Abstract
A series of tricyclic CGRP receptor antagonists was optimized in order to improve oral bioavailability. Attenuation of polar surface area and incorporation of a weakly basic indoline nitrogen led to compound 5, a potent antagonist with good oral bioavailability in three species.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Calcitonin Gene-Related Peptide Receptor Antagonists*
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Cell Line
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Dogs
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Haplorhini
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Heterocyclic Compounds, 3-Ring / administration & dosage
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Heterocyclic Compounds, 3-Ring / chemistry
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Heterocyclic Compounds, 3-Ring / pharmacokinetics*
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Humans
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Rats
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Receptors, Calcitonin Gene-Related Peptide / metabolism
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Spiro Compounds / administration & dosage
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Spiro Compounds / pharmacokinetics*
Substances
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Calcitonin Gene-Related Peptide Receptor Antagonists
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Heterocyclic Compounds, 3-Ring
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Receptors, Calcitonin Gene-Related Peptide
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Spiro Compounds