Article

Analogues of the dopamine D2 receptor antagonist L741,626: Binding, function, and SAR.

Medicinal Chemistry, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Bioorganic & Medicinal Chemistry Letters (impact factor: 2.55). 03/2007; 17(3):745-9. DOI:10.1016/j.bmcl.2006.10.076 pp.745-9
Source: PubMed

ABSTRACT A series of analogues of the dopamine D2 receptor antagonist L741,626 were synthesized and evaluated for binding and function at D2 family receptor subtypes. Several analogues showed comparable binding profiles to the parent ligand, however, in general, chemical modification served to reduce D2 binding affinity and selectivity.

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    Article: Predictions of binding for dopamine D2 receptor antagonists by the SIE method.
    Yeng-Tseng Wang, Zhi-Yuan Su, Chang-Huain Hsieh, Cheng-Lung Chen
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    ABSTRACT: The control of tetralindiol derivative antagonists released through the inhibition of dopamine D2 receptors has been identified as a potential target for the treatment of schizophrenia. We employed molecular dynamics simulation techniques to identify the predicted D2 receptor structure. Homology models of the protein were developed on the basis of crystal structures of four receptor crystals. Compound docking revealed the possible binding mode. In addition, the docking analyses results indicate that five residues (Asp72, Val73, Cys76, Leu183, and Phe187) were responsible for the selectivity of the tetralindiol derivatives. Our molecular dynamics simulations were applied in combination with the solvated interaction energies (SIE) technique to predict the compounds' docking modes in the binding pocket of the D2 receptor. The simulations revealed satisfactory correlations between the calculated and experimental binding affinities of all seven tetralindiol derivative antagonists, as indicated by the obtained R2 value of 0.815.
    Journal of Chemical Information and Modeling 09/2009; 49(10):2369-75. · 4.68 Impact Factor
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Keywords

binding
 
chemical modification
 
comparable binding profiles
 
D2 binding affinity
 
D2 family receptor subtypes
 
dopamine D2 receptor antagonist L741,626
 
selectivity