Abstract
Several new potent CGRP receptor antagonists have been prepared in which the amide bond of lead compound 1 has been replaced by bioisosteric imidazole moieties. Substitution at N-1 of the imidazole was optimized to afford compounds with comparable potency to that of lead 1. Conformational restraint of the imidazole to form tetrahydroimidazo[1,5-a]pyrazine 43 gave substantially improved permeability.
Keywords:
CGRP; CGRP receptor antagonists; Imidazoles; Migraine; Migraineurs.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Calcitonin Gene-Related Peptide Receptor Antagonists*
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Cell Line, Tumor
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Cell Membrane Permeability / drug effects
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / pharmacology
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Microsomes / metabolism
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Protein Binding
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Quinolones / chemical synthesis
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Quinolones / chemistry*
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Quinolones / pharmacology
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Receptors, Calcitonin Gene-Related Peptide / metabolism
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Structure-Activity Relationship
Substances
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Calcitonin Gene-Related Peptide Receptor Antagonists
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Imidazoles
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Quinolones
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Receptors, Calcitonin Gene-Related Peptide
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imidazole