Synthesis of basic substituted pyridines: a new class of antiasthmatic- antiallergic agents

Article abstract of DOI:10.1016/0223-5234(89)90003-2

A series of pyridines were synthesized and evaluated as bronchospasmolytic / anti-allergic agents.Several of these compounds were found to: 1) inhibit the release of histamine; 2) antagonize histamine, bradykinin, LTD₄ and PAF; 3) suppress the IgE-mediated passive cutaneous anaphylaxis (PCA) reaction.The most interesting substance of this series 2,6-dimethyl-3-nitro-4<(2-(4-diphenylmethyl-1-piperazinyl)ethyl)amino>pyridine 1, (HWA 214), was selected for further pharmacological evaluation.The novel, orally active agent 1 does not have such drawbacks as causing drowsiness or being effective only as a prophylactic drug, and could provide advantages over other non-sedative compounds, such as terfenadine and astemizole, in that it is water soluble and thus can be administered through inhalation or through intravenous application.Keywords: pyridines / H₁-antagonistic activity / antiallergic property / antiasthmatic property