Small molecule sodium ion channel blockers with a pharmacophore of a-aminoamide have exhibited anti-allodynia effects on neuropathic pain. A library of new a-aminoamide derivatives containing a scaffold of substituted...Small molecule sodium ion channel blockers with a pharmacophore of a-aminoamide have exhibited anti-allodynia effects on neuropathic pain. A library of new a-aminoamide derivatives containing a scaffold of substituted benzene were designed and synthesized. These compounds were evaluated in mice formalin model and they exhibited significant analgesic activities. However, the anti-allodynia mechanism of these compounds remains unclear; some of the target compounds can only moderately inhibit the sodium ion channel, Navl.7, in a whole-cell patch clamp assay. These results suggest that introduction of the moiety of substituted benzene to a-aminoamide derivatives can improve their bioactivity and further study is warranted.展开更多
Novel liver-specific nitric oxide(NO) releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-Ohydrox...Novel liver-specific nitric oxide(NO) releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-Ohydroxyl alkyl derivatives,with the intact 24-COOH being preserved for hepatocyte specific recognition.Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride.The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change.Co-administration of ursodeoxycholic acid(UDCA) significantly antagonized the increase of nitrate in the liver resulted by administration of 1e.展开更多
基金the Beijing Municipal Science and Technology Project(No.Z131100002713004)National Science and Technology Major Project of China(No.2012ZX09301003)
文摘Small molecule sodium ion channel blockers with a pharmacophore of a-aminoamide have exhibited anti-allodynia effects on neuropathic pain. A library of new a-aminoamide derivatives containing a scaffold of substituted benzene were designed and synthesized. These compounds were evaluated in mice formalin model and they exhibited significant analgesic activities. However, the anti-allodynia mechanism of these compounds remains unclear; some of the target compounds can only moderately inhibit the sodium ion channel, Navl.7, in a whole-cell patch clamp assay. These results suggest that introduction of the moiety of substituted benzene to a-aminoamide derivatives can improve their bioactivity and further study is warranted.
基金supported by the National High Technology Research and Development (863) Project (No. 2006AA02A4C6)National Natural Science Foundation of China (Nos. 30572220 and 30972626)
文摘Novel liver-specific nitric oxide(NO) releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-Ohydroxyl alkyl derivatives,with the intact 24-COOH being preserved for hepatocyte specific recognition.Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride.The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change.Co-administration of ursodeoxycholic acid(UDCA) significantly antagonized the increase of nitrate in the liver resulted by administration of 1e.