Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, D-91052 Erlangen, Germany.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5446-50. doi: 10.1016/j.bmcl.2011.06.120. Epub 2011 Jul 2.
The highly constitutively active G-protein coupled receptor US28 of human cytomegalovirus (HCMV) is an interesting pharmacological target because of its implication on viral dissemination, cardiovascular diseases and tumorigenesis. We found that dihydroisoquinolinone and tetrahydroisoquinoline scaffolds may be promising lead structures for novel US28 allosteric inverse agonists. These scaffolds were rapidly synthesized by radical carboamination reactions followed by non-radical transformations. Our novel US28 allosteric modulators provide valuable scaffolds for further ligand optimization and may be helpful chemical tools to investigate molecular mechanisms of US28 constitutive signaling and its role in pathogenesis.
人巨细胞病毒（HCMV）高度组成型激活的 G 蛋白偶联受体 US28 是一个有趣的药理学靶点，因为它与病毒传播、心血管疾病和肿瘤发生有关。我们发现二氢异喹啉酮和四氢异喹啉骨架可能是新型 US28 变构别构抑制剂的有前途的先导结构。这些支架通过自由基碳氨化反应和非自由基转化快速合成。我们的新型 US28 变构调节剂为进一步的配体优化提供了有价值的支架，并且可能是研究 US28 组成型信号传导的分子机制及其在发病机制中的作用的有用化学工具。
