College of Pharmacy, University of Sharjah, University City Road, P.O. Box 27272, Sharjah, United Arab Emirates.
Eur J Med Chem. 2010 Oct;45(10):4615-21. doi: 10.1016/j.ejmech.2010.07.026. Epub 2010 Jul 21.
Polysubstituted hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one and tetrahydropyrano[3,2-b]pyrrol-2(1H)-one derivatives were synthesized and biologically evaluated as novel anticancer agents. These motifs were produced by five steps reaction sequence in which Achmatowicz oxidative cyclization, is the basic protocol for such synthesis. To understand the structure-activity relationships of the newly synthesized motifs, two traditional medicinal chemistry strategies namely, ring expansion and contraction, were followed in this article. These studies indicated that tetrahydropyrano[3,2-b]pyrrol-2(1H)-one derivatives are more selective for breast cancer cell line compared to other cell lines under investigations. Furthermore, it was found that hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one derivatives are potent anticancer agents compared to tetrahydropyrano[3,2-b]pyrrol-2(1H)-one analogs. These findings, however, form the foundation for further investigation in our continuing efforts to develop selective anticancer agents.
合成了多取代的六氢吡喃并[3,2-c][1,2]二氮嗪-3(4H)-酮和四氢吡喃并[3,2-b]吡咯-2(1H)-酮衍生物，并将其作为新型抗癌药物进行了生物学评价。这些结构是通过五步反应序列合成的，其中 Achmatowicz 氧化环化是这种合成的基本方案。为了了解新合成结构的构效关系，本文遵循了两种传统的药物化学策略，即环扩张和收缩。这些研究表明，与其他研究的细胞系相比，四氢吡喃并[3,2-b]吡咯-2(1H)-酮衍生物对乳腺癌细胞系更具选择性。此外，还发现与四氢吡喃并[3,2-b]吡咯-2(1H)-酮类似物相比，六氢吡喃并[3,2-c][1,2]二氮嗪-3(4H)-酮衍生物是有效的抗癌剂。然而，这些发现为我们继续努力开发选择性抗癌剂奠定了基础。
