- Synthesis and biological evaluation of calcioic acid
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Herein, we describe the synthesis of calcioic acid following a recently developed synthetic strategy for calcitroic acid. Several improvements to reaction conditions were made, which resulted in higher yields. The improved workup and isolation procedures
- Arnold, Leggy A.,Di Milo, Elliot S.,Mutchie, Tania R.,Yu, Olivia B.
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- A protecting group-free synthesis of (-)-hortonones A-C from the Inhoffen-Lythgoe diol
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A synthesis of hortonones A-C has been accomplished from vitamin D2via the Inhoffen-Lythgoe diol without the use of protective groups. Key steps in the syntheses include a TMS-diazomethane mediated regioselective homologation of the cyclohexano
- Stambulyan, Hovsep,Minehan, Thomas G.
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supporting information
p. 8728 - 8731
(2016/10/03)
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- Carborane-based design of a potent Vitamin D receptor agonist
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The vitamin D nuclear receptor (VDR) is a potential target for cancer therapy. It is expressed in many tumors and its ligand shows anticancer actions. To combine these properties with the application of boron neutron capture therapy (BNCT), we design and
- Otero, Rocio,Seoane, Samuel,Sigüeiro, Rita,Belorusova, Anna Y.,Maestro, Miguel A.,Pérez-Fernández, Roman,Rochel, Natacha,Mouri?o, Antonio
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p. 1033 - 1037
(2016/02/05)
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- Design, synthesis, and evaluation of hybrid vitamin D3 side chain analogues as hedgehog pathway inhibitors
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Vitamin D3 (VD3) is a moderately potent and non-selective inhibitor of the Hedgehog (Hh) signaling cascade. Previous studies have established that the CD-ring region of VD3 serves as the Hh inhibitory pharmacophore. Subsequently, compound 3, an ester link
- Banerjee, Upasana,Deberardinis, Albert M.,Hadden, M. Kyle
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p. 548 - 555
(2015/01/30)
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- Synthesis and preliminary biological evaluation of new antiproliferative aromatic analogues of 1α,25-dihydroxyvitamin D3
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In an effort to develop novel vitamin D3 analogues, a series of aromatic compounds was synthetized, using efficient Negishi cross coupling between alkenylzinc reagents of the C,D-ring moiety of vitamin D3, and various substituted aromatic halides as A-ring mimics. The study aimed at exploring the influence of the replacement of the original vitamin D3 diene by a styrene unit on the biological activities. Potency in the induction of the differentiation of HL-60 cells for the lead compound 36 was 12 fold less important than calcitriol correlating with a weaker binding affinity for VDR.
- Thomas, Emmanuel,Brion, Jean-Daniel,Peyrat, Jean-Fran?ois
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p. 381 - 393
(2014/11/07)
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- Efficient and scalable total synthesis of calcitroic acid and its 13C-labeled derivative
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Calcitroic acid, the deactivated form of the physiological active vitamin D3 metabolite calcitrol, and its 13C labeled derivative has been synthesized starting from the commercially available Inhoffen-Lythgoe diol in 11 steps with an
- Meyer, Daniel,Rentsch, Lara,Marti, Roger
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p. 32327 - 32334
(2014/08/18)
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- 26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25- dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo
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Twelve new analogs of 19-nor-1α,25-dihydroxyvitamin D3 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, o
- Grzywacz, Pawel,Plum, Lori A.,Clagett-Dame, Margaret,Deluca, Hector F.
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- Analogues of the Inhoffen-Lythgoe diol with anti-proliferative activity
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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
- Deberardinis, Albert M.,Lemieux, Steven,Hadden, M. Kyle
-
supporting information
p. 5367 - 5370
(2013/09/23)
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- Synthesis and biological activities of vitamin D-like inhibitors of CYP24 hydroxylase
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Selective inhibitors of CYP24A1 represent an important synthetic target in a search for novel vitamin D compounds of therapeutic value. In the present work, we show the synthesis and biological properties of two novel side chain modified 2-methylene-19-no
- Chiellini, Grazia,Rapposelli, Simona,Zhu, Jinge,Massarelli, Ilaria,Saraceno, Marilena,Bianucci, Anna Maria,Plum, Lori A.,Clagett-Dame, Margaret,Deluca, Hector F.
