Synthesis of (5R,8R)-2-(3,8-Dimethyl-2-oxo-1,2,4,5,6,7,8,8￥á-octahydroazulen-5-yl)
Acrylic Acid (Rupestonic Acid) Amide Derivatives and in vitro Inhibitive Activities
against Influenza A₃,B and Herpes Simplex Type 1 and 2 Virus

摘要

19 Aromatic ring and L-amino acid ester contained rupestonic acid amide derivatives 2a~2l, 3a~3g were synthesized and preliminarily evaluated in vitro against influenza virus A₃,B and herpes simplex virus type 1 (HSV-1), 2(HSV-2) by the national center for drug screening of China. The rusults showed that 2i possessed the highest inhibition against both influenza virus A₃ (TC₅₀ = 120.6 レmol/L, IC₅₀ = 19.2 レmol/L, SI = 6.3) and B (TC₅₀ = 120.6 レmol/L, IC₅₀ = 29.9 レmol/L, SI = 4.0); 2g was more active against influenza A₃ virus at very low cytotoxicity (TC₅₀ 2092.1 レmol/L, IC₅₀ = 143.7 レmol/L, SI 14.6) than the parent compound; Compounds 2b, 2c, 2f showed higher activities both against HSV-1 and HSV-2 than that of the parent compound, and 2f was the most potent inhibitor of HSV-1 (TC₅₀ = 200.0 レmol/L, IC₅₀ = 11.3 レmol/L, SI = 17.7 ) and HSV-2 (TC₅₀ = 200.0 レmol/L, IC₅₀ = 20.7 レmol/L , SI = 9.7).