Literature DB >> 24900728

Synthesis of 2α-heteroarylalkyl active vitamin d3 with therapeutic effect on enhancing bone mineral density in vivo.

Miki Matsuo1, Asami Hasegawa1, Masashi Takano1, Hiroshi Saito2, Shinji Kakuda2, Takayuki Chida2, Ken-Ichiro Takagi2, Eiji Ochiai2, Kyohei Horie2, Yoshifumi Harada2, Midori Takimoto-Kamimura2, Kazuya Takenouchi2, Daisuke Sawada1, Atsushi Kittaka1.   

Abstract

2α-Heteroarylethyl-1α,25-dihydroxyvitamin D3 analogues, which were designed to form a hydrogen bond between Arg274 of human vitamin D receptor (hVDR) and a nitrogen atom of the heteroaromatic ring at the 2α-position, were synthesized. Among them, 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats, osteoporosis model animals, on enhancing bone mineral density than those of active vitamin D3. X-ray cocrystallographic analysis of the hVDR-ligand complex confirms that the new hydrogen bond formation stabilized the complex.

Entities:  

Keywords:  Vitamin D; X-ray cocrystallographic analysis; bone mineral density; in vivo antiosteoporotic effect; osteocalcin; vitamin D receptor

Year:  2013        PMID： 24900728      PMCID： PMC4027143          DOI： 10.1021/ml400098w

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  7 in total

1.  The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand.

Authors:  N Rochel; J M Wurtz; A Mitschler; B Klaholz; D Moras
Journal:  Mol Cell       Date:  2000-01       Impact factor: 17.970

2.  Efficient and versatile synthesis of novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D(3) analogues and their docking to vitamin D receptors.

Authors:  Y Suhara; K I Nihei; M Kurihara; A Kittaka; K Yamaguchi; T Fujishima; K Konno; N Miyata; H Takayama
Journal:  J Org Chem       Date:  2001-12-28       Impact factor: 4.354

3.  Probing a water channel near the A-ring of receptor-bound 1 alpha,25-dihydroxyvitamin D3 with selected 2 alpha-substituted analogues.

Authors:  Shinji Hourai; Toshie Fujishima; Atsushi Kittaka; Yoshitomo Suhara; Hiroaki Takayama; Natacha Rochel; Dino Moras
Journal:  J Med Chem       Date:  2006-08-24       Impact factor: 7.446

4.  Design and efficient synthesis of 2 alpha-(omega-hydroxyalkoxy)-1 alpha,25-dihydroxyvitamin D3 Analogues, including 2-epi-ED-71 and their 20-epimers with HL-60 cell differentiation activity.

Authors:  Nozomi Saito; Yoshitomo Suhara; Masaaki Kurihara; Toshie Fujishima; Shinobu Honzawa; Hitoshi Takayanagi; Toshiro Kozono; Masahiko Matsumoto; Masayuki Ohmori; Naoki Miyata; Hiroaki Takayama; Atsushi Kittaka
Journal:  J Org Chem       Date:  2004-10-29       Impact factor: 4.354

Review 5.  Vitamin D and human health: lessons from vitamin D receptor null mice.

Authors:  Roger Bouillon; Geert Carmeliet; Lieve Verlinden; Evelyne van Etten; Annemieke Verstuyf; Hilary F Luderer; Liesbet Lieben; Chantal Mathieu; Marie Demay
Journal:  Endocr Rev       Date:  2008-08-11       Impact factor: 19.871

6.  Human cytochrome P450-dependent differential metabolism among three 2α-substituted-1α,25-dihydroxyvitamin D(3) analogs.

Authors:  Kaori Yasuda; Shinichi Ikushiro; Masaki Kamakura; Masashi Takano; Nozomi Saito; Atsushi Kittaka; Tai C Chen; Miho Ohta; Toshiyuki Sakaki
Journal:  J Steroid Biochem Mol Biol       Date:  2012-09-13       Impact factor: 4.292

Review 7.  The nuclear receptor superfamily: the second decade.

Authors:  D J Mangelsdorf; C Thummel; M Beato; P Herrlich; G Schütz; K Umesono; B Blumberg; P Kastner; M Mark; P Chambon; R M Evans
Journal:  Cell       Date:  1995-12-15       Impact factor: 41.582
  7 in total
  4 in total

Review 1.  Tetrazoles via Multicomponent Reactions.

Authors:  Constantinos G Neochoritis; Ting Zhao; Alexander Dömling
Journal:  Chem Rev       Date:  2019-02-01       Impact factor: 60.622

Review 2.  Vitamin D and Its Synthetic Analogs.

Authors:  Miguel A Maestro; Ferdinand Molnár; Carsten Carlberg
Journal:  J Med Chem       Date:  2019-04-02       Impact factor: 7.446

3.  Robust osteogenic efficacy of 2α-heteroarylalkyl vitamin D analogue AH-1 in VDR (R270L) hereditary vitamin D-dependent rickets model rats.

Authors:  Miyu Nishikawa; Naruhiro Murose; Hiroki Mano; Kaori Yasuda; Yasuhiro Isogai; Atsushi Kittaka; Masashi Takano; Shinichi Ikushiro; Toshiyuki Sakaki
Journal:  Sci Rep       Date:  2022-07-22       Impact factor: 4.996

4.  Confirmation of high-throughput screening data and novel mechanistic insights into VDR-xenobiotic interactions by orthogonal assays.

Authors:  Debabrata Mahapatra; Jill A Franzosa; Kyle Roell; Melaine Agnes Kuenemann; Keith A Houck; David M Reif; Denis Fourches; Seth W Kullman
Journal:  Sci Rep       Date:  2018-06-11       Impact factor: 4.379
  4 in total

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