100928-03-8Relevant articles and documents
Synthesis and preliminary biological evaluation of 20-epi-eldecalcitol [20-epi-1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71]
Hatakeyama, Susumi,Yoshino, Madoka,Eto, Kohei,Takahashi, Keisuke,Ishihara, Jun,Ono, Yoshiyuki,Saito, Hitoshi,Kubodera, Noboru
, p. 25 - 28 (2010)
Eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3, developing code: ED-71] is an analog of active vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] that possesses a hydroxypropoxy substituent at the 2β-position of 1,25(OH)2D3. Eldecalcitol has potent biological effects on bone and is now in preparation for approval as a promising medicine for the treatment of osteoporosis in Japan. To explore chemical structure-biological activity relationships between eldecalcitol and related analogs, we have already synthesized 1-epi-eldecalcitol, 3-epi-eldecalcitol, and 1,3-diepi-eldecalcitol with inherent biological interests of each targeted analog and evaluated their biological responses. It has been reported that 20-epi-1,25(OH)2D3, a diastereomer of 1,25(OH)2D3 that possesses an inverted methyl substituent at the 20-position of the side chain, shows remarkably enhanced biological activities compared to parental compound, 1,25(OH)2D3. As a continuation of our modification studies on eldecalcitol, we took great interest in 20-epi-eldecalcitol and its biological responses. In this paper, the synthesis of 20-epi-eldecalcitol by the Trost coupling reaction between the A-ring fragment and the C/D-ring fragment as well as in vitro preliminary biological evaluation of 20-epi-eldecalcitol are described. In the induction of human myeloid leukemia cell (HL-60) differentiation, inhibition of the human histiocytic lymphoma cell (U937) proliferation, and increase in osteocalcin concentration in the human osteosarcoma cell (MG-63), 20-epi-eldecalcitol showed significantly enhanced activity compared to eldecalcitol.
Design and efficient synthesis of novel vitamin D analogues bearing an aniline moiety in their side chains
Obelleiro, Antonio,Gómez-Bouzó, Uxía,Gómez, Generosa,Fall, Yagamare,Santalla, Hugo
, (2020)
Six novel vitamin D analogues bearing an aniline moiety in their side chains were designed and synthesized using a convergent route. The CD ring fragments were prepared from Inhoffen-Lythgoe diol in five- or six-steps with high yields. Secondary amines we
Synthesis of a trans-hydrindanone, precursor for the preparation of vitamin D analogues
Gandara, Zoila,Rivadulla, Marcos L.,Perez, Manuel,Gomez, Generosa,Fall, Yagamare
, p. 5678 - 5682 (2013)
We developed a very efficient and practical method for the large-scale synthesis of a trans-hydrindan derivative related to vitamin D, based on the Criegee rearrangement. This ketone is a valuable synthon for the preparation of Gemini-type vitamin D analogues or other calcitriol analogues modified at C-20, C-21 or the D-ring. Our methodology is superior to those previously reported when considering efficiency and expediency. The Criegee rearrangement was the key step for a large-scale synthesis of a trans-hydrindan derivative related to vitamin D. This work is superior to previous approaches with regards to efficiency and expediency. Copyright
Modified Julia olefination and α aminoxylation reactions mediated convergent synthesis of 1α, 24 (R)-dihydroxyvitamin D3 (tacalcitol)
Martínez, Andrea,Santalla, Hugo,Garrido, Fátima,Gómez, Generosa,Fall, Yagamare
supporting information, p. 3568 - 3570 (2017/10/06)
A convergent synthesis of tacalcitol has been achieved starting from inexpensive and commercially available isovaleraldehyde and easily available Inhoffen-Lythgoe diol. Key steps include a proline catalyzed α aminoxylation and a Julia-Kocienski olefination.
