Phosphodiesterase inhibitors. Part 5: hybrid PDE3/4 inhibitors as dual bronchorelaxant/anti-inflammatory agents for inhaled administration

…, A Kojima, T Eiraku, K Iwase, T Kishi, A Ohinata…

Index: Ochiai, Koji; Takita, Satoshi; Kojima, Akihiko; Eiraku, Tomohiko; Iwase, Kazuhiko; Kishi, Tetsuya; Ohinata, Akira; Yageta, Yuichi; Yasue, Tokutaro; Adams, David R.; Kohno, Yasushi Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 1 p. 375 - 381

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Citation Number: 20

Abstract

(−)-6-(7-Methoxy-2-(trifluoromethyl) pyrazolo [1, 5-a] pyridin-4-yl)-5-methyl-4, 5- dihydropyridazin-3 (2H)-one (KCA-1490) exhibits moderate dual PDE3/4-inhibitory activity and promises as a combined bronchodilatory/anti-inflammatory agent. N-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses PDE3 inhibition. Addition of a 6-aryl-4, 5-dihydropyridazin-3 (2H)-one extension to the N-alkyl ...