118-92-3

The reaction conditions for an enantiospecific synthesis of various N-aryl-oxazolidinones from N-aryl-carbamates and (R) or (S) epichlorohydrin were optimized. The N-aryl-oxazolidinones were applied to the synthesis of compounds of biological interest such as DuP 721, toloxatone and a linezolid analogue.

The invention relates to the field of organic functional new material chemicals, and discloses a novel process technology for preparation of a hydroxamic acid precursor body weight discharge method of a plurality of o-amino aromatic acids in the first time. These substances are well known dyes and pigment and pharmaceutical pesticide-related fields and have a wide range of critical fine chemicals.

A mild transition-metal- and photosensitizer-free photoredox system based on the combination of NaI and PPh3 was found to enable highly selective reduction of nitroarenes. This protocol tolerates a broad range of reducible functional groups such as halogen (Cl, Br, and even I), aldehyde, ketone, carboxyl, and cyano. Moreover, the photoredox catalysis with NaI and stoichiometric PPh3 provides also an alternative entry to Cadogan-type reductive amination when o-nitrobiarenes were used.

The development of chemoselective and heterogeneous earth-abundant metal catalysts is essential for environmentally friendly chemical synthesis. We report a highly efficient, chemoselective, and reusable single-site nickel(II) hydride catalyst based on robust and porous aluminum metal-organic frameworks (MOFs) (DUT-5) for hydrogenation of nitro and nitrile compounds to the corresponding amines and hydrogenolysis of aryl ethers under mild conditions. The nickel-hydride catalyst was prepared by the metalation of aluminum hydroxide secondary building units (SBUs) of DUT-5 having the formula of Al(μ2-OH)(bpdc) (bpdc = 4,4′-biphenyldicarboxylate) with NiBr2 followed by a reaction with NaEt3BH. DUT-5-NiH has a broad substrate scope with excellent functional group tolerance in the hydrogenation of aromatic and aliphatic nitro and nitrile compounds under 1 bar H2 and could be recycled and reused at least 10 times. By changing the reaction conditions of the hydrogenation of nitriles, symmetric or unsymmetric secondary amines were also afforded selectively. The experimental and computational studies suggested reversible nitrile coordination to nickel followed by 1,2-insertion of coordinated nitrile into the nickel-hydride bond occurring in the turnover-limiting step. In addition, DUT-5-NiH is also an active catalyst for chemoselective hydrogenolysis of carbon-oxygen bonds in aryl ethers to afford hydrocarbons under atmospheric hydrogen in the absence of any base, which is important for the generation of fuels from biomass. This work highlights the potential of MOF-based single-site earth-abundant metal catalysts for practical and eco-friendly production of chemical feedstocks and biofuels.

Abstract: A procedure for practical synthesis of CuNPs from CuSO4·5H2O is established, under appropriate reaction conditions, using rice (Oryza sativa) as an economic source of reducing as well as a stabilizing agent. Optical and microscopic techniques are employed for the characterization of the synthesized CuNPs and the sizes of the particles were found to be in the range of 8 ± 2 nm. The nanoparticles are used as a catalyst for chemoselective reduction of aromatic nitro compounds to corresponding amines under ambient conditions and water as a reaction medium. Graphic abstract: CuNPs are synthesized using hydrolysed rice and used as catalyst for chemoselective reduction of nitroarenes to their corresponding amines in water. [Figure not available: see fulltext.]

Developing and/or modifying fundamental chemical reactions using chemical industry-favorite heterogeneous recoverable catalytic systems in the water solvent is very important. In this paper, we developed convenient, green, and efficient approaches for the chemoselective reduction of nitroarenes, N-acetylation of arylamines, and one-pot reductive acetylation of nitroarenes in the presence of the recoverable heterogeneous carbon-supported palladium (Pd/C) catalytic system in water. The utilize of the simple, effective, and recoverable catalyst and also using of water as an entirely green solvent along with relatively short reaction times and good-to-excellent yields of the desired products are some of the noticeable features of the presented synthetic protocols. Graphic abstract: [Figure not available: see fulltext.].

Efficient reduction of nitro compounds into amines is an important industrial transformation. So, it is a great deal to design new catalysts for efficient reduction of the nitro compounds especially in water. In this work, a new magnetic Pd/activated carbon nanocomposite (CoFe2O4@Pd/AC) was synthesized via metal-impregnation-pyrolysis method. The CoFe2O4@Pd/AC was fully characterized by FT-IR, PXRD, FESEM, TEM, VSM, EDX-mapping and BET techniques. The results showed that CoFe2O4@Pd/AC is a highly reactive and easily recoverable magnetic catalyst for the reduction of the nitro compounds by using NaBH4 in water. For instance, aniline was obtained in high yield (99%) after 75 ?min at 25 ?C by using just 6 ?mg of the catalyst. In addition, CoFe2O4@Pd/AC was recovered by a simple magnetic decantation and it exhibits stable activity and remains intact during the catalytic process with no significant loss in activity (8 cycles).

