Synthesis, Crystal Structure, Absolute Configuration and Antitumor Activity of the Enantiomers of 5-Bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide.

ABSTRACT: Pyridinesulfonamide is an important fragment which has a wide range of applications in novel drugs. R- and S-isomers of 5-bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide have been synthesized, and the stereostructures have been researched. Single crystals of both compounds were obtained for X-ray analysis, and the absolute configurations (ACs) have been further confirmed by electronic circular dichroism (ECD), optical rotation (OR) and quantum chemical calculations. The crystal structures and calculated geometries were extremely similar, which permitted a comparison of the relative reliabilities of ACs obtained by ECD analyses and theoretical simulation. In addition, the effect of stereochemistry on the PI3K? kinase and anticancer activity were investigated. Compounds 10a and 10b inhibit the activity of PI3K? kinase with IC50 values of 1.08 and 2.69 ?M, respectively. Furthermore, molecular docking was performed to analyze the binding modes of R- and S-isomers.

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC6332033 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature