Computational Design and Discovery of 鈥淢inimally Structured鈥?hERG Blockers

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• 作者：Andrea Cavalli ; Rosa Buonfiglio ; Cristina Ianni ; Matteo Masetti ; Luisa Ceccarini ; Rachel Caves ; Michael W. Y. Chang ; John S. Mitcheson ; Marinella Roberti ; Maurizio Recanatini
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：April 26, 2012
• 年：2012
• 卷：55
• 期：8
• 页码：4010-4014
• 全文大小：253K
• 年卷期：v.55,no.8(April 26, 2012)
• ISSN：1520-4804

文摘

Molecular knowledge of hERG blocking liability can offer the possibility of optimizing lead compounds in a way that eliminates potentially lethal side effects. In this study, we computationally designed, synthesized, and tested a small series of 鈥渕inimally structured鈥?molecules. Some of these compounds were remarkably potent against hERG (6, IC₅₀ = 2.4 nM), allowing us to identify the minimal structural requirements for hERG blocking liability.