Using the latest reported homologous Chemokine receptors (PDB ID:3ODU,3OE0 and 3OE6) as templates,twenty models of angiotensin II (Ang II) type 1 (AT1) receptor (known as p30556) were generated by multiple templates homology modeling.According to the results of the initial validation of these twenty models,the model 0020 was finally chosen as the best one for further studies.Then,a 2 ns molecular dynamic (MD) simulation for model 0020 was conducted in normal saline (0.9%,w/V) under periodical boundary conditions,which was followed by docking studies of model 0020 with several existing AT1 receptor blockers (ARBs).The docking results reveal that model 0020 possesses good affinities with these docked ARBs which are in accordance with both the IC50 inhibitor values and their curative effects.The results also show more potent interactions between the model 0020 and its ARBs than those of ever reported results,such as hydrogen bonds,hydrophobic interactions,and especially cation-π interactions and π-π interactions which have never been reported before.This may reveal that the structure of the model 0020 is quite close to its real crystal structure and the model 0020 may have the potential to be used for structure based drug design.
The quantitative structure-activity relationship(QSAR) of 2-alkyl-4-(biphenylylmethoxy) pyridine derivatives was studied.Three different alignment methods were used to get the models of the comparative molecular field analysis(CoMFA),the comparative molecular similarity indices analysis(CoMSIA),and the hologram quantitative structure?activity relationship(HQSAR).The statistical results from the established models show believable predictivity based on the cross-validated value(q2>0.5) and the non-validated value(r2>0.9),The analysis on contour maps of CoMFA and CoMSIA models suggests that hydrophobic and hydrogen-bond acceptor fields are important factors that affect the AT1 antagonistic activity of 2-alkyl-4-(biphenylylmethoxy) pyridine derivatives besides the steric and electrostatic fields,The structural modification information from different atom contributions in the HQSAR model is in agreement with that in the 3D-QSAR models.
A new environmentally friendly photo-acid generator(PAG), 1-{4'-[4,6-bis(trichloromethyl)-1,3,5-triazin-2-yl][1,1'-biphenyl]-4-yl}-O-acetyloxime ethanone(TZ4) consisting of both an oxime ester group and a triazine group was designed and synthesized. From the measurements of absorption, fluorescence and the photo-acid generation, it was found that the novel PAG has an excellent radical-generating efficiency. And the other three bis-(trichloromethyl) triazine derivatives 2-[2-(4-methoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-1,3,5-triazine(TZ1), 2-[2-(3,4-dimeth-oxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-1,3,5-triazine(TZ2) and 2-(1,3-benzodioxol-5-yl)-4,6-bis(trichloromethyl)-1,3,5-triazine(TZ3) were synthesized and studied in this work. In the acid measurement, the acid-forming performance of S-triazinyl derivatives was evaluated by the method ascertained in our laboratory. The results indicate that the novel triazine has the better acid-forming performance that subsequently catalyzes the deblocking of a protecting group in copolymers.