The interaction of isomeric dinitrobenzenes (DNBs) with titanium(III), tin(II), and vanadium(II) chlorides, which are reducing agents used as electron carriers in the electrosynthesis of diaminobenzenes, has been studied. Rate constants of the reduction of isomeric DNBs and nitrophenylhydroxylamines by SnCl2 and TiCl3 in a 2 M water-alcohol solution (10 vol.% C2H5OH) of HCl were measured, and activation energies of the reduction of isomeric DNBs were determined. The rates of interaction of DNBs with the listed mediators increase in the series SnCl2 3 2. It is shown that the electrolysis of DNBs in the presence of an excess of these mediators makes it possible to obtain the corresponding diaminobenzenes with a yield of 60–90%.

A new heterogeneous catalyst was obtained by growing graphene quantum dots on chitosan and subsequent immobilization of Pd nanoparticles. The catalyst after characterization was used in the reduction of nitroarenes to the corresponding amines by NaBH4 as a weak reducing agent of nitro compounds. The catalyst exhibited excellent catalytic activity and selectivity under mild reaction conditions in water as a green solvent during 1?h. Additionally, the catalyst can be reused for five consecutive runs without any significant decrease in its activity and selectivity.

Many metal complexes are potent candidates as mitochondrial-targeting agents. In this study, four novel Zn(II) complexes, [Zn(BPQA)Cl2] (Zn1), [Zn(BPQA)(Curc)]Cl (Zn2), [Zn(PQA)Cl2] (Zn3), and [Zn(PQA)(Curc)]Cl (Zn4), containing N,N-bis(pyridin-2-ylmethyl)benzofuro[3,2-b]quinolin-11-amine (BPQA), N-(pyridin-2-ylmethyl)benzofuro[3,2-b]quinolin-11-amine (PQA), and curcumin (H-Curc) were synthesized. An MTT assay showed that Zn1–Zn4 had strong anticancer activities against SK-OV-3/DDP and T-24 tumor cells with IC50 values of 0.03–6.19 μM. Importantly, Zn1 and Zn2 displayed low toxicities against normal HL-7702 cells. Mechanism experiments demonstrated that probe Zn2 showed appreciable fluorescence in the red region of the spectrum, and substantial accumulation of Zn2 occurred in the mitochondria after treatment, indicating increases in Ca2+ and reactive oxygen species levels, loss of the mitochondrial membrane potential, and consequent induction of mitochondrial dysfunction at low concentrations. In addition, the probe Zn2 effectively (50.7%) inhibited the growth of T-24 bladder tumor cells in vivo. The probe Zn2 shows potential for use in cancer therapy while retaining the H-Curc as an imaging probe.

Two mononuclear Pt(II) compounds, [Pt(BQL1)Cl]Cl (BQL1-Pt) and [Pt(BQL2)Cl]Cl (BQL2-Pt), with [5-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-pentyl]-bis-pyridin-2-ylmethyl-amine (BQL1) and [9-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-nonyl]-bis-pyridin-2-ylmethyl-amine (BQL2), were prepared as new chemotypes for potential antitumor agents. In this study, the effects of cryptolepine derivatives in BQL1-Pt, 2,2′-dipicolylamine Pt(II) complex, and BQL2-Pt on cellular Pt(II) accumulation, cytotoxicity, and in vitro and in vivo antitumor activities against T-24 cancer cells and normal HL-7702 cells were evaluated. BQL1-Pt and BQL2-Pt displayed cytotoxic activities in the micromolar range (1.3 ± 0.1 and 0.2 ± 0.2 μM, respectively) on T-24 cancer cells; however, they did not exhibit any toxicity against HL-7702 cells. They triggered T-24 cell apoptosis through a mitochondrial dysfunction pathway. BQL1-Pt and BQL2-Pt prepared from the neutral BQL1 and BQL2 ligands with cryptolepine derivatives showed better antitumor activities than 2,2′-dipicolylamine. Furthermore, BQL2-Pt effectively inhibited the growth of bladder T-24 tumor in vivo. BQL2-Pt could be a potential therapeutic candidate for cancers. [Figure not available: see fulltext.]

Anthranilic acids (AAs) are significant basic chemicals used in pharmaceuticals, agrochemicals, dyes, fragrances,etc. Superfluous steps are always involved in obtaining AAs. Herein, we demonstrate a straightforward strategy to transform abundanto-nitrotoluenes into biologically and pharmaceutically significant AAs without any extra reductants, oxidants and protecting groups. Various sensitive groups, such as halogens, sulfide, aldehyde, pyridines, quinolines,etc., can be tolerated in this transformation. A hundred-gram-scale operation is realized efficiently with almost quantitative selenium recycling. Further mechanistic studies and DFT calculations disclosed the proposed atom-exchange processes and the key roles of the selenium species.

In the reaction solvent, o-methyl (hetero) aryl nitro compound is taken as a reaction raw material and is used for water. The anthranilic acid and its derivatives are synthesized by the action of a catalyst, a base and an additive. The synthetic method has the advantages of cheap and easily available raw materials, simple reaction operation, high yield and excellent functional group tolerance, and provides a simple and efficient method for synthesizing o-aminobenzoic acid which is widely used in the aspects of dyes, medicines, pesticides, spices and the like. The invention further discloses the anthranilic acid and derivatives and application thereof, and has a wide application prospect.

A simple, efficient and pot-economic approach in a single vessel has been developed for conversion of aromatic and aliphatic carboxamides into primary amines with one fewer carbom atom (Hofmann reaction) in 38–89 % yield by reacting with trichloro- or tribromoisocyanuric acid and sodium hydroxide in aqueous acetonitrile. Under the same reaction conditions, cyclic imides gave amino acids (69–83 %). The role of the trihaloisocyanuric acids is the in situ generation of N-haloamides, key-intermediates for the Hofmann reaction. The scalability of the methodology was demonstrated by a multigram-scale transformation of phthalimide into anthranilic acid in 77 % yield.

A new diphenylamine derivative, scediphenylamine A (1), together with six phthalimide derivatives (2–7) and ten other known compounds (8–17) were obtained from the marine-derived fungus Scedosporium apiospermum F41-1 fed with synthetically prepared anthranilic acid and phthalimide. The structure and absolute configuration of the new compound were determined by HRMS, NMR, and X-ray crystallography. Evaluation of their lipid-lowering effect in 3T3-L1 adipocytes showed that scediphenylamine A (1), N-phthaloyl-tryptophan-methyl ester (4), 5-(1,3-dioxoisoindolin-2-yl) pentanamide (5), perlolyrine (10) and flazine (11) significantly reduced triglyceride level in 3T3-L1 cells by inhibiting adipogenic differentiation and synthesis with the EC50 values of 4.39, 2.79, 3.76, 0.09, and 4.52 μM, respectively. Among them, perlolyrine (10) showed the most potent activity, making it a candidate for further development as a potential agent to treat hyperlipidemia.

Seven tacrine/CHR21 conjugates have been designed and synthesized. Compound 8-7 was confirmed as the most active AChE inhibitor with IC50 value of 5.8 ± 1.4 nM, which was 7.72-fold stronger than tacrine. It was also shown as a strong BuChE inhibitor (IC50 value of 3.7 ± 1.3 nM). 8-7 was clearly highlighted not only as an excellent ChEs inhibitor, but also as a good modulator on protein expression of AChE, p53, Bax, Bcl-2, LC3, p62, and ULK, indicating its functions against programmed cell apoptosis and decrease of autophagy. 8-7 significantly reversed the glutamate-induced dysfunctions including excessive calcium influx and release from internal organelles, overproduction of nitric oxide (NO) and Aβ high molecular weight oligomer. This compound can penetrate blood?brain barrier (BBB). The in vivo hepatotoxicity assay indicated that 8-7 was much less toxic than tacrine. Altogether, these data strongly support that 8-7 is a potential multitarget-directed ligand (MTDL) for treating Alzheimer's disease (AD).

Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC50 = 51.1 nM; GSK-3β: IC50 = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound 27g exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound 27g suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.

A novel diarylethene derivative 1O with the unit of N-(2-(hydrazinecarbonyl)phenyl)benzamide was designed and synthesized successfully. The sensor showed excellent photochromism and specific fluorescent detection toward aluminum ion with rarely interfering. The emission intensity could increase nearly by 100 folds with aluminum ion and the color changed from dark to Aqua green. The low limit of detection (LOD) of 1O was determined as 3.26 × 10-8 mol L-1. Additionally, the sensor could be used in logic circuit and aluminum ion detection in untreated water.

The invention relates to the field of antifungal drugs, and discloses a benzoselenazolone compound and application thereof and a bactericide, and the benzoselenazolone compound has a structural general formula shown in a formula (I). The benzoselenazolone compound provided by the invention can take candida albicans fructose-1, 6-diphosphate aldolase (Ca-FBA-II) as a target spot to inhibit the activity of the candida albicans fructose 1, 6-diphosphate aldolase (Ca-FBA-II), and has a good resistance effect on drug-resistant bacteria generated by taking cytochrome P450 as an action target.

The transient receptor potential melastatin 2 (TRPM2) channel is associated with ischemia/reperfusion injury, inflammation, cancer, and neurodegenerative diseases. However, the limit of specific inhibitors impedes the development of TRPM2-targeted therapeutic agents. To discover more potent and selective TRPM2 inhibitors, 59 N-(p-amylcinnamoyl) anthranilic acid (ACA) derivatives were synthesized and evaluated using calcium imaging and electrophysiology approaches. Systematic structure-activity relationship studies resulted in some potent compounds inhibiting the TRPM2 channel with sub-micromolar half-maximal inhibitory concentration values. Among them, the preferred compound A23 exhibited TRPM2 selectivity over TRPM8 and TRPV1 channels as well as phospholipase A2 and showed neuroprotective activity in vitro. Following pharmacokinetic studies, A23 was further evaluated in a transient middle cerebral artery occlusion model in vivo, which significantly reduced cerebral infarction. These data indicate that A23 might serve as a useful tool for TRPM2-related research as well as a lead compound for the development of therapeutic agents for ischemic injury.