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experimental part
p. 212 - 223
(2012/04/04)
-
- (20S)-2-METHYLENE-19-NOR-22-DIMETHYL-1alpha,25-DIHYDROXYVITAMIN D3 AND (20R)-2-METHYLENE-19-NOR-22-DIMETHYL-1alpha,25-HYDROXYVITAMIN D3
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Compounds of formula I are provided where X1, X2 and X3 are independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a varie
- -
-
Page/Page column 7-9; 11; 12
(2011/10/12)
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- DIASTEREOMERS OF 2-METHYLENE-19-NOR-22-METHYL-1ALPHA,25-DIHYDROXYVITAMIN D3
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Compounds of formula I are provided where X1, X2, and X3 are independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a vari
- -
-
Page/Page column 10; 11; 13
(2011/10/12)
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- 2-Methylene-(17Z)-17(20)-Dehydro-19,21-Dinor-Vitamin D Analogs
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This invention discloses 2-methylene-(17Z)-17(20)-dehydro-19,21-dinor-vitamin D analogs, and specifically 2-methylene-(17Z)-17(20)-dehydro-19,21-dinor-1α, 25-dihydroxyvitamin D3, and pharmaceutical uses therefor. This compound exhibits relative
- -
-
Page/Page column 4; 6-7
(2010/02/17)
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- 2-Methylene-(20E)-20(22)-Dehydro-19-Nor-Vitamin D Analogs
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This invention discloses 2-methylene-(20E)-20(22)-dehydro-19-nor-vitamin D analogs, and specifically 2-methylene-(20E)-20(22)-dehydro-19-nor-1α,25-dihydroxyvitamin D3, and pharmaceutical uses therefor. This compound exhibits relatively high tra
- -
-
Page/Page column 4; 6
(2010/02/17)
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- 2-Methylene-20(21)-Dehydro-19-Nor-Vitamin D Analogs
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This invention discloses 2-methylene-20(21)-dehydro-19-nor-vitamin D analogs, and specifically 2-methylene-20(21)-dehydro-19-nor-1α,25-dihydroxyvitamin D3, and pharmaceutical uses therefor. This compound exhibits relatively high transcription a
- -
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Page/Page column 4
(2010/02/17)
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- Synthesis of 20-epi-eldecalcitol [20-epi-1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71]
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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.
- Yoshino, Madoka,Eto, Kohei,Takahashi, Keisuke,Ishihara, Jun,Hatakeyama, Susumi,Ono, Yoshiyuki,Saito, Hitoshi,Kubodera, Noboru
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experimental part
p. 381 - 394
(2010/09/05)
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- Synthesis and preliminary biological evaluation of 20-epi-eldecalcitol [20-epi-1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71]
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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.
- Hatakeyama, Susumi,Yoshino, Madoka,Eto, Kohei,Takahashi, Keisuke,Ishihara, Jun,Ono, Yoshiyuki,Saito, Hitoshi,Kubodera, Noboru
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scheme or table
p. 25 - 28
(2011/12/01)
-
- 19,23,24,25,26,27-Hexanor-1alpha-hydroxyvitamin D3
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A compound or composition is provided that comprises a compound of formula 1A, where, X1 and X2 are independently selected from H or hydroxy-protecting groups. Also provided are compounds that form the compound of formula 1A after th
- -
-
Page/Page column 4-5
(2010/11/26)
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- 2-Methylene-19-nor-1alpha-hydroxy-17-ene-homopregnacalciferol and its uses
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This invention discloses 2-methylene-19-nor-17-ene vitamin D analogs, and specifically 2-methylene-19-nor-α-hydroxy-17-ene-homopregnacalciferol and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of
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-
Page/Page column 5
(2010/11/08)
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- 2-METHYLENE-18,19-DINOR-1α-HYDROXY-HOMOPREGNACALCIFEROL AND ITS USES
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This invention discloses 2-methylene-18,19-dinor-vitamin D analogs, and specifically 2-methylene-18,19-dinor-1α-hydroxy-homopregnacalciferol and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of und
- -
-
Page/Page column 9; 10
(2010/11/08)
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- Synthesis of putative metabolites of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)
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1α,25-Dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71), an analog of active vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is under phase III clinical trials in Japan for the treatment of osteop
- Ono, Yoshiyuki,Watanabe, Hiroyoshi,Taira, Ikuo,Takahashi, Keisuke,Ishihara, Jun,Hatakeyama, Susumi,Kubodera, Noboru
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p. 529 - 540
(2007/10/03)
-
- 2-Methylene-19-nor-(23S)-25-dehydro-1alpha-hydroxyvitamin D3-26,23-lactone and 2-methylene-19-nor-(23R)-25-dehydro-1alpha-hydroxyvitamin D3-26,23-lactone
-
Compounds of formula 1A and 1B are provided where X1 and X2 are independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of b
- -
-
Page/Page column 6-7; 9
(2008/06/13)
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- Vitamin D analogs for obesity prevention and treatment
-
Methods for treating and preventing obesity, inhibiting adipocyte differentiation, inhibiting increased SCD-1 gene transcription, and/or reducing body fat in a subject include administering at least one analog of 1α,25-dihydroxyvitamin D3 or 1α
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-
Page/Page column 47-49
(2008/06/13)
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- Vitamin D and click chemistry. Part 1: A stereoselective route to vitamin D analogues with triazole rings in their side chains
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Efficient preparation of vitamin D CD ring system synthons with triazole rings in their side chains is based on the formation of the triazole ring from a [3+2]-cycloaddition of a vitamin D side chain terminal azide with a terminal acetylene.
