Novel and highly potent histamine H3 receptor ligands. Part 1: withdrawing of hERG activity
| Autor: | Thierry Calmels, Marc Capet, Jean-Charles Schwartz, Olivia Poupardin-Olivier, Nicolas Levoin, Isabelle Berrebi-Bertrand, Jeanne-Marie Lecomte, Olivier Labeeuw |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Quantitative structure–activity relationship Molecular model Stereochemistry Clinical Biochemistry hERG Pharmaceutical Science Quantitative Structure-Activity Relationship Ether Stereoisomerism Ligands Biochemistry chemistry.chemical_compound Transcriptional Regulator ERG Drug Discovery Humans Molecular Biology Binding Sites biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry biology.protein Trans-Activators Molecular Medicine Histamine H3 receptor Histamine Ethers Histamine H3 Antagonists |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(18) |
| ISSN: | 1464-3405 |
| Popis: | Pre-clinical investigation of some aryl-piperidinyl ether histamine H3 receptor antagonists revealed a strong hERG binding. To overcome this issue, we have developed a QSAR model specially dedicated to H3 receptor ligands. This model was designed to be directly applicable in medicinal chemistry with no need of molecular modeling. The resulting recursive partitioning trees are robust (80-85% accuracy), but also simple and comprehensible. A novel promising lead emerged from our work and the structure-activity relationships are presented. |
| Databáze: | OpenAIRE |
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