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 |
| |
Authors: | Ochiai Koji Takita Satoshi Eiraku Tomohiko Kojima Akihiko Iwase Kazuhiko Kishi Tetsuya Fukuchi Kazunori Yasue Tokutaro Adams David R Allcock Robert W Jiang Zhong Kohno Yasushi |
| |
Affiliation: | Discovery Research Laboratories, Kyorin Pharmaceutical Co. Ltd., 2399-1 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, Japan. |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|