Loading...
|
Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/1172
|
| Title: | Design, synthesis, and structure-activity relationship of pyridyl imidazolidinones: A novel class of potent and selective human enterovirus 71 inhibitors |
| Authors: | Shia, KS;Li, WT;Chang, CM;Hsu, MC;Chern, JH;Leong, MK;Tseng, SN;Lee, CC;Lee, YC;Chen, SJ;Peng, KC;Tseng, HY;Chang, YL;Tai, CL;Shih, SR |
| Contributors: | Division of Biotechnology and Pharmaceutical Research;Division of Molecular and Genomic Medicine |
| Abstract: | When skeletons of Win compounds were used as templates, computer-assisted drug design led to the identification of a novel series of imidazolidinone derivatives with significant antiviral activity against enterovirus 71(EV 71), the infection of which had resulted in about 80 fatalities during the 1998 epidemic outbreak in Taiwan. In addition to inhibiting all the genotypes (A, B, and C) of EV 71 in the submicromolar to low micromolar range, compounds 1 and 8 were extensively evaluated against a variety of viruses, showing potent activity against coxsackievirus A9 (IC50 = 0.47-0.55 muM) and coxsackievirus A24 (IC50 = 0.47-0.55 muM) as well as moderate activity against enterovirus 68 (IC50 = 2.13 muM) and echovirus 9 (IC50 = 2.6 muM). Our SAR studies revealed that imidazolidinone analogues with an aryl substituent at the para position of the phenoxyl ring, such as compounds 20, 21, 27, 57, 58, and 61, in general exhibited the highest activity against EV 71. Among them, compound 20 and its corresponding hydrochloride salt 57, in terms of potency and selectivity index, appear to be the most promising candidates in this series for further development of anti-EV-71 agents. Preliminary results of the study on the mode of action by a time-course experiment suggest that test compounds 1 and 8 can effectively inhibit the virus replication at the early stages, referring to virus attachment or uncoating. This indicates that the surface protein may be the target for this type of compounds. |
| Keywords: | Chemistry, Medicinal |
| Date: | 2002-04-11 |
| Relation: | Journal of Medicinal Chemistry. 2002 Apr;45(8):1644-1655. |
| Link to: | http://dx.doi.org/10.1021/jm010536a |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000174844600011 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037061609 |
| Appears in Collections: | [陳志豪] 期刊論文
[夏克山] 期刊論文
[許明珠(1997-2001)] 期刊論文
[張仲明] 期刊論文
[陳淑貞(1998-2001)] 期刊論文
|
Files in This Item:
| File |
Description |
Size | Format | |
|---|
| 000174844600011.pdf | | 195Kb | Adobe PDF | 983 | View/Open |
|
All items in NHRI are protected by copyright, with all rights reserved.
|
