Underwood Mark R, Ferris Robert G, Selleseth Dean W, Davis Michelle G, Drach John C, Townsend Leroy B, Biron Karen K, Boyd F Leslie
Department of International Clinical Virology, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
Antimicrob Agents Chemother. 2004 May;48(5):1647-51. doi: 10.1128/AAC.48.5.1647-1651.2004.
New human cytomegalovirus (HCMV) therapies with novel mechanisms of action are needed to treat drug-resistant HCMV that arises during therapy with currently approved agents. 2-Bromo-5,6-dichloro-1-beta-D-ribofuranosyl-1H-benzimidazole (BDCRB) is an effective anti-HCMV agent with a novel mechanism of action, but problems with in vivo stability preclude clinical development. A D-ribopyranosyl derivative of BDCRB, GW275175X, displays similar antiviral activity without the in vivo stability problems. We present an initial description of the activity of GW275175X against HCMV, other herpesviruses, and selected nonherpesviruses. In addition, we show that it acts as a DNA maturation inhibitor like the parent compound, BDCRB, rather than via the mechanisms of action of 1263W94 or any anti-HCMV drugs approved for marketing. GW275175X is a promising candidate for clinical development as an anti-HCMV agent.
需要具有新型作用机制的新型人类巨细胞病毒（HCMV）疗法来治疗在使用当前获批药物治疗期间出现的耐药性HCMV。2-溴-5,6-二氯-1-β-D-呋喃核糖基-1H-苯并咪唑（BDCRB）是一种具有新型作用机制的有效抗HCMV药物，但体内稳定性问题阻碍了其临床开发。BDCRB的一种D-吡喃核糖基衍生物GW275175X具有相似的抗病毒活性，且不存在体内稳定性问题。我们首次描述了GW275175X对HCMV、其他疱疹病毒和选定的非疱疹病毒的活性。此外，我们表明它与母体化合物BDCRB一样，作为一种DNA成熟抑制剂发挥作用，而不是通过1263W94或任何已获批上市的抗HCMV药物的作用机制。GW275175X作为一种抗HCMV药物，是临床开发的一个有前景的候选药物。
Zotero 插件