Design,synthesis and biological evaluation of indole derivatives as novel inhibitors targeting B-Raf kinase

A series of novel indole derivatives were designed and synthesized and their inhibitory activity against B-Raf and HepG2 cell were also described. Among them, compounds 7a and 7b exhibited excellent potency, which showed the potential for further research as lead compounds.     

An Expeditious Synthesis of β-Indolylketones Catalyzed by p-Toluenesulfonic Acid (PTSA) Using Ultrasonic Irradiation

The investigation of the chemistry of indoles has been, and continues to be, one of the most active areas of heterocyclic chemistry.[1] In particular, β-indolylketones have received much attention as important building blocks for the synthesis of many natural products and other biologically active compounds.[2] In continuation of our work in the synthesis of indole derivates,[3] we describe the remarkable catalytic of PTSA as a cheaper catalyst in ultrasound-accelerated Michael reaction of indole with α, β-unsaturated ketones (2), which provide one of the most efficient routes to the synthesis of β-indolyketones. In all cases, the substitution on the indole nucleus occurred exclusively at the 3-position, and N-alkylation products have not been observed. In addition, the structure of 3a was further confirmed by single crystal X-ray crystallography.     

Design, synthesis and primary activity of thiomorpholine derivatives as DPP-IV inhibitors

Thirteen thiomorpholine-bearing compounds were designed and synthesized as dipeptidyl peptidase IV（DPP-IV） inhibitors, with natural and non-natural L-amino acids as the starting materials.Their structures were characterized by ¹H NMR,¹³C NMR and HR-MS.The target compounds were screened for the DPP-IV inhibition,and the preliminary SAR result was obtained.Particularly, compounds 4c,4d and 4f with good DPP-IV inhibition in vitro were further evaluated through a mouse oral glucose tolerance test （OGTT）.The preliminary result showed the potential value for further studies on those thiomorpholine-bearing compounds as DPP-IV inhibitors.     

Design, synthesis, and screen of cathepsin K inhibitors

We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e,9d,9p,9j and 9k (IC₅₀≤0.005μmol/L) were equal to or greater than that of the lead compound 9a.Less hydrophobic compounds showed weaker potency,which can be explained by the hydrophobic nature of the cathepsin K binding pockets.     

Synthesis and preliminary cytotoxic evaluation of substituted indoles as potential anticancer agents

A variety of indole derivatives were designed,synthesized and preliminarily evaluated for their in vitro cytotoxic activity in the A431 and H460 cell lines.All the compounds examined conferred unusual potency in a tumor cell cytotoxicity assay.The findings showed the indole derivatives would be a promising candidate for the development of new anticancer agents.     

Synthesis and biological evaluation of piperidyl benzimidazole carboxamide derivatives as potent PARP-1 inhibitors and antitumor agents

We have synthesized a series of compounds based on a piperidyl benzimidazole carboxamide structure,and tested their PARP-1 inhibitory activity,as well as cellular inhibitory activity.Some of them show great potency as PARP-1 inhibitors and antitumor activity,which are valuable for further research.In addition,the predicted ADME properties and proposed binding mode with PARP-1 of the compounds were obtained via computational simulation.     

Correlation between Chromatograph Capacity Factors and Structural Parameters of Indole Derivatives

1 INTRODUCTION thods with which the retention factor of a series of compounds could be predicted accurately[1, . In 2] The capacity factor of reversed phased high per- addition, indole and its derivatives have been widely formance liquid chromatograph (RP-HPLC) is a used in the synthesis of medical intermediate, co- basis for quantifying chromatograph peaks and se- loring agent and pesticide etc. Dai et al. have repor- parating compounds. And it has been universally ac- ted the relation…     

Design, Synthesis and Synergistic Effects of Novel Derivatives of Solanesol

To further explore the biological activities of solanesylamine derivatives,several novel solanesylpiperazinotriamines and their amides were designed and synthesized,the chemical structures of target compounds were confirmed by IR,1H NMR,MS,and element analysis.The in vitro antitumor activities of the synthetic compounds were assessed by MTT test on L1210 and CHO cells.The preliminary results showed that at low micromolar concentrations these compounds exhibit obvious toxicity against tumor cells,and the synergistic effect on clinical antitumor agent indicated that at noncytotoxic concentrations,they also evidently enhance the curative effect of vincristine(VCR).The synergistic effects of compounds 4a,4c,and 9 were even superior to that of reference compound N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-ethylenediamine(SDB).     