Developing novel fungicide candidates are intensively promoted by the rapid emergences of resistant fungi that outbreak on agricultural production. Aiming to discovery novel antifungal leads, a series of 1,3,4-oxadiazole derivatives bearing a quinazolin-4(3H)-one fragment were constructed for evaluating their inhibition effects against phytopathogenic fungi in vitro and in vivo. Systematically structural optimizations generated the bioactive molecule I32 that was identified as a promising inhibitor against Rhizoctonia solani with the in vivo preventative effect of 58.63% at 200 μg/mL. The observations that were captured by scanning electron microscopy and transmission electron microscopy demonstrated that the bioactive molecule I32 could induce the sprawling growth of hyphae, the local shrinkage and rupture on hyphal surfaces, the extreme swelling of vacuoles, the striking distortions on cell walls, and the reduction of mitochondria numbers. The above results provided an indispensable complement for the discovery of antifungal lead bearing a quinazolin-4(3H)-one and 1,3,4-oxadiazole fragment.

The invention discloses an aluminum ion detection fluorescent probe based on a bifunctional organic small molecule as a matrix and a preparation method and application of the fluorescence probe, and the structural formula is shown I. To the invention, 1, 8 - naphthalimide and isoquinoline hydrazide or 2 - benzamide benzoyl hydrazine are used as fluorescent groups, and the prepared Schiff base type probe NIQ or NBP is prepared into a solution Al through condensation reaction. 3 + High sensitivity and high selectivity are exhibited, and at the same time, the structure is stable. The low toxicity and cell infiltration capability is strong, and the trace metal aluminum ions in the living Hela cells are successfully detected. The preparation method of the fluorescent probe is simple, the raw materials are easily available, the obtained product is solid powder, is easy to store, and has a high application development prospect.

The invention discloses 1,oxadiazole Nrf2 activator - tacrine split products as well as a preparation method and application thereof. The invention relates to an acetylcholinesterase inhibitory activity. Nrf2 Activation activity, selective screening and Morris water maze test was carried out to evaluate the compound of general formula I, II, III for the treatment of's disease (in particular, severe's disease), found to have good in vitro, in vivo activity and extremely high selectivity, and can be used as a precursor substance for further development through selective inhibition of acetylcholinesterase and activation Nrf2.

A new series of quinazoline derivatives bearing a 1,3-diphenylpyrazole core was synthesized starting from 3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(4-oxo-4H-benzo[d][1,3]oxazin-2yl)propenonitrile (4) through reactions with some nitrogen nucleophiles. Hydrazinolysis of 4 furnished the biquinazoline and diheterylazine derivatives depending on the reaction conditions. Noteworthy, the benzimidazole derivatives were obtained via treatment with 2-aminoaniline under different reaction conditions. Inspect of the reactions of 4 with hydrazinecarbothioamide and hydrazinecarbothiohydrazide provided thiosemicarbazide, triazepinoquinazoline, and mercaptotetrazine derivatives. The antioxidant screening disclosed that some of these compounds such as 3, 5, 11, 12, and 13 exhibited significant potency.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an β-amyloid (Aβ) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Aβ1-42 aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Aβ1-42 pentamers. Moreover, 13a effectively attenuated Aβ1-42 oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.

The invention relates to aldoxime-containing tacrine derivative selective butyrylcholine esterase inhibitors, and a preparation method and application thereof. The compounds have a structure represented by a formula I or a formula II. The invention also relates to a pharmaceutical composition containing the compounds with the structures of the formula I or the formula II. The invention also provides application of the compounds and the composition containing one or more of the compounds in preparation of anti-Alzheimer's disease drugs.

The reduction of nitroarenes is the most efficient route for the preparation of aromatic primary amines. These reductions are generally performed in the presence of heterogeneous transition metal catalysts, which are rather efficient but long and tedious to prepare. In addition, they contain very expensive metals that are in most cases difficult to reuse. Therefore, the development of efficient, easily accessible and reusable Pd catalysts obtained rapidly from safe and non-toxic starting materials was implemented in this report. Two bottom-up synthesis methods were used, the first consisted in the impregnation of a micro/mesoporous carbon support with a Pd salt solution, followed by thermal reduction (at 300, 450 or 600 °C) while the second involved a direct synthesis based on the co-assembly and pyrolysis (600 °C) of a mixture of a phenolic precursor, glyoxal, a surfactant and a Pd salt. The obtained composites possess Pd nanoparticles (NPs) of tunable sizes (ranging from 1-2 to 7.0 nm) and homogeneously distributed in the carbon framework (pores/walls). It turned out that they were successfully used for mild and environment-friendly hydrogenations of nitroarenes at room temperature under H2(1 atm) in EtOH in the presence of only 5 mequiv. of supported Pd. The determinations of the optimal characteristics of the catalysts constituted a second objective of this study. It was found that the activity of the catalysts was strongly dependent on the Pd NPs sizes,i.e., catalysts bearing small Pd NPs (1.2 nm obtained at 300 °C and 3.4 nm obtained at 450 °C) exhibited an excellent activity, while those containing larger Pd NPs (6.4 nm and 7.0 nm obtained at 600 °C, either by indirect or direct methods) were not active. Moreover, the possibility to reuse the catalysts was shown to be dependent on the surface chemistry of the Pd NPs: the smallest Pd NPs are prone to oxidation by air and their surface was gradually covered by a PdO shell decreasing their activity during reuse. A good compromise between intrinsic catalytic activity (i.e. during first use) and possibility of reuse was found in the catalyst made by impregnation followed by reduction at 450 °C since the hydrogenation could be performed in only 2 h in EtOH or even in water. The catalyst was quantitatively recovered after reaction by filtration, used at least 7 times with no loss of efficiency. Advantageously, almost Pd-free primary aromatic amines were obtained since the Pd leaching was very low (0.1% of the introduced amount). Compared to numerous reports from the literature, the catalysts described here were both easily accessible from eco-friendly precursors and very active for hydrogenations under mild and “green” reaction conditions.

