Docking and quantitative structure-activity relationship studies for imidazo[1,2-a]pyrazines as inhibitors of checkpoint kinase-1

作者：Caballero Julio^*; Zilocchi Szymon; Tiznado William; Collina Simona

来源：Medicinal Chemistry Research, 2012, 21(8): 1912-1920.

DOI：10.1007/s00044-011-9714-1

• Checkpoint kinase-1 inhibitors
• Molecular docking
• Quantitative structure-activity relationships
• CoMSIA

We have performed docking of imidazo[1,2-a]pyrazines complexed with checkpoint kinase1 (Chk1) to better understand the structural requirements and preferred conformations of these inhibitors. The study was performed on a selected set of 33 compounds with variation in structure and activity. In addition, the predicted inhibitor concentrations (IC50) of the imidazo[1,2-a]pyrazines as Chk1 inhibitors were obtained by comparative molecular similarity analysis (CoMSIA). The best CoMSIA model included electrostatic and hydrophobic fields, had a good Q (2) value of 0.589, and adequately predicted the compounds contained in the test set. Furthermore, plots of the CoMSIA fields allowed conclusions to be drawn for the selection of suitable inhibitors.

• 出版日期2012-8
• 单位上海生物信息技术研究中心