PMID- 8410972
OWN - NLM
STAT- MEDLINE
DCOM- 19931029
LR  - 20190709
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 36
IP  - 18
DP  - 1993 Sep 3
TI  - Conformational effects on retinoid receptor selectivity. 1. Effect of 9-double 
      bond geometry on retinoid X receptor activity.
PG  - 2605-13
AB  - A major challenge is the development of retinoids with selective biological 
      activities. Recently, studies on retinoid response mechanisms indicate that 
      retinoids activate two classes of nuclear receptor proteins, the retinoic acid 
      receptors (RARs) and the retinoid X receptors (RXRs). Here, we analyze the 
      activity of a series of (E)- and (Z)-stilbenecarboxylic acids for gene 
      transcriptional activation of the RARs and RXR-alpha to determine the optimum 
      pharmacophore for receptor activation. The data obtained indicate that RAR and 
      RXR response pathways can be separated by using the appropriate ligand. The 
      conformations of 
      (Z)-4-[2-(5-,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)prop 
      en-1-yl]benzoic acid (Z)-4-[1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- 
      naphthalenyl)propen-2-yl]benzoic acid were examined by experimental and 
      theoretical methods to establish the appropriate conformation of the latter that 
      specifically activated the retinoid RXR. A palladium(0)-catalyzed aryl 
      bromide-arylboronic acid coupling under nonanhydrous conditions was used to 
      construct a biaryl bond in the conformationally restricted retinoid 2'- 
      (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthaleny)biphenyl-4-c arboxylic 
      acid, which had RXR activity.
FAU - Jong, L
AU  - Jong L
AD  - Bio-Organic Chemistry Laboratory, SRI International, Menlo Park, California.
FAU - Lehmann, J M
AU  - Lehmann JM
FAU - Hobbs, P D
AU  - Hobbs PD
FAU - Harlev, E
AU  - Harlev E
FAU - Huffman, J C
AU  - Huffman JC
FAU - Pfahl, M
AU  - Pfahl M
FAU - Dawson, M I
AU  - Dawson MI
LA  - eng
GR  - 5 P01 CA51993/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Carboxylic Acids)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Stilbenes)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Binding Sites
MH  - Carboxylic Acids/*chemistry/pharmacology
MH  - Cell Line
MH  - Computer Simulation
MH  - Magnetic Resonance Spectroscopy
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Molecular Structure
MH  - Receptors, Cytoplasmic and Nuclear/*drug effects/genetics/physiology
MH  - *Receptors, Retinoic Acid
MH  - Retinoid X Receptors
MH  - Retinoids/chemical synthesis/*chemistry/pharmacology
MH  - Stilbenes/*chemistry/pharmacology
MH  - Structure-Activity Relationship
MH  - *Transcription Factors
MH  - Transcription, Genetic/drug effects
MH  - Transcriptional Activation
MH  - Transfection
MH  - X-Ray Diffraction
EDAT- 1993/09/03 00:00
MHDA- 1993/09/03 00:01
CRDT- 1993/09/03 00:00
PHST- 1993/09/03 00:00 [pubmed]
PHST- 1993/09/03 00:01 [medline]
PHST- 1993/09/03 00:00 [entrez]
AID - 10.1021/jm00070a003 [doi]
PST - ppublish
SO  - J Med Chem. 1993 Sep 3;36(18):2605-13. doi: 10.1021/jm00070a003.