Silica-supported Thionyl Chloride-assisted Synthesis and Bioassay of Novel Tetrazinan-3-thione and 3-Oxo-pyrazolidine-4-carbonitrile Derivatives of Steroids

A series of tetrazinan-3-thione and 3-oxo-pyrazolidine-4-carbonitrile derivatives of steroids（1-3） were synthesized with silica-chloride as a heterogeneous catalyst.The synthesized compounds 4-9 were obtained in substantial yields.In vitro evaluation of anticancer and antioxidant activity of the synthesized compounds was carried out via 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） and 1,1-diphenyl-2-picrylhydrazyl（DPPH）assays,respectively.Compound 6 exhibited promising anti-proliferative activity towards a panel of cancer cell lines.The significant activity of compound 6 was further ascertained on structural,molecular modelling and docking studies.This study may provide a valuable insight into the further design and development of more potent biologically active compounds.     

SYNTHESIS AND CRYSTAL STRUCTURE OF WCu_4S_4Cl_2Py_6

<正> Introduction. In recent years, the di-, tetra-. hexa-nuclear mixed metal cluster compounds of tungsten have been studied. In these compounds, more stable (WO_4-nSn)~2- skeleton remains unchanged. So far the penta-, hepta- and other polynuclear cluster compounds of tungsten have not yet been found. We describe here the preparation and structure of a new pentanuclear tungstencopper mixed metal cluster compound WCu_4S_4Cl_2y_6     

A novel solid state Michael addition reaction of N-heterocyclic compounds containing active C-H bond

In this paper,a novel solid state Michael-type addition reaction of N-heterocyclic compounds containing the active-CH group was investigated.3-Methyl-l-phenyl-5-pyrazolone (MPP) and indole (In) reacted with 4-arylmethylene-3-methyl-l-phenyl-5-pyrazolone (1) hi the solid state at room temperature to give the corresponding adducts,aryl-4,4'-bis(5-hydroxy-3-methyl-l-phenyl-pyrazolyl) methane (2a-n) and l-aryl-l-(5'-hydroxy-3'-methyl-1'-phenyl-4'-pyrazolyl)-l-(3"-indolyl) methane (3a-n),respectively.This is a feasible method for preparing the compound which contains two heterocyclic groups on the same carbon.     

Solid state reactions of nitrogenous heterocyclic compounds (Ⅱ)——Solid state reactions of indole with carbonyl compounds

Solid state Michael addition reaction of indole with α,β-unsaturaled carbonyl compounds was carried out,by which a series of compounds containing three different heterocyclic groups binding to one carbon atom were obtained.In the presence of Lewis acid,indole could undergo the solid state condensation reaction with aromatic ketones and aldehydes or quinones.The solid state reaction showed higher selectivity and yield than solution reaction The structures of products were identified by IR,1H NMR,MS,elemental analysis and X-ray crystal analysis.The reaction mechanism was also proposed.     

THE STRUCTURE AND SYNTHESIS OF [MoFe_3S_4(Etadtc)·_5]MeCN

<正> INTRODUCTION. More and more models of active center were suggested with wide study on the MoFe-protain and FeMo-cofactor of nitrogenase. Most of them contain MFe_3S_(3+4) (M=Mo,Fe) cubane-type core, so a great interest has been focused on the Studies of MoFe_4, cubane-type compounds. The type species have been reported by holm et al. We have also made researches on the single cubane-like compounds. Here we describe the synthesis and structure of [MoFe_3S_4(Et_2dtc)_5MeCN (1).     

A STUDY ON MULTIPLE METAL TO METAL BONDS IN TRANSITION METAL COMPLEXES

<正> We report here the calculation on electronic structures of model compounds of dimetal tetracarboxylate M2(O2CH)4 (M=V, Cr, Mo) by means of a DPS8 computer CNDO program. On the basis of molecular orbital components and contour maps of wave functions the character of the multiple metal to metal bonds are analysed and discussed.     

No-solvent Condensation Reaction of Amino Acids and their Derivatives with Pyrandione

Pyrandione rings are contained within a number of natural products1, pharmaceutical intermediates2 and agrochemicals3. They have drawn great interest recently because some of them have high activity of inhibiting HIV protease4. We have reported the fungicidal activity of 15. Later we found that 2 also could inhibit S. Sclerotiorum (85.7% at a concentration of 500 ppm). This result led us to study the biological activity of the derivatives of this kind of compounds. We have synthesized a ser…     

Two Ni~Ⅱ/Cu~Ⅱ Coordination Polymers Based on Pyridyl-carboxylate Ligand: Synthesis,Crystal Structures and Magnetic Properties

Under hydrothermal conditions, the reactions of Ni~Ⅱ/Cu~Ⅱ ions with 3-(6-aminpyridinium-3-yl) benzoate(HL) afford two compounds [NiL 2]n(1) and [Cu L2(H2 O)]n(2). On the basis of X-ray diffraction analysis of the two compounds, the results show that compound 1 features one-dimensional(1 D) double-strand coordination arrays, while 2 presents the 63-hcb layers. Both compounds are further constructed into a 3 D supramolecular structure with the aid of weak secondary interactions. Thermal stabilities and magnetic properties of compounds 1 and 2 were also investigated.     

