurihara M,Saito N,Kishimoto S,Sugiura T,Waku K. Tetrahedron, 2005, 61: 11253.
[7] Sikervar V, Fleet J C, Fuchs P L. J. Org. Chem., 2012, 77: 5132.
[8] Sibilska I K, Sicinski R R, Ochalek J T, Plum L A, DeLuca H F. J. Med. Chem., 2014, 57: 8319.
[9] Sibilska I K, Szybinski M, Sicinski R R, Plum L A, DeLuca H F. J. Steroid. Biochem. Mol. Biol., 2013, 136: 9.
[10] Sawada D, Tsukuda Y, Saito H, Kakuda S, Takimoto-Kamimura M, Ochiai E, Takenouchi K, Kittaka A. J. Am. Chem. Soc., 2011, 133: 7215.
[11] Sawada D, Tsukuda Y, Saito H, Takagi K, Kakuda S, Takimoto-Kamimura M, Ochiai E, Takenouchi K, Kittaka A. J. Steroid. Biochem. Mol. Biol., 2013, 136: 27.
[12] Takano M, Sawada D, Yasuda K, Nishikawa M, Takeuchi A, Takagi K I, Horie K, Reddy G S, Chen T C, Sakaki T. J. Steroid. Biochem. Mol. Biol., 2015, 148: 34.
[13] (a) Saito N, Suhara Y, Kurihara M, Fujishima T, Honzawa S, Takayanagi H, Kozono T, Matsumoto M, Ohmori M, Miyata N. J. Org. Chem., 2004, 69: 7463.; (b) Saito N, Honzawa S, Kittaka A. Current Topics in Medicinal Chemistry, 2006, 6: 1273.; (c) Takahashi E, Nakagawa K, Suhara Y, Kittaka A, Nihei K I, Konno K, Takayama H, Ozono K, Okano T. Biological and Pharmaceutical Bulletin, 2006, 29: 2246.
[14] Takano M, Ohya S, Yasuda K, Nishikawa M, Takeuchi A, Sawada D, Sakaki T, Kittaka A. Chemical and Pharmaceutical Bulletin, 2014, 62: 182.
[15] Sawada D, Tsukuda Y, Yasuda K, Sakaki T, Saito H, Takagi K I, Takenouchi K, Chen T C, Reddy G S, Kittaka A. Chemical and Pharmaceutical Bulletin, 2012, 60: 1343.
[16] Thomas E, Brion J D, Peyrat J F. Eur. J. Med. Chem., 2014, 86: 381.
[17] DeBerardinis A M, Banerjee U, Miller M, Lemieux S, Hadden M K. Bioorg. Med. Chem. Lett., 2012, 22: 4859.
[18] DeBerardinis A M, Banerjee U, Hadden M K. ACS Med. Chem. Lett., 2013, 4: 590.
[19] Banerjee U, de Berardinis A M, Hadden M K. Bioorg. Med. Chem., 2015, 23: 548.
[20] DeBerardinis A M, Madden D J, Banerjee U, Sail V, Raccuia D S, de Carlo D, Lemieux S M, Meares A, Hadden M K. J. Med. Chem., 2014, 57: 3724.
[21] Barrack S A, Gibbs R A, Okamura W H. J. Org. Chem., 1988, 53: 1790.
[22] Glebocka A, Sicinski R R, Plum L A, DeLuca H F. J. Steroid. Biochem. Mol. Biol., 2013, 136: 39.
[23] Hernández-Martín A, González-García T, Lawlor M, Preston L, Gotor V, Fernández S, Ferrero M. Bioorg. Med. Chem., 2013, 21: 7779.
[24] Grzywacz P, Chiellini G, Plum L A, Clagett-Dame M, DeLuca H F. J. Med. Chem., 2010, 53: 8642.
[25] Chiellini G, Grzywacz P, Plum L A, Clagett-Dame M, DeLuca H F. Steroids, 2014, 83: 27.
[26] Chen B, Kawai M, Wu-Wong J R. Bioorg. Med. Chem. Lett., 2013, 23: 5949.
[27] Liu C, Zhao G D, Mao X, Suenaga T, Fujishima T, Zhang C M, Liu Z P. Eur. J. Med. Chem., 2014, 85: 569.
[28] Saito H, Chida N, Takagi K, Horie K, Sawai Y, Nakamura Y, Harada Y, Takenouchi K, Kittaka A. Org. Biomol. Chem., 2011, 9: 3954.
[29] Saito H, Takagi K, Horie K, Kakuda S, Takimoto-Kamimura M, Ochiai E, Chida T, Harada Y, Takenouchi K, Kittaka A. J. Steroid. Biochem. Mol. Biol., 2013, 136: 3.
[30] Igarashi M, Yoshimoto N, Yamamoto K, Shimizu M, Ishizawa M, Makishima M, DeLuca H F, Yamada S. Archives of Biochemistry and Biophysics, 2007, 460: 240.
[31] Kudo T, Ishizawa M, Maekawa K, Nakabayashi M, Watarai Y, Uchida H, Tokiwa H, Ikura T, Ito N, Makishima M. J. Med. Chem., 2014, 57: 4073.
[32] Carballa D M, Zacconi F, Kulesza U, Mouriño A, Torneiro M. J. Steroid. Biochem. Mol. Biol., 2013, 136: 34.
[33] Kulesza U, Mouriño A, Plum L A, DeLuca H F, Sicinski R R. J. Steroid. Biochem. Mol. Biol., 2013, 136: 23.
[34] Sokolowska K, Sicinski R R, Mouriño A, Plum L A, DeLuca H F. J. Steroid. Biochem. Mol. Biol., 2013, 136: 30.
[35] Sokolowska K, Carballa D, Seoane S, Perez-Fernandez R, Mouriño A, Sicinski R R. J. Org. Chem., 2014, 80: 165.
[36] Ciesielski F, Sato Y, Chebaro Y, Moras D, Dejaegere A, Rochel N. J. Med. Chem., 2012, 55: 8440.
[37] (a) Fujii S, Masuno H, Taoda Y, Kano A, Wongmayura A, Nakabayashi M, Ito N, Shimizu M, Kawachi E, Hirano T. J. Am. Chem. Soc., 2011, 133: 20933.; (b) Wongmayura A, Fujii S, Ito S, Kano A, Taoda Y, Kawachi E, Kagechika H, Tanatani A. Bioorg. Med. Chem. Lett., 2012, 22: 1756.
[38] Fujii S, Kano A, Songkram C, Masuno H, Taoda Y, Kawachi E, Hirano T, Tanatani A, Kagechika H. Bioorg.Med. Chem., 2014, 22: 1227.
[39] Fujii S, Sekine R, Kano A, Masuno H, Songkram C, Kawachi E, Hirano T, Tanatani A, Kagechika H. Bioorg. Med. Chem., 2014, 22: 5891.
[40] Fujii S, Kano A, Masuno H, Songkram C, Kawachi E, Hirano T, Tanatani A, Kagechika H. Bioorg. Med.Chem. Lett., 2014, 24: 4515.
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