Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series

Background:The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals.However,no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans.This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.Methods:This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022.The entire course of the incidents was described in detail.Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer.Hema-toxylin and eosin staining was performed to assess liver injury,and immunofluorescence was used to evaluate hepatic mitophagy.Results:The 2-amino-5-chloro-N,3-dimethylbenzamide powder(99%purity)entered the human body mainly via the skin and respiratory tract due to poor personal protective measures.The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency,rash,fever,organic dam-age,and recovery phases in accordance with the clinical evolution.Rash and fever may be the important premonitory symptoms for further organ injuries.The chemical was detected in the blood of all patients and caused multiple organ injuries,predominantly liver injury,including kidney,myocardium,and micro-circulation.Three patients recovered smoothly after comprehensive treatments,including artificial liver therapy,continuous renal replacement therapy,glucocorticoids,and other symptomatic and supportive treatments.One patient survived by liver transplantation.The postoperative pathological findings of the removed liver showed acute liver failure,and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes.Conclusions:This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.The chemical enters the body through the respiratory tract and skin during industrial production.The 2-amino-5-chloro-N,3-dimethylbenzamide poisoning causes multiple-organ dysfunction with a predominance of liver injury.Liver transplantation may be an effective option for patients with severe liver failure.The mechanisms of liver injury induced by 2-amino-5-chloro-N,3-dimethylbenzamide might involve abnormal mitochondrial function and mitophagy.

Synthesis and antiangiogenic activities of 5-amino-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanoic acid derivatives

Based on the structure-activity relationships and antiangiogenic mechanism of RGD-containing peptides, a series of 5-amino- 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. The structures were characterized by ^1H NMR, MS and elementary analysis. There ability to inhibit angiogenesis were evaluated by chick embryo chorioallantoic membrane assay at 10^-5 mol/L. Compounds 7a and 7b displayed obvious antiangiogenic activity.

Removal of 5-Amino-2-chlorotoluene-4-sulfonic and Chlorhydric Acids From Wastewater by Weakly Basic Resin: Equilibrium and Kinetics

Objective To study the adsorption of 5-Amino-2-chlorotoluene-4-sulfonic (CLT) and chlorhydric (HCl) acids from wastewater by weakly basic resin. Methods The kinetics and isotherm were studied. Thermodynamic parameters for the adsorption of acids were calculated and discussed. Results The adsorption of CLT and HCl acids followed Langmuir isotherm and the first-order kinetics model. Conclusion The adsorptive affinity of the two acids on D301R is in the order of CLT acid 〉 HCl acid. CLT and HCl acids can be separated.

Syntheses and Characterization of Two New Alkaline Earth Metal-organic Topological Frameworks with 3-Amino-1H-1,2,4-triazole-5-carboxylate

Two new alkaline earth metal coordination polymers constructed from the deriva-tive of 1,2,4-triazole are presented herein,namely,{[Sr（AmTAZAc）2（H2O）]}（1） and {[Ba（AmTAZAc）2（H2O）]}（2）（AmTAZAc = 3-amino-1H-1,2,4-triazole-5-carboxylate）,which have been synthesized by using the layering method and structurally characterized by elemental analysis,IR,and single-crystal X-ray diffraction.Complexes 1 and 2 are isostructural,and both crystallize in the orthorhombic system,space group Fdd2.X-ray structural analysis shows that 1 or 2 has an intriguing 3-D infinite network of（318.438.510） topology based on a 2-D sheet structure of（4,4） net.The result shows that noncovalent interactions play an important role in strengthening the whole structures of the compounds.

Theoretical Study on the Reaction Mechanism of 2-Methoxybenzaldehyde,4-Bromo-indanone,Malononitrile and Ammonium Acetate One-pot to Form 6-(2-Methoxyphenyl)-2-amino-6-bromo-5H-indeno[1,2-b]pyridine-3-carbonitrile

The reaction mechanism of 2-methoxybenzaldehyde, 4-bromo-indanone, malononitrile and ammonium acetate one-pot to form 6-（2-methoxyphenyl）-2-amino-6-bromo-5 Hindeno[1,2-b]pyridine-3-carbonitrile was studied by density functional theory. The geometries of the reactants, transition states, intermediates and products were optimized at the PW91/DNP level. Vibration analysis was carried out to confirm the transition state structure. Reaction pathways were investigated in this study. The result indicates that the reaction Re→ TSB1→IMB1→ TSB2→ IMB2→TSB3→IMB3→TSB4→IMB4→TSB5→IMB5→TSB6→IMB6→TSB7→IMB7→ TSB8→IMB8→TSB9→IMB9→P2 is the main pathway, the activation energy of which is the lowest. The dominant product predicted theoretically is in agreement with the experiment results.

