Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors
Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors
复制标题
DOI：
10.1016/j.bmcl.2012.04.131
复制
发表时间：
2012-07-01
影响因子：
2.7
通讯作者：
Carlson, Robert O.
中科院分区：
文献类型：
--
作者：
Kumar, D. Vijay;Hoarau, Christophe;Carlson, Robert O.
本信中描述了从基于嘌呤的先导化合物MPI-0479605中优化Mps 1抑制剂的生物活性、新奇、选择性和口服生物利用度的努力。Mps 1在HCT-116细胞中的生化活性和细胞毒活性得到提高。通过基于机制的G2/M逃逸试验证实了中靶活性。优化了理化和ADME性质，以提高小鼠口服生物利用度。(C)2012爱思唯尔有限公司保留所有权利。
Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse. (C) 2012 Elsevier Ltd. All rights reserved.