Synthesis, Conformational Analysis, and Biological Evaluation of 19-nor-Vitamin D3 Analogues with A-Ring Modifications

被引：17
|
作者：
Sanchez-Abella, Laura [1 ,2 ]
Fernandez, Susana [1 ,2 ]
Verstuyf, Annemieke [3 ]
Verlinden, Lieve [3 ]
Gotor, Vicente [1 ,2 ]
Ferrero, Miguel [1 ,2 ]
机构：
[1] Univ Oviedo, Dept Quim Organ & Inorgan, E-33006 Oviedo, Asturias, Spain
[2] Univ Oviedo, Inst Univ Biotecnol Asturias, E-33006 Oviedo, Asturias, Spain
[3] Katholieke Univ Leuven, Lab Expt Geneeskunde & Endocrinol, B-3000 Louvain, Belgium
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 19期
关键词：
1-ALPHA; 25-DIHYDROXY-19-NORVITAMIN D-3; EFFICIENT SYNTHESIS; DERIVATIVES; ACID;
D O I：
10.1021/jm900711d
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
We have synthesized several isomers of 19-nor-vitamin D analogues possessing a hydroxy group at C-2 as well as novel derivatives bearing an epoxy substituent at the A-ring. All vitamins were prepared in convergent syntheses utilizing the modified Julia olefination. 1 alpha,2 alpha,25-Trihydroxy-19-nor-vitamin D-3 (3) and 2 beta,3 beta-epoxy-1 alpha,25-dihydroxy-3-deoxy-19-nor-vitamin D-3 (10), which showed the highest affinity to the vitamin D receptor, displayed the highest potency among the tested compounds to inhibit the proliferation of MCF-7 breast cancer cells.
引用
收藏
页码：6158 / 6162
页数：5
相关论文
共 50 条
  • [1] Synthesis of vitamin D3 analogues with A-ring modifications to directly measure vitamin D levels in biological samples
    Hernandez-Martin, Alba
    Gonzalez-Garcia, Tania
    Lawlor, Margaret
    Preston, Lesley
    Gotor, Vicente
    Fernandez, Susana
    Ferrero, Miguel
    BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (24) : 7779 - 7789
  • [2] Synthesis and biological activity of previtamin D3 analogues with A-ring modifications
    Sanchez-Abella, Laura
    Fernandez, Susana
    Verstuyf, Annemieke
    Verlinden, Lieve
    Gotor, Vicente
    Ferrero, Miguel
    BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (24) : 10244 - 10250
  • [3] Enzymatic Desymmetrization of 19-nor-Vitamin D3 A-Ring Synthon Precursor: Synthesis, Structure Elucidation, and Biological Activity of 1α,25-Dihydroxy-3-epi-19-nor-vitamin D3 and 1β,25-Dihydroxy-19-nor-vitamin D3
    Gonzalez-Garcia, Tania
    Verstuyf, Annemieke
    Verlinden, Lieve
    Fernandez, Susana
    Ferrero, Miguel
    ADVANCED SYNTHESIS & CATALYSIS, 2018, 360 (14) : 2762 - 2772
  • [4] Synthesis of 19-Nor-Vitamin D A-Ring Synthons via Ring-Closing Olefin Metathesis
    Nagai, Yu
    Tanami, Tomoe
    Abe, Junko
    Nagai, Hazuki
    Hamamizu, Toru
    Kominato, Kaichiro
    Iida, Keisuke
    Nagasawa, Kazuo
    ASIAN JOURNAL OF ORGANIC CHEMISTRY, 2014, 3 (09) : 994 - 999
  • [5] Evaluation of vitamin D3 A-ring analogues as Hedgehog pathway inhibitors
    Banerjee, Upasana
    Ghosh, Manuka
    Hadden, M. Kyle
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (03) : 1330 - 1334
  • [6] Synthesis of an intermediate for A-ring of 19-nor-1α,25-dihydroxyvitamin D3 analogues
    Wu, Y
    Guan, M
    Ji, T
    Cheng, L
    INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY, 2001, 40 (02): : 136 - 138
  • [7] A practical synthesis of a-ring precursors for 19-nor-1a,25-dihydroxyvitamin D3 analogues
    Tetrahedron Lett, 42 (7637):
  • [8] Strategies for the Synthesis of 19-nor-Vitamin D Analogs
    Fernandez, Susana
    Ferrero, Miguel
    PHARMACEUTICALS, 2020, 13 (08) : 1 - 30
  • [9] Synthesis and Biological Activity of 25-Hydroxy-2-methylene-vitamin D3 Analogues Monohydroxylated in the A-ring
    Sibilska, Izabela K.
    Sicinski, Rafal R.
    Ochalek, Justin T.
    Plum, Lori A.
    DeLuca, Hector F.
    JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (20) : 8319 - 8331
  • [10] Methyl-introduced A-ring analogues of 1α,25-dihydroxyvitamin D3:: Synthesis and biological evaluation
    Fujishima, Toshie
    Tsutsumi, Ryuji
    Negishi, Yoichi
    Fujii, Shinya
    Takayama, Hiroaki
    Kittaka, Atsushi
    Kurihara, Masaaki
    ANTICANCER RESEARCH, 2006, 26 (4A) : 2633 - 2636
12345