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

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Kubota K, Kurebayashi H, Miyachi H, Tobe M, Onishi M, Isobe Y

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

Bioorg Med Chem Lett. 2009 May 15;19(10):2766-71. doi: 10.1016/j.bmcl.2009.03.124. Epub 2009 Mar 28.

PubMed ID

19362477 [ View in PubMed

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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 H(1) 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 OVA-induced biphasic cutaneous reaction model. Among the compounds tested, phenothiazineacetic acid compound 27 showed both histamine H(1)-receptor antagonistic activity and anti-inflammatory activity in vivo model.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Fexofenadine	Histamine H1 receptor	IC 50 (nM)	78	N/A	N/A	Details