Synthesis and Biological Evaluation of Benzodioxanylpiperazine Derivatives as Potent Serotonin 5-HT1A Antagonists: The Discovery of Lecozotan
| Autor: | Gan Zhang, Lisa Potestio, Donna M. Huryn, Stacey J. Sukoff, Deborah L. Smith, Jean Schmid, Terrance H. Andree, Sharon Rosenzweig-Lipson, Lee E. Schechter, Michael G. Kelly, Geoffrey Hornby, Boyd L. Harrison, Douglas M. Ho, Wayne E. Childers, Magid Abou-Gharbia |
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| Rok vydání: | 2005 |
| Předmět: |
Intrinsic activity
CHO Cells Serotonin 5-HT1 Receptor Antagonists Pharmacology Crystallography X-Ray Chemical synthesis Piperazines Dioxanes Radioligand Assay Structure-Activity Relationship Cricetulus GTP-Binding Proteins In vivo Cricetinae Drug Discovery Cyclic AMP medicine Animals Humans Receptor Molecular Structure Chemistry Antagonist Stereoisomerism Biological activity In vitro Lecozotan Biochemistry Receptor Serotonin 5-HT1A Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 48:3467-3470 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A series of benzodioxanylpiperazine derivatives possessing a 4-aryl amide substituent was prepared and evaluated for 5-HT(1A) affinity and functional antagonist activity in vitro and in vivo. All of the compounds in this series possessed high affinity for the human 5-HT(1A) receptor and many displayed potent antagonist activity in vitro and varying degrees of intrinsic activity in vivo. Compound 11c (Lecozotan) was selected for further development and is currently in clinical trials. |
| Databáze: | OpenAIRE |
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