We report a novel strategy for the synthesis of magnetic nanocomposite for highly efficient catalysis. Poly(glycidyl methacrylate) (PGMA) chains were grafted to the surface of magnetic nanoparticles (MNPs) through surface-initiated reversible addition-fragmentation chain transfer polymerization. Then, the oxirane rings in the PGMA chains were opened with 2,6-diamino pyridine (DAP) molecules as ligands to prepare the solid support. Finally, this magnetic nanocomposite was used for the immobilization of gold nanoparticles. Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, transmission electron microscopy, scanning electron microscopy, gel permeation chromatography, vibrating sample magnetometry, and atomic absorption spectroscopy were used for characterization of the catalyst. The loading of gold nanoparticles on the solid support was 0.52 mmol/g. The catalytic activity of the prepared catalyst (MNP@PGMA@DAP@Au) was evaluated for the reduction of nitro compounds and C–C coupling reaction in water. The catalyst can be easily recovered and reused seven times without significant loss of catalytic activity.

Disclosed is a dianhydride having Formula (I). In Formula (I): Q1 is CR4, SiR4, GeR4, PR4, or N; Q2 is CR5, SiR5, GeR5, PR5, or N; R1, R2, and R3 are the same or different at each occurrence and are F, CN, alkyl, fluoroalkyl, unsubstituted or substituted hydrocarbon aryl, unsubstituted or substituted heteroaryl, alkoxy, fluoroalkoxy, unsubstituted or substituted aryloxy, silyl, or siloxy, where adjacent R1 groups can be joined together to form a fused aromatic ring; R4 and R5 are the same or different and are H, F, CN, alkyl, fluoroalkyl, unsubstituted or substituted hydrocarbon aryl, unsubstituted or substituted heteroaryl, alkoxy, fluoroalkoxy, unsubstituted or substituted aryloxy, silyl, or siloxy; a is an integer from 0-4; b and c are the same or different and are an integer from 0-2; and the double dashed lines between two rings indicate that the two rings can be fused at any available position.

The invention relates to a method for reducing aromatic nitro to arylamine. The method comprises the following steps: (1) taking an aromatic nitro compound as a raw material, water as a hydrogen source, a palladium compound, cheap and easy to obtain, as a catalyst and tetrahydroxydiboron as an additive to reduce nitro to obtain a product; (2) taking the aromatic nitro compound as the raw material, a copper salt, cheap and easy to obtain, as the catalyst, the tetrahydroxydiboron as the additive to reduce the nitro to obtain a product; and (3) taking the aromatic nitro compound as the raw material, water as the hydrogen source, and the tetrahydroxydiboron as the additive, without needing a metal catalyst, to reduce the nitro to obtain a product. A preparation method for the arylamine, which is provided by the invention, is mild in reaction condition, low in costs, environment-friendly, high in yield, and suitable for industrial production.

Abstract: A Heterogeneous catalyst developed for selective reduction of nitroarenes to the analogous anilines using formic acid as hydrogen source. This catalytic procedure offers a simplistic path to prepare aromatic amines in good to excellent yields. Especially, even anilines functionalized with other potentially reducible moieties are obtained with high selectivity. Herein, we report convenient and stable bimetallic AgPd nanocatalyst supported on metal organic framework coated with polyaniline. Hydrogenation of nitroarenes gave analogues anilines with excellent yields at 90?°C in 6?h with no use of additives. Catalyst maintained stable performance in five repeated cycles. Graphic Abstract: [Figure not available: see fulltext.].

Novel red Zn(ii) complex-based fluorescent probes featuring cryptolepine-curcumin derivatives, namely, [Zn(BQ)Cl2] (BQ-Zn) and [Zn(BQ)(Cur)]Cl (BQCur-Zn), were developed for the simple and fluorescent label-free detection of apoptosis, an important biological process. The probes could synergistically promote mitochondrion-mediated apoptosis and enhance tumor therapeutic effects in vitro and vivo.

Although Pd(II)-catalyzed C-H activation in arenes has been widely successful in organic synthesis with many palladacycle compounds isolated as the intermediates in ligand-directed C-H activation, direct identification of the reaction intermediates such as the π-complex prior to the C-H activation is still not successful because of their instability. In the present study, we introduce a Pd(II)/LA (LA: Lewis acid)-catalyzed oxidative olefination/annulation reaction between N-methoxybenzamides and acrylates with oxygen as the oxidant source, in which two intermediates, including an unsymmetrical η6-complex and a palladacycle species without the proton releasing to the environment, were identified through NMR characterizations. The in situ formation of the heterobimetallic Pd(II)/LA species such as Pd(II)/Sc(III) may have enhanced the electrophilic properties of the Pd2+ cation, thus improving the stability of the π-complex, herein, an unsymmetrical η6-complex, and improving its catalytic efficiency. The observed insensitive electronic effect preferred the concerted metalation-deprotonation (CMD) mechanism for this C-H activation, and the detected palladacycle intermediate without the proton releasing to the environment offered an experimental clue to support the proposed CMD mechanism.

