title: Synthesis and antienteroviral activity of a series of novel, oxime ether-containing pyridyl imidazolidinones.
abstract: A series of novel, oxime ether-containing pyridyl imidazolidinones were synthesized and their antiviral activity was evaluated in a plaque reduction assay. It is very interesting that this class of compounds is specific for human enteroviruses, in particular, enterovirus 71 (EV71). Some derivatives strongly inhibited enterovirus replication with activities higher or comparable to those of the reference compounds such as A1 and A2. Preliminary SAR studies revealed that the chain length of the alkyl linker and the alkyl substituent at the oxime ether group largely influenced the in vitro anti-EV71 activity of this new class of potent antiviral agents. Among this series of compounds synthesized, the pyridyl imidazolidinone with an ethyl oxime ether group located at the para position of the phenoxyl ring (8b) was identified as the most potent enterovirus 71 inhibitor (IC50=0.001 microM) with no apparent cytotoxic effect toward RD (rhabdomyosarcoma) cell lines (CC50>25 microM). Furthermore, this compound has been shown broad-spectrum activity against most of the serotypes of enteroviruses tested in the nanomolar range.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 9F, 161, Sec. 6, Min-Chiuan East Road, Taipei 114, Taiwan, ROC. jhchen@nhri.org.tw
authors.forename: Jyh-Haur
authors.initials: JH
authors.lastname: Chern
authors.forename: Chung-Chi
authors.initials: CC
authors.lastname: Lee
authors.forename: Chih-Shiang
authors.initials: CS
authors.lastname: Chang
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Lee
authors.forename: Chia-Liang
authors.initials: CL
authors.lastname: Tai
authors.forename: Ying-Ting
authors.initials: YT
authors.lastname: Lin
authors.forename: Kak-Shan
authors.initials: KS
authors.lastname: Shia
authors.forename: Ching-Yin
authors.initials: CY
authors.lastname: Lee
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004770:Enterovirus / Q000187:drug effects; D029822:Enterovirus B, Human / Q000187:drug effects; D004987:Ethers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D004987:Ethers; D048289:Imidazolidines; D010091:Oximes; D011725:Pyridines