Synthesis, Crystal Structure and Biological Activities of 3-[2-(4-Fluoro-phenyl)-ethyl]-5-methyl-4-hydroxyl-4-methyl-7-methylsulfanyl-3,4-dihydro-pyrido[4,3-d]pyrimidine-8-carbonitrile

The title compound, 3-[2-（4-fluoro-phenyl）-ethyl]-5-methyl-4-hydroxyl-4-methyl- 7-methylsulfanyl-3,4-dihydro-pyrido[4,3-d]pyrimidine-8-carbonitrile, has been prepared and detemined by single-crystal X-ray diffraction. The crystal belongs to the triclinic system, space group P1 with a = 6.8754（8）, b = 10.2617（12）, c = 13.3491（16） A, α = 93.163（2）, β = 96.704（2）, γ = 102.421（2）°, V= 910.35（19）A^3, Z= 2, Mr= 370.44, Dc= 1.351 g/cm^3,μ = 0.203 mm^-1,F（000） = 388, the final R = 0.0573 and wR = 0.1497. X-ray analysis reveals that the pyridine and pyrimidine rings are almost coplanar.

Syntheses, Crystal Structures, and Antitumor Activities of Two 2-Trifluoromethyl-5,6,7,8-tetrahydrobenzo[4,5]-thieno[2,3-d]pyrimidin-4-amine Derivatives

Two novel 2-trifluoromethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two appropriate amines with 4-chloro-2-(trifluoromethyl)-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidine, which started from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile, trifluoroacetic acid(TFA) and phosphorous oxychloride by one-pot procedure. Their structures were determined by single-crystal X-ray diffraction. Compound 1, N-(furan-2-ylmethyl)-2-trifluoromethyl-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4-amine, crystallizes in the monoclinic system, space group C2/c with a = 26.352(3), b = 7.5991(8), c = 17.1423(18) A, β = 114.667(2)°, V = 3119.5(6) A3 and Z = 8. Compound 2, N-(3-silatranylpropyl)-2-trifluoromethyl-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4-amine, crystallizes in the monoclinic system, space group P21/n with a = 13.4394(13), b = 8.9446(9), c = 18.9657(18) A, β = 101.9640(10)°, V = 2230.3(4) A3 and Z = 4. The preliminary bioassay indicated that compound 2 exhibits more potent antitumor activity against BCG-823 than 5-fluorouracil(5-FU).

Synthesis,Crystal Structure and Antitumor Activities of Ethyl 5-methyl-4-morpholino-2-(3-Methyl-phenylamino)-furo[2,3-d] pyrimidine-6-carboxylate

The title compound （C21H24N4O4, Mr = 396.44） has been synthesized by the func- tionalized ethyl 4-chloro-6-methyl-2-arylamino-furo[2,3-d]pyrimidine-5-carboxylates and mor- pholine. Its structure was confirmed by means of 1H NMR IR, MS and elemental analysis. The crystal structure of the title compound was determined by X-ray single-crystal diffraction. The compound crystallizes in triclinic system, space group P1, a = 7.9919（8）, b = 9.9312（1）, c = 12.9380（13） A, aα = 86.987（2）, β = 83.604（2）, γ = 89.641（2）°, V = 1019.08（18） A3, Z = 2, F（000） = 420, Dc = 1.292 g/cm3,μ = 0.091 mm-1, R = 0.0602 and wR = 0.1548 for 3943 independent （Rint = 0.0639） and 3414 observed （I 〉 2σ（I）） reflections, lntermolecular N-H…O and π-π stacking interactions contributed to the stability of the structure. The preliminary biological test indicated the title compound exhibited cytotoxicity against human lung cancer cell lines.

Syntheses and Vasodilatory Activities of New Pyrazolo[4,3-d]pyrimidin-7-ones

A series of novel pyrazolo [ 4,3-d ] pyrimidin-7-ones was designed and synthesized in order to find new potent phosphodiesterase 5 inhibitors（PDE5）. The structures of all the compounds were confirmed by IR, ^1H NMR and MS; their in vitro vasodilatory activities were tested on isolated rabbit aortic spiral strips. Among them, compound X3 displays a significant vasodilatory activity, which is more potent than verapamil.

