Zhu, Fang; Wang, Yujie; Du, Qian; Ge, Wenxiang; Li, Zhanhui; Wang, Xu; Fu, Chunyan; Luo, Lusong; Tian, Sheng; Ma, Haikuo; Zheng, Jiyue; Zhang, Yi; Sun, Xiaotian; He, Sudan; Zhang, Xiaohu published the artcile< Structural optimization of aminopyrimidine-based CXCR4 antagonists>, Reference of 60705-25-1, the main research area is aminopyrimidine synthesis SAR CXCR4 CXCL12 chemotaxis hERG; Antagonist; CXCR4; Chemokine; GPCR; Structural optimization.
Structural optimization of aminopyrimidine-based CXCR4 antagonists is reported. The optimization is guided by mol. docking studies based on available CXCR4-small mol. crystal complex. The optimization identifies a number of compounds with improved receptor binding affinity and functional activity exemplified by compound 23 (inhibition of APC-conjugate clone 12G5 for CXCR4 binding in a cell based assay: IC50 = 8.8 nM; inhibition of CXCL12 induced cytosolic calcium increase: IC50 = 0.02 nM). In addition, compound 23 potently inhibits CXCR4/CXLC12 mediated chemotaxis in a matrigel invasion assay. Furthermore, compound 23 exhibits good physicochem. properties (MW 367, clogP 2.1, PSA 48, pKa 7.2) and in vitro safety profiles (marginal/moderate inhibition of CYP isoenzymes and hERG). These results represent significant improvement over the initial hit from scaffold hybridization and suggest that compound 23 can be used as a starting point to support lead optimization.
European Journal of Medicinal Chemistry published new progress about Cardiotoxicity. 60705-25-1 belongs to class esters-buliding-blocks, and the molecular formula is C7H12O5, Reference of 60705-25-1.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics