Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide,and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds in...Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide,and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration(IC_(50)) values ranging from2.9 μmol/L to 21.4 μmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy to improve the Nav1.7 inhibition of ralfinamide analogues. Compound 19h was efficacious in antinociception in the mouse spared nerve injury(SNI) model of neuropathic pain without causing sedation in the open field test.展开更多
A series of 4-anilino-6-phenylpyrimidines containing urea moiety were synthesized and the structures of all products were confirmed by^(1)H NMR,^(13)C NMR and HRMS.The antiproliferative activities of these compounds w...A series of 4-anilino-6-phenylpyrimidines containing urea moiety were synthesized and the structures of all products were confirmed by^(1)H NMR,^(13)C NMR and HRMS.The antiproliferative activities of these compounds were evaluated against three human tumor cell lines(MGC-803,MCF-7 and EC-109)by applying the MTT assay method.compounds 4a,4b and 6a showed the most effective activity,among which,6a was more cytotoxic than 5-fluorouracil against all tested human cancer cell lines with IC_(50) values ranging from 1.80 to 2.72μmol·L^(-1).展开更多
基金Financial supports by National Natural Science Foundation of China (Nos. 82003565 and 81973162)the Science and Technology Commission of Shanghai Municipality (No. 20S11902300,China)。
文摘Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide,and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration(IC_(50)) values ranging from2.9 μmol/L to 21.4 μmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy to improve the Nav1.7 inhibition of ralfinamide analogues. Compound 19h was efficacious in antinociception in the mouse spared nerve injury(SNI) model of neuropathic pain without causing sedation in the open field test.
基金This work was supported by the National Natural Science Foundation of China(Nos.81172937,U1204206)China Postdoctoral Science Foundation(Nos.20100480857,201104402)New Teachers’Fund for Doctor Stations,Ministry of Education(No.20114101120013).
文摘A series of 4-anilino-6-phenylpyrimidines containing urea moiety were synthesized and the structures of all products were confirmed by^(1)H NMR,^(13)C NMR and HRMS.The antiproliferative activities of these compounds were evaluated against three human tumor cell lines(MGC-803,MCF-7 and EC-109)by applying the MTT assay method.compounds 4a,4b and 6a showed the most effective activity,among which,6a was more cytotoxic than 5-fluorouracil against all tested human cancer cell lines with IC_(50) values ranging from 1.80 to 2.72μmol·L^(-1).
