Design of Phthalazinone Amide Histamine H1 Receptor Antagonists for Use in Rhinitis

ACS Medicinal Chemistry Letters
Panayiotis A ProcopiouClarissa J Watts

Abstract

The synthesis of potent amide-containing phthalazinone H1 histamine receptor antagonists is described. Three analogues 3e, 3g, and 9g were equipotent with azelastine and were longer-acting in vitro. Amide 3g 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.

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Citations

Jan 27, 2019·Chemistry, an Asian Journal·Kristiana T SantosoMattie S M Timmer
Jun 27, 2019·Pharmaceuticals·Daria A BelinskaiaNatalia N Shestakova
Nov 6, 2018·European Journal of Medicinal Chemistry·Carmen TeránMa Carmen Costas-Lago
Mar 18, 2021·Beilstein Journal of Organic Chemistry·Zbigniew MalinowskiMonika Nowak

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