A Facile Synthesis of 2-Amino-5-Cyano-4, 6-Disubstitutedpyrimidines under MWI

Microwave Assisted Organic Synthesis (MAOS) is energy efficient and effective tool to speed up the synthesis for drug discovery process. In the present study we report a novel protocol for the rapid, high throughput synthesis of mononuclear 2-amino-5-cyano-4,6-disubstituted pyrimidines, adaptable to parallel synthesis for compound libraries. The overall reaction time in hrs has been reduced to 25 - 50 minutes with improved yields.

2-氨基-5-氟酚-N,N,O-三乙酸三甲酯的合成

为了合成核磁共振法测定镁离子的指示剂中间体2-氨基-5氟酚-N,N,O-三乙酸三甲酯,采用了三步反应:碱性水解、催化氢化和酯化。由2,4-二氟硝基酚与氢氧化钾合成5-氟-2-硝基酚,再用催化氢化法制得5-氟-2-氨基酚,最后用溴乙酸甲酯酯化得到2-氨基-5-氟酚-N,N,O-三乙酸三甲酯。产物结构通过HPLC、H NMR、MS、UV等方法进行确证,三步反应产率分别为75％、48％和7.9％。

Auxiliary Ligands Mediated One- and Two-dimensional Cd(Ⅱ) Coordination Polymers Incorporating Methyl-3- hydroxy-5-carboxy-2-Thiophenecarboxylate Ligand

Two N-donor ligands mediated Cd（Ⅱ） coordination polymers, namely,[Cd（L）（dmpz）2]n （1） and {[Cd（L）（atr）05（H20）]（H2O）}n （2） （H2L = methyl-3-hydroxy-5-carboxy-2-thiophenecarboxylate, dmpz = 3,5-dimethylpyrazole, and atr= 4-amino-l,2,4-triazole）, havebeen produced. Their structures were characterized by single-crystal X-ray diffraction analysis,elemental analyses and infrared spectra. Compound 1 possesses a one-dimensional （1D） chainstructure and is finally extended into a three-dimensional （3D） supramolecular architecturethough hydrogen bonding interactions. Compound 2 features a two-dimensional （2D） networkwith 4-connected sql topology based on dinuclear Cd（Ⅱ） clusters as nodes, which is alsoassembled into a 3D supramolecular architecture through hydrogen bonding interactions.Furthermore, compounds 1 and 2 exhibit high thermal stabilities and intense fluorescent emissionin the solid, and can be explored as potential luminescent materials.

5-氟-2-氨基酚合成研究

合成了能与Mg2+结合的指示剂5F-APTRA-AM的中间体。本实验采用了2种方案即铁粉还原法(方案一)和催化氢化法(方案二),通过实验可知,方案二得到的产物质量、收率均比方案一优;并对2种方案的合成反应条件、影响因素、5-氟-2-氨基酚中的杂质来源分别进行了讨论。

Synthesis, Crystal Structure, Antibacterial Activities and Theoretical Computation of 3-(2-Hydroxybenzly)-4-(4-isopropylbenzyl- ideneamino)-(1H)-1,2,4-triazole-5-thione

The title compound C18H18N4OS has been synthesized by the reaction of 3-（2-hydroxy- benzyl）-4-amino-（1H）-1,2,4-triazole-5-thione with 4-isopropylbenzaldehyde in ethanol and characterized by IR, ^1H NMR spectra and elemental analysis. Its structure was determined by X-ray diffraction analysis. The crystal belongs to monoclinic, space group P21/c with a = 11.605（2）, b = 7.401（1）, c = 20.339（2） A, β= 103.05（2）°, V= 1701.8（4） A^3, Z = 4, Mr = 338.42,μ = 0.202 mm^-1, Dc = 1.321 g/cm^3 and F（000） = 712. The structure was solved by direct methods and refined to R = 0.0428 and wR = 0.1069. Due to the intramolecular O-H…N hydrogen bond and π-π stacking interactions between the benzene （C（1）～C（6）） and triazole rings, the two planes are essentially coplanar. Their biological activities have been measured, showing this type of compound has certain antibacterial activity for Staphylococous aureus and Bacillus subtilis. Based on the quantum chemistry calculation at the RHF/6-31G level, the frontier orbitals and electrostatic potential of the title compound were also discussed.

