Structure-activity relationship of new anti-hepatitis C virus agents: heterobicycle-coumarin conjugates.
For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- 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 EC(50) of 6.8, 2.0, and 12 microM, respectively. The heteroatoms in bicycles and the substituent effect on coumarin played essential roles.
Neyts
Johan
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. johan.neyts@rega.kuleuven.be
De Clercq
Erik
E
Singha
Raghunath
R
Chang
Yung Hsiung
YH
Das
Asish R
AR
Chakraborty
Subhasish K
SK
Hong
Shih Ching
SC
Tsay
Shwu-Chen
SC
Hsu
Ming-Hua
MH
Hwu
Jih Ru
JR
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012367:RNA, Viral / Q000187:drug effects; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001583:Benzoxazoles; D003374:Coumarins; D006574:Heterocyclic Compounds, 2-Ring; D007093:Imidazoles; D011687:Purines; D011725:Pyridines; D012367:RNA, Viral