Combrink Keith D, Gulgeze H Belgin, Thuring Jan W, Yu Kuo-Long, Civiello Rita L, Zhang Yi, Pearce Bradley C, Yin Zhiwei, Langley David R, Kadow Kathleen F, Cianci Christopher W, Li Zhufang, Clarke Junius, Genovesi Eugene V, Medina Ivette, Lamb Lucinda, Yang Zheng, Zadjura Lisa, Krystal Mark, Meanwell Nicholas A
Department of Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
Bioorg Med Chem Lett. 2007 Sep 1;17(17):4784-90. doi: 10.1016/j.bmcl.2007.06.065. Epub 2007 Jun 26.
The effect of structural variation of the benzimidazol-2-one ring of RSV fusion inhibitors related to BMS-433771 (1) was examined in conjunction with side chain modifications and the introduction of an aminomethyl substituent at the 5-position of the core benzimidazole moiety. Replacement of the benzimidazol-2-one moiety with benzoxazole, oxindole, quinoline-2-one, quinazolin-2,4-dione and benzothiazine derivatives provided a series of potent RSV fusion inhibitors 4. However, the intrinsic potency of 6,6-fused ring systems was generally less than that of comparably substituted 5,6-fused heterocycles of the type found in BMS-433771 (1). The introduction of an aminomethyl substituent to the benzimidazole ring enhanced antiviral activity in the 6,6-fused ring systems.
结合侧链修饰以及在核心苯并咪唑部分的5位引入氨甲基取代基，研究了与BMS-433771（1）相关的呼吸道合胞病毒（RSV）融合抑制剂苯并咪唑-2-酮环结构变异的影响。用苯并恶唑、吲哚酮、喹啉-2-酮、喹唑啉-2,4-二酮和苯并噻嗪衍生物取代苯并咪唑-2-酮部分，得到了一系列有效的RSV融合抑制剂4。然而，6,6-稠合环系统的内在活性通常低于BMS-433771（1）中发现的类似取代的5,6-稠合杂环。在苯并咪唑环上引入氨甲基取代基增强了6,6-稠合环系统中的抗病毒活性。
