Abstract：
:5-HT(7) receptor antagonists generated antidepressant-like effects in animal model and the involvement of the 5-HT(7) 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-HT(7) receptor antagonists, we here report on the synthesis and binding affinities to the 5-HT(7) receptor of the quinazolinone library 1, which was designed with various substituents (X, Y, R(1), and R(2)) on the aromatic rings 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-HT(7) receptor. Among the 85 compounds, 24 compounds show very good binding affinities with IC(50) values below 100 nM. Mainly the compounds with IC(50) 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 IC(50) value is 12 nM. In in vivo animal study, some synthesized compounds really have the antidepressant activity in the forced swimming test in mice.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Na YH,Hong SH,Lee JH,Park WK,Baek DJ,Koh HY,Cho YS,Choo H,Pae ANdoi
10.1016/j.bmc.2007.11.049subject
Has Abstractpub_date
2008-03-01 00:00:00pages
2570-8issue
5eissn
0968-0896issn
1464-3391pii
S0968-0896(07)01017-6journal_volume
16pub_type
杂志文章abstract：:The Maillard reaction is a complex network of reactions that has been shown to result in the non-enzymatic crosslinking of proteins. Recent attention has focussed on the role of alpha-dicarbonyl compounds as important in vivo contributors to protein crosslinking but, despite extensive research, the molecular mechanism...
journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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更新日期：2016-09-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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更新日期：2007-12-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
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更新日期：2006-12-01 00:00:00
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