Na, Yong Ho Hong, Sung Ho Lee, Jung Hyang Park, Woo-Kyu Baek, Du-Jong Koh, Hun Yeong Cho, Yong Seo Choo, Hyunah Pae, Ae Nim 2024-01-20T23:33:47Z 2024-01-20T23:33:47Z 2021-09-03 2008-03-01 0968-0896 https://pubs.kist.re.kr/handle/201004/133660 5-HT7 receptor antagonists generated antidepressant-like effects in animal model and the involvement of the 5-HT7 receptor in other pathophysiological mechanisms such as thermoregulation, learning and memory, and sleep has been highlighted by various studies. As one of our efforts to discover a new type of 5-HT7 receptor antagonists, we here report on the synthesis and binding affinities to the 5-HT7 receptor of the quinazolinone library 1, which was designed with various substituents (X, Y, R-1, and R-2) on the aromatic rinas and different carbon chain length. Total 85 compounds of the quinazolinone library 1 were synthesized and the binding affinities of all the synthesized compounds were obtained by radioligand binding assay for the 5-HT7 receptor. Among the 85 compounds, 24 compounds show very good binding affinities with IC50 values below 100 nM. Mainly the compounds with IC50 values below 100 nM have o-OMe or o-OEt as R-2 substituent. The compound with the best binding affinity is 1-68 of which the IC50 value is 12 nM. In in vivo animal study, some synthesized compounds really have the antidepressant activity in the forced swimming test in mice. (C) 2007 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD SEROTONIN RECEPTOR MOLECULAR-CLONING AFFINITY SERIES TETRAHYDROBENZINDOLES ARYLPIPERAZINE ANTAGONIST AGONISTS Novel quinazolinone derivatives as 5-HT7 receptor ligands Article 10.1016/j.bmc.2007.11.049 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.16, no.5, pp.2570 - 2578 BIOORGANIC & MEDICINAL CHEMISTRY 16 5 2570 2578 scie scopus 000255002400036 2-s2.0-40749098472 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article SEROTONIN RECEPTOR MOLECULAR-CLONING AFFINITY SERIES TETRAHYDROBENZINDOLES ARYLPIPERAZINE ANTAGONIST AGONISTS quinazolinone derivatives small molecule library 5-HT7 receptor 5-HT7 receptor antagonist