Jin Haihong, Cianchetta Giovanni, Devasagayaraj Arokiasamy, Gu Kunjian, Marinelli Brett, Samala Lakshman, Scott Sheldon, Stouch Terry, Tunoori Ashok, Wang Ying, Zang Yi, Zhang Chengmin, David Kimball S, Main Alan J, Ding Zhi-Ming, Sun Weimei, Yang Qi, Yu Xiang-Qing, Powell David R, Wilson Alan, Liu Qingyun, Shi Zhi-Cai
Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, USA.
Bioorg Med Chem Lett. 2009 Sep 1;19(17):5229-32. doi: 10.1016/j.bmcl.2009.07.005. Epub 2009 Jul 8.
Tryptophan hydroxylase (TPH) is a key enzyme in the synthesis of serotonin. As a neurotransmitter, serotonin plays important physiological roles both peripherally and centrally. Here we describe the discovery of substituted triazines as a novel class of tryptophan hydroxylase inhibitors. This class of TPH inhibitors can selectively reduce serotonin levels in murine intestine after oral administration without affecting levels in the brain. These TPH inhibitors may provide novel treatments for gastrointestinal disorders associated with dysregulation of the serotonergic system, such as chemotherapy-induced emesis and irritable bowel syndrome.
色氨酸羟化酶（TPH）是血清素合成中的关键酶。作为一种神经递质，血清素在周围和中枢都发挥着重要的生理作用。在此，我们描述了取代三嗪作为一类新型色氨酸羟化酶抑制剂的发现。这类TPH抑制剂在口服给药后可选择性降低小鼠肠道中的血清素水平，而不影响大脑中的水平。这些TPH抑制剂可能为与血清素能系统失调相关的胃肠道疾病提供新的治疗方法，如化疗引起的呕吐和肠易激综合征。
