Synthesis and biological evaluation of triazolothienopyrimidine derivatives as novel HIV-1 replication inhibitors

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• 作者：Junwon Kim^a ; Jeongjin Kwon^a ; Doohyun Lee^a ; Suyeon Jo^a ; Dong-Sik Park^a ; Jihyun Choi^a ; Eunjung Park^a ; Jong Yeon Hwang^a ; Yoonae Ko^b ; Inhee Choi^b ; Moon Kyeong Ju^c ; JiYe Ahn^c ; Junghwan Kim^c ; Sung-Jun Han^c ; Tae-Hee Kim^d ; ⁱ ; Jonathan Cechetto^d ; Jiyoun Nam^e ; Sujin Ahn^e ; Peter Sommer^f ; Michel Liuzzi^g ; Zaesung No^h ; Jinhwa Lee^h ; ^{jinhwalee@ip-korea.org}
• 关键词：HIV-1 ; Inhibitor ; Triazolothienopyrimidine ; Synthesis ; Structure&ndash ; activity relationship (SAR)
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 January, 2013
• 年：2013
• 卷：23
• 期：1
• 页码：153-157
• 全文大小：2683 K

文摘

We identified a novel class of triazolothienopyrimidine (TTPM) compounds as potent HIV-1 replication inhibitors during a high-throughput screening campaign that evaluated more than 200,000 compounds using a cell-based full replication assay. Herein, we report the optimization of the antiviral activity in a cell-based assay system leading to the discovery of aryl-substituted TTPM derivatives (38, 44, and 45), which exhibited significant inhibition of HIV-1 replication with acceptable safety margins. These novel and potent TTPMs could serve as leads for further development.