1. Identification of potent CNS-penetrant thiazolidinones as novel CGRP receptor antagonists.
- Author
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Joshi P, Anderson C, Binch H, Hadida S, Yoo S, Bergeron D, Decker C, terHaar E, Moore J, Garcia-Guzman M, and Termin A
- Subjects
- Animals, Azepines chemistry, Azepines pharmacokinetics, Calcitonin Gene-Related Peptide metabolism, Dipeptides pharmacokinetics, Humans, Imidazoles chemistry, Imidazoles pharmacokinetics, Inhibitory Concentration 50, Migraine Disorders drug therapy, Molecular Structure, Molecular Weight, Piperazines, Protein Binding drug effects, Quinazolines chemistry, Quinazolines pharmacokinetics, Quinazolinones pharmacokinetics, Rats, Thiazolidinediones pharmacokinetics, Urea chemistry, Urea pharmacokinetics, Urea pharmacology, Dipeptides chemistry, Dipeptides pharmacology, Quinazolinones chemistry, Quinazolinones pharmacology, Receptors, Calcitonin Gene-Related Peptide agonists, Thiazolidinediones chemistry, Thiazolidinediones pharmacology, Urea analogs & derivatives
- Abstract
Calcitonin gene-related peptide (CGRP) has been implicated in acute migraine pathogenesis. In an effort to identify novel CGRP receptor antagonists for the treatment of migraine, we have discovered thiazolidinone 49, a potent (Ki=30 pM, IC50=1 nM), orally bioavailable, CNS-penetrant CGRP antagonist with good pharmacokinetic properties., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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