title: Anti-influenza drug discovery: identification of an orally bioavailable quinoline derivative through activity- and property-guided lead optimization.
abstract: From a high-throughput screening (HTS) hit with inhibitory activity against virus-induced cytophathic in the low micromolar range, we have developed a potent anti-influenza lead through careful optimization without compromising the drug-like properties of the compound. An orally bioavailable compound was identified as a lead agent with nanomolar activity against influenza, representing a 140-fold improvement over the initial hit.
authors: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Rd, Zhunan, Miaoli County 350, Taiwan, RoC.
authors: Jiann-Yih
authors: JY
authors: Yeh
authors: Mohane Selvaraj
authors: MS
authors: Coumar
authors: Hui-Yi
authors: HY
authors: Shiao
authors: Ta-Jen
authors: TJ
authors: Lin
authors: Yen-Chun
authors: YC
authors: Lee
authors: Hui-Chen
authors: HC
authors: Hung
authors: Shengkai
authors: S
authors: Ko
authors: Fu-Ming
authors: FM
authors: Kuo
authors: Ming-Yu
authors: MY
authors: Fang
authors: Yu-Lin
authors: YL
authors: Huang
authors: John T A
authors: JT
authors: Hsu
authors: Teng-Kuang
authors: TK
authors: Yeh
authors: Shin-Ru
authors: SR
authors: Shih
authors: Yu-Sheng
authors: YS
authors: Chao
authors: Jim-Tong
authors: JT
authors: Horng
authors: Hsing-Pang
authors: HP
authors: Hsieh
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D055808:Drug Discovery; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy; D008297:Male; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D011804:Quinolines