A new isochroman-4-one derivative from the peel of Musa sapientum L.and its total synthesis

A new isochroman-4-one, 7,8-dihydroxy-3-methylisochroman-4-one was isolated from water soluble fraction of Musa sapientum L. Its structure was determined by spectroscopic evidences and its total synthesis has also been reported. The compound showed potent antihypertensive activity.

Quantum Chemical Studies on the Corrosion Inhibition of Mild Steel by Piperidin-4-One Derivatives in 1 M H₃PO₄

The corrosion inhibition properties of 2,6-diphenylpiperidin-4-one (DPP) (1A) and 2,6-diphenyldihydro-2H-thiopyran-4(3H)-one (DPDT) (1B) for mild steel in 1 M phosphoric acid were studied using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopic techniques. The effect of temperature on the corrosion behavior of mild steel has been examined in the temperature range 303 - 328 K. The inhibition efficiency increases with increasing inhibitor concentration but decreases with increasing temperature. Potentiodynamic polarization studies indicated the mixed nature of inhibitors. The adsorption of the inhibitors on mild steel surface obeyed the Langmuir adsorption isotherms. The density functional theory (DFT) at the B3LYP/6- 31G (d) basis set level was performed on 1A and 1B to investigate the correlation between molecular structure and the corresponding inhibition efficiency (%). The quantum chemical parameters such as EHOMO, ELUMO, the energy gap (E), hardness (η), softness (S), dipole moment (μ), electron affinity (A), ionization potential (I), the absolute electronegativity (χ), the fraction of electron transferred (N), electrophilicity index (ω), the back-donation (EBack-donation) and Mulliken population analysis have been calculated.

Design and Synthesis of 3,4-Dihydropyrrolo[2, 1-c][1, 4]oxazin-1-oneand its 7-Acyl Derivatives

Starting from 1H-pyrrole, unreported 3, 4-dihydropyrrolo[2, 1-c][l, 4]oxazin-1-one 4, 7-(4-chlorobenzoyl)-3, 4-dihydropyrrolo[2, 1-c][1, 4]oxazin-1-one 5 and 7-benzoyl-3, 4-dihydro-pyrrolo [2, 1-c][1, 4]oxazin-1-one 9 were designed and synthesized. They may have antipyretic and analgesic activities.

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.

1,5-Dimethy-4-[(3-nitro-benzylidene)-amino]-2-pheyl-1,2-dihydro-pyrazol-3-one

The title compound C18H16N4O3 （Mr = 336.35） has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The Schiff base compound is a derivative of 4-aminoantipyrine. As expected, the molecular structure adopts a trans configuration about the central C=N double bond. It crystallizes in orthorhombic, space group P2dc with a = 7.632（1）, b = 7.816（1）, c = 28.082（5） A,β = 96.18（1）°, V= 1665.48（51） A^3, Z= 4, Dc = 1.341 g/cm^3, F（000） = 704,μ = 0.094 mm^-1, the final R = 0.0448 and wR = 0.1058. Of the total 3748 collections, 3105 were unique. In the molecule there exist two different planes of pyrazoline and C（11）-C（16） phenyl ring, which are approximately coplanar （r.m.s. de deviation from the combined mean plane is 0.03 A） with the dihedral angle between them of 9.8%.

4-[(Furan-2-ylmethylene)-amino]-1,5-dimethyl-1,2-dihyl-1,2-dihydo-pyrazol-3-one

The title compound （C16H15N3O2, Mr= 281.31） has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The Schiff base compound is a derivative of 4-aminoantipyrine. As expected, the molecular structure adopts a trans configuration about the C=N double bond. It crystallizes in the monoclinic system, space group P2 1/c with a = 11.150（3）, b = 9.906（3）, c = 13.624（4） A, β = 106.360（4）°, V= 1443.9（7） ,A^3, Z = 4, Dc = 1.294 g/cm^3, F（000） = 592,μ（MoKa） = 0.088 mm ^-1, R = 0.0577 and wR = 0.1214. Of the 5766 total reflections, 2540 were unique. In the molecule there exist two different planes of pyrazoline and O（2）-C（10） phenyl ring, which are approximately coplanar （r.m.s. de deviation from the combined mean plane is 0026 A） with the dihedral angle between them of 6.3°.

Synthesis and antiviral activities of novel 1,4-pentadien-3-one derivatives bearing an emodin moiety

A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus（TMV） and cucumber mosaic virus（CMV） in vivo were evaluated. Some of the derivatives displayed promising curative effect and protective activity against TMV. Compound D5 showed appreciable curative bioactivity on TMV approximately of 50% at 306.2 mg/m L, which was superior to ningnanmycin（409.3 mg/m L）.

