Abstract
The previously disclosed spirohydantoin-based CGRP receptor antagonists were optimized for potency through modification of the benzimidazolone substituents. Compounds were identified which had minimal shift in the cAMP functional assay containing 50% human serum. Blockade of CGRP-mediated vasodilation was observed with these compounds in a rhesus pharmacodynamic assay and the in vivo potency correlated with the in vitro activity in the serum-shifted functional assay.
MeSH terms
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Animals
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Benzimidazoles / blood
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology*
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Calcitonin Gene-Related Peptide Receptor Antagonists*
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Combinatorial Chemistry Techniques
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Humans
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Indans / chemistry*
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Macaca mulatta
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Molecular Structure
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology*
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Structure-Activity Relationship
Substances
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Benzimidazoles
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Calcitonin Gene-Related Peptide Receptor Antagonists
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Indans
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Spiro Compounds
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benzimidazolone