- Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy
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Overexpression of protein tyrosine phosphatase 1B (PTP1B) induces insulin resistance in various basic and clinical research. In our previous work, a synthetic oleanolic acid (OA) derivative C10a with PTP1B inhibitory activity has been reported. However, C10a has some pharmacological defects and cytotoxicity. Herein, a structure-based drug design approach was used based on the structure of C10a to elaborate the smaller tricyclic core. A series of tricyclic derivatives were synthesised and the compounds 15, 28 and 34 exhibited the most PTP1B enzymatic inhibitory potency. In the insulin-resistant human hepatoma HepG2 cells, compound 25 with the moderate PTP1B inhibition and preferable pharmaceutical properties can significantly increase insulin-stimulated glucose uptake and showed the insulin resistance ameliorating effect. Moreover, 25 showed the improved in vivo antihyperglycaemic potential in the nicotinamide–streptozotocin-induced T2D. Our study demonstrated that these tricyclic derivatives with improved molecular architectures and antihyperglycaemic activity could be developed in the treatment of T2D.
- Chen, Feng,Chen, Jiabao,Gao, Cheng,Li, Junyan,Liu, Siyan,Qian, Shan,Wang, Zhouyu,Yang, Lingling,Zhang, Yuanyuan
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p. 152 - 164
(2019/11/25)
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- Copper(ii)-catalyzed c-n coupling of aryl halides and n-nucleophiles promoted by quebrachitol or diethylene glycol
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Herein, we report the natural ligand quebrachitol (QCT) as a promoter for a Cu(II) catalyst, which is highly effective for N-Arylation of various amines and related aryl halides. A series of diarylamine derivatives were obtained in high yields by using diethylene glycol (DEG) as both ligand and solvent. The C-N coupling reactions proceed under mild conditions and exhibit good functional group tolerance.
- Chen, Guoliang,Chen, Yuanguang,Du, Fangyu,Fu, Yang,Wu, Ying,Zhou, Qifan
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supporting information
p. 2161 - 2168
(2019/11/25)
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- Ortho-directed lithiation of ω-phenoxy alcohols
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ω-Phenoxy alcohols, PhO(CH2)(n)OH (n = 2-7), have been subjected to metalation with 2 equiv of n-butyllithium in tetrahydrofuran/methylcyclohexane solvent. Reaction of the resulting lithiated compounds with carbon dioxide (n = 2-7), benzaldehyde (n = 2-6), benzophenone (n = 2, 3), dimethylformamide (n = 2), ethyl formate (n = 2), and chlorodiphenylphosphine (n = 3) afforded the corresponding ortho- substituted hydroxyalkoxybenzenes in yields ranging from 45 to 83%. The synthesis is also reported of five new bis[o-(ω-hydroxyalkoxy)phenyl]mercury compounds (n = 2-6), four crystal structures of which have been determined.
- Salteris, Constantinos S.,Kostas, Ioannis D.,Micha-Screttas, Maria,Heropoulos, George A.,Screttas, Constantinos G.,Terzis, Aris
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p. 5589 - 5592
(2007/10/03)
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- Nucleophilic Aromatic Substitution with Elimination in a Dinitrosalicylic Lactone or Ester via Meisenheimer Intermediates
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The dinitro lactone 1b and dinitro ester 2b derived from salicylic acid undergo SNAr reactions in the presence of a variety of N-,O-, and S-nucleophiles.Substitution is accompanied by elimination of the β-ethylenoxy group, the ester group in no
- Jones, Paul R.,Rothenberger, Scott D.
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p. 3016 - 3023
(2007/10/02)
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