Design, synthesis, and biological evaluation of quinazolin-4(3H)-one derivatives co-targeting poly (ADP-ribose) polymerase-1 and bromodomain containing protein 4 for breast cancer therapy

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly(ADP-ribose)polymerase-1(PARP1)and bromodomain containing protein 4(BRD4),which had important cross relation in the global network of breast cancer,reflecting the synthetic lethal effect.A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragmentbased combinatorial screening and activity assays that together led to the chemical optimization.Among these compounds,19 d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1,respectively.Compound 19 d was further shown to efficiently modulate the expression of BRD4 and PARP1.Subsequently,compound 19 d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase.Following pharmacokinetic studies,compound 19 d showed its antitumor activity in breast cancer susceptibility gene 1/2(BRCA1/2)wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight.These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.

Design,synthesis characterization and in vitro biological activity of a series of 3-aryl-6-(bromoarylmethyl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as the novel acetylcholinesterase inhibitors

Bromination is used as a strategy to improve biological activity in medicinal chemistry.In order to study on the structure-activity relationships of the novel acetylcholinesterase inhibitors with 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one scaffold,based on our previous work and molecular modeling,a series of novel 3-aryl-6-（bromoarylrnethyl）-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were designed by molecular docking,synthesized and characterized by mass spectra,infrared spectra,proton NMR and elemental analyses.The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control.Most of all target compounds exhibited more than 45%inhibition at 10μmol/L.The preliminary structureactivity relationship was the bromine atoms and the hydroxyl group at the phenyl ring at the C6 position of the parent nucleus played significant roles in the AChE inhibitory activity of the target compounds.

Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists

A series of tri-substituted chiral pyrrolidin-2-one derivatives have been designed and synthesized as CC chemokine receptor 4 （CCR4） antagonists. The structure of CCR4 was built by homology modeling. Asymmetric synthesis was applied to synthesize the R,R configuration chiral pyrrolidin-2-one scaffold. The stereoisomeric con- figurations of the compounds were identified by 2D I H-~H COSY spectroscopy and 1D NOESY spectroscopy. This method was more economical and convenient than traditional X-ray single crystal diffraction. In addition, the inter- actions between these compounds and the N-terminal extracellular tail of CCR4 were studied using capillary zone electrophoresis. The CCR4 chemotaxis inhibition effect was tested in CCR4-transfected HEK293 cells. Several compounds showed potent activities as CCR4 antagonists. Among these compounds, lc is the most active one. Its apparent binding constant of CZE experiment result is （1.569±0.11）× 10s L·mol ^-1, and its percentage inhibition of the HEK293/CCR4 cells migration with the concentration of I gmol·L ^-1 in DMSO is 59%. And compound If has slightly higher affinity to N-terminal of CCR4 according to its apparent binding constant than lb because of the in- troduced ester linkage. Further studies on the mechanism of these compounds are in progress.

Design, Synthesis, Inhibiting HDACs Ability and Antitumor Activity of Pyrimidin-4（3H）-one Hydroxamate Derivatives

A series of novel pyrimidin-4（3H）-one hydroxamate derivatives was designed, synthesized and studied for their activities against histone deacetylases（HDACs）. The results indicate that all the compounds show HDACs inhibitiory activity. The antiproliferative activities of the compounds against HeLa and A549 cells were also investigated. The pharmacological results show compound 9g has potent activity in the enzymatic inhibition assay and cell-based assay.

A Direct Route to Tetrahydropyridazine Derivatives via DMAP-Catalyzed [4+2] Annulation of Allenoates with Arylazosulfones

Herein,a DMAP-catalyzed[4+2]annulation ofα-substituted allenoates with arylazosulfones is reported,which affords facile access to tetrahydropyridazine derivative in synthetically useful yields.This reaction features mild conditions and good functional group tolerance.Moreover,the resultant products can be readily transformed into pyridazin-3-one derivatives in the presence of DDQ.

An effcient one-pot multi-component synthesis of 3,4,5-substituted furan-2(5H)-ones catalyzed by tetra-n-butylammonium bisulfate

A facile one-pot synthesis of 3,4,5-substituted furan-2（5H）-one derivatives from a three-component reaction of aniline derivatives, dialkylacetylenedicarboxylates and aromatic aldehydes under mild conditions using tetra-n-butylammonium bisulfate as a catalyst has been developed.