title: Design, synthesis, and evaluation of 2-substituted ethenesulfonic acid ester derivatives as protein tyrosine phosphatase 1B inhibitors.
abstract: Thirty-two 2-substituted ethenesulfonic acid ester derivatives were designed, synthesized, and evaluated for their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and selectivity over T-Cell protein tyrosine phosphatase (TCPTP). Preliminary structure-activity relationship studies demonstrated that the substitution at the aromatic center and the length of linker between the hydrophobic tail and aromatic center markedly affected the inhibitory activity against PTP1B and the selectivity over TCPTP. Specifically, compounds 43 and 36 revealed excellent inhibitory activity to PTP1B with IC(50) = 1.3 μM and 1.5 μM, respectively, and marked 10- and 20-fold selectivity over TCPTP. Cytotoxicity data showed low cytotoxicity for COS-7 cell with IC(50) values >100 μM for most synthesized chemicals.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, PR China.
authors.forename: Jingbao
authors.initials: J
authors.lastname: Liu
authors.forename: Faqin
authors.initials: F
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Wenlu
authors.initials: W
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Fu
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D000069604:Dabigatran; D015195:Drug Design; D004952:Esters; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology; D020246:Venous Thrombosis / Q000188:drug therapy / Q000378:metabolism
chemical_list: C115263:2-hydroxymethyl-3,5,6-trimethylpyrazine; D001562:Benzimidazoles; D004952:Esters; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; D011719:Pyrazines; D011725:Pyridines; D000244:Adenosine Diphosphate; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D013917:Thrombin; D000069604:Dabigatran