Design of Phthalazinone Amide Histamine H1 Receptor Antagonists for Use in Rhinitis.
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ABSTRACT:
SUBMITTER: Procopiou PA
PROVIDER: S-EPMC5430406 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
Design of Phthalazinone Amide Histamine H<sub>1</sub> Receptor Antagonists for Use in Rhinitis.
Procopiou Panayiotis A PA Ford Alison J AJ Gore Paul M PM Looker Brian E BE Hodgson Simon T ST Holmes Duncan S DS Vile Sadie S Clark Kenneth L KL Saunders Ken A KA Slack Robert J RJ Rowedder James E JE Watts Clarissa J CJ
ACS medicinal chemistry letters 20170421 5
The synthesis of potent amide-containing phthalazinone H<sub>1</sub> histamine receptor antagonists is described. Three analogues <b>3e</b>, <b>3g</b>, and <b>9g</b> were equipotent with azelastine and were longer-acting in vitro. Amide <b>3g</b> had low oral bioavailability, low brain-penetration, high metabolic clearance, and long duration of action in vivo, and it was suitable for once-daily dosing intranasally, with a predicted dose for humans of approximately 0.5 mg per day. ...[more]
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