- Suarez, Pedro Lois,Gándara, Zoila,Gómez, Generosa,Fall, Yagamare
-
p. 4619 - 4621
(2007/10/03)
-
- Synthesis of 1alpha,25-dihydroxyvitamin D3-26,23-lactams (DLAMs), a novel series of 1 alpha,25-dihydroxyvitamin D3 antagonist.
-
Novel vitamin D(3) analogs having a lactam structure in their side chains, 1 alpha,25-dihydroxyvitamin D(3)-26,23-lactams (DLAMs), were designed based on the principle of regulation of the folding of helix-12 in the vitamin D nuclear receptor (VDR). The n
- Kato, Yuko,Nakano, Yusuke,Sano, Hiroko,Tanatani, Aya,Kobayashi, Hisayoshi,Shimazawa, Rumiko,Koshino, Hiroyuki,Hashimoto, Yuichi,Nagasawa, Kazuo
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p. 2579 - 2583
(2007/10/03)
-
- Novel heteroatom-containing vitamin D3 analogs: Efficient synthesis of 1α,25-dihydroxyvitamin D3-26,23-lactam
-
Vitamin D3 and its synthetic analogs are promising compounds for controlling various types of cell differentiation. In this article, we describe the synthesis of novel vitamin D3 analogs containing heteroatoms in their side chains - so-called vitamin D3 lactam analogs - via 1,3-dipolar cycloaddition reaction as a key step.
- Kato, Yuko,Hashimoto, Yuichi,Nagasawa, Kazuo
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p. 488 - 499
(2007/10/03)
-
- Vitamin D heterocyclic analogues. Part 1: A stereoselective route to CD systems with pyrazole rings in their side chains
-
Efficient preparation of two vitamin D CD ring system synthons with pyrazole rings in their side chains is based on the formation of the pyrazole ring from an α-acetylenic ketone.
- Fall, Yagamare,Barreiro, Candida,Fernández, Carlos,Mouri?o, Antonio
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p. 1433 - 1436
(2007/10/03)
-
- Convergent synthesis of 1α-hydroxyvitamin D5
-
An eleven-step, high-yielding (46%) synthesis of 1α-hydro-xyvitamin D5 (2) starting from Vitamin D2 (4) is described, in which a Julia olefination sequence is used for the construction of the (24R)-ethyl-substituted side chain.
- Gao, Ling-Jie,Zhao, Xu-Yang,Vandewalle, Maurits,De Clercq, Pierre
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p. 2755 - 2759
(2007/10/03)
-
- Synthesis of 14,20-Bis-epi-1α,25-dihydroxy-19-norvitamin D3 and analogues
-
14,20-Bis-epi-1α,25-dihydroxy-19-norvitamin D3 and side chain analogues thereof have been synthesised via the 14,20-bis-epi-Inhoffen- Lythgoe diol 9. The synthesis of this precursor was performed via degradation of vitamin D2 and by total synthesis starting from Hajos-Wiechert ketone 24.
