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Zheng X, Wang L, Wang B, et al. Discovery of Piperazinylquinoline Derivatives as Novel Respiratory Syncytial Virus Fusion Inhibitors. ACS Med Chem Lett. 2016;7(6):558-62doi: 10.1021/acsmedchemlett.5b00234.
Zheng, X., Wang, L., Wang, B., Miao, K., Xiang, K., Feng, S., Gao, L., Shen, H. C., & Yun, H. (2016). Discovery of Piperazinylquinoline Derivatives as Novel Respiratory Syncytial Virus Fusion Inhibitors. ACS medicinal chemistry letters, 7(6), 558-62. https://doi.org/10.1021/acsmedchemlett.5b00234
Zheng, Xiufang, et al. "Discovery of Piperazinylquinoline Derivatives as Novel Respiratory Syncytial Virus Fusion Inhibitors." ACS medicinal chemistry letters vol. 7,6 (2016): 558-62. doi: https://doi.org/10.1021/acsmedchemlett.5b00234
Zheng X, Wang L, Wang B, Miao K, Xiang K, Feng S, Gao L, Shen HC, Yun H. Discovery of Piperazinylquinoline Derivatives as Novel Respiratory Syncytial Virus Fusion Inhibitors. ACS Med Chem Lett. 2016 Apr 20;7(6):558-62. doi: 10.1021/acsmedchemlett.5b00234. eCollection 2016 Jun 09. PMID: 27326326; PMCID: PMC4904258.
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ACS Med Chem Lett. 2016 Apr 20;7(6):558-62. doi: 10.1021/acsmedchemlett.5b00234. eCollection 2016 Jun 09.

Discovery of Piperazinylquinoline Derivatives as Novel Respiratory Syncytial Virus Fusion Inhibitors.

ACS medicinal chemistry letters

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

Affiliations

  1. Roche Innovation Center Shanghai, Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.

PMID: 27326326 PMCID: PMC4904258 DOI: 10.1021/acsmedchemlett.5b00234

Abstract

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.

Keywords: Respiratory syncytial virus (RSV); antiviral; fusion inhibitors; piperazine; quinoline

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