The title compound has been synthesized by the reaction of 4-tert-butyl-5-（1,2,4- triazol-1-yl）-2-aminothiazole with propionic anhydride, and its crystal structure was determined by single-crystal X-ray diffraction....The title compound has been synthesized by the reaction of 4-tert-butyl-5-（1,2,4- triazol-1-yl）-2-aminothiazole with propionic anhydride, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to the orthorhombic system, space group Pbca with α = 18.441（2）, b = 8.3284（9）, c = 19.257（2） A, Z = 8, V = 2957.5（5） A3, Mr = 279.37, Dc = 1.255 mg/m3, S = 1.033, μ =0.219 mm^-1, F（000） = 1184, the final R = 0.0349 and wR = 0.0876 for 2629 observed reflections （I 〉 2σ（I））. X-ray crystal structure presents the intermolecular N–H···N hydrogen bond, which plays an important role in stabilizing the crystal structure. The preliminary bioassay indicates that the title compound exhibits potent fungicidal activity against R. Solani （25 mg/L） with inhibition rate of 80.0%.展开更多
Propionamide complexes of rare earth chlorides were synthesized. Formula of the complexes is LnCl 3·3PA. The ligand is shown to behave as a normal amide donor with the oxygen of the carbonyl group coordinated to...Propionamide complexes of rare earth chlorides were synthesized. Formula of the complexes is LnCl 3·3PA. The ligand is shown to behave as a normal amide donor with the oxygen of the carbonyl group coordinated to the metal ions. Binary system composed of propionamide and aluminum alkyl shows higher activity and stereospecificity for butadiene polymerization. The cis 1,4 content of polybutadiene is more than 98%.展开更多
Na_(v)1.7 is considered a promising target for developing next-generation analgesic drugs,given its critical role in human pain pathologies.Although most reported inhibitors with strong in vitro activity and high sele...Na_(v)1.7 is considered a promising target for developing next-generation analgesic drugs,given its critical role in human pain pathologies.Although most reported inhibitors with strong in vitro activity and high selectivity share the aryl sulfonamide scaffold,they failed to demonstrate marked clinical efficacy.Therefore,exploring new Na_(v)1.7-selective antagonists is quite urgent to the development of next-generation analgesic drugs.Here,we report a highly effective 1H-indole-3-propionamide inhibitor,WN2,identified through an integrated drug discovery strategy.Notably,the structure of WN2 is quite different from previously reported aryl sulfonamide inhibitors.Molecular dynamics simulations and experimental findings reveal that the R configuration of WN2(WN2-R)is the preferred form(IC_(50)=24.7±9.4 nM)within the VSDIV pocket of Na_(v)1.7.WN2-R exhibits impressive analgesic effects in acute and chronic inflammatory pain,as well as neuropathic pain models in mice.Additionally,it displays favorable subtype selectivity and positive drug safety in acute toxicity studies.Pharmacokinetic studies indicate that WN2-R has high bioavailability(F=20.29%),highlighting its considerable potential for drug development.Our study establishes WN2-R as a novel Na_(v)1.7-selective inhibitor with a unique structural scaffold,offering a promising candidate for the next generation of analgesic drugs.展开更多
基金supported by the Natural Science Foundation of Hunan Province(No.12jj3012)
文摘The title compound has been synthesized by the reaction of 4-tert-butyl-5-（1,2,4- triazol-1-yl）-2-aminothiazole with propionic anhydride, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to the orthorhombic system, space group Pbca with α = 18.441（2）, b = 8.3284（9）, c = 19.257（2） A, Z = 8, V = 2957.5（5） A3, Mr = 279.37, Dc = 1.255 mg/m3, S = 1.033, μ =0.219 mm^-1, F（000） = 1184, the final R = 0.0349 and wR = 0.0876 for 2629 observed reflections （I 〉 2σ（I））. X-ray crystal structure presents the intermolecular N–H···N hydrogen bond, which plays an important role in stabilizing the crystal structure. The preliminary bioassay indicates that the title compound exhibits potent fungicidal activity against R. Solani （25 mg/L） with inhibition rate of 80.0%.
文摘Propionamide complexes of rare earth chlorides were synthesized. Formula of the complexes is LnCl 3·3PA. The ligand is shown to behave as a normal amide donor with the oxygen of the carbonyl group coordinated to the metal ions. Binary system composed of propionamide and aluminum alkyl shows higher activity and stereospecificity for butadiene polymerization. The cis 1,4 content of polybutadiene is more than 98%.
基金supported in part by the National Natural Science Foundation of China(22220102001,22303081,and 32371322)the China Postdoctoral Science Foundation(2022M722795)the Postdoctoral Fellowship Program of CPSF(GZB20230656).
文摘Na_(v)1.7 is considered a promising target for developing next-generation analgesic drugs,given its critical role in human pain pathologies.Although most reported inhibitors with strong in vitro activity and high selectivity share the aryl sulfonamide scaffold,they failed to demonstrate marked clinical efficacy.Therefore,exploring new Na_(v)1.7-selective antagonists is quite urgent to the development of next-generation analgesic drugs.Here,we report a highly effective 1H-indole-3-propionamide inhibitor,WN2,identified through an integrated drug discovery strategy.Notably,the structure of WN2 is quite different from previously reported aryl sulfonamide inhibitors.Molecular dynamics simulations and experimental findings reveal that the R configuration of WN2(WN2-R)is the preferred form(IC_(50)=24.7±9.4 nM)within the VSDIV pocket of Na_(v)1.7.WN2-R exhibits impressive analgesic effects in acute and chronic inflammatory pain,as well as neuropathic pain models in mice.Additionally,it displays favorable subtype selectivity and positive drug safety in acute toxicity studies.Pharmacokinetic studies indicate that WN2-R has high bioavailability(F=20.29%),highlighting its considerable potential for drug development.Our study establishes WN2-R as a novel Na_(v)1.7-selective inhibitor with a unique structural scaffold,offering a promising candidate for the next generation of analgesic drugs.
