Synthesis of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives and their biological evaluation against protein tyrosine phosphatase 1B

Wen-Long Wang; Xia Chen; Li-Xin Gao; Li Sheng; Jing-Ya Li; Jia Li; Bainian Feng

doi:10.1111/cbdd.12587

Synthesis of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives and their biological evaluation against protein tyrosine phosphatase 1B

Chem Biol Drug Des. 2015 Nov;86(5):1161-7. doi: 10.1111/cbdd.12587. Epub 2015 Jun 23.

Authors

Wen-Long Wang^{1

2}, Xia Chen¹, Li-Xin Gao², Li Sheng², Jing-Ya Li², Jia Li², Bainian Feng¹

Affiliations

¹ School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, China.
² State key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

PMID: 25996453
DOI: 10.1111/cbdd.12587

Abstract

A series of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives were designed, synthesized, and evaluated as a new class of inhibitors against protein tyrosine phosphatase 1B. Among them, compound 6f displayed moderate inhibitory activity with IC50 of 2.87 ± 0.24 μm and can be used as a novel lead compound for the design of inhibitors of protein tyrosine phosphatase 1B.

Keywords: 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives; inhibitors; one-pot synthesis; protein tyrosine phosphatase 1B; structure-activity relationships.

Publication types

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

MeSH terms

Drug Design*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Humans
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry*
Spiro Compounds / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Spiro Compounds
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1