Molecules (Dec 2013)
1H-2,3-Dihydroperimidine Derivatives: A New Class of Potent Protein Tyrosine Phosphatase 1B Inhibitors
- Wen-Long Wang,
- Dong-Lin Yang,
- Li-Xin Gao,
- Chun-Lan Tang,
- Wei-Ping Ma,
- Hui-Hua Ye,
- Si-Qi Zhang,
- Ya-Nan Zhao,
- Hao-Jie Xu,
- Zhao Hu,
- Xia Chen,
- Wen-Hua Fan,
- Hai-Jun Chen,
- Jing-Ya Li,
- Fa-Jun Nan,
- Jia Li,
- Bainian Feng
Affiliations
- Wen-Long Wang
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- Dong-Lin Yang
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- Li-Xin Gao
- State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Chun-Lan Tang
- State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Wei-Ping Ma
- State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Hui-Hua Ye
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- Si-Qi Zhang
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- Ya-Nan Zhao
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- Hao-Jie Xu
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- Zhao Hu
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- Xia Chen
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- Wen-Hua Fan
- Jiangshu Alpha Biopharmaceuticals, Inc. Wuxi 214122, China
- Hai-Jun Chen
- State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Jing-Ya Li
- State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Fa-Jun Nan
- State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Jia Li
- State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Bainian Feng
- School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China
- DOI
- https://doi.org/10.3390/molecules19010102
- Journal volume & issue
-
Vol. 19,
no. 1
pp. 102 – 121
Abstract
A series of 1H-2,3-dihydroperimidine derivatives was designed, synthesized, and evaluated as a new class of inhibitors of protein tyrosine phosphatase 1B (PTP1B) with IC50 values in the micromolar range. Compounds 46 and 49 showed submicromolar inhibitory activity against PTP1B, and good selectivity (3.48-fold and 2.10-fold respectively) over T-cell protein tyrosine phosphatases (TCPTP). These results have provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.
Keywords
- 1H-2,3-dihydroperimidine derivatives
- PTP1B
- inhibitors
- selectivity
- structure-activity relationships (SAR)
