- 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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- THIAZOLIDINONE COMPOUNDS AND USE THEREOF
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A pharmaceutical composition containing a compound of Formula (I) for treating an opioid receptor-associated condition. Also disclosed is a method for treating an opioid receptor-associated condition using such a compound. Further disclosed are two sets of thiazolidinone compounds of formula (I): (i) compounds each having an enantiomeric excess greater than 90% and (ii) compounds each being substituted with deuterium.
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Paragraph 1136-1137
(2017/09/21)
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- Al2O3/MeSO3H (AMA) as a new reagent with high selective ability for monoesterification of diols
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A new facile method for monoesterification of diols has been developed. A variety of diols, in particular oligoethylene glycols, were selectively monoesterified in excellent yields by reaction with aromatic and aliphatic acids in the presence of Al2O3/MeSO3H as a new reagent without use of any solvents.
- Sharghi, Hashem,Sarvari, Mona Hosseini
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p. 3627 - 3633
(2007/10/03)
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- Highly selective methodology for the direct conversion of aromatic aldehydes to glycol monoesters
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Al2O3/MeSO3H (AMA) was found to be an extremely efficient reagent for the conversion of aromatic aldehydes and diols to glycol monoesters. The remarkable selectivity achieved with this reagent is an attractive feature of t
- Sharghi, Hashem,Sarvari, Mona Hosseini
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p. 4096 - 4099
(2007/10/03)
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- Acyl Transfer Reaction Catalyzed by Cu(2+) Ion Complex of a Lipolhilic Hydroxyimidazole-ligand in AOT Reverse Micelles. Effects of Change of Core Solvent from Water to DMF
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The transfer of acyl group of p-nitrophenyl picolinate to alcohol acceptors has been investigated kinetically in AOT reverse micelles using hexane and DMF as the bulk and the core solvents, respectively.The reaction was found to be remarkably catalyzed by a 1:2 complex of Cu(2+) ion and N-dodecyl-2-hydroxymethylimidazole ligand involving the acylated ligand as the intermediate.It was also observed that the reaction in the reverse micelles was much faster than in pure DMF.
- Fujita, Tsunehisa,Minami, Hajimu,Ogino, Kenji,Tagaki, Waichiro
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p. 2289 - 2292
(2007/10/02)
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