Syntheses, Crystal Structures, and Biological Activities of Two Enantiomeric 2-Trifluoromethylthieno[2,3-d]pyrimidin-4-amine Derivatives

Two enantiomeric 2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d] pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two chiral amines with 4-chloro-2-trifiuoromethyl-6,7-dihydro-5H-cyclopenta[4~5]thieno[2-3-d]pyrimidine, which started from 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, trifluoroacetic acid （TFA） and phosphoryl trichloride via one-pot procedure. Their structures were determined by single-crystal X-ray diffraction. Enantiomer （R）-3,（R）-N-（1-phenylethyl）-2-trifluoromethyl-6,7- dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system, space group P43 with a = 8.6847（6）, b = 8.6847（6）, c = 22.419（2） A, V= 1690.9（3） A3, Z = 4, Dc = 1.428 g/cm^3, p = 0.228 mm-1, F（000） = 752, the final R = 0.0463 and wR = 0.1257 for 3442 observed reflections with 1〉 20（/）. Enantiomer （S）-3,（S）-N-（1-phenylethyl）-2-trifluoromethyl-6,7-dihydro- 5H-cycloperita[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system, space group P41 with a = 8.688, b = 8.688, c = 22.421 A, V = 1692.4 A3, Z = 4, Dc = 1.426 g/cm^3, μ= 0.227 mm^-1, F（000） = 752, the final R = 0.0682 and wR = 0.1806 for 3182 observed reflections with ≥20（I）. The preliminary bioassay indicated that the R-enantiomer exhibits higher antitumor activity against MCF-7 than gefitinib.

A Three-Dimensional Ray Tracing Study on Whistler-Mode Chorus During Geomagnetic Activities

A three-dimensional ray tracing study of a whistler-mode chorus is conducted for different geomagnetic activities by using a global core plasma density model. For the upperband chorus, the initial azimuthal wave angle affects slightly the projection of ray trajectories onto the plane （Z, √（x^2 ＋ y^2））, but controls the longitudinal propagation. The trajectory of the upper-band chorus is strongly associated with the plasmapause and the magnetic local time （MLT） of chorus source region. For the high geomagnetic activity, the chorus trajectory moves inward together with the plasmapause. In the bulge region, the plasmapause extends outward, while the chorus trajectory moves outward together with the plasmapause. For moderately or high geomagnetic activity, the lower-band chorus suffers low hybrid resonance （LHR） reflection before it reaches the plasmapause, leading to a weak correlation with the geomagnetic activity and magnetic local time of the chorus source region. For low geomagnetic activity, the lower-band chorus may be reflected firstly at the plasmapause instead of suffering LHR reflection, exhibiting a propagation characteristic similar to that of the upper-band chorus. The results provide a new insight into the propagation characteristics of the chorus for different geomagnetic activities and contribute to further understanding of the acceleration of energetic electron by a chorus wave.

Synthesis and Vasodilatory Activities of New Pyrazolo[3,4-d] pyrimidin-4-one Derivatives

A series of pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and tested for vasodilatory activities. All of them were new compounds and their structures were confirmed by IR, 1H NMR, MS and elemental analysis.

Synthesis and Bronchodilatory Activities of New Pyrazolo[4,3-d]pyrimidin-7-ones

Twelve novel pyrazolo [4,3-d] pyrimidin-7-ones were synthesized and their structures were confirmed by IR, 1H NMR and MS. Their in vitro bronchodilatory activities were tested in guinea-pigs. The pharmacological results show that compound 11c has more potent activity than aminophylline.

Synthesis, Structure and Biological Activity of 2-[2-(4-Fluorobenzylidene)hydrazinyl]-4-(1-methyl-1H-indol-3-yl)thieno[3,2-d]pyrimidine

The title compound 2-[2-(4-fluorobenzylidene)hydrazinyl]-4-(1-methyl-1 H-indol-3-yl)thieno[3,2-d] pyrimidine(8) was synthesized by the condensation of 4-fluorobenzaldehyde(7) with 2-hydrazinyl-4-(1-methyl-1 H-indol-3-yl)thieno[3,2-d]pyrimidine(6). This intermediate was prepared from methyl 3-aminothiophene-2-carboxylate(1) by the condensation with urea, chlorination with phosphorus oxychloride and then condensation with hydrazine hydrate. The crystal of 8 belongs to monoclinic system, space group P21/c with a = 14.0453(18), b = 17.436(2), c = 18.0982(17) ? and β = 122.969(7)°. In addition, 8 possesses marked inhibition against the proliferation of human colon cancer cell line HT-29(IC50 = 6.09 μM) and human gastric cancer cell line MKN45(IC50 = 3.04 μM), displaying promising anticancer activity.

