化学
化学空间
药物发现
卤化物
卤键
溶解度
化学稳定性
计算化学
芳基
组合化学
硫族元素
卤素
结合亲和力
分子
化学生物学
化学位移
立体化学
有机化学
氢键
物理化学
生物化学
烷基
受体
作者
Sebastian Vaas,Markus O. Zimmermann,Dieter Schollmeyer,Jason Stahlecker,Michael Engelhardt,Janosch Rheinganz,Bernhard Drotleff,Matthias Olfert,Michael Lämmerhofer,M. Krämer,Thilo Stehle,Frank M. Boeckler
标识
DOI:10.1021/acs.jmedchem.3c00634
摘要
As an orthogonal principle to the established (hetero)aryl halides, we herein highlight the usefulness of CF2X (X = Cl, Br, or I) moieties. Using tool compounds bearing CF2X moieties, we study their chemical/metabolic stability and their logP/solubility, as well as the role of XB in their small molecular crystal structures. Employing QM techniques, we analyze the observed interactions, provide insights into the conformational flexibilities and preferences in the potential interaction space. For their application in molecular design, we characterize their XB donor capacities and its interaction strength dependent on geometric parameters. Implementation of CF2X acetamides into our HEFLibs and biophysical evaluation (STD-NMR/ITC), followed by X-ray analysis, reveals a highly interesting binding mode for fragment 23 in JNK3, featuring an XB of CF2Br toward the P-loop, as well as chalcogen bonds. We suggest that underexplored chemical space combined with unconventional binding modes provides excellent opportunities for patentable chemotypes for therapeutic intervention.
科研通智能强力驱动
Strongly Powered by AbleSci AI