Structure−Activity Relationship of New Anti-Hepatitis C Virus Agents: Heterobicycle−Coumarin Conjugates

• Published in: Journal of medicinal chemistry Vol. 52; no. 5; pp. 1486 - 1490
• Main Authors: Neyts, Johan, Clercq, Erik De, Singha, Raghunath, Chang, Yung Hsiung, Das, Asish R, Chakraborty, Subhasish K, Hong, Shih Ching, Tsay, Shwu-Chen, Hsu, Ming-Hua, Hwu, Jih Ru
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.03.2009; Amer Chemical Soc
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Benzoxazoles - chemical synthesis; Benzoxazoles - chemistry; Benzoxazoles - pharmacology; Biological and medical sciences; Cell Line; Cell Proliferation - drug effects; Chemistry, Medicinal; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - pharmacology; Hepacivirus - drug effects; Hepacivirus - genetics; Heterocyclic Compounds, 2-Ring - chemical synthesis; Heterocyclic Compounds, 2-Ring - chemistry; Heterocyclic Compounds, 2-Ring - pharmacology; Humans; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; Life Sciences & Biomedicine; Medical sciences; Models, Molecular; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Purines - chemical synthesis; Purines - chemistry; Purines - pharmacology; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; RNA, Viral - drug effects; Science & Technology; Structure-Activity Relationship; Virus Replication - drug effects; NS5B POLYMERASE; POTENT; BENZIMIDAZOLE DERIVATIVES; ANTICANCER; BIOLOGICAL-ACTIVITY; INHIBITORS; RIBAVIRIN; ANTITUMOR-ACTIVITY; Purine derivatives; Benzoxazole derivatives; Nitrogen heterocycle; Coumarine derivatives; Lactone; Oxygen heterocycle; In vitro; Virus; Imidazopyridine derivatives; Structure activity relation; Bicyclic compound; Antiviral; Flaviviridae; Conjugated compound; Hepatitis C virus; Hepacivirus; Oxygen nitrogen heterocycle
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm801240d

For establishment of the structure−activity relationship, 19 heterobicycle-coumarin conjugated compounds with the −SCH2− linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which inhibited HCV replication at an EC50 of 6.8, 2.0, and 12 μM, respectively. The heteroatoms in bicycles and the substituent effect on coumarin played essential roles.