Design, Synthesis and Antifungal Activity of 6-Fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]-quinoline-2-carboxamide Derivatives

A series of 6-fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]quinoline-2-carboxamide derivatives was designed based on the bioisosterism and combination principle in drug design. The target compounds were synthesized from substituted aniline through Michael addition, cyclization, Mannich reaction and condensation with 4-substituted semicarbazides, and the structures were confirmed by mass spectrometry（MS） and 1H NMR. The antifungal assay was carried out in vitro by two-fold dilution. The result shows that all the compounds are of antifungal activities against the tested fungi at different levels.

The effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on fatty acid oxidation in hepatocytes isolated from neonatal piglets

In the present study, the effect of 5-aminoimidazole-4-carboxamide ribonucleoside （AICAR） on long-chain fatty acid oxidation by hepatocytes isolated from suckled neonatal pig liver （a low ketogenic and lipogenic tissue） was tested Incubation of hepatocytes with AICAR （0.5 raM） in the presence of ] mM of carnitine and 10 mM of glucose for 1 hour at 37℃ had no significant effect on total [1-14C]-palrnitate （0.5 mM） oxidation （14CO2 and 14C-Acid soluble products （ASP））. Consistent with the fatty acid oxidation, carnitine palmitoyltransferase I activity and inhibition of its activity by malonyI-CoA （10 MM） assayed in cell homogenate also remained constant. However, addition of AICAR to the hepatocytes decreased 14CO2 production by 18% compared to control （p 〈 0.06）. The reduction of labeled carboxylic carbon accumulated in C02 caused a significant difference in distribution of oxidative products between 14C02 and 14C-ASP （p 〈 0.03） compared with the control. It was also noticed that acetyI-CoA carboxylase （ACC） was increased by AICAR （p 〈 0.03）, indicating that ACC might drive acetyI-CoA toward fatty acid synthesis pathway and induce an increase in distribution of fatty acid carbon to 14C-ASP. Addition of insulin to hepatocyte incubations with AICAR did not change the oxidative product distribution between CO2 and ASP, but further promoted ACC activity. The increased ACC activity was 70% higher than in the control group when citrate was absent in the reaction medium and was 30% higher when citrate was present in the medium. Our results suggest that AICAR may affect the distribution of metabolic products from fatty acid oxidation by changing ACC activity in hepatocyte isolated from suckled neonatal piglets; however, the basis for the increase in ACC activity elicited by AICAR is not apparent.

Hydrothermal Synthesis,Crystal Structure and Magnetic Properties of a Novel Cobalt Complex Based on Biphenyl-3,3',4,4'-tetracarboxylate

A novel cobalt complex,[Co2（bptc）（bix）1.5]（1,H4bptc=3,3＇,4,4＇-biphenyltetra-carboxylic acid,bix = 1,4-bis（imidazol-1-ylmethyl）benzene）,has been hydrothermally prepared and characterized by IR spectroscopy,elemental analysis and single-crystal X-ray diffraction.The crystal is of triclinic system,space group P1 with a=10.770（7）,b=12.245（8）,c=13.514（9）,α=102.829（8）,β=107.734（8）,γ=98.833（9）°,C37H27N6O8Co2,Mr=801.51,V=1607.5（18）3,Dc=1.656g/cm3,F（000）=818,μ=1.100mm-1,Z=2,the final R = 0.0694 and wR = 0.1543 for 3034 observed reflections（I2σ（I））.In the title complex,the two Co（Ⅱ） ions are in different coordination environments with distorted octahedral and trigonal bipyramidal geometries,respectively.The Co atoms are linked together through hexadentate bptc ligands,giving rise to 2D layers which are bridged by the bix ligands into a 3-D supramolecular network.Magnetic susceptibilities of 1 reveal weak antiferromagnetic exchange interactions between the adjacent Co（Ⅱ） ions.

Synthesis, Structure and Electrochemical Property of a New 3D Ag(I) Coordination Polymer Constructed by Biphenyl-2,2ˊ,4,4ˊ-tetracarboxylate

A new 3D Ag（I） coordination polymer, [Ag8（btc）2（bpp）2]n（1, H4btc = biphenyl- 2,2ˊ,4,4ˊ-tetracarboxylic acid, bpp = 1,2-bis（4-pyridyl）propane）, has been hydrothermally synthesi- zed and characterized by single-crystal X-ray diffraction analysis, elemental analysis and IR spectroscopy. Complex 1 crystallizes in the triclinic system, space group P1 with a = 13.4899（8）, b = 13.4928（8）, c = 16.4575（10） , α = 102.7640（10）, β = 108.8100（10）, γ = 101.4940（10）°, V = 2644.1（3） 3, Z = 2, Dc = 2.401 Mg·m-3, μ = 2.978 mm-1, F（000） = 1840, the final R = 0.0481 and wR = 0.0955 for 6794 observed reflections with I 〉 2σ（I）. Complex 1 features a 3D framework formed by Ag（I）-carboxylate chains containing [Ag16（COO）16] secondary building block. Furthermore, thermal stability and electrochemical property of 1 are also investigated in detail.

