Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: Optimization of the 4-substituted piperidine
| Autor: | Beth R. Norton, Ruth Z. Rutledge, Amy G. Quigley, Diem N. Nguyen, Theresa M. Williams, Scott D. Mosser, Christopher S. Burgey, Joseph P. Vacca, James Z. Deng, Samuel L. Graham, Stefanie A. Kane, Ian M. Bell, Christopher A. Salvatore, Craig A. Stump, Kenneth S. Koblan |
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| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Migraine Disorders Clinical Biochemistry Pharmaceutical Science Neuropeptide Calcitonin gene-related peptide Biochemistry Benzodiazepines Structure-Activity Relationship chemistry.chemical_compound Drug Stability Piperidines Calcitonin Gene-Related Peptide Receptor Antagonists Internal medicine Drug Discovery Cyclic AMP medicine Humans Structure–activity relationship Molecular Biology Benzodiazepine Organic Chemistry Antagonist medicine.disease Endocrinology chemistry Migraine Molecular Medicine Piperidine Pharmacophore Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 16:5052-5056 |
| ISSN: | 0960-894X |
| Popis: | In our continuing effort to identify CGRP receptor antagonists for the acute treatment of migraine, we have undertaken a study to evaluate alternative 4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone structures which, when incorporated into the benzodiazepine core, afford potent CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent analog (18) which overcomes the instability issues associated with the lead structure 1. A general pharmacophore for the 4-substituted piperidine component of these CGRP receptor antagonists is also presented. |
| Databáze: | OpenAIRE |
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