Synthesis and structure–activity relationships of phenothiazine carboxylic acids having pyrimidine-dione as novel histamine H 1 antagonists

K Kubota, H Kurebayashi, H Miyachi, M Tobe…

Index: Kubota, Katsumi; Kurebayashi, Hirotaka; Miyachi, Hirotaka; Tobe, Masanori; Onishi, Masako; Isobe, Yoshiaki Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 10 p. 2766 - 2771

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Citation Number: 31

Abstract

A series of phenothiazine carboxylic acid derivatives, having 6-amino-pyrimidine-2, 4 (1H, 3H)-dione moiety via a appropriate linker, were synthesized and evaluated for their affinity toward human histamine H1 receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice and bioavailability in rats. Finally, promising compounds were examined for their anti-inflammatory potential in mice ...