Synthesis and Crystal Structure of Dinuclear Copper(Ⅱ)Complex Cu_2(μ-PhCOO)_4(amet)_2·2CH_3COCH_3

Reaction of copper powder, dibenzoyl peroxide and 2-amino-4methyl-5-ethoxycarbonyl thiazole (amet) by refluxing in acetone yielded the dinuclearcopper(Ⅱ) complex Cu2 (μ-PhCOO)4 (amet)2- 2CH3COCH3. Crystal structure determination showed that each copper atom is coordinated by four bridged benzoxy and oneamet molecule with an M-M bond (Cu-Cu (A) = 2.6899 (7 ) ), therefore the coor-dination environment around the copper center is a distorted square pyramid with N(1)at the apical position. Blocks of Cu2 (μ-PhCOO)4 (amet)2·2CH3COCH3 crystallize inthe triclinic space group Ph, with Mr= 1100.14, a= 9. 631 (1), b=10. 446 (2), c=12. 758(2) ; a=91. 31 (1), β=95. 50(1),γ= 94. 87(1)°, V=1272. 4(3), Z=1, Dc= 1. 436 g/cm3, F(000) = 570, μ=0. 986 mm-1 and R=0.033, Rw=0.049.The IR spectra, which are of great interest since the molecule has ketone, ester andcarboxylate group simultaneously, are also discussed.

5-Amino-4-oxopentanoic acid photodynamic diagnosis guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model

Background Complete tumour resection is important for improving the prognosis of brain tumour patients. However, extensive resection remains controversial because the tumour margin is difficult to be distinguished from surrounding brain tissue. It has been established that 5-amino-4-0xopentanoic acid （5-aminolevulinic acid, ALA） can be used as a photodynamic diagnostic marker and a photosensitizer for photodynamic therapy in surgical treatment of brain tumours. We investigated the efficacy of ALA photodynamically guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model. Methods Eighty New Zealand rabbits implanted with VX2 brain tumours were randomly assigned to five groups： control, conventional white light microsurgery, a photodynamic therapy group, a photodynamically guided microsurgery group and a group in which guided microsurgery was followed by photodynamic therapy. The VX2 tumour was resected under a surgical microscope. The tumour resection was confirmed with histological analysis. All animals were examined with MRI for presence of any residual tumour tissue. The survival time of each rabbit was recorded. Results All treatment groups showed a significantly extended survival time compared with the control group. Photodynamically guided microsurgery combined with photodynamic therapy significantly prolonged survival time, compared with guided microsurgery alone. MRI and the autopsy results confirmed removal of most of the tumours. Conclusions Our results suggest that photodynamically guided surgery and photodynamic therapy significantly reduce or delay local recurrence, increase the effectiveness of radical resection and prolong the survival time of tumour bearing rabbits. Their combination has the potential to be used as a rapid and highly effective treatment of metastatic brain tumours.

Preparation of 2-amino-5,7-dimethoxy-4-aryl/alkyl-4H-chromene-3-carbonitriles using Na_2O-Al_2O_3-P_2O_5 glass–ceramic system

A highly efficient and environmentally benign protocol for the synthesis of 2-amino-5,7-dimethoxy-4- aryl/alkyl-4H-chromene-3-carbonitrile derivatives by one-pot three-component coupling reacting of aromatic aldehydes, malononitrile and 3,5-dimethoxy phenol under reflux condition has been developed in aqueous EtOH media using Na2O-Al2O3-P2O5 glass-ceramic system.

Structure identification of 4-amino-2-(arylamino)thiazole-5-carboxylic esters

In our previous work,we found a new method by chance for the synthesis of thiazole derivatives with diversified substitutes on 2-and 5-positions of the thiazole scaffold which was published in Chinese Chemical Letters[2014,Vol.25 p.411].The structures were identified by ~1H NMR,^（13）C NMR and HRMS as 2-alkoxy-4-amino-Narylthiazole-5-carboxamides.

Improvement in the synthesis of 2-(5-amino-1,2,4-thiadiazol-3- yl)-2-(Z)-methoxyiminoacetic acid 2-benzothiazolyl thioester

2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-meth-oxyiminoacetic acid 2-benzothiazolyl thioester(III),an important intermediate of the fourth generation cephalos-porins,was efficiently synthesized by reacting 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid(I)with 2,29-dibenzothiazole disulfide(II)in the presence of triphenylphosphine.Effects of reaction time,temperature,solvents,catalysts and feeding molar ratio on the yield and quality of products were investigated,and an im-proved procedure suitable for industrial production was established.Using 1