期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 19, 期 17, 页码 5229-5232出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.07.005
关键词
5-HT; TPH1; Tryptophan hydroxylase; Gastrointestinal disorders
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. (C) 2009 Elsevier Ltd. All rights reserved.
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