Synthesis and pharmacological investigation of novel 2-substituted-3-carboxamido-4H-pyrimidobenzothiazole derivatives as a new class of H1-antihistaminic agent

Abstract

With the aim of developing potential H1-antihistaminic agents, a series of novel 2-substituted-3-carboxamido-4-oxo-4H-pyrimido[2,1-b][1,3]benzothiazole (8a–g) and 2-substituted-3-carboxamido-8-chloro-4-oxo-4H-pyrimido[2,1-b][1,3]benzothiazole (9a–g) were synthesized and evaluated in vitro for H1-antihistaminic activity on guinea pig ileum preparation. IC50 values of the compounds were found to be in the micromolar range. Chlorpheniramine maleate was used as a standard drug. The active derivatives (8d–8g and 9d–9g) were found to have IC50 values comparable to reference standard chlorpheniramine maleate. The sedative potential of both series (8a–g and 9a–g) is less than the reference drug. Hence, it could serve as prototype molecules for further development as a new class of H1-antihistaminic agents.