Phosphodiesterase inhibitors. Part 3: Design, synthesis and structure-activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-dihydropyridazinones with anti-inflammatory and bronchodilatory activity

Koji Ochiai, Satoshi Takita, Tomohiko Eiraku, Akihiko Kojima, Kazuhiko Iwase, Tetsuya Kishi, Kazunori Fukuchi, Tokutaro Yasue, David R Adams, Robert W Allcock, Zhong Jiang, Yasushi Kohno

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

(-)-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. A survey of potential bicyclic heteroaromatic replacement subunits for the pyrazolo[1,5-a]pyridine core of KCA-1490 has identified the 4-methoxy-2-(trifluoromethyl)benzo[d]thiazol-7-yl and 8-methoxy-2-(trifluoromethyl)quinolin-5-yl analogues as dual PDE3/4-inhibitory compounds that potently suppress histamine-induced bronchoconstriction and exhibit anti-inflammatory activity in vivo.
Original languageEnglish
Pages (from-to)1644-58
Number of pages15
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number5
DOIs
Publication statusPublished - 2012

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