Slater M J, Cockerill S, Baxter R, Bonser R W, Gohil K, Gowrie C, Robinson J E, Littler E, Parry N, Randall R, Snowden W
GlaxoWellcome Medicines Research Centre, Stevenage, UK.
Bioorg Med Chem. 1999 Jun;7(6):1067-74. doi: 10.1016/s0968-0896(99)00032-2.
In our search for new, safer anti-HCMV agents, we discovered that the natural product Arcyriaflavin A (la) was a potent inhibitor of HCMV replication in cell culture. A series of analogues (symmetrical indolocarbazoles) was synthesised to investigate structure activity relationships in this series against a range of herpes viruses (HCMV, VZV, HSV1, and 2). This identified a number of novel, selective and potent inhibitors of HCMV, 12,13-dihydro-2,10-difluoro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol e-5,7-(6H)-dione (1d) being the best example (IC50=40 nM, therapeutic index > 1450). Compounds described in this series were generally poor inhibitors of protein kinase C betaII, and no correlation was found between the ability to inhibit HCMV and the enzyme PKC.
在寻找新型、更安全的抗人巨细胞病毒（HCMV）药物的过程中，我们发现天然产物刺盘孢黄素A（1a）是细胞培养中HCMV复制的有效抑制剂。合成了一系列类似物（对称吲哚咔唑），以研究该系列化合物对多种疱疹病毒（HCMV、水痘带状疱疹病毒、单纯疱疹病毒1型和2型）的构效关系。这确定了一些新型、选择性且有效的HCMV抑制剂，12,13-二氢-2,10-二氟-5H-吲哚并[2,3-a]吡咯并[3,4-c]咔唑-5,7-(6H)-二酮（1d）是最佳实例（IC50 = 40 nM，治疗指数>1450）。该系列中描述的化合物通常是蛋白激酶CβII的低效抑制剂，并且在抑制HCMV的能力与酶PKC之间未发现相关性。
