【摘 要】
：
Scaffold hopping of isoquinoline to quinazoline and derivatization of carboxylic acid 7b into N-benzylcarboxamide led to identification of novel β-N-hydroxy-γ-ketocarboxamide pharmacophore.Subsequentl
【出 处】
：
第九届IUPAC化学生物学国际研讨会暨第八届世界华人药物化学研讨会
论文部分内容阅读
Scaffold hopping of isoquinoline to quinazoline and derivatization of carboxylic acid 7b into N-benzylcarboxamide led to identification of novel β-N-hydroxy-γ-ketocarboxamide pharmacophore.Subsequently,N-arylalkyl-3-hydroxy-4-oxo-3,4-dihydro-quinazolin-2-carboxamide derivatives 9were synthesized as hepatitis C virus(HCV) NS5B polymerase inhibitors.Structure activity relationship(SAR) optimization led to the identification of N-phenylpropyl carboxamide 9k(IC50=8.8μM) as the most active compound in this series.Compound 9k possessed selectivity toward HCV1b replicon Ava.5 cells(EC50=17.5 μM) over parent Huh-7 cells(CC50=187.5μM).
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