title: Synthesis and biological evaluation of novel bis-aromatic amides as novel PTP1B inhibitors.
abstract: A series of bis-aromatic amides was designed, synthesized, and evaluated as a new class of inhibitors with IC50 values in the micromolar range against protein tyrosine phosphatase 1B (PTP1B). Among them, compound 15 displayed an IC50 value of 2.34±0.08 μM with 5-fold preference over TCPTP. More importantly, the treatment of CHO/HIR cells with compound 15 resulted in increased phosphorylation of insulin receptor (IR), which suggested extensive cellular activity of compound 15. These results provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: wwenlong2011@163.com.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Chun-Lan
authors.initials: CL
authors.lastname: Tang
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China.
authors.forename: Jun-Qing
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China.
authors.forename: Min-Chen
authors.initials: MC
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Nan
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jli@mail.shcnc.ac.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China; Jiangsu Alpha Biopharmaceuticals, Inc., Wuxi 214122, China. Electronic address: fengbainian@jiangnan.edu.cn.
authors.forename: Bainian
authors.initials: B
authors.lastname: Feng
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Bis-aromatic amides; Cellular activity; PTP1B inhibitors; Selectivity; Structure–activity relationships (SARs)