1. The identification of potent, orally bioavailable tricyclic CGRP receptor antagonists.
- Author
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Bell IM, Bednar RA, Corcoran HA, Fay JF, Gallicchio SN, Johnston VK, Hershey JC, Miller-Stein CM, Moore EL, Mosser SD, Roller SA, Salvatore CA, Theberge CR, Wong BK, Blair Zartman C, Kane SA, Williams TM, Graham SL, and Vacca JP
- Subjects
- Administration, Oral, Animals, Biological Availability, Cell Line, Dogs, Haplorhini, Heterocyclic Compounds, 3-Ring administration & dosage, Heterocyclic Compounds, 3-Ring chemistry, Humans, Rats, Receptors, Calcitonin Gene-Related Peptide metabolism, Spiro Compounds administration & dosage, Calcitonin Gene-Related Peptide Receptor Antagonists, Heterocyclic Compounds, 3-Ring pharmacokinetics, Spiro Compounds pharmacokinetics
- 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.
- Published
- 2009
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