Synthesis and anti-inflammatory-analgesic activity of 2',4'-difluoro-3-(carbamoyl)biphenyl-4-yl benzoates

Eighteen 2′,4′-difluoro-3-（carbamoyl）biphenyl-4-yl benzoates were synthesized from diflunisal in three steps with total yields from 72% to 86%. All compounds were identified by IR, 1^H NMR, MS and elemental analysis. The anti-inflammatory activity and analgesic activity for 18 compounds were evaluated. The preliminary assay results showed that compounds 4a and 4p exhibited potent anti-inflammatory-analgesic activity.

Synthesis and Characterization of Cr(III) &Fe(II) Bis(2-Methoxybenzylidene)Biphenyl-4,4'-Diamine Complexes

Bis(2-methoxybenzylidene)biphenyl-4,4'-diamine Schiff base was prepared by the reaction of benzidine and O-methoxy benzaldehyde 1:2 reaction. Two complexes of this ligand with Cr(III) and Fe(II) were prepared. All prepared compounds were analysed using elemental analysis, IR, 1H NMR and mass spectroscopy. The formation of proposed structures, including the free ligand and complexes were confirmed.

Synthesis and Crystal Structure of N-(Biphenyl-2-thiocarbamoyl)-4-(1,3-dichlorophenyl) Carboxamide

The synthesis of the title molecule was achieved by the reaction of 2,4-dichloro- benzoyl chloride with potassium thiocyanate in 1：1 molar ratio in dry acetonitrile to afford the corresponding isothiocyante in situ followed by the treatment with 2-aminobiphenyl. The structure of the target compound was established by elemental analysis, FTIR, 1H, 13C NMR and mass spectroscopy and unequivocally confirmed by the crystallographic data. The title compound crystallizes in the monoclinic space group P21/n with a = 13.356（2）, b = 7.0761（11）, c = 20.539（3） A, β = 105.723（4）°, V= 1868.5（5） A3 and Z = 4.

Syntheses, Structures, and Properties of Three Coordination Polymers: [Cd_2(bpp)_(1.5)(Hbpp)(phen)_2]_n, [Mn_3(Htptc)_2(phen)_2(H_2O)_2]_n, and {[Cu(btc)_(0.5)(1,4-bib)]·2H_2O}_n

Hydrothermal reactions of three aromatic polycarboxylic acids and the transitional metal cations in the presence of phen and 1,4-bib afford three new coordination polymers： [Cd2（bpp）1.5（Hbpp）（phen）2]n （1）, [Mn3（Htptc）2（phen）2（H2O）2]n （2）, and {[Cu（btc）0.5（1,4- bib）]·2H2O}n（3） （H2bpp = 2,6-bis（4＇-carboxyphenyl）-4-phenylpyridine, H4tptc = terphenyl-2,5,2＇,5＇-tetracar- boxylic acid, H4btc =biphenyl-2,2＇,4,4＇-tetracarboxylic acid, phen =1,10-phenanthroline, and 1,4-bib = 1,4-bis（1H-imidazol-1-yl）benzene）. Their structures have been determined by single- crystal X-ray diffraction analyses, elemental analyses, IR spectra, and powder X-ray diffraction （PXRD） analyses. In compound 1, the CdII cations are linked by bpp2- to form one ladder structure, based on which a 3D network is constructed with the help of non-covalent interactions. The topology of 2 is a 3D （3,4,5）-connected framework with the Point Schl？fli symbol of （42.6）2（43.62.8）（45.64.8）2. Compound 3 shows an unprecedented 3D （4,4）-connected framework with the Point Schl？fli symbol of （64.82）2（65.8）. Moreover, the luminescent property of 1 has been investigated.

Synthesis and anti-TMV activity of novel N-(3-alkyl-1H-pyrazol-4-yl)-3-alkyl-4-substituted-1H-pyrazole-5-carboxamides

In order to investigate the biological activity of novel bis-pyrazole compounds, a series of N-（3-alkyl-5-（N-methylcarbamyl）- 1H-pyrazol-4-yl）-3-alkyl-4-substituted-lH-pyrazole-5-carboxamides were designed and synthesized with ethyl 3-alkyl-lH-pyr- azole-5-carboxylate 1 as starting materials. N-Methyl-3-alkyl-4-amino-lH-pyrazole-5-carboxamides 6 were obtained from 1 via 5 steps. 3-Alkyl-4-substitued-lH-pyrazole-5-carboxyl chlorides 4a, 4b, lla, llb, llc or 12 were also obtained from 1 via several steps. Target compounds 7a-Tg were obtained after the reaction of 6 with the above 1H-pyrazole-5-carboxyl chlorides. Preliminary bioassay showed some compounds possessing good inactivation effect against TMV （tobacco mosaic virus）. Compound 7a showed higher activity superior to ningnanmycin at a concentration of 5.0 × 10^-4 g/mE and equal activity at 1.0 × 10^-4 g/mE; 7b and 7c showed equal activity to virazole both at concentrations of 5.0 × 10^-4 g/mE and 1.0 × 10^-4 g/mL.

