Synthesis and potential anti-inflammatory activity of some tetrahydrophthalazinones
Synthesis and potential anti-inflammatory activity of some tetrahydrophthalazinones
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DOI：
10.1080/14756360412331280536
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发表时间：
2004-12-01
影响因子：
5.6
通讯作者：
David, M
中科院分区：
文献类型：
--
作者：
Gouault, N;Pinel, B;David, M
开发了利用 Diels-Alder 反应制备 4a,5,8,8a-四氢酞嗪酮-1-酮的固相路线。一些新化合物已经过测试，可抑制慢性阻塞性肺病 (COPD) 患者全血中 LPS 刺激的 TNF-α 产生。该评估揭示了两种令人感兴趣的化合物 17 和 18，其中包含芳基哌嗪部分，它们被发现可以抑制 LPS 诱导的 TNF-α 释放，就像众所周知的抗炎 PDE4 抑制剂咯利普兰和罗氟司特一样。
A solid-phase route for the preparation of 4a,5,8,8a-tetrahydrophthalazinon-1-ones employing the Diels-Alder reaction has been developed. Some of the new compounds have been tested for inhibition of LPS-stimulated TNF-alpha production in human whole blood from patients with chronic obstructive pulmonary disease (COPD). This evaluation revealed two compounds 17 and 18 of interest, incorporating an arylpiperazine moiety, which were found to inhibit LPS- induced TNF-alpha release like the well known anti-inflammatory PDE4 inhibitors, rolipram and roflumilast.