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

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 1; pp. 153 - 157
• Main Authors: Kim, Junwon, Kwon, Jeongjin, Lee, Doohyun, Jo, Suyeon, Park, Dong-Sik, Choi, Jihyun, Park, Eunjung, Hwang, Jong Yeon, Ko, Yoonae, Choi, Inhee, Ju, Moon Kyeong, Ahn, JiYe, Kim, Junghwan, Han, Sung-Jun, Kim, Tae-Hee, Cechetto, Jonathan, Nam, Jiyoun, Ahn, Sujin, Sommer, Peter, Liuzzi, Michel, No, Zaesung, Lee, Jinhwa
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.01.2013; Elsevier
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; antiviral properties; Cell Line; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Drug Evaluation, Preclinical; High-Throughput Screening Assays; HIV-1; HIV-1 - drug effects; HIV-1 - metabolism; Human immunodeficiency virus 1; Humans; Inhibitor; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Science & Technology; screening; Structure-Activity Relationship; Structure–activity relationship (SAR); Synthesis; Triazoles - chemistry; Triazolothienopyrimidine; Virus Replication - drug effects; HIV-1; Structure–activity relationship (SAR); Inhibitor; Synthesis; Triazolothienopyrimidine; Structure-activity relationship (SAR); ENTRY INHIBITORS; RISK; AIDS; DISCOVERY
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.10.134

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. 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.