Synthesis, Crystal Structure and Antitumor Activity of (E)-4-tert-Butyl-N-(2,4-dichlorobenzylidene)-5-(1,2,4-triazol-1-yl)-thiazol-2-amine

The title compound （E）-4-tert-butyl-N-（2,4-dichlorobenzylidene）-5-（1,2,4-triazol-1-yl）-thiazol-2-amine was synthesized by the reaction of 4-tert-butyl-5-（1,2,4-triazol-1-yl）-thiazol-2-amine with 2,4-dichlorobenzaldehyde, and its crystal structure was determined by singlecrystal X-ray diffraction. The crystal belongs to the triclinic system, space group P1 with a = 7.9748（4）, b = 10.1803（5）, c = 11.4603（6）, α = 102.882（1）, β = 100.253（1）, γ = 104.457（1）°, V = 850.95（7）3, Z = 2, F（000） = 392, C16H15Cl2N5S, Mr = 380.29, Dc = 1.484 g/cm3, S = 1.095, μ = 0.512 mm-1, the final R = 0.0301 and wR = 0.0965 for 3334 observed reflections （I 〉 2σ（I））. The preliminary antitumor activity shows that for the title compound the IC50 of Hela is 0.175 μmol/mL and that of Bel7402 is 0.156 μmol/mL.

Synthesis, Crystal Structure and Antitumor Activity of 4-tert-Butyl-N-(2-fluorophenyl)-5- (1H-1,2,4-triazol-1-yl)-thiazol-2-amine

The title compound has been synthesized by the reaction of 1-bromo-3,3-dime- thyl- 1 - （1 H- 1,2,4-triazol- 1 -yl）butan-2-one with 1 -（2-fluorophenyl）thiourea, and its crystal struc- ture was determined by single-crystal X-ray diffraction. The crystal belongs to the orthorhombic system, space group Pbca with a = 15.2568（6）, b = 12.1533（5）, c = 16.7307（7） A, Z = 8, V = 3102.2（2） A3, Mr = 317.39, Dc = 1.359 g/cm3, S = 1.05, μ = 0.223 mm-1, F（000） = 1328, the final R = 0.034 and wR = 0.097 for 2590 observed reflections （I 〉 2σ（I））. X-ray crystal structure presents the intramolecular N-H…N hydrogen bond, which plays an important role in stabilizing the crystal structure. In addition, the preliminary biological test on the title compound shows good antitumor activity, with IC50 of 0.122 μmol/mL against the Hela cell line.

Synthesis, Crystal Structure and Antitumor Activity of 4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)-N-(2-hydroxy-3,5-diiodinebenzyl)-thiazol-2-amine

The title compound, 4-（tert-butyl）-5-（1 H- 1,2,4-triazol- 1 -yl）-N-（2-hydroxy-3,5-diio- dinebenzyl）thiazol-2-amine, was synthesized via the reduction of 4-（tert-butyl）-5-（1H-l,2,4- triazol-l-yl）-N-benzylidene-thiazol-2-amine with NaBH4, and its crystal structure was determined by single-crystal X-ray diffraction. The compound crystallizes in monoclinic system, space group P21/c with a = 7.91944（19）, b = 10.5250（3）, c = 24.4985（6） A, Z = 4, V = 2041.66（9） A3, Mr = 599.22, Dc = 1,949 Mg/m3, S = 1.120, p = 3.203 mm-1, F（000） = 1152, the final R = 0.0283 and wR = 0.0592 for 3490 observed reflections （I 〉 2σ（I））. X-ray analysis displays that the crystal water takes part in three intermolecular hydrogen bonds of O（2）-H（2A）…O（1）, O（2）-H（2B）…N（I） and N（5）-H（5）…O（2）, and an octatomic ring R^（8） is formed via intramolecular hydrogen bond of O（I）-H（IA）…N（4）. Furthermore, the I…I contacts are involved in stabilizing the overall three-dimensional network structure. The preliminary biological test shows the title compound has good antitumor activity with the IC50 value of 26 μM against the Hela cell line.

Synthesis, Crystal Structure and Antitumor Activities of N,N,1-Triphenyl-1H-benzo[d]imidazol-5-amine Derivatives

In order to discover the novel antitumor agents,a series of N,N,1-triphenyl-1Hbenzo[d]imidazol-5-amine derivatives were designed and synthesized,and the structures were characterized by IR,H-RMS,1H and 13C NMR.X-ray crystallography showed that 4c is in monoclinic system,space group P1 with a=9.209(2),b=9.533(3),c=14.097(3)?,β=102.069(3)°,V=1202.2(5)?3,Z=2,F(000)=528,μ=1.74 mm–1,S=1.024,the final R=0.0448 and wR=0.1109.The in vitro antitumor activities of target compounds were evaluated by MTT assay against human cancer cell lines K562,HL-60,HeLa and BGC-823.The target compounds demonstrated weak or moderate antitumor activities against these cell lines.

