Xianbing Ke

Synthesis and potential anticonvulsant activity of new N-3-substituted 5,5-cyclopropanespirohydantoins

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.

16-morpholino quaternary ammonium steroidal derivatives as neuromuscular blocking agents: synthesis, biological evaluation and in silico probe of ligand-receptor interaction.

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.

Significant steroids: effective and general synthesis of 4alpha- and 4beta-amino-5alpha-androstanes.

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.

3,16-Bisquaternary ammonium steroid derivatives as neuromuscular blocking agents: synthesis and biological evaluation.

Neuromuscular blocking agents (NMBAs) are widely used in surgery to achieve skeleton muscles relaxation under light anesthesia status. In this work, we synthesized a series of 3,16-bisquaternary ammonium steroidal NMBAs. Among them, three compounds exhibited higher in vitro activities than the commenced drug rocuronium. In addition, structure-activity relationship was unveiled. We found that the intact acetylcholine-like moiety in D-ring was not necessary for maintaining activity but both the acetyl group and the quaternary nitrogen were very essential.