Phosphodiesterase inhibitors. Part 4: Design, synthesis and structure-activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-4, 4- …

…, K Iwase, T Kishi, A Ohinata, Y Yageta, T Yasue…

文献索引：Ochiai, Koji; Takita, Satoshi; Kojima, Akihiko; Eiraku, Tomohiko; Ando, Naoki; Iwase, Kazuhiko; Kishi, Tetsuya; Ohinata, Akira; Yageta, Yuichi; Yasue, Tokutaro; Adams, David R.; Kohno, Yasushi Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 18 p. 5833 - 5838

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被引用次数: 12

摘要

(–)-6-(7-Methoxy-2-trifluoromethylpyrazolo [1, 5-a] pyridin-4-yl)-5-methyl-4, 5-dihydro-3-(2H)- pyridazinone (KCA-1490) is a dual PDE3/4 inhibitor that exhibits potent combined bronchodilatory and anti-inflammatory activity. Here we show that a 4, 4-dimethylpyrazolone subunit serves as an effective surrogate for the 5-methyl-4, 5-dihydropyridazin-3 (2H)-one ring of KCA-1490 whilst lacking a stereogenic centre. The 2-and 7-substituents in the ...