Structure−Activity Relationship of Triazafluorenone Derivatives as Potent and Selective mGluR1 Antagonists
| Autor: | Meena V. Patel, Marie E. Uchic, Marie P. Honore, Jerome F. Daanen, Loan N. Miller, Renjie Chang, Andrew O. Stewart, Masaki Nakane, Steven P. Latshaw, Pramila Bhatia, Sonya G. Lehto, Teodozyj Kolasa, Odile F. El Kouhen, Jorge D. Brioni, Robert B. Moreland, Guo Zhu Zheng |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Stereochemistry Receptor Metabotropic Glutamate 5 Allosteric regulation Pharmacology Receptors Metabotropic Glutamate Cell Line Rats Sprague-Dawley Radioligand Assay Structure-Activity Relationship In vivo Cerebellum Drug Discovery Animals Humans Structure–activity relationship Receptor IC50 Pain Measurement Analgesics Aza Compounds Fluorenes Chemistry Antagonist In vitro Rats Molecular Medicine Metabotropic glutamate receptor 1 Calcium Heterocyclic Compounds 3-Ring |
| Zdroj: | Journal of Medicinal Chemistry. 48:7374-7388 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | SAR (structure-activity relationship) studies of triazafluorenone derivatives as potent mGluR1 antagonists are described. The triazafluorenone derivatives are non-amino acid derivatives and noncompetitive mGluR1 antagonists that bind at a putative allosteric recognition site located within the seven-transmembrane domain of the receptor. These triazafluorenone derivatives are potent, selective, and systemically active mGluR1 antagonists. Compound 1n, for example, was a very potent mGluR1 antagonist (IC50 = 3 nM) and demonstrated full efficacy in various in vivo animal pain models. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|