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Updated: Jun 29, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Synthesis and evaluation of structurally constrained quinazolinone derivatives as potent and selective histamine H3
Tsuyoshi Nagase1, Takashi Mizutani, Etsuko Sekino
1Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba 300-2611, Japan.
Abstract:
A series of structurally constrained derivatives of the potent H 3 inverse agonist 1 was designed, synthesized, and evaluated as histamine H 3 receptor inverse agonists. As a result, the N-cyclobutylpiperidin-4-yloxy group as in 2f was identified as an optimal surrogate structure for the flexible 1-pyrrolidinopropoxy group of 1. Subsequent optimization of the quinazolinone core of 2f revealed that substitution at the 5-position of the quinazolinone ring influences potency. Representative derivatives 5a and 5s showed improved potency in a histamine release assay in rats and a receptor occupancy assay in mice.
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