A novel, facile, and efficient one-step copolymerization strategy was developed for the preparation of β-cyclodextrin (β-CD) methacrylate monolithic columns using click chemistry. The novel mono-(1H-1,2,3-triazol-4-ylmethyl)-2-methylacryl-β-CD monomer was synthesized by a click reaction between propargyl methacrylate and mono-6-azido-β-CD, and then monolithic columns were prepared through a one-step in situ copolymerization of the mono-(1H-1,2,3-triazol-4-ylmethyl)-2-methylacryl-β-CD monomer and ethylene dimethacrylate. The physicochemical properties and column performance of the fabricated monolithic columns were characterized by elemental analysis, SEM, and micro-HPLC. Satisfactory column permeability, efficiency, and separation performance were obtained for the optimized poly(mono-(1H-1,2,3-triazol-4-ylmethyl)-2-methylacryl-β-CD-co-ethylene dimethacrylate) monolithic columns. Additionally, typical hydrophilic interaction chromatography retention behavior was observed on the monoliths at high acetonitrile content in the mobile phase. Although the enantioselectivity of our monolithic columns did not meet the level of other reported β-CD monolithic columns, this one-step strategy based on click chemistry still provides an interesting and effective model as it offers the possibility to easily prepare related novel CD methacrylate monoliths through a one-step copolymerization strategy.

Selective S1P1 receptor agonists have therapeutic potential to treat a variety of immune-mediated diseases. A series of 2-imino-thiazolidin-4-one derivatives displaying potent S1P1 receptor agonistic activity were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross-validation techniques were investigated as well as some measures including region focusing, progressive scrambling, bootstraping and leave-group-out. The satisfactory CoMFA model predicted a q2 value of 0.751 and an r2 value of 0.973, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic, hydrophobic and H-bond donor descriptors, predicted a q2 value of 0.739 and an r2 value of 0.923. The models were graphically interpreted using contour plots which gave more insight into the structural requirements for increasing the activity of a compound, providing a solid basis for future rational design of more active S1P1 receptor agonists.

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Seventy-five 1,5,6,7-tetrahydro-pyrrolo[3,2-C]pyridinone derivatives displaying potent activities against Cdc7 kinase were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross-validation techniques were investigated as well as some measures including region focusing, progressive scrambling, bootstraping and leave-group-out. The satisfactory CoMFA model predicted a q (2) value of 0.836 and an r (2) value of 0.950, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic and H-bond acceptor effects, predicted a q (2) value of 0.636 and an r (2) value of 0.907. The models were graphically interpreted using contour plots which provided insight into the structural requirements for increasing the activity of a compound. The final 3D-QSAR results could be used for rational design of potent inhibitors against Cdc7 kinase.