title: Design and synthesis of novel 1,2-dithiolan-4-yl benzoate derivatives as PTP1B inhibitors.
abstract: A series of novel 1,2-dithiolan-4-yl benzoate compounds were synthesized and evaluated for in vitro PTP1B inhibitory activity. Some derivatives exhibited improved PTP1B inhibitory activity and selectivity compared to hit 6a, a compound from in-house library screening inspired by marine cyclic disulfide. The preliminary SAR analysis with assistance of molecular modeling approach revealed 6j (IC50=0.59μM) as the most potent PTP1B inhibitor among all derivatives.
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
authors: Jing
authors: J
authors: Chen
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
authors: Li-Xin
authors: LX
authors: Gao
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
authors: Jing-Xu
authors: JX
authors: Gong
authors: School of Biological Science and Technology, University of Jinan, Jinan 250022, Shandong, PR China.
authors: Cheng-Shi
authors: CS
authors: Jiang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
authors: Li-Gong
authors: LG
authors: Yao
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
authors: Jing-Ya
authors: JY
authors: Li
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China. Electronic address: jli@mail.shcnc.ac.cn.
authors: Jia
authors: J
authors: Li
authors: Kanion Pharmaceutical Co. Ltd, 58 Haichang South Road, Xinpu District, Lianyungang, Jiangsu 222001, PR China.
authors: Wei
authors: W
authors: Xiao
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China. Electronic address: ywguo@mail.shcnc.ac.cn.
authors: Yue-Wei
authors: YW
authors: Guo
mesh_terms: D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001592:Benzyl Alcohols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D016503:Drug Delivery Systems; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C585107:(thiolan-2-yl)diphenylmethanol; D001565:Benzoates; D001592:Benzyl Alcohols; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Diabetes; Disulfide derivative; PTP1B inhibitor; Selectivity