Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2 ',2 '-dimethyldihydropyrano-chromone (DCP) analogs as potent anti-HIV agents

作者：Zhou Ting; Shi Qian; Chen Chin Ho; Zhu Hao; Huang Li; Ho Phong; Lee Kuo Hsiung^*

来源：Bioorganic & Medicinal Chemistry, 2010, 18(18): 6678-6689.

DOI：10.1016/j.bmc.2010.07.065

• 3 ' R,4 ' R-Di-O-(-)-camphanoyl-2 ',2 '-dimethyldihydropyrano[2,3-f]chromone (DCP)
• derivatives
• HIV-1
• Reverse transcriptase (RT)
• Structure-activity relationship (SAR)

In a continued study, 23 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIV(NL4-3) with EC(50) and therapeutic index (TI) values ranging from 0.036 mu M to 0.14 mu M and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC(50) 0.049 and 0.054 mu M; TI 310 and 200, respectively), and were twofold more potent than the leads 4 and 35 (EC(50) 0.11 and 0.19 mu M; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5-10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates.

• 出版日期2010-9-15
• 单位中国医科大学