Synthesis of Denosomin-Vitamin D3 Hybrids and Evaluation of Their Anti-Alzheimer's Disease Activities
Sugimoto, Kenji,Yajima, Hisanari,Hayashi, Yusuke,Minato, Daishiro,Terasaki, Sayuri,Tohda, Chihiro,Matsuya, Yuji
supporting information, p. 5910 - 5913 (2015/12/11)
As an extension of previously conducted studies on developing an anti-Alzheimer's disease agent, denosomin (1-deoxy-24-norsominone, an artificial inducer of neurite elongation), derivatives were designed and synthesized based on the hypothesis that our denosomin would exhibit axonal extension activity via a 1,25D3-membrane-associated, rapid response steroid-binding protein (1,25D3-MARRS) pathway. The biological assay revealed that the hybridization of characteristic δ-lactone in denosomin and the triene moiety in VD3 was effective to enhance the nerve re-extension activity in amyloid β (Aβ)-damaged neurons.
Analogues of the Inhoffen-Lythgoe diol with anti-proliferative activity
Deberardinis, Albert M.,Lemieux, Steven,Hadden, M. Kyle
, p. 5367 - 5370 (2013/09/23)
The anti-proliferative activity of a series of ester- and amide-linked Inhoffen-Lythgoe side chain analogues is reported. Whereas the Inhoffen-Lythgoe diol was inactive in these studies, a number of aromatic and aliphatic ester-linked side chains demonstr
Design, synthesis, evaluation, and structure of vitamin D analogues with furan side chains
Fraga, Ramon,Zacconi, Flavia,Sussman, Fredy,Ordonez-Moran, Paloma,Munoz, Alberto,Huet, Tiphaine,Molnar, Ferdinand,Moras, Dino,Rochel, Natacha,Maestro, Miguel,Mourino, Antonio
supporting information; experimental part, p. 603 - 612 (2012/02/15)
Based on the crystal structures of human vitamin D receptor (hVDR) bound to 1α,25-dihydroxy-vitamin D3 (1,25 D) and superagonist ligands, we previously designed new superagonist ligands with a tetrahydrofuran ring at the side chain that optimize the aliphatic side-chain conformation through an entropy benefit. Following a similar strategy, four novel vitamin D analogues with aromatic furan side chains (3 a, 3 b, 4 a, 4 b) have now been developed. The triene system has been constructed by an efficient stereoselective intramolecular cyclization of an enol triflate (A-ring precursor) followed by a Suzuki-Miyaura coupling of the resulting intermediate with an alkenyl boronic ester (CD-side chain, upper fragment). The furan side chains have been constructed by gold chemistry. These analogues exhibit significant pro-differentiation effects and transactivation potency. The crystal structure of 3 a in a complex with the ligand-binding domain of hVDR revealed that the side-chain furanic ring adopts two conformations. Copyright
Synthesis of 20-epi-eldecalcitol [20-epi-1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71]
Yoshino, Madoka,Eto, Kohei,Takahashi, Keisuke,Ishihara, Jun,Hatakeyama, Susumi,Ono, Yoshiyuki,Saito, Hitoshi,Kubodera, Noboru
experimental part, p. 381 - 394 (2010/09/05)
A convergent synthesis of biologically interesting 20-epi-eldecalcitol which possesses an inverted C-21 methyl substituent at the 20-position of the side chain of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (eldecalcitol) is described.
Vitamin D receptor agonist/histone deacetylase inhibitor molecular hybrids
Lamblin, Marc,Dabbas, Basel,Spingarn, Russell,Mendoza-Sanchez, Rodrigo,Wang, Tian-Tian,An, Beum-Soo,Huang, Dao Chao,Kremer, Richard,White, John H.,Gleason, James L.
experimental part, p. 4119 - 4137 (2010/08/06)
Incorporation of zinc-binding groups into the side-chain of 1α,25-dihydroxyvitamin D3 (1,25D) fully bifunctional hybrid molecules which act both as vitamin D receptor agonists and histone deacetylase inhibitors. These bifunctional hybrids displ
HYBRID MOLECULES HAVING MIXED VITAMIN D RECEPTOR AGONISM AND HISTONE DEACETYLASE INHIBITORY PROPERTIES
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Page/Page column 23; 35, (2009/10/22)
Hybrid molecules comprising a vitamin D receptor agonist moiety and an HDAC inhibitor moiety are described herein. The HDAC inhibitor moiety can be derived from an HDAC inhibitor comprising a functionality selected from the group consisting of an N-hydrox
