Construction of a Detailed Serotoninergic 5‐HT2a Receptor Model
- 1 January 1995
- journal article
- Published by Wiley in Archiv der Pharmazie
- Vol. 328 (7-8) , 577-584
- https://doi.org/10.1002/ardp.19953280704
Abstract
We have been able to show that the most important 5‐HT2a antagonists and agonists, belonging to chemically diverse classes can be fitted accurately into a common pharmacophoric pattern. In this paper we make use of the developed pharmacophore models to construct a fragmental amino acid model reflecting binding properties and affinity data of the structures under study. The proposed fragment model is then superimposed onto the transmembraneous part of the 5‐HT2a receptor. For this purpose the helix coordinates from the known structure of bacteriorhodopsin serve as a matrix. New structures with high affinity for the 5‐HT2a sites were designed and their biological activities were predicted on the basis of interaction energies calculated with the fragment model. The predicted data show excellent agreement with experimental binding affinities.Keywords
This publication has 7 references indexed in Scilit:
- Selectivity of Sterically Fixed Tryptamine and 5‐Methoxytryptamine Derivatives for Serotonin Receptor Subtypes, II:Structure‐Activity Relationships and in vitro Pharmacology of N‐Alkyl‐ and N,N‐Dialkyl‐3‐indolylbicyclo‐[2.2.1]‐heptane‐2‐aminesArchiv der Pharmazie, 1993
- Ketanserin analogs: structure-affinity relationships for 5-HT2 and 5-HT1C serotonin receptor bindingJournal of Medicinal Chemistry, 1992
- Molecular cloning of a human gene (S31) encoding a novel serotonin receptor mediating inhibition of adenylyl cyclaseFEBS Letters, 1992
- Binding of indolylalkylamines at 5-HT2 serotonin receptors: examination of a hydrophobic binding regionJournal of Medicinal Chemistry, 1990
- Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopyJournal of Molecular Biology, 1990
- 5-HT1 and 5-HT2 binding profiles of the serotonergic agents .alpha.-methylserotonin and 2-methylserotoninJournal of Medicinal Chemistry, 1990
- Serotonin receptor binding affinities of tryptamine analogsJournal of Medicinal Chemistry, 1979