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Hao Hu,
Zhigang Rao,
Jianrong Xu,
Qingfu Zhu,
Hans-Josef Altenbach,
Hongzhuan Chen,
Dingshan Zhou,
Yuling Xiao, Xianbing Ke,
Hao Guo,
Zhongyuan Wu,
Peng Liu,
Xianming Hu
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ABSTRACT: A series of steroidal 3,16-bis-quaternary ammonium salts were synthesized and screened on mouse hemi-diaphragm to explore new steroidal neuromuscular blocking agents. There were two compounds, 3β-piperidino derivate 8d (IC(50) = 3.49 μM) and 3β-N-methylbenzylamino derivate 8g (IC(50) = 4.54 μM), showing activity close to rocuronium (IC(50) = 2.50 μM). The preliminary structure-activity relationship was deduced from the bioactivity results with the aid of the calculated N-N distance and log P. Meanwhile, the interactions between the ligand and binding pocket were revealed by docking 8d to the ligand binding domain of the mouse muscle nicotinic acetylcholine receptor (nAChR). This nAChR was modeled using Molecular Operating Environment (MOE) package indirectly from mollusca acetylcholine binding protein with mouse neuron α7 nAChR as intermediary template.
European journal of medicinal chemistry 08/2012; 56:332-47. · 3.27 Impact Factor
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ABSTRACT: 4alpha-Aminosteroids were synthesized by the substitution of a 2alpha-bromo ketone using K(2)CO(3) as an activator; 4beta-aminosteroids were synthesized in excellent yields by a highly regioselective and trans-stereospecific ring opening of a steroidal 3,4alpha-epoxide using ZnCl(2)-H(2)O as a catalyst.
Chemical Communications 04/2009; · 6.17 Impact Factor
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ABSTRACT: Thirteen new 5-cyclopropanespirohydantoins with various N-3 substituents were synthesized and their pharmacological activity was determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by maximal electroshock seizure (MES) test and subcutaneous pentylenetetrazole (scPTZ) test models in mice. All compounds substituted with cyclopropyl group at fifth position of hydantoin ring showed better protection against MES test. Compounds 5b, 5d, 5e, 5g and 5j were found to be the most potent compounds of this series and compared with the reference drug phenytoin sodium in MES test. Compound 5j also showed equipotent activity with the standard drug sodium valproate at the doses of 20 and 40 mg kg(-1) in scPTZ test.
European journal of medicinal chemistry 04/2008; 44(1):296-302. · 3.27 Impact Factor
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ABSTRACT: A series of novel α,α-disubstituted aziridinemethanols have been developed for the enantioselective reduction of ketones in
refluxing tetrahydrofuran. The optically active secondary alcohol products were obtained in good enantiomeric excess (~96.8%)
and excellent yields. The results showed that the substituent groups on the hydroxyl-bearing carbon of aziridinemethanols
obviously affected the enantioselectivity.
Catalysis Letters 01/2008; 125(3):302-307. · 2.24 Impact Factor
