Fuse Shinichiro, Ohuchi Toshiaki, Asawa Yasunobu, Sato Shinichi, Nakamura Hiroyuki
Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.
Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.
Bioorg Med Chem Lett. 2016 Dec 15;26(24):5887-5890. doi: 10.1016/j.bmcl.2016.11.009. Epub 2016 Nov 5.
1,3-Disubstituted-imidazopyridines were designed for developing inhibitors against HIF-1 transcriptional activity. Designed compounds were rapidly synthesized from a key aromatic scaffold via microwave-assisted Suzuki-Miyaura coupling/CH direct arylation sequence. Evaluation of ability to inhibit the hypoxia induced transcriptional activity of HIF-1 revealed that the compound 2i and 3a retained the same level of the inhibitory activity comparing with that of known inhibitor, YC-1 (1). Identified, readily accessible 1-aryl-3-furanyl/thienyl-imidazopyridine templates should be useful for future drug development.
设计1,3-二取代咪唑并吡啶以开发针对缺氧诱导因子-1（HIF-1）转录活性的抑制剂。通过微波辅助的铃木-宫浦偶联/碳氢键直接芳基化序列，从关键的芳香骨架快速合成了设计的化合物。对抑制HIF-1缺氧诱导转录活性能力的评估表明，与已知抑制剂YC-1相比，化合物2i和3a保留了相同水平的抑制活性。已确定的、易于获得的1-芳基-3-呋喃基/噻吩基咪唑并吡啶模板应有助于未来的药物开发。