Synthesis, Crystal Structure, and Biological Activity of 4-Chlorobenzaldehyde (2-trifluoromethylTrifluoromethyl-5,6,7,8-tetrahydrobenzo[4 ,5]-thieno[2,3-d]pyrimidin-4-yl)hydrazone Monohydrate

The novel title compound 4-chlorobenzaldehyde （2-trifluoromethyl-5,6,7,8- tetrahydro- benzo[4,5]thieno[2,3-d]pyrimidin-4-yl）hydrazone monohydrate （C18H14C1F3N4S.H20, Mr = 428.86） has been synthesized by a condensation reaction of 4-chlorobenzaldehyde with （2-trifuoromethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl）hydrazine, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21/c with a = 7.4252（7）, b = 26.344（2）, c = 10.3095（9） A, /3 = 109.407（2）~, V= 1902.0（3） A3, Z = 4, Dc = 1.498 g/cm^3, p = 0.356 mm-1, F（000） = 880, the final R = 0.0564 and wR = 0.1681 for 2343 observed reflections with I 〉 2o（/）. X-ray diffraction analysis reveals that the title hydrazone molecule is nearly planar except for the cyclohexene and trifluoromethyl moieties. In the crystal packing, the molecules form stacks by a three-dimensional framework, which results from intermolecular N（3）-H（3）...O（1）, O（1）-H（1B）...N（2）, O（1）- H（1B）...N（4） and O（1）-H（1A）...F（1） hydrogen bonds via water molecules together with π-π stacking interactions. Molecular geometry of the title compound in the ground state optimized by B3LYP functional with 6-311G＊＊ basis sets indicates that the calculations are in agreement with the experimental data. The preliminary bioassay suggested that the title compound exhibits relatively good fungicidal activity against Fusarium oxysporium fsp.vasinfectum and Dothiorella gregaria.

Synthesis, Crystal Structure, and Antitumor Activity of 1-(4-Methoxybenzylidene)-2-(1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)hydrazine Monohydrate

The novel title compound 1-（4-methoxybenzylidene）-2-（1-phenyl-6-trifluoromethyl- 1H-pyrazolo[3,4-d]pyrimidin-4-yl）hydrazine monohydrate （C20HisF3N60-H20, Mr = 430.40） has been synthesized by a four-step procedure including the cyclization, chlorination, hydrazinolysis and condensation reaction, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to orthorhombic, space groupPbca with a = 8.3779（13）, b = 17.607（3）, c = 26.774（4） A, V= 3949.2（11） A3, Z=8, Dc = 1.448 g/cm3, μ = 0.117 mm-l, F（000） = 1776, the final R = 0.0553 and wR = 0.1516 for 2354 observed reflections with 1 〉 2σ（/）. X-ray diffraction analysis reveals that the title compound is almost coplanar except for the trifluoromethyl and phenyl moieties. In the crystal packing, the molecules are linked by intermolecular O（lW）-H（1WA）-＂N（2）, O（1W）-H（1WA）.--N（4） and N（5）-H（5A）...O（lW） hydrogen bonds via water molecules and stacked through π-π stacking interactions. The preliminary bioassay suggested that the title compound exhibits relatively good antitumor activity against HepG2 and BCG-823.

云南省R&D经费投入结构动态研究

为研究云南省“十二五”以来R&D经费投入结构变化,分析R&D经费投入现状,并与全国,东、中、西部地区及临近省份进行了对比;从资金来源和资金配置视角,运用Cobb-Douglas效用函数及其修正模型对R&D经费投入结构展开动态分析。结果表明:云南省R&D经费投入结构不尽合理,资金来源中政府资金占比较低且呈下降趋势,资金配置中基础研究和应用研究投入不足,与最优结构偏离程度较大。针对存在的问题,提出持续加大政府R&D经费投入力度、围绕产业链提升基础研究和应用研究比重的建议。

Ultra-deep adsorptive removal of thiophenic sulfur compounds from FCC gasoline over the specific active sites of CeHY zeolite

