Please use this identifier to cite or link to this item:
https://scholarbank.nus.edu.sg/handle/10635/14180
Title: | Pharmacophoric models of sodium channel antagonists | Authors: | POON THONG YUEN | Keywords: | sodium channels, pharmacophore, triazines, benzyloximes, BTX. | Issue Date: | 12-Aug-2004 | Citation: | POON THONG YUEN (2004-08-12). Pharmacophoric models of sodium channel antagonists. ScholarBank@NUS Repository. | Abstract: | A pharmacophoric model, which consists of one H-bond donor (D), one H-bond acceptor (A) and one hydrophobic group (H), was derived from five good neuronal (type II) sodium channel blockers. The A-H, A-D and D-H distances are 4.02 ??, 5.65 ??, and 3.27 ?? respectively.The model was validated and subsequently adapted into a screening process which identified the 4,6-diamino-1,2-dihydro-2,2-substituted-1-phenyl-1,3,5-triazines (phenyldihydro-1,3,5-triazines) as good sodium channel blockers while the benzyloximes were predicted to be weak blockers. Synthesis and testing of the compounds in the [3H]-batrachotoxin (BTX) assay verified the predictions. The most active compounds in the phenyldihydro-1,3,5-triazines series (compound 34) and benzyloxime series (compound 51) have IC50 values of 4.0 microM and 0.4 mM respectively. The phenyldihydro-1,3,5-triazines did not possess epileptic protection in the Maximal Electroshock (MES) assay but were found to have analgesic properties in the hot-plate assay, while the benzyloximes displayed epileptic protection in the MES assay, and one compound possesses slight analgesic properties. | URI: | http://scholarbank.nus.edu.sg/handle/10635/14180 |
Appears in Collections: | Ph.D Theses (Open) |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
PoonTY.pdf | 934.3 kB | Adobe PDF | OPEN | None | View/Download |
Google ScholarTM
Check
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.