Multistructure 3D-QSAR Studies on a Series of Conformationally Constrained Butyrophenones Docked into a New Homology Model of the 5-HT2A Receptor

详细信息    查看全文

• 作者：Cristina Dezi ; Jos&eacute ; Brea ; Mario Alvarado ; Enrique Raviñ ; a ; Christian F. Masaguer ; Marí ; a Isabel Loza ; Ferran Sanz ; Manuel Pastor
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：July 12, 2007
• 年：2007
• 卷：50
• 期：14
• 页码：3242 - 3255
• 全文大小：425K
• 年卷期：v.50,no.14(July 12, 2007)
• ISSN：1520-4804

文摘

The present study is part of a long-term research project aiming to gain insight into the mechanism ofaction of atypical antipsychotics. Here we describe a 3D-QSAR study carried out on a series of butyrophenoneswith affinity for the serotonin-2A receptor, aligned by docking into the binding site of a receptor model.The series studied has two peculiarities: (i) all the compounds have a chiral center and can be representedby two enantiomeric structures, and (ii) many of the structures can bind the receptor in two alternativeorientations, posing the problem of how to select a single representative structure for every compound. Wehave used an original solution consisting of the simultaneous use of multiple structures, representing differentconfigurations, binding conformations, and positions. The final model showed good statistical quality (n =426, r² = 0.84, q²_LOO = 0.81) and its interpretation provided useful information, not obtainable from thesimple inspection of the ligand-receptor complexes.