In order to provide a facile and practical access to structurally diverse aryl -diketoacids, An improved and highly efficient oxalylation method was developed which employed commercially available and cheap reagents. ...In order to provide a facile and practical access to structurally diverse aryl -diketoacids, An improved and highly efficient oxalylation method was developed which employed commercially available and cheap reagents. The oxalylation of aryl methyl ketones, the key step to construct the pharmacophore of aryl -diketoacids, was con-siderably facilitated by a new combination of dimethyl oxalate as an oxalic source and sodium tert-butoxide as a base. A wide variety of aryl -diketoacids bearing different functional groups can be prepared rapidly in high yields at room temperature with this method, which has significant advantages over the previously reported procedures in a wider application range, much less amount of reagents, pretty higher yields and quite shorter reaction time. The bis-aryldiketoacids 3k and 3l, readily prepared by this method, displayed interesting and promising inhibitory ac-tivities against HIV-1 integrase and HIV-1 replication in cells.展开更多
An efficient procedure for the synthesis of caffeoyl- and galloyl-containing β-diketoacid derivatives linked by arylamide was reported by, in the key step, dissolving the corresponding phenyl methyl ketone in THF/DME...An efficient procedure for the synthesis of caffeoyl- and galloyl-containing β-diketoacid derivatives linked by arylamide was reported by, in the key step, dissolving the corresponding phenyl methyl ketone in THF/DME in the presence of NaOMe as base and dimethyl oxalate as oxalylation reagent, and then separating the sodium ketoenolate ester. The resulting β-diketoacids underwent further condensation reaction with o-phenylenediamine to generate quinoxalone derivatives in good yield, rather than 2-benzimidazol. The preliminary ion binding properties of quinoxalone derivatives were also investigated. UV-Vis spectra showed that these compounds could selectively recognize Cu^2 ＋ ion in ethanol and form a 1 ： 2 complex.展开更多
应用遗传算法相似性程序(GASP),以作用于I型人类免疫缺陷病毒(humanimmun-odeficiency virustype1,HIV-1)整合酶(IN)的二酮酸类(diketoacids,DKAs)抑制剂构建药效团模型.所选训练集分子均具有可靠的类药性特征及DKAs药效团特征.尝试将...应用遗传算法相似性程序(GASP),以作用于I型人类免疫缺陷病毒(humanimmun-odeficiency virustype1,HIV-1)整合酶(IN)的二酮酸类(diketoacids,DKAs)抑制剂构建药效团模型.所选训练集分子均具有可靠的类药性特征及DKAs药效团特征.尝试将抑制剂与药效团叠合后的构象和抑制剂与IN的对接构象进行叠合,得到药效团模型与分子对接构象中IN残基的相对位置,并基于抑制剂的药效团模型特征与周围IN氨基酸残基位置的匹配情况进行药效团特征的修改.所得最优药效团由1个疏水特征、3对氢键特征和1个氢键供体特征组成.该药效团的命中物质量(goodness of hit,GH)为0.56,产出率(Y)达63.6%,假阳性率(FP)为0.41%.该药效团具有较好的置信度,产出率较高而假阳性率较低,可用于数据库搜索发现新的具有DKAs药效团特征的活性化合物,也可为先导化合物的改造提供帮助.展开更多
Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase（IN） inhibitor approved by the United States Food and Drug Administration（US FDA）, were designed, synth...Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase（IN） inhibitor approved by the United States Food and Drug Administration（US FDA）, were designed, synthesized and characterized by ^1H NMR, IR and MS. The biological activities of these compounds against HIV-1 IN in vitro were evaluated. The assay results indicate that the replacement of pyrimidinone with furanone decreased the inhibitory activity of the compounds to HIV-1 IN. Compounds 3i, 3j and 3t show moderate inhibitory activity against HIV-1 IN and selectively inhibit the strand transfer reaction.展开更多
基金Shanghai Municipal Committee of Science and Technology (Nos.02QB14056 and 03DZ19219)the Chinese Academy of Sciences (KSCX1-SW-11)the Ministry of Personnel of China.
文摘In order to provide a facile and practical access to structurally diverse aryl -diketoacids, An improved and highly efficient oxalylation method was developed which employed commercially available and cheap reagents. The oxalylation of aryl methyl ketones, the key step to construct the pharmacophore of aryl -diketoacids, was con-siderably facilitated by a new combination of dimethyl oxalate as an oxalic source and sodium tert-butoxide as a base. A wide variety of aryl -diketoacids bearing different functional groups can be prepared rapidly in high yields at room temperature with this method, which has significant advantages over the previously reported procedures in a wider application range, much less amount of reagents, pretty higher yields and quite shorter reaction time. The bis-aryldiketoacids 3k and 3l, readily prepared by this method, displayed interesting and promising inhibitory ac-tivities against HIV-1 integrase and HIV-1 replication in cells.
基金Project supported by the National Natural Science Foundation of China （No. 20402001）, the Special Foundation for Beijing Municipal （No. 2004D0501520 and Beijing Novel Project （No. 2005B 10）.
文摘An efficient procedure for the synthesis of caffeoyl- and galloyl-containing β-diketoacid derivatives linked by arylamide was reported by, in the key step, dissolving the corresponding phenyl methyl ketone in THF/DME in the presence of NaOMe as base and dimethyl oxalate as oxalylation reagent, and then separating the sodium ketoenolate ester. The resulting β-diketoacids underwent further condensation reaction with o-phenylenediamine to generate quinoxalone derivatives in good yield, rather than 2-benzimidazol. The preliminary ion binding properties of quinoxalone derivatives were also investigated. UV-Vis spectra showed that these compounds could selectively recognize Cu^2 ＋ ion in ethanol and form a 1 ： 2 complex.
文摘应用遗传算法相似性程序(GASP),以作用于I型人类免疫缺陷病毒(humanimmun-odeficiency virustype1,HIV-1)整合酶(IN)的二酮酸类(diketoacids,DKAs)抑制剂构建药效团模型.所选训练集分子均具有可靠的类药性特征及DKAs药效团特征.尝试将抑制剂与药效团叠合后的构象和抑制剂与IN的对接构象进行叠合,得到药效团模型与分子对接构象中IN残基的相对位置,并基于抑制剂的药效团模型特征与周围IN氨基酸残基位置的匹配情况进行药效团特征的修改.所得最优药效团由1个疏水特征、3对氢键特征和1个氢键供体特征组成.该药效团的命中物质量(goodness of hit,GH)为0.56,产出率(Y)达63.6%,假阳性率(FP)为0.41%.该药效团具有较好的置信度,产出率较高而假阳性率较低,可用于数据库搜索发现新的具有DKAs药效团特征的活性化合物,也可为先导化合物的改造提供帮助.
基金Supported by the National Natural Science Foundation of China(No.20872082)the Natural Science Foundation of Shandong Province,China(No.Y2007C060)
文摘Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase（IN） inhibitor approved by the United States Food and Drug Administration（US FDA）, were designed, synthesized and characterized by ^1H NMR, IR and MS. The biological activities of these compounds against HIV-1 IN in vitro were evaluated. The assay results indicate that the replacement of pyrimidinone with furanone decreased the inhibitory activity of the compounds to HIV-1 IN. Compounds 3i, 3j and 3t show moderate inhibitory activity against HIV-1 IN and selectively inhibit the strand transfer reaction.