Adsorption desulfurization performance of Na Y,HY and Ce HY zeolites is evaluated in a miniature fixedbed flow by model gasoline containing with thiophene,tetrahydrothiophene,2-methylthiophene,benzothiophene or mixed sulfur compounds.The structural properties of adsorbents are characterized by XRD,N2-adsorption and XPS techniques.Adsorption desulfurization mechanisms of these sulfur compounds over the specific active sites of adsorbents as a major focus of this work,have been systematically investigated by using in situ FT-IR spectroscopy with single and double probing molecules.Desulfurization experimental results show that the Ce HY adsorbent exhibits superior adsorption sulfur capacity at breakthrough point of zero sulfur for ultra-deep removal of each thiophenic sulfur compound,especially in the capture of aromatic 2-methylthiophene(about ca.28.6 mgS/gadsorbent).The results of in situ FT-IR with single probing molecule demonstrate an important finding that high oligomerization ability of thiophene or 2-methylthiophene on the CeHY can promote the breakthrough adsorption sulfur capacity,mainly resulting from the synergy between Br?nsted acid sites and Ce(III)hydroxylated species active sites located in the supercages of Ce HY.Meanwhile,the result of in situ FT-IR with double probing molecules further reveals the essence of oligomerization reactions of thiophene and 2-methylthiophene molecules on those specific active sites.By contrast,the oligomerization reaction of benzothiophene molecules on the active sites of Ce HY cannot occur due to the restriction of cavity size of supercages,but they can be adsorbed on the Br?nsted acid sites via protonation,and on Ce(III)hydroxylated species and extra-framework aluminum hydroxyls species via direct"S-M"bonding interaction.As to the tetrahydrothiophene,adsorption mechanism is similar to that of benzothiophene,except in the absence of protonation.The paper can provide a new design idea of specific adsorption active sites in excellent desulfurization adsorbents for elevating higher quality of FCC gasoline in the future.

Synthesis of Pyrroles and Condensed Pyrroles as Anti-Inflammatory Agents with Multiple Activities and Their Molecular Docking Study

We herein disclose a series of novel pyrrole derivatives as well as fused pyrrolopyridines 6a,b and 7a,b, pyrrolopyrazoles 8a, b, pyrrolo[2,3-d]pyrimidine derivatives 10a-d, 12a,b, 14a,b, 18a,b, 20a,b, 21a,b, 22a,b, 23a,b, 24a,b, 31a,b, 36a,b, 40a,b, pyrrolo[1,2,6]thiadiazine derivatives 19a,b, pyrrolotriazolopyrimidines 25a,b, 26a,b, 27a,b and 28a,b, pyrrolo[2,3-d][1,2,3]triazine derivatives 32a,b and pyrrolo[2,3-d][1,3]oxazine derivatives 39a,b as novel compounds. All compounds were evaluated for their anti-inflammatory, analgesic (compared to the reference drug Indomethacin) and antimicrobial activities (compared to the reference drug Ampicillin and Fluconazole). Compounds 4d, 5b-d, 6a,b, 9c,d, 10d, 12ab, 13b, 19a,b, 21b, 23b, 31a,b, 38b and 40a were found to be the most active anti-inflammatory drugs exhibiting potency ranging from 1 - 1.01 compared to the reference drug indomethacin. In addition to docking study of these highly active twenty compounds against the active site of cyclooxygenase-2 enzyme (COX-2), among the tested compounds, compounds 5d, 9d, 11b, 12a, 13b and 32a showed multiple activities;anti-inflammatory, analgesic and anti-bacterial activities.

Determination of contents of eight alkaloids in fruits of Macleaya cordata (Willd) R. Br. from different habitats and antioxidant activities of extracts

A reliable ultrasound-assisted extraction (UAE) method combined with HPLC-UV for quantification of eight active alkaloids in fruits of Macleaya cordata (Willd) R. Br. was developed. The optimization conditions of UAE were obtained by using Box-Behnken design of response surface methodology. Chromatography was carried out using a Kromasil C_(18) column by gradient elution with 0.1% phosphoric acid aqueous solution for HPLC-UV. All calibration curves showed good linear correlation coefficients (R^2>0.999 6) and recoveries (from 97.3% to 104.9%) were acceptable. 1,1-diphenyl-2-picrylhydrazyl (DPPH) method was employed to test the antioxidant activity of the extract from the samples. The proposed method was successfully applied to quantifying eight components in nine samples of M.cordata, and significant variations of alkaloid contents and antioxidant activity of the samples from different habitats were demonstrated. It presents a powerful proof for the selection of the best sources to extract eight kinds of alkaloids.

Influence of extraction solvents on antioxidant and antimicrobial activities of the pulp and seed of Anisophyllea laurina R.Br.ex Sabine fruits

