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.

Synthesis and Crystal Structure of Ethyl 2-(6-(1,3-Dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) Butanoate

The title compound ethyl 2-（6-（1,3-dioxo-4,5,6,7-tetrahydro-lH-isoindol-2（3H）- yl）-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4（3H）-yl） butanoate 3 was synthesized by the reaction of ethyl 2-（6-amino-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4（3H）-yl） butanoate with 4,5,6,7- tetraydrophthalic anhydride, and its structure was determined by X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P2 1/n with a = 9.3469（2）, b = 16.7715（5）, c = 13.7153（4） A, β= 104.9680（10）°, μ = 0.107 mm^-1, Mr = 430.42, V= 2077.08（10） ,A3, Z= 4, Dc = 1.376 g/cm3, F（000） = 904, T= 296（2） K, R = 0.0508 and wR = 0.1478.

STUDIES ON THE SYNTHESIS OF D-GLUCURONIC ACID DERIVATIVES OF 2-BUTOXY-5-FLUORO-3H-4-PYRIMIDONE AND THEIR ANTICANCER ACTIVITIES

2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having 0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticancer activity tested.Their structures were confirmed by elementary analysis,IR spectra and ~1HNMR.

Comparison of Positron Emission Tomography Using 2-[^18F]-fluoro-2-deoxy-D-glucose and 3-deoxy-3-[^18F]-fluorothymidine in Lung Cancer Imaging

Background： The detection of solitary pulmonary nodules （SPNs） that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography （CT） imaging results remains a significant challenge. The 2-[^18F]-fluoro-2-deoxy-D-glucose （^18F-FDG） positron emission tomography （PET）/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[^18F]-fluorothymidine （^18F-FLT） in lung cancer PET/CT imaging. Methods： The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established （n = 12）, and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values （SUVs）, and Ki-67 proliferation marker expression were investigated. Results： The cell-tracer binding ratio for the A549 cells using the ^18F-FDG was greater than the ratio using 18F-FLT （P 〈 0.05）. The Ki-67 expression showed a significant positive correlation with the ^18F-FLT binding ratio （r = 0.824, P〈 0.01）. The tumor-to-nontumor uptake ratio of ^18F-FDG imaging in xenografts was higher than that of ^18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of ^18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of ^18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of ^18F-FDG and ^18F-FLT （r = 0.658, P〈 0.05 and r = 0.724, P〈 0.01, respectively）. Conclusions： The ^18F-FDG uptake ratio is higher than that of ^18F-FLT in A549 cells at the cellular level.^18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.

Propylphosphonic anhydride(T3P~) catalyzed one-pot synthesis of α-aminonitriles

The Strecker reaction was performed via a one-pot three component condensation of hetero aromatic/ aromatic aldehydes, secondary amines and trimetylsilyl cyanide in the presence of propylphosphonic anhydride （T3P） to accomplish the corresponding α-aminonitriles. The main advantages of this method are very short reaction time and excellent yields.