Synthesis and biological evaluation of (3'-amino-[1,1'-biphenyl]-4-yl) sulfamic acid derivatives as novel HPTPβ inhibitors

Wenjuan Zhang; Zhao Wei; Xueying Feng; Zhibing Zheng; Song Li

doi:10.1016/j.bioorg.2018.06.014

Synthesis and biological evaluation of (3'-amino-[1,1'-biphenyl]-4-yl) sulfamic acid derivatives as novel HPTPβ inhibitors

Bioorg Chem. 2018 Dec:81:270-277. doi: 10.1016/j.bioorg.2018.06.014. Epub 2018 Jun 6.

Authors

Wenjuan Zhang¹, Zhao Wei², Xueying Feng³, Zhibing Zheng⁴, Song Li⁵

Affiliations

¹ School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China; Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
² Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 300071, China.
³ Pharmarcon Beijing Co. Ltd., Beijing 100176, China.
⁴ Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: zbzheng@bmi.ac.cn.
⁵ School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China; Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: lis@bmi.ac.cn.

PMID: 30165257
DOI: 10.1016/j.bioorg.2018.06.014

Abstract

A series of novel (3'-amino-[1,1'-biphenyl]-4-yl) sulfamic acid derivatives were designed as nonphosphonate-based phosphotyrosy (pTyr) mimetics, synthesized and screened for use as HPTPβ inhibitors. Compounds C22 and C2 showed favorable HPTPβ inhibitory activity and better selectivity for HPTPβ than for PTP1B and SHP2. Docking results suggested that compounds C2 and C22 could not only efficiently fit into the catalytic site of the HPTPβ enzyme but also interact with the Lys1807, Arg1809 and Lys1811 residues of the secondary binding site, which was next to the catalytic center of the enzyme. The mode of interaction of the synthesized compound with the protein was different from the one found in a complex crystal of small molecules with HPTPβ (2I4H), in which the inhibitory molecule formed hydrogen bonds with the Gln1948 and Asn1735 residues of the secondary binding site.

Keywords: Activity evaluation; Drug design; HPTPβ; Inhibitor; Synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biphenyl Compounds / chemical synthesis
Biphenyl Compounds / chemistry*
Catalytic Domain
Drug Design
Humans
Molecular Docking Simulation
Molecular Structure
Receptor-Like Protein Tyrosine Phosphatases, Class 3 / antagonists & inhibitors*
Receptor-Like Protein Tyrosine Phosphatases, Class 3 / chemistry
Structure-Activity Relationship
Sulfonic Acids / chemical synthesis
Sulfonic Acids / chemistry*

Substances

Biphenyl Compounds
Sulfonic Acids
PTPRB protein, human
Receptor-Like Protein Tyrosine Phosphatases, Class 3