A SERIES OF TRINUCLEAR MOLYBDENUM CLUSTERS WITH LOOSE COORDINATION SITES

<正> The cluster compound Mo3S4[S2P(OEt)2]4(H2O) with a comparatively stable cluster core [Mo3(μ3-S)(μ-S)3]4+ and some labile ligands or loosely coordination sites has been already prepared successfully by a self-assembly reaction. Its surprising chemical reactivity in the reactions of substitution, addition, and oxidation has been noted and used widely for the syntheses of a series of new, trinuclear Mo cluster compounds, of which the structures of the 12 selected compounds characterized by X-ray diffraction analysis are exhibited in diagrams. Meanwhile, those compounds with the same cluster core [Mo3(μ3-S)(μ-S)2]4+ show two groups of characteristic IR bands at ~480 cm-1 for the Mo-(μ-S) vibration and -450cm-1. for the Mo- (μ3-S), and their selected bond distances are tabulated as well.In a cluster-catalyzed homogeneous process, it is important that clusters have loose coordination sites or are coordination unsaturated. In our further research on the medium-valence molybdenum clusters[1], we have foun     

Two New Schiff Bases Based on 5-Chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde: Syntheses,Crystal Structures and Properties

Two new Schiff bases based on 5-chloro-3-methyl-1-phenyl-1 H-pyrazole-4-carbaldehyde, namely, N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-4-morpholinoaniline(Ⅲa) and N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-3-fluoro-4-morpholinoaniline(Ⅲb), were synthesized and characterized by IR, LC-MS, 1 H NMR and 13 C NMR spectroscopy. Meanwhile, the three-dimensional configurations of the two title compounds were further characterized by single-crystal X-ray diffraction analyses. Both the compounds are thermodynamically stable trans-isomers. Moreover, the fluorescence properties and antioxidant activities against DPPH of the two target compounds have been investigated, and the results showed that the title compounds both have fluorescence performance and certain antioxidant activities against DPPH radical.     

Peptidase Activities of Tripeptidyl Peptidase Ⅰ(TPP Ⅰ): Exopeptidase and Endopeptidase

The defect of TPP Ⅰ causes a disease, late infantile neuronal ceroid lipofuscinosis(LINCL, CLN2). To investigate the bio-activity of tripeptidyl peptidase Ⅰ(TPP Ⅰ) from rat kidneys, the effects of digestion of angiotensin Ⅱ(Ang Ⅱ) and a synthetic endo-type substrate(Gly1-Lys-Pro-Iie-Pro5-Phe-Phe-Arg-Leu-Lys10) via TPP Ⅰ were analyzed by HPLC and TOF-MS. The data suggest that the degradation rate of Ang Ⅱ can reach 18.2% by the rat TPP Ⅰ and DRV(Asp-Arg-Val) can be released from N-termini of Ang Ⅱ within 16 h. In addition, the synthetic endo-type substrate is cleaved at the same position between Phe6 and Phe7. Accordingly, TPP Ⅰ shows two kinds of peptidase activities. One is a tripeptidyl peptidase activity and the other is a pepstatin insensitive carboxyl endopeptidase activity. Tripeptidyl peptidase activity and pepstatin insensitive carboxyl endopeptidase activity seem to be dual phases of one enzyme, TPP Ⅰ.     

Design,synthesis and antimicrobial activities of 1,2,3-triazole derivatives

Fifteen 1-(4-substituted phenyl)-4-(4-bromophenyl)-5-(halo-o-hydroxyphenyl)imino-1,2,3-triazoles were designed and synthesized based on rational combination of 1,2,3-triazoles and(halo)o-hydroxyphenyl group according to the superposition principle of reinforcement of biological activities.All the compounds were tested to an in vitro antimicrobial screening against M.a.and E.c..Compounds IIe-IIo exhibited more potent antimicrobial activities against M.a.and E.c.than triclosan and fluconazole,which provided valuable information to further study of novel antimicrobial research.