Strasser, Andrea and Wittmann, Hans-Joachim (2010) 3D-QSAR CoMFA Study to Predict Orientation of Suprahistaprodifens and Phenoprodifens in the Binding-Pocket of Four Histamine H-1-Receptor Species. MOLECULAR INFORMATICS, 29 (4). pp. 333-341. ISSN 1868-1743,
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Several phenylhistamines and histaprodifens were identified to act as (partial) agonists at the histamine H-1-receptor (H1R). The large diversity of these compounds led to pK(i) values in a range between 4.5-7.5 at human, rat, bovine and guinea-pig histamine H1R. Hybrid molecules, consisting of two different H1R-agonist partial structures, like suprahistaprodifens or phenoprodifens for example, or compounds with a dimeric histamine moiety are able to bind in two different orientations into the binding-pocket of the H1R. In order to predict the percentage of ligand bound in orientation 1 or in orientation 2, 3D-QSAR studies at four H1R species were performed. The training set contains ligands which can only bind in one orientation and the test set all ligands with two possible orientations. In general, the predicted pK(i) values of the test compounds were in good correlation to the experimental ones. Additionally, the predicted pK(i) values for all ligands with two possible orientations were used to calculate the percentage of the hybrid ligands bound in orientation 1 and 2. Our models suggest that the preferred orientation of these hybrid molecules is dependent on ligand and H1R species.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTOR; MOLECULAR-FIELD ANALYSIS; IN-VITRO EVALUATION; H-1 RECEPTOR; CRYSTAL-STRUCTURE; AGONISTS; ANTAGONIST; HISTAPRODIFENS; PHARMACOLOGY; Histamine H-1-receptor; G-Protein-coupled receptor; 3D-QSAR; CoMFA; Affinity |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Aug 2020 09:46 |
| Last Modified: | 03 Aug 2020 09:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24933 |
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