Abstract CC chemokine receptor 4 （CCR4） is a kind of G-protein-coupled receptor, which plays a pivotal role in allergic inflammation. The interaction between 2-（2-（4-chloro-phenyl）-5-{[（naphthalen-1- ylmethyl）-...Abstract CC chemokine receptor 4 （CCR4） is a kind of G-protein-coupled receptor, which plays a pivotal role in allergic inflammation. The interaction between 2-（2-（4-chloro-phenyl）-5-{[（naphthalen-1- ylmethyl）-carbamlyl]-methyl-4-oxo-thiazolidin-3-yl）-N-（3-morpholin-4-yl-propyi）-acetamide （S009） and the N-terminal extracellular tail （ML40） of CCR4 has been validated to be high affinity by capillary zone electrophoresis （CZE）.The S009 is a known CCR4 antagonist. Now, a series of new thiourea derivatives have been synthesized. Compared with positive control S009, they were screened using ML40 as target by CZE to find some new drugs for allergic inflammation diseases. The synthesized compounds XJH-5, XJH-4, XJH-17 and XJH-1 displayed the interaction with ML40, but XJH-9, XJH-10, XJH-I 1, XJH-12, XJH-13, XJH-14, XJH-3, XJH-8, XJH-6, XJH-7, XJH-15, XJH-16 and XJH-2 did not bind to ML40. Both qualification and quantification characterizations of the binding were determined. The affinity of the four compounds was valued by the binding constant, which was similar with the results of chemotactic experiments. The established CEZ method is capable of sensitive and fast screening for a series of lactam analogs in the drug discovery for allergic inflammation diseases.展开更多
基金supported by the National Key New Drug Creation Program of China (2009ZX09103-724)the National Natural Science Foundation of China grants(30872292,90813025 and 81072612)+2 种基金the Natural Science Foundation of Beijing (7102107)the Open Foundation of State Key Laboratory of Natural and Biomimetic Drugs(K20090207)the National New Drug Research and Development Project of China (2009ZX09301-010)
文摘Abstract CC chemokine receptor 4 （CCR4） is a kind of G-protein-coupled receptor, which plays a pivotal role in allergic inflammation. The interaction between 2-（2-（4-chloro-phenyl）-5-{[（naphthalen-1- ylmethyl）-carbamlyl]-methyl-4-oxo-thiazolidin-3-yl）-N-（3-morpholin-4-yl-propyi）-acetamide （S009） and the N-terminal extracellular tail （ML40） of CCR4 has been validated to be high affinity by capillary zone electrophoresis （CZE）.The S009 is a known CCR4 antagonist. Now, a series of new thiourea derivatives have been synthesized. Compared with positive control S009, they were screened using ML40 as target by CZE to find some new drugs for allergic inflammation diseases. The synthesized compounds XJH-5, XJH-4, XJH-17 and XJH-1 displayed the interaction with ML40, but XJH-9, XJH-10, XJH-I 1, XJH-12, XJH-13, XJH-14, XJH-3, XJH-8, XJH-6, XJH-7, XJH-15, XJH-16 and XJH-2 did not bind to ML40. Both qualification and quantification characterizations of the binding were determined. The affinity of the four compounds was valued by the binding constant, which was similar with the results of chemotactic experiments. The established CEZ method is capable of sensitive and fast screening for a series of lactam analogs in the drug discovery for allergic inflammation diseases.
