A 3D-quantitative structure-activity relationship study of benzamide type serotonin 5-HT4 receptor agonists based on a comparative molecular field analysis model, and the design and synthesis of potent agonists

Authors
Kakigami, T Tsuruta, N Tsukamoto, K Usui, T Ikami, T
Citation
T. Kakigami et al., A 3D-quantitative structure-activity relationship study of benzamide type serotonin 5-HT4 receptor agonists based on a comparative molecular field analysis model, and the design and synthesis of potent agonists, CHEM PHARM, 46(12), 1998, pp. 1881-1886
Citations number
13
Categorie Soggetti
Chemistry & Analysis
Journal title
CHEMICAL & PHARMACEUTICAL BULLETIN
ISSN journal
00092363 → ACNP
Volume
46
Issue
12
Year of publication
1998
Pages
1881 - 1886
Database
ISI
SICI code
0009-2363(199812)46:12<1881:A3SRSO>2.0.ZU;2-J
Abstract
A 3D-quantitative structure-activity relationship (3D-QSAR) study was carri ed out using comparative molecular field analysis (CoMFA) of the 5-HT4 agon istic activity of benzamide type compounds, which had been already synthesi zed and reported to show 5-HT4 agonistic activity. The chosen alignment yie lded a good cross-validated result (r(cv)(2)=0.628). This CoMFA model was a ble to predict the 5-HT4 agonistic activity of three structurally different compounds. Consequently, 5-amino-N-[2-(1-azabicyclo [3.3.0]octan-5-yl)ethy l]-6-chloro-3,4-dihydro-2H-1-benzopyran-8-carboxamide (22) was obtained as the most potent 5-HT4 agonist.