Two New d10 Supramolecular Polymers Constructed by 1H-Pyrazolo[3,4-b]pyridin-3-amine and 1,4-Benzenedicarboxylic Acids

Two new coordination polymers, [Cd(BDC)(HL)]n(I) and {[Zn(BDC)(HL)2]·(H2 O)}n(Ⅱ), have been synthesized under solvothermal conditions, based on 1 H-pyrazolo[3,4-b]pyridin-3-amine(HL) along with 1,4-benzenedicarboxylic acid(H2 BDC). Polymers I and Ⅱ have been characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction(PXRD) and single-crystal X-ray diffraction analysis. Polymer I features a two-dimensional 4-connected sql structure and further extends into a three-dimensional supramolecular framework directed by hydrogen-bonding interactions and π-π interactions. Polymer Ⅱ exhibits a layered packing supramolecular structure. Hydrogen bonding interactions involved between the free water molecules and carboxylate O atoms of H2 BDC ligands as well as the amino N atom of HL ligands play a critical role in constructing the three-dimensional supramolecular structure of Ⅱ. The solid-state photoluminescent properties of the two polymers were also investigated.

Facile Synthesis of [1,2,4]Triazolo[4,3-a]pyrazin-3-amines via Oxidative Cyclization of 1-(Pyrazin-2-yl)guanidine Derivatives

In this study, we applied a novel, mild, and convenient synthetic method involving the oxidative cyclization of 1-(pyrazin-2-yl)guanidine derivatives to produce [1,2,4]triazolo[4,3-a ]pyrazin-3-amines. We optimized the reaction procedure to easily obtain 5-chloro-[1,2,4]triazolo[4,3-a ]pyrazin-3-amine. Various types of halogenated pyrazines can successfully undergo this process. We synthesized a series of 1-(pyrazin-2-yl)guanidines and [1,2,4]triazolo[4,3-a ]pyrazin-3-amines, and then elucidated their structures based on their ~1H-NMR, ^(13)C-NMR, ESI-HRMS, and nuclear Overhauser effect spectra.

A New Mn(Ⅱ)Coordination Polymer Based on 1H-pyrazolo[3,4-b]pyridin-3-amine:Crystal Structure,Magnetic and Electrochemical Properties

A new polymer formulated as [Mn3（1,3-BDC）3（L）（H2O）3]（1） based on linear trinuclear unit Mn3（COO）6 has been synthesized under solvothermal conditions with 1,3-benzenedicarboxylic acid（1,3-H2BDC） and 1H-pyrazolo[3,4-b]pyridin-3-amine（L） as ligands. The polymer was characterized by the single-crystal X-ray diffraction analysis, infrared spectra, elemental analyses, power X-ray diffraction and TG analysis. It crystallizes in orthorhombic system, space group Pna21, with a = 7.9252（3）, b = 17.9740（8）, c = 22.3027（10）A°, Mr = 845.35, Z = 4, V = 3177.0（2）A°^3, F（000） = 1708, Dc = 1.767 g/cm^3, μ（Mo Kα） = 1.257 mm^-1, the final refinement give R = 0.0388 and w R = 0.0955 for 5595 reflections with I 〉 2σ（I）. The polymer 1 can be symbolized as a pcu topology based on the Mn3（COO）6 as a secondary building unit. Furthermore, the magnetic properties and electrochemical properties of 1 are also investigated.

Synthesis,Crystal Structure and Fluorescent Properties of 1-(4-(Dimethylamino)benzylidene)-4-(naphthalen-1-yl) Thiosemicarbazide

The title compound, 1-4-（dimethylamino）benzylidene）-4-（naphthalene-1-yl） thiosemicarbazide （DMABNTS, C20H20N4S, Mr = 348.47）, was synthesized and characterized by elemental analysis, 1R, ^1H NMR and MS. The crystal structure of DMABNTS with 1,4-dioxane （Diox, C4H8O2） solvent molecules （DMABNTS·2Diox, C28H36N4O4S, Mr = 524.67） was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic system, space group P21/c with a = 14.418（4）, b = 7.1702（19）, c = 28.350（7）°A,β= 101.154（6）°, V= 2875.4（13） °A^3, Z= 4, Dc= 1.212 g/cm^3, F（000） = 1120 and μ= 0.151 mm^-1. A total of 6458 reflections were collected, of which 4671 were unique. The structure was solved by direct methods and refined to the final R = 0.0732 and wR = 0.2127 for 3921 observed reflections （I〉 2σ（I））. There exist intermolecular hydrogen bonds （N（2）-H（2B）…S（1A）and N（1）-H（1A）…O（4B）） in the structure. The study of fluorescent properties ＇shows that DMABNTS emits bright solid-state fluorescence in the visible region and exhibits blue photoluminescence.

