Synthesis, biological activity and structure-activity relationship of 4,5-dimethoxybenzene derivatives inhibitor of rhinovirus 14 infection

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• 作者：Manon Roche^a ; Cé ; line Lacroix^b ; Omar Khoumeri^a ; David Franco^b ; Johan Neyts^b ; ^{johan.neyts@rega.kuleuven.be" class="auth_mail} ; Thierry Terme^a ; Pieter Leyssen^b ; Patrice Vanelle^a ; ^{patrice.vanelle@univ-amu.fr" class="auth_mail}
• 关键词：Human rhinovirus 14 ; Tetrakis(DimethylAmino)Ethylene ; 4 ; 5-Dimethoxybenzenes ; Antiviral activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：9 April, 2014
• 年：2014
• 卷：76
• 期：Complete
• 页码：445-459
• 全文大小：1628 K

文摘

Human rhinoviruses are a common cause of respiratory infections, and thus constitute an important target for medicinal chemistry. Still, no drug has been approved for clinical use. We report herein the discovery of dibenzenic derivatives with potent and specific in聽vitro anti-rhinoviral 14 activity. A total of 99 structural analogues were synthesized by an original synthesis method, i.e. through one organic agent Tetrakis(DimethylAmino)Ethylene (TDAE) and a structure-activity relationship was established. It was shown that 4,5-dimethoxy scaffold and the presence of a聽C-4 substituted aromatic moiety were necessary to the in聽vitro activity of these original agents. However, modifications on liker were not convincing. The benzonitrile derivative 23 was identified as the most potent and selective inhibitor of rhinovirus replication in these series (EC₅₀ of 2聽卤聽0.5聽渭M, CC₅₀ of 184聽渭M, selectivity index of 92).