A solid-phase approach to DDB derivatives.
Since the discovery of 2,2'-dimethoxycarbonyl-4,4-dimethoxy-5,6,5',6'-biomethylenedioxy-biphenyl (DDB) as a potent anti-HBV agent, we have studied the structure-activity relationships of 4,4'-dimethoxy-5,6,5',6'-dimethenedioxy-2-alkyloxycarbonyl-2'-(4-substituted benzyl piperazin-1-yl)carbonyl-biphenyl as anti-HBV agents. Therefore, it is rational to extend this study to the 3,3'-disustituted-4,4'-dimethoxy-5,6,5',6'-dimethenedioxy-2-alkyloxycarbonyl-2'-Serine derivatives. Thus, in an attempt to develop an efficient method for the preparation of a large number of DDB derivatives, the reaction between a DDB acid chloride and serine derivatives on solid support was studied. The structure of resulted compounds was confirmed by LC-MS and (1)H NMR analysis. Compounds 2a, 2d, 2f, 2j showed in vitro anti-HBV activity without significant toxicity up to 100 microM.
Qi
Xiuxiang
X
Lanzhou Institute of Chemical Physics, The Chinese Academy of Sciences, Lanzhou 730000, China.
Wang
Xiaolai
X
Wang
Limin
L
Wang
Qiang
Q
Cheng
Senxiang
S
Suo
Jishuan
J
Chang
Junbiao
J
D001577:Benzophenones / Q000737:chemistry; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006515:Hepatitis B virus / Q000187:drug effects*; D012694:Serine / Q000737:chemistry; D013329:Structure-Activity Relationship
D001577:Benzophenones; D001713:Biphenyl Compounds; D012694:Serine