Novel highly potent serotonin 5-HT7 receptor ligands: structural modifications to improve pharmacokinetic properties
| Autor: | Enza Lacivita, Marcello Leopoldo, Francesco Berardi, Giovanni Laviola, Nicola Antonio Colabufo, Bianca De Filippis, Pantaleo Di Pilato, Madia Letizia Stama, Walter Adriani, Mauro Niso, Roberto Perrone |
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| Rok vydání: | 2013 |
| Předmět: |
Male
ATP Binding Cassette Transporter Subfamily B Stereochemistry Clinical Biochemistry Pharmaceutical Science Ligands Biochemistry Piperazines 5-HT7 receptor chemistry.chemical_compound Mice Radioligand Assay Structure-Activity Relationship Drug Discovery Animals Humans Receptor Molecular Biology 5-HT receptor Ligand Organic Chemistry Propanamide Amides In vitro chemistry Blood-Brain Barrier Receptors Serotonin Molecular Medicine Serotonin Caco-2 Cells Selectivity |
| Zdroj: | Bioorganicmedicinal chemistry letters. 23(22) |
| ISSN: | 1464-3405 |
| Popis: | Here we report the synthesis, pharmacological and pharmacokinetic evaluation of a pilot set of compounds structurally related to the potent and selective 5-HT7 ligand LP-211. Among the studied compounds, N-pyridin-3-ylmethyl-3-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]ethoxy]propanamide (4b) showed high affinity for 5-HT7 receptors (Ki = 23.8 nM), selectivity over 5-HT1A receptors (>50-fold), in vitro metabolic stability (82%) and weak interaction with P-glycoprotein (BA/AB = 3.3). Compound 4b was injected ip in mice to preliminarily evaluate its distribution between blood and brain. |
| Databáze: | OpenAIRE |
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