Green Chemistry Approach to Fast and Highly Efficient One-Pot Synthesis of Bis-Isoxazolyl-1,2,5,6-Tetrahydro Pyridine-3-Carboxylates

The synthesis of the bis-isoxazolyl-1,2,5,6-tetrahydro pyridine-3-carboxylates is achieved in high yield without the production of toxic waste products by using room temperature ionic liquid (RTILs) triethyl ammonium acetate (TEAA). The RTIL TEAA played the dual role of efficient green solvent as well as recyclable catalyst.

Synthesis and Anti-influenza Virus Activity of Ethyl 6-Bromo-5-hydroxyindole-3-carboxylate Derivatives

A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.

Synthesis of (2S,4S)-2-Substituted-3- (3-Sulfanylpropanoyl)-6- Oxohexahydropyrimidine-4-Carboxylic Acids as Potential Antihypertensive Drugs

Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.

A Facile Synthesis of 9,10-Dimethoxybenzo[6,7]- ox-epino[3,4-<i>b</i>]quinolin-13(6<i>H</i>)-one and Its Derivatives

A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.

Synthesis, Reactions and Characterization of 1,1’-(1,4-Phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(ethan-1-one)

Reaction of 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile) (1) with methyl iodide afforded the 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-(methylthio)nicotinonitrile) (2). The reaction of 2 with hydrazine hydrate followed by diazotization reaction af-forded the 1,1’-(1,4-phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(e-than-1-one) (3) and 1,1’-(1,4-phenylenebis(3-(chlorodiazenyl)-6-methyl-1H-pyrazolo[3,4-b]-pyridine-4,5-diyl))bis(ethan-1-one) (4) respectively. On the other hand, reaction of 4 with malononitrile, 2-cyanoethanethioamide, ethyl acetoacetate, acetyl acetone, ethyl benzoylacetate, diethylmalonate, ethyl cyanoacetate and phenacylbromide aiming to build up pyrazolotriazine or pyrazole ring on the ring system of 4. Structures of all newly synthesized heterocyclic compounds in the present study were confirmed by considering the data of IR, 1H NMR, mass spectra as well as that of elemental analyses.

Two 1-(6'-O-acyl-β-D-glucopyranosyl)pyridinium-3-carboxylates from the flower buds of Lonicera japonica

Two new l-（6＇-O-acyl-β-D-glucopyranosyl）pyridinium-3-carboxylates,lonijaponinicotinosides A（1）and B（2）,were isolated from an aqueous extract of the flower buds of Lonicera japonica.Their structures were determined by spectroscopic data analysis,and confirmed by comparison with synthetic 1-β-Dglucopyranosylpyridinium-3-carboxylate.

Novel plant activators with thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate scaffold: Synthesis and bioactivity

The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were designed and synthesized and their biological activity as plant activators was studied.The structures of the novel compounds were identifed by1H NMR,19F NMR and HRMS.The in vivo bioassay showed that these novel compounds had good effcacy against seven plant diseases.Especially,compounds 1a and 1c were more potent than the commercialized plant activator BTH.Almost no fungicidal activity was observed for the active compounds in the in vitro assay,which matched the requirements as plant activators.

Pre-clinical evaluation of a new indirectly labeled 99mTc-6-hydrazinopyridine-3-carboxylic acid （HYNIC）-depreotide with HYNIC as bifunctional chelator

Background Technetium-99m or 99mTC is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new 99rnTc-6-hydrazinopyridine-3-carboxylic acid （HYNIC）-depreotide, indirect 99rnTc labeling of depreotide using HYNIC as a bifunctional chelator. Methods The cyclopeptide, cyclo-[（N-Me） Phe-Tyr-D-Trp-Lys-VaI-Hcy], the linear peptide, and [CICH2-CO.^-Dap-Lys- Cys-Lys-amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with egmTc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new 99mTc-HYNIC-depreotide was tested by high-performance liquid chromatography （HPLC）. The internalization and externalization rates of the new 99mTc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1. Results The molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of 99mTc-HYNIC-depreotide was highest at pH 6.0 and 15℃, about （70.95±0.84）%. The labeling rate of the new 99mTc-HYNIC-depreotide rose to a peak of （20.75±0.48）% at 60 minutes in A549 cells at 37℃ and decreased slightly later, while it elevated gradually during the time course at 4℃ and 25℃. The internalization rate of the new 99rnTc-HYNIC-depreotide at 37℃ increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new 99mTc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new 99mTc-HYNIC-depreotide demonstrated a high tumor uptake of （4.05±0.04）% ID/g at 1.5 hpi and remained high （（2.51±0.06）% ID/g） at 4 hpi. The tumor-to-lung activity concentration ratio （T/Lu） was very high for the new 99mTc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity （T/Mu） and tumor-to-blood activity concentration ratios （T/BI）. Conclusion The findings suggested that the new 99mTc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.