- Van Gool, Michiel,Zhao, Xu-Yang,Sabbe, Katrien,Vandewalle, Maurits
-
p. 2241 - 2248
(2007/10/03)
-
- Stereoselective synthesis and structural establishment of (25S)-24,24- difluoro-1α,25,26-trihydroxyvitamin D3, a major metabolite of 24,24- difluoro-1α,25-dihydroxyvitamin D3
-
(25S)-24,24-Difluoro-1α,25,26-trihydroxyvitamin D3 (3a) and its (25R)- epimer (3b), either of which is expected to be a major metabolite of 24,24- difluoro-1α,25-dihydroxyvitamin D3 (2), were synthesized. Asymmetric addition to β-ket
- Iwasaki, Hiroshi,Hosotani, Ryuzo,Miyamoto, Yoichi,Nakano, Yoshio,Yamamoto, Keiko,Yamada, Sachiko,Shinki, Toshimasa,Suda, Tatsuo,Yamaguchi, Kentaro,Konno, Katsuhiro,Takayama, Hiroaki
-
p. 14705 - 14724
(2007/10/03)
-
- A new approach to the synthesis of the 25-hydroxy-22-oxa-vitamin D3 side chain
-
An efficient new method is described for the construction of the 25-hydroxy-22-oxavitamin D3 side-chain, which is present in several analogues of calcitriol with antitumour activity.
- Fall, Yagamare
-
p. 4909 - 4912
(2007/10/03)
-
- An efficient stereoselective synthesis of 1α,24(R)-dihydroxyvitamin D3 by the dienyne route
-
1α,24(R)-Dihydroxyvitamin D3 (5e) was synthesized. The key step in the preparation of the side-chain was opening of the chiral epoxide 10 by the α-anion of the nitrile 9. The triene system was synthesized by the dienyne route.
- Fall, Yagamare,Torneiro, Mercedes,Castedo, Luis,Mourino, Antonio
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p. 4703 - 4714
(2007/10/03)
-
- Antiproliferative hybrid analogs of the hormone 1α,25-dihydroxyvitamin D3: Design, synthesis, and preliminary biological evaluation
-
The combination of 10-12 kbar pressure plus Lewis acidic zinc dichloride promotes highly regioselective and stereoselective Diels-Alder cycloaddition between 3-bromo-2-pyrone, prepared in a new way, and unactivated terminal alkene 4-(tert-butyldimethylsiloxy)-1-butene. The conjugate base of A-ring allylic phosphine oxide 20 adds chemospecifically to the C-8 keto group of some C-8,C-24-diketones to form directly metabolically resistant 24-oxo analogs of 1α,25-dihydroxyvitamin D3 (calcitriol). Several of these new hybrid analogs are as efficacious in vitro as calcitriol at inhibiting growth of murine keratinocytes even at physiologically relevant 10-100 nanomolar concentrations.
- Posner,Lee,White,Hutchings,Dai,Kachinski,Dolan,Kensler
-
p. 3299 - 3314
(2007/10/03)
-
- Two Novel Allenic Side Chain Analogues of 1α,25-Dihydroxyvitamin D3 (1a)
-
Two new analogues of the steroid hormone 1α,25-dihydroxyvitamin D3 (1) in which allenic functionality has been incorporated into the side chain have been synthesized.Both the 22S and 22R allene analogues (2a and 2b) were each separately synthesized in nin
- Craig, Andrew S.,Norman, Anthony W.,Okamura, William H.
-
p. 4374 - 4380
(2007/10/02)
-
- PALLADIUM-CATALYZED SYNTHESIS OF DIENYNES RELATED TO 1α,25-DIHYDROXYVITAMIN D3
-
This note describes an efficient synthesis of a 25-functionalized dienyne precursor of the natural hormone 1α,25-dihydroxyvitamin D3 which allows easy labelling on the side chain.
- Castedo, L.,Mascarenas, J. L.,Mourino, A.,Sarandeses, L. A.
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p. 1203 - 1206
(2007/10/02)
-
- Studies on the Synthesis of Side-Chain Hydroxylated Metabolites of Vitamin D. 2. Stereocontrolled Synthesis of 25-Hydroxyvitamin D2
-
An efficient synthesis of 25-hydroxyvitamin D2 is described.The chiral center at C-24 was introduced by the stereospecific and regioselective displacement of an allylic carbamate by a cuprate.The triene system was assembled by Horner-Wittig coupling of ke
- Sardina, F. Javier,Mourino, Antonio,Castedo, Luis
-
p. 1264 - 1269
(2007/10/02)
-