Design, Synthesis and Evaluation of Substituted N-（3-Arylpropyl）-9,10-dihydro-9-oxoacridine-4-carboxamides as Potent MDR Reversal Agents in Cancer

A novel class of molecules with structure N-（3-arylpropyl）-9,10-dihydro-9-oxoacridine-4-carboxamides （20- 29） were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design software. The designed molecules were synthesized by a novel synthesis route and evaluated for their inhibitory effects on the transport activity of P-glycoprotein （P-gp） by standard Hoechst 33342 assay method. Based on the pIC50 values of ten title compounds screened, three compounds exhibited better activity as compared to Verapamil used as standard.

Design, synthesis and insecticidal activities of novel 1-substituted-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives

A series of novel 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives（6a–6n, 7a, 7b, and 8a-8f）were synthesised by placing the amide bond at the 4-position of the pyrazole ring. These derivatives differed from the structure of chlorantraniliprole analogues with the amide bond at the 5-position of the pyrazole ring. Preliminary bioassay results revealed that a few title compounds exhibited good insecticidal activities against lepidopteran pests, such as Plutella xylostella, Mythimna separate, Heliothis armigera, and Ostrinia nubilalis. Some title compounds also elicited broad-spectrum insecticidal activities against dipterous insects including Culex pipiens pallens after altering the amide position. Similar to pyrazole-5-carboxamide analogues, compounds 6b and 6e showed 100% insecticidal activity against P. xylostella, C. pipiens pallens, and M. separate at concentrations of 200, 2, and 200 mg/m L, respectively.This finding suggested that 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives are potential alternative insecticides for management of agriculture pests.

Regioselective Synthesis and Base Catalyzed Transacylation of Substituted 1H-Pyrazole-4-carboxamides

New type of substituted 1H-pyrazole-4-carboxamides were obtained byregioselective synthesis under the catalysis of different bases. The structures of the titlecompounds were confirmed by elemental analysis, ~1H NMR, IR, MS and X-ray crystallography. Compounds1 were transacylated into their corresponding amides 3 in the presence of sodium hydride.Preliminary bioassays indicated that some compounds showed fungicidal activities against Rhizoctoniasolani and Sclerotinia sclerotiorum.

AIC AR and Decitabine Enhance the Sensitivity of K562 Cells to Imatinib by Promoting Mitochondrial Activity

Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.

怀中1号鲜地黄化学成分研究

采用Toyopreal HW-40C、Sephadex LH-20、硅胶和半制备液相等多种色谱学技术从怀中1号鲜地黄中分离得到20个化合物。根据理化性质与波谱数据鉴定其结构,分别为3-methyl-2-(hydroxymethyl)-4H-pyrone-4-one(1)、3-氨基-2-吡啶乙醇(2)、(5’S)-2-oxo-N-phenylpyrrolidine-3-carboxamide (3)、焦谷氨酸甲酯(4)、吲唑(5)、尿苷(6)、腺苷(7)、rehmanalkaloid C (8)、1-(3-乙基苯基)-1,2-乙二醇(9)、(3-乙基苯基)-1,2-乙二醇(10)、2-羟甲基苯基-1-O-β-D-葡萄糖苷(11)、玉叶金花苷酸甲酯(12)、11-methylforsythide (13)、7-去氧栀子新苷(14)、1-O-α-L-鼠李糖苷(1→6)-β-D-吡喃葡萄糖苷(15)、6-deoxy-D-mannono-1,4-lactone (16)、富马酸单甲酯(17)、daphneresinol (18)、二氢槲皮素(19)、rhamnopyranosyl vaniloyl (20)。其中化合物1为新化合物,命名为3-methyl-2-(hydroxymethyl)-4H-pyrone-4-one,化合物2和3为新天然产物,化合物4、5、9~11、13、14以及16~19是从地黄属中首次分离得到的。

Microwave Irradiation for Accelerating Synthesis of Diarylimidizo[1,5-a]pyrimidine Based on Isoflavones

Microwave irradiation was used to accelerate the cyclocondensation of i soflavones and 5-amino-1H-imidazole- 4-carboxamide in the presence of sodium hydroxide to produce 3,4-diphenyl-imidazo[ 1,5-a]pyrimidines in good to moderate yields.