Synthesis, Crystal Structure, Absolute Configuration and Antitumor Activity of the Enantiomers of 5-Bromo-2-chloro-N-1-phenylethylpyridine-3-sulfonamideReport as inadecuate




Synthesis, Crystal Structure, Absolute Configuration and Antitumor Activity of the Enantiomers of 5-Bromo-2-chloro-N-1-phenylethylpyridine-3-sulfonamide - Download this document for free, or read online. Document in PDF available to download.

1

Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang 110016, China

2

Pharmacy Department, Shenyang Pharmaceutical University, Shenyang 110016, China





*

Authors to whom correspondence should be addressed.



Academic Editor: Maria Emília de Sousa

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-phenylethylpyridine-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 PI3Kα kinase and anticancer activity were investigated. Compounds 10a and 10b inhibit the activity of PI3Kα kinase with IC50 values of 1.08 and 2.69 μM, respectively. Furthermore, molecular docking was performed to analyze the binding modes of R- and S-isomers. View Full-Text

Keywords: pyridinesulfonamide; enantiomer; X-ray diffraction; absolute configuration; DFT; ECD; PI3K; antitumor activity pyridinesulfonamide; enantiomer; X-ray diffraction; absolute configuration; DFT; ECD; PI3K; antitumor activity





Author: Zhixu Zhou 1, Linwei Li 1, Ning Yan 1, Lei Du 1, Changshan Sun 2,* and Tiemin Sun 1,*

Source: http://mdpi.com/



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