PMID- 22162241
OWN - NLM
STAT- MEDLINE
DCOM- 20120417
LR  - 20121115
IS  - 1521-3765 (Electronic)
IS  - 0947-6539 (Linking)
VI  - 18
IP  - 2
DP  - 2012 Jan 9
TI  - Design, synthesis, evaluation, and structure of vitamin D analogues with furan 
      side chains.
PG  - 603-12
LID - 10.1002/chem.201102695 [doi]
AB  - Based on the crystal structures of human vitamin D receptor (hVDR) bound to 
      1alpha,25-dihydroxy-vitamin D(3) (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 (3a, 3b, 4a, 4b) 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 3a in a complex with the ligand-binding domain 
      of hVDR revealed that the side-chain furanic ring adopts two conformations.
CI  - Copyright (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Fraga, Ramon
AU  - Fraga R
AD  - Departamento de Quimica Organica, Universidad de Santiago y Unidad Asociada al 
      CSIC, Avda de las Ciencias s/n, 15782 Santiago de Compostela, Spain.
FAU - Zacconi, Flavia
AU  - Zacconi F
FAU - Sussman, Fredy
AU  - Sussman F
FAU - Ordonez-Moran, Paloma
AU  - Ordonez-Moran P
FAU - Munoz, Alberto
AU  - Munoz A
FAU - Huet, Tiphaine
AU  - Huet T
FAU - Molnar, Ferdinand
AU  - Molnar F
FAU - Moras, Dino
AU  - Moras D
FAU - Rochel, Natacha
AU  - Rochel N
FAU - Maestro, Miguel
AU  - Maestro M
FAU - Mourino, Antonio
AU  - Mourino A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111208
PL  - Germany
TA  - Chemistry
JT  - Chemistry (Weinheim an der Bergstrasse, Germany)
JID - 9513783
RN  - 0 (Furans)
RN  - 0 (Receptors, Calcitriol)
RN  - 1406-16-2 (Vitamin D)
RN  - UC0XV6A8N9 (furan)
SB  - IM
MH  - Cell Adhesion/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Crystallography, X-Ray
MH  - Furans/*chemistry/*pharmacology
MH  - Humans
MH  - Models, Molecular
MH  - Protein Binding
MH  - Receptors, Calcitriol/*metabolism
MH  - Transcriptional Activation/drug effects
MH  - Vitamin D/*analogs & derivatives/*pharmacology
EDAT- 2011/12/14 06:00
MHDA- 2012/04/18 06:00
CRDT- 2011/12/14 06:00
PHST- 2011/08/29 00:00 [received]
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/04/18 06:00 [medline]
AID - 10.1002/chem.201102695 [doi]
PST - ppublish
SO  - Chemistry. 2012 Jan 9;18(2):603-12. doi: 10.1002/chem.201102695. Epub 2011 Dec 8.