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Bioorg Med Chem Lett. 2010 Jan 1;20(1):213-7. doi: 10.1016/j.bmcl.2009.10.131. Epub 2009 Oct 31.
A series of potent 5-lipoxygenase-activating protein (FLAP) inhibitors are herein described. SAR studies focused on the discovery of novel alicyclic moieties appended to an indole core to optimize potency, physical properties and off-target activities. Subsequent SAR on the N-benzyl substituent of the indole led to the discovery of compound 39 (AM679) which showed potent inhibition of leukotrienes in human blood and in a rodent bronchoalvelolar lavage (BAL) challenge model.
本文描述了一系列强效的 5-脂氧合酶激活蛋白（FLAP）抑制剂。SAR 研究集中在发现新的脂环族基团连接到吲哚核心上，以优化其效力、物理性质和非靶标活性。随后对吲哚的 N-苄基取代基进行 SAR 研究，发现了化合物 39（AM679），它在人血液和啮齿动物支气管肺泡灌洗（BAL）挑战模型中显示出对白细胞三烯的有效抑制作用。
