PMID- 26827960
OWN - NLM
STAT- MEDLINE
DCOM- 20170118
LR  - 20170118
IS  - 0083-6729 (Print)
IS  - 0083-6729 (Linking)
VI  - 100
DP  - 2016
TI  - Vitamin D Analogs with Nitrogen Atom at C2 Substitution and Effect on Bone 
      Formation.
PG  - 379-94
LID - S0083-6729(15)00062-X [pii]
LID - 10.1016/bs.vh.2015.10.010 [doi]
AB  - The Arg274 residue of the ligand binding domain of human vitamin D receptor 
      (hVDR) is important for 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) binding as a 
      specific ligand through forming a hydrogen bond with the 1alpha-OH group of the 
      active vitamin D3, 1alpha,25(OH)2D3. An additional pincer-type hydrogen bond 
      formation with Arg274 from a 2alpha-substituent of a synthetic 1alpha,25(OH)2D3 analog 
      would enhance the binding affinity and biological activity. A series of 
      2alpha-[2-(heteroaryl)ethyl]-, 2alpha-(4-cyanobutyl)-, 2alpha-(omega-cyanoalkoxy)-, and 
      2beta-(3-cyanopropoxy)-1alpha,25(OH)2D3 were designed and synthesized based on our 
      original hVDR super agonists of 2alpha-(3-hydroxypropyl)- and 
      2alpha-(3-hydroxypropoxy)-1alpha,25(OH)2D3. Their potential biological activities, i.e., 
      hVDR binding affinity, transactivation activity in HOS cells, and therapeutic 
      effect on enhancing the bone mineral density of OVX rats, were studied.
CI  - (c) 2016 Elsevier Inc. All rights reserved.
FAU - Kittaka, Atsushi
AU  - Kittaka A
AD  - Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan. Electronic 
      address: akittaka@pharm.teikyo-u.ac.jp.
FAU - Takano, Masashi
AU  - Takano M
AD  - Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan.
FAU - Saitoh, Hiroshi
AU  - Saitoh H
AD  - Teijin Institute for Bio-medical Research, Teijin Pharma Ltd., Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151217
PL  - United States
TA  - Vitam Horm
JT  - Vitamins and hormones
JID - 0413601
RN  - 0 (Ligands)
RN  - 0 (Receptors, Calcitriol)
RN  - 1406-16-2 (Vitamin D)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Bone Density/drug effects
MH  - Bone Development/*drug effects
MH  - Calcium/blood/metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Ligands
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Osteosarcoma/metabolism
MH  - Ovariectomy
MH  - Protein Binding
MH  - Protein Conformation
MH  - Rats
MH  - Receptors, Calcitriol/metabolism
MH  - Structure-Activity Relationship
MH  - Transcription, Genetic
MH  - Vitamin D/*analogs & derivatives/*chemistry/pharmacology
OTO - NOTNLM
OT  - 2alpha-Functionalized vitamin D
OT  - Binding affinity
OT  - Bone mineral density
OT  - Synthesis
OT  - Vitamin D
OT  - Vitamin D receptor
OT  - X-Ray cocrystallographic analysis
EDAT- 2016/02/02 06:00
MHDA- 2017/01/19 06:00
CRDT- 2016/02/02 06:00
PHST- 2016/02/02 06:00 [entrez]
PHST- 2016/02/02 06:00 [pubmed]
PHST- 2017/01/19 06:00 [medline]
AID - S0083-6729(15)00062-X [pii]
AID - 10.1016/bs.vh.2015.10.010 [doi]
PST - ppublish
SO  - Vitam Horm. 2016;100:379-94. doi: 10.1016/bs.vh.2015.10.010. Epub 2015 Dec 17.