Details

Autor(en) / Beteiligte

• Zheng, Xiufang
• Wang, Lisha
• Wang, Baoxia
• Miao, Kun
• Xiang, Kunlun
• Feng, Song
• Gao, Lu
• Shen, Hong C
• Yun, Hongying

Titel

Discovery of Piperazinylquinoline Derivatives as Novel Respiratory Syncytial Virus Fusion Inhibitors

Ist Teil von

• ACS medicinal chemistry letters, 2016-06, Vol.7 (6), p.558-562

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2016

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• A novel series of piperazinylquinoline derivatives were discovered as respiratory syncytial virus (RSV) fusion inhibitors by the ligand-based screening approach. Among 3,000 hits, 1-amino-3-[[2-(4-phenyl-1-piperidyl)-4-quinolyl]­amino]­propan-2-ol (7) was proven to be active against the RSV long (A) strain. The anti-RSV activity was improved by converting piperidine to benzylcarbonyl substituted piperazine. The basic side chain was also found to be crucial for anti-RSV activity. The selected analogues, 45 and 50, demonstrated anti-RSV activities up to EC50 = 0.028 μM and 0.033 μM, respectively. A direct anti-RSV effect was confirmed by a plaque reduction assay and a fusion inhibition assay. Both 45 and 50 showed promising DMPK properties with good oral bioavailability, and could potentially lead to novel therapeutic agents targeting the RSV fusion process.