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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Nagase T,Mizutani T,Sekino E,Ishikawa S,Ito S,Mitobe Y,Miyamoto Y,Yoshimoto R,Tanaka T,Ishihara A,Takenaga N,Tokita S,Sato Ndoi
10.1021/jm800569wsubject
Has Abstractpub_date
2008-11-13 00:00:00pages
6889-901issue
21eissn
0022-2623issn
1520-4804journal_volume
51pub_type
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