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Bioorg Med Chem Lett. 2011 Jan 1;21(1):58-61. doi: 10.1016/j.bmcl.2010.11.080. Epub 2010 Nov 21.
Serotonin type 3 (5-HT(3)) receptor partial agonists are being targeted as potential new drugs for the treatment of irritable bowel syndrome (IBS). Two new chemical series bearing indazole and indole cores have exhibited nanomolar binding affinity for the h5-HT(3)A receptor. A range of partial agonist activities in HEK cells heterologously expressing the h5-HT(3)A receptor were measured for the indazole series. Excellent 5-HT(3) receptor selectivity, favorable in vitro metabolic stability and CYP inhibition properties, and good oral in vivo potency in the murine von Bezold-Jarisch reflex model is exemplified thereby indicating the series to have potential utility as improved IBS agents.
血清素 3 型（5-HT3）受体部分激动剂被作为治疗肠易激综合征（IBS）的潜在新药进行研究。两个含有吲唑和吲哚核心的新化学系列对 h5-HT3A 受体具有纳摩尔结合亲和力。为吲唑系列，在异源表达 h5-HT3A 受体的 HEK 细胞中测量了一系列部分激动剂活性。该系列具有良好的 5-HT3 受体选择性、体外代谢稳定性和 CYP 抑制特性，以及在鼠 von Bezold-Jarisch 反射模型中的良好口服体内效力，表明该系列具有作为改良 IBS 药物的潜力。