The invention discloses a pyrimidinone compound with a structure represented by a general formula I or a pharmaceutically acceptable salt, and a preparation method and application thereof. Tacrine fragments and pyrimidinone structures are fused in a molecular skeleton, and the application of the skeleton structure in a multi-target anti-AD strategy is realized for the first time. Pharmacological experiments show that the pyrimidinone compound disclosed by the invention has an obvious inhibition effect on AChE/GSK-3[beta] double targets.

Carbohydrates such as glucose are an abundant renewable resource that can be employed in synthetic processes as a source of carbon and/or hydrogen to yield products of high economical and biological impact. Herein, we report a versatile and environmentally friendly protocol for the one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones, a privileged scaffold in medicinal chemistry, based on the use of glucose as an eco-friendly reductant in alkaline aqueous medium. This method can be viewed as a blueprint for the development of further one-pot sequences involving glucose as a reductant.

In this work, we have synthesized two new [C, C] cyclometalated Ir(iii)-NHC complexes, [IrCp?(C∧C:NHC)Br](1a,b), [Cp? = pentamethylcyclopentadienyl; NHC = (2-flurobenzyl)-1-(4-methoxyphenyl)-1H-imidazoline-2-ylidene (a); (2-flurobenzyl)-1-(4-formylphenyl)-1H-imidazoline-2-ylidene (b)] via intramolecular C-H bond activation. The molecular structure of complex 1a was determined by X-ray single crystal analysis. The catalytic potentials of the complexes were explored for acceptorless dehydrogenation of alcohols to carboxylic acids with concomitant hydrogen gas evolution. Under similar experimental conditions, complex 1a was found to be slightly more efficient than complex 1b. Using 0.1 mol% of complex 1a, good-to-excellent yields of carboxylic acids/carboxylates have been obtained for a wide range of alcohols, both aliphatic and aromatic, including those involving heterocycles, in a short reaction time with a low loading of catalyst. Remarkably, our method can produce benzoic acid from benzyl alcohol on a gram scale with a catalyst-to-substrate ratio as low as 1?:?5000 and exhibit a TON of 4550. Furthermore, the catalyst could be recycled at least three times without losing its activity. A mechanism has been proposed based on controlled experiments and in situ NMR study.

A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.

Using ultraviolet-visible (UV-vis) absorption spectroscopy, we have tested the reactivity of various indicator molecules combined with catalytic bimetallic gold-palladium nanoparticles (Au-Pd NPs) in solution for an irreversible and visual response to H2. Our aim was to identify the most suitable indicator/Au-Pd NP system for the future development of a thin, wearable, and visual H2 sensor for noninvasive monitoring of in vivo Mg-implant biodegradation in research and clinical settings with fast response time. The indicators studied were bromothymol blue, methyl red, and resazurin, and the reactions of each system with H2 in the presence of Au-Pd NPs caused visual and irreversible color changes that were concluded to proceed via redox processes. The resazurin/Au-Pd NP system was deemed best-suited for our research objectives because (1) this system had the fastest color change response to H2 at levels relevant to in vivo Mg-implant biodegradation compared to the other indicator/Au-Pd NP systems tested, (2) the observed redox chemistry with H2 followed well-understood reaction pathways reported in the literature, and (3) the redox products were nontoxic and appropriate for medical applications. Studying the effects of the concentrations of H2, Au-Pd NPs, and resazurin on the color change response time within the resazurin/Au-Pd NP system revealed that the H2-sensing elements can be optimized to achieve a faster or slower color change with H2 by varying the relative amounts of resazurin and Au-Pd NPs in solution. The results from this study are significant for future optical H2 sensor design.

A green chemical preparation of Pd nanoparticles (NPs) embedded in phytochemical resins using a plant extract from Pulicaria odora L. and PdCl2 under ambiant conditions is reported. Two batches of Pd NPs have been prepared: they present homogeneous sizes of respectively 2.2 nm and 3.2 nm depending on the preparation conditions. The Pd NPs were characterized by different techniques (TEM, HRTEM, XRD, XPS and BET) and have been successfully used for the reduction of nitroarenes in EtOH under H2 at atmospheric pressure at rt in the presence of only 5 mequiv. of Pd. Finally the Pd NPs embedded in resin particles were easily recovered by filtration and used at least seven times without significant loss in efficiency. The residual amount of palladium found in the reaction product is very low (0.6% of the initial amount). Therefore both preparation of the Pd NPs and their use for hydrogenations of nitroarenes are environmentally benign.