Objective:To evaluate the influence of extraction solvents on antioxidant and antimicrobial activities of the pulp and seed of Anisophyllea laurina R.Br.ex Sabine fruits.Methods:The antibacterial activities of pulp and seed extracts were tested by using disk diffusion method against eight bacterial strains and three fungal strains.Total phenolic,flavonoid,monomeric anthocyanin and tannin contents,and antioxidant activities were determined by spectrometric methods.Results:The antioxidant analysis of pulp extract revealed the strong radical scavenging capacity and total phenolic content(4 329.66 mg of gallic acid/100 g),while seed extract showed the high antioxidant activity and total tannin content(5 326.78 mg catechin equivalent/100 g).Antibacterial and antifungal activities of methanol and ethanol extracts exhibited potent growth inhibitory activity against Aeromonas hydrophila,Bacillus subtilis,Escherichia coli O157:H7,Pseudomonas aeruginosa,Salmonella Typhimurium and Staphylococcus aureus ATCC 6538 with minimum inhibitory concentration values ranged from 125 to 250 μg/mL.However,seed extract had the strongest potential activity against Aspergillus niger and Candida albicans with minimum inhibitory concentration value of 500 μg/mL compared to pulp extract.Conclusions:Our results therefore demonstrated that ethanol and methanol extractions were more efficient in extracting antioxidants and bioactive compound in pulp and seed.These results support that these plant extracts can be used for the treatment of bacterial infections.

Synthesis, Crystal Structure and Antitumor Activity of 3,3-(1,4-Phenylene)-bisfuro[3,2-d]pyrimidin-4(3H)-ones

3,3-(1,4-Phenylene)-bis(polysubstituted furo[3,2-d]pyrimidin-4(3 H)-ones 3 were synthesized from the starting material of functionalized iminophosphorane 1 by aza-Wittig reaction. All of the title compounds were characterized by 1H NMR, MS and elemental analysis. Meanwhile, the single crystal of compound 3 c, C46H68N6O10, was also obtained and determined by X-ray crystallography. Crystal data: triclinic, space group P1, a = 9.0017(3), b = 10.5908(4), c = 14.0116(5) A, α = 108.582(2)°, β = 94.296(1)°, γ = 105.059(2)°, V = 1204.40(7) ?3, Z = 1, F(000) = 466, Dc = 1.193 g/cm3, μ = 0.084 mm-1, R = 0.0998 and wR = 0.2146 for 4213 independent reflections(Rint = 0.0689) and 2796 observed ones(I > 2σ(I)). The in vitro antitumor activities of compounds 3 a^3 c were preliminarily evaluated by the standard MTT assay.

Crystal Structure and Biological Activities of (R)-N′-[2-(4-Methoxy-6-chloro)-pyrimidinyl]-N-[3-methyl-2-(4-chlorophenyl)butyryl]-urea

The title compound （R）-N′-[2-（4-methoxy-6-chloro）-pyrimidyl]-N-[3-methyl-2-（4- chlorophenyl）butyryl]-urea has been synthesized, and its crystal structure and biological behaviors were studied. Crystallographic data： C17H18C12N4O3, Mr = 397.25, monoclinic, space group P21/c, a = 12.331（2）, b = 14.025（3）, c = 23.085（5） A, β = 99.607（4）°, Z = 8, V = 3936.2（13） A3, Dc = 1.341 g/cm^3, F（000） = 1648, R = 0.0718, wR = 0.1585 and/t（MoKα） = 0.353 mm^-1. The preliminary biological tests showed that the title compound has definite insecticidal and fungicidal activities.

Synthesis, Crystal Structure and Antitumor Activity of 4-(5-(2,6-Difluorophenyl)-1,3,4-oxadiazol-2-ylthio)-2-(trifluoromethyl)thieno[2,3-d]pyrimidine

The title compound 4-(5-(2,6-difluorophenyl)-1,3,4-oxadiazol-2-ylthio)-2-(trifluoromethyl)thieno[2,3-d]pyrimidine(C15H5F5N4OS2, Mr = 416.35) was designed and synthesized as antitumor agent, and its structure was determined by 1H NMR, 13C NMR, MS, elemental analysis and single-crystal X-ray diffraction. The crystal belongs to monoclinic system, space group P21/c with a = 9.904(2), b = 10.057(2), c = 16.595(3) ?, β = 100.000(3)°, V = 1627.9(6) ?3, Z = 4, F(000) = 832, Dc = 1.699 g/cm3, μ = 0.395 mm-1, R = 0.0468 and wR = 0.1255 for 4726 independent reflections(Rint = 0.0336) and 2847 observed ones(I > 2σ(I)). The in vitro antitumor activity of the title compound was preliminarily evaluated by the standard MTT assay.

A NEW OPTICALLY ACTIVE POLYURETHANE DERIVED FROM CHIRAL(2R,3R)(+)-DIETHYL L-TARTRATE AND DIISOCYANATE

Optically active polyurethane was synthesized by the polyaddition of (2R, 3R)-(+)-diethyl L-tartrate (DET), 4,4'-diphenylmethane diisocyanate (MDI) and polyethylene glycol (PEG) with various molecular weights at 60 degrees C in DMSO. The polymers were characterized by specific rotation, DSC and H-1 NMR spectra.