Synthesis and Crystal Structure of 4-Bromo-5-ethoxy-3-methyl-5- (naphthalen-1-yl)-1-tosyl-1H-pyrrol-2(5H)-one

The title compound 4-bromo-5-ethoxy-3-methyl-5-（naphthalen-l-yl）-l-tosyl-lH- pyrrol-2（5H）-one 1 （C24H22BrNO4S, Mr = 500.40） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in monoclinic, space group P21/n with a = 8.8562（15）, b = 18.118（3）, c = 14.055（2）A, β = 99.855（3）^o, V= 2221.9（6）A3, Z = 4, Dc = 1.496 g/cm^3,μ= 1.975 mm^-1, 2 = 0.71073A, F（000） = 1024, R = 0.0607 and wR = 0.1371.

Screening of chemokine receptor CCR4 antagonists by capillary zone electrophoresis

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.

Syntheses, Crystal Structures and Antibacterial Activities of Copper(Ⅱ) and Zinc(Ⅱ) Complexes Based on (E)-4-fluoro-2-((3-morpholinopropylimino)methyl)phenol

Two Schiff base complexes [Cu（L）2] （1） and [Zn（L）2]·3H2O（2） of （E）-4-fluoro-2-（（3-morpholino propylimino）methyl）phenol （HL） have been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. Crystal data for 1： triclinic, space group Pī with a=4.8000（10）, b=11.109（2）, c=13.921（3）,α=66.55（3）,β=80.35（3）,γ=81.09（3）°, V=668.2（2）3 , Z=1, Dc=1.477g/cm 3 , F（000）=311, and the final R=0.0744 and wR=0.1601 for 2301 observed reflections with I 〉 2σ（I）. And those for 2： monoclinic, space group P21 /c with a=14.789（3）, b=11.713（2）, c=18.846（4）,β=107.85（3）°, V=3107.4（11）3 , Z=4, D c=1.389 g/cm 3 , F（000）=1368, and the final R=0.0749 and wR=0.1348 for 5423 observed reflections with I 〉 2σ（I）. Both 1 and 2 are four-coordinated complexes, with a square-planar geometry of copper（Ⅱ） in 1 and a slightly distorted tetrahedral geometry of zinc（Ⅱ） in 2. An asymmetric unit consists of only one half of a Cu ion and one L ligand in 1, while an asymmetric unit is composed of one Zn ion, two L ligands and three water molecules in 2. Non-classical C-H···O and C-H F hydrogen bonds play important roles in the formation of a 1D chain of 1, but O-H O and O-H N hydrogen bonds play dominant roles in the self-assembly of a 3D network of 2. The antibacterial activities of 1 and 2 against B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. coli and E. cloacae have been evaluated by MTT method.

Conformational isomerization of N-(naphthalen-1-yl)-N-(phenyl(quinolin-3-yl)methyl)amide derivatives

A series of N-(naphthalen-1-yl)-N-(phenyl(quinolin-3-yl)methyl)amide derivatives were designed and synthesized as anti-Mycobacterium tuberculosis drugs. NMR spectra showed that two conformational isomers of these compounds exist in solution,which is not due to cis-trans isomerization of amide bond. We proposed that the spatial interactions between three large aromatic groups caused the conformational isomerization,which was supported by molecular modeling and X-ray diffraction.

促肾上腺皮质激素释放激素1型受体拮抗剂CP154,526潜在靶点预测研究

目的虚拟筛选促肾上腺皮质激素释放激素1型受体拮抗剂(CP154,526)的潜在作用靶点。方法本研究以CP154,526为研究对象,以PharmMapper服务器为工具,采用反向分子对接法筛选它的潜在靶点,并采用PyRx 0.8软件中Autodock vina进行正向分子对接验证。结果靶蛋白转甲状腺素蛋白(TTR)与CP154,526的打分排前,它们的药效团分子特征一致。CP154,526与TTR的核心氨基酸有相互作用。结论 TTR可能是CP154,526的作用靶蛋白之一。