The present methodology described the chemo-selective hydrogenation of various nitroarenes in a flow reactor under polystyrene supported rhodium in a catalyst-cartridge (Cart-Rh@PS) as a heterogeneous nano-catalyst. The polystyrene supported Rh (Rh@PS) nanoparticles (NPs) were prepared by following our earlier reported protocol and packed inside the catalyst-cartridge (Cat-Cart) to obtain Cart-Rh@PS, which is compatible with ThalesNano's H-Cube Pro flow system. The advantages of the prepacked catalyst Cart-Rh@PS are as follows: no need for catalyst activation up to 12 runs, negligible metal leaching detected by ICP-AES analysis and significantly less back pressure generated under the flow conditions. The same catalyst, Cart-Rh@PS, was also effective up to a 1 gram scale for the reduction of nitroarenes and reusable for successive runs. The hydrogenation in the flow reactor is a greener approach for the reduction of nitroarenes to their corresponding anilines in high yields.

Abstract: In this study, firstly, CuFe2O4 nanoparticles were prepared by a simple operation. The structure of the mentioned nanoparticles was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma-optical emission spectrometry, vibrating sample magnetometer and also Brunauer–Emmett–Teller and Barrett–Joyner–Halenda analyses. The prepared magnetically copper ferrite nanocomposite was successfully applied as a simple, cost-effective, practicable, and recoverable catalyst on the green, highly efficient, fast, base-free, and ligand-free reduction of nitriles and also on the affordable and eco-friendly reduction of nitro compounds with the broad substrate scope to the corresponding amines with NaBH4 in water at reflux in high to excellent yields. Graphical abstract: [Figure not available: see fulltext.].

A series of novel isoflavone analogs were designed, synthesized, and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease. In vitro evaluations revealed that some ligands had multifunctional profiles, including potent blockage of histamine 3 receptor (H3R), excellent inhibition of acetylcholinesterase (AChE), neuroprotective effects and anti-neuroinflammatory properties. Among these derivatives, compound 9b exhibited the highest ability to block H3R (IC50 = 0.27 μM) and good inhibitory activity against AChE (IC50 = 0.08 μM). Additionally, compound 9b showed obvious neuroprotective effect on SH-SY5Y by preventing copper-induced neuronal damage and potent anti-neuroinflammatory activity by inhibiting the production of inflammatory factors on BV-2 cells. A molecular modeling study revealed that 9b acts as a mixed-type inhibitor that interacts simultaneously with H3R and AChE. Moreover, in vivo data revealed that compound 9b did not cause acute toxicity in mice at doses up to 1000 mg/kg, and had desirable pharmacokinetic properties, as well as a good blood-brain barrier (BBB) permeability (log BB = 1.24 ± 0.07). Further studies demonstrated that chronic oral treatment with 9b significantly improved cognitive dysfunction in scopolamine-induced AD mice in the step-down passive avoidance test. Taken together, the present study showed that compound 9b is a promising multifunctional drug candidate for the treatment of Alzheimer's disease.

A series of new indole-3-acetic acid (IAA)-tacrine hybrids as dual acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitors were designed and prepared based on the molecular docking mode of AChE with an IAA derivative (1a), a moderate AChE inhibitor identified by screening our compound library for anti-Alzheimer's disease (AD) drug leads. The enzyme assay results revealed that some hybrids, e.g. 5d and 5e, displayed potent dual in vitro inhibitory activities against AChE/BChE with IC50 values in low nanomolar range. Molecular modeling studies in tandem with kinetic analysis suggest that these hybrids target both catalytic active site and peripheral anionic site of cholinesterase (ChE). Molecular dynamic simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations indicate that 5e has more potent binding affinity than hit 1a, which may explain the stronger inhibitory effect of 5e on AChE. Furthermore, their predicted pharmacokinetic properties and in vitro influences on mouse brain neural network electrical activity were discussed. Taken together, compound 5e can be highlighted as a lead compound worthy of further optimization for designing new anti-AD drugs.

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by progressive loss of memory and cognitive function, and is associated with the deficiency of synaptic acetylcholine, as well as chronic neuroinflmmation. Tacrine, a potent acetylcholinesterase (AChE) inhibitor, was previously a prescribed clinical therapeutic agent for AD, but it was recently withdrawn because it caused widespread hepatotoxicity. Hydrogen sulfide (H2S) has neuroprotective, hepatoprotective, and anti-inflammatory effects. In this study, we synthesized a new compound, a tacrine-H2S donor hybrid (THS) by introducing H2S-releasing moieties (ACS81) to tacrine. Subsequently, pharmacological and biological evaluations of THS were conducted in the aluminum trichloride (AlCl3)-induced AD mice model. We found that THS (15 mmol/kg) improved cognitive and locomotor activity in AD mice in the step-through test and open field test, respectively. THS showed strong AChE inhibitory activity in the serum and hippocampus of AD mice and induced increased hippocampal H2S levels. Furthermore, THS reduced mRNA expression of the proinflammatory cytokines, TNF-α, IL-6, and IL-1β and increased synapse-associated proteins (synaptophysin and postsynaptic density protein 95) in the hippocampus of AD mice. Importantly, THS, unlike tacrine, did not increase liver transaminases (alanine transaminase and aspartate transaminase) or proinflammatory cytokines, indicating THS is much safer than tacrine. Therefore, the multifunctional effects of this new hybrid compound of tacrine and H2S indicate it is a promising compound for further research into the treatment of AD.

Augmenting the modified naturally occurring clay clinochlore with ppm amounts of palladium leads to a new and very effective reagent for the reduction of numerous aromatic nitro species. When palladium nanoparticles are supported on pyridyltriazole-modified clinochlore, iron within clinochlore acts synergistically with palladium to catalyze the reduction of a wide variety of nitroarenes at room temperature in aqueous media. Based on E-factor calculations, the catalyst system is found to be in line with green chemistry standards and can be recycled up to five times.

Molecular hybridization is a powerful strategy in drug discovery. A series of novel diarylbenzopyrimidine (DABP) analogues were developed by the hybridization of FDA-approved drugs etravirine (ETR) and efavirenz (EFV) as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant. 12d also had a favorable pharmacokinetic (PK) profile with liver microsome clearances of 14.4 μL/min/mg (human) and 33.2 μL/min/mg (rat) and an oral bioavailability of 15.5% in rat. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment. Further optimizations resulted in a highly potent compound (12z) with no substituents on the phenyl ring and a 2-methyl-6-nitro substitution pattern on the 4-cyanovinyl-2,6-disubstitued phenyl motif. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. In particular, this compound exhibited acceptable intrinsic liver microsome stability (human, 34.5 μL/min/mg; rat, 33.2 μL/min/mg) and maintained the good PK profile of its parent compound EFV and showed an oral bioavailability of 16.5% in rat. Molecular docking and structure-activity relationship (SAR) analysis provided further insights into the binding of the DABPs with HIV-1 reverse transcriptase and provided a deeper understanding of the key structural features responsible for their interactions.

A Chiral Br?nsted acid catalyzed asymmetric intramolecular ring-closing alkylation of inert pyrroles with α, β-unsaturated ketones has been developed. This approach gave a wide range of 4-phenyl-4,5-dihydro-6H-benzo[f]pyrrolo[1,2-a]azepin-6-ones in high yields with good enantioselectivities under mild reaction conditions. (Figure presented.).

The invention relates to the technical field of chemical synthesis, and specifically relates to a 2-carboxyl piperazine linked tacrine-8-amino(hydroxyl) quinoline derivative as well as preparation andapplication. The 2-carboxyl piperazine linked tacrine-8-amino(hydroxyl) quinoline derivative is a chemical compound shown in a formula I (the formula I is shown in the description) or a pharmaceutically acceptable salt thereof, and a solvent chemical compound, an enantiomer, a diastereoisomer, a tautomer or a mixture in any proportion of the chemical compound shown in the formula I or the pharmaceutically acceptable salt thereof, and includes a racemic mixture. Confirmed by a pharmacological test, the kind of chemical compound has an inhibiting effect on the activity of acetylcholinesterase(AChE) and butyrylcholinesterase(BuChE), and belongs to a cholinesterase inhibitor; the chemical compound also has an inhibiting effect on self-aggregation of beta-amyloid protein, and has delayed action on hydrolysis of acetylcholine and self-aggregation of the beta-amyloid protein, thereby improving the effect of the acetylcholine on a synapse, and finally realizing the purpose of effectively treating alzheimer's disease (AD).

Kynureninase from Pseudomonas fluorescens (Pfkynase)catalyzes the pyridoxal-5′-phosphate (PLP)dependent hydrolytic cleavage of L-kynurenine to give anthranilate and L-alanine. Asp-132 and Asp-201 are located in the structure near the pyridine NH of the PLP, with Asp-201 forming a hydrogen bond. Mutation of Asp-132 to alanine and glutamate and Asp-201 to glutamate results in reduced catalytic activity with L-kynurenine and β-benzoyl-L-alanine, but not O-benzoyl-L-serine. D132A, D132E D201E and S36A mutant Pfkynases all can form quinonoid and vinylogous amide intermediates with β-benzoyl-L-alanine, similar to wild-type enzyme. D132A, D132E, and D201E Pfkynase react more slowly with β-benzoyl-L-alanine and benzaldehyde to form an aldol product absorbing at 490 nm than wild-type, with D132E reacting the slowest. The 1H NMR spectra of wild-type and D201E Pfkynase are very similar in the low field region from 10 to 18 ppm, but that of D132A Pfkynase is missing a resonance at 13.1 ppm. These results show that these residues modulate the reactivity of the PLP at different stages during the reaction cycle. Ser-36 is located near the expected location of the carbonyl oxygen of the substrate. Mutation of Ser-36 to alanine results in a 230-fold reduction of kcat and 30-fold reduction in kcat/Km with L-kynurenine, but very little effect on the reaction of O-benzoyl-L-serine. Thus, the rate-determining step in the reaction of S36A Pfkynase is the Cβ-Cγ bond cleavage. These results support the hypothesis that Ser-36 together with Tyr-226 is part of an oxyanion hole that polarizes the carbonyl of the substrate in the catalytic mechanism of Pfkynase.

The invention provides a multi-target tacrine derivative and a preparation method and application thereof. The compound has the structure shown in a formula (I) (please see the specification in the formula (I)), wherein n is a natural number greater than 1; m is 1 or 2; p is 0 or 1; R1 is H or halogen; and Y is selected from the following structures (please see the specification for the structures) or, a pharmaceutically acceptable salt of a compound in a formula (X). According to the compound, activity of histone deacetylase (HDACs), acetylcholinesterase (AChE) or butyryl cholinesterase (BChE) can be effectively inhibited.