Synthesis and Structure–Activity Relationship of Novel Indole Acrylamide Derivatives as HCV Replication Inhibitors. (January 2015)

• Record Type: Journal Article
• Authors: Son, Seohyun; Kim, Dahee; Lee, Sungjin; Jin, Guanghai; Park, Jin‐Ah; Han, Hyo‐Kyung; Lee, Kyeong; Lee, Choongho
• Is Part Of: Bulletin of the Korean Chemical Society. Volume 36:Number 1(2015:Jan.)
• Page Start: 88
• Page End: 98
• Publication Date: 2015-01
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1002/bkcs.10021
• Languages: English
• ISSNs: 0253-2964

Abstract

<abstract abstract-type="main" id="bkcs10021-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="bkcs10021-para-0001">A series of indole acrylamide derivatives were synthesized and evaluated for their inhibitory effects on hepatitis C virus (HCV) replication. Previously, we have identified (<italic>E</italic>)‐<italic>N</italic>‐(4‐<italic>tert</italic>‐butylphenyl)‐3‐(5‐cyano‐1<italic>H</italic>‐indol‐3‐yl)‐2‐methylacrylamide (<bold>6c</bold>) as one of the promising leads for anti‐HCV chemotherapy. Based on the structural features of indole acrylamide, we have explored extended structure–activity relationship study using analogs with substituted indoles, various amides, and N‐substitution at the indole ring. Among the newly synthesized series, 5‐cyanoindole acrylamide analog with <italic>N</italic>‐acetyl substitution (<bold>13c</bold>) (EC₅₀ = 0.98 μM, CC₅₀ = 40.74 μM, and SI = 41.6) exhibited the most potent antiviral activity with reasonable cytotoxicity in a cell‐based J6/JFH1 reporter assay using Huh7.5 cells. In addition, improved water solubility of <bold>13c</bold> compared to <bold>6c</bold> further merits consideration of <bold>13c</bold> as a valuable candidate for anti‐HCV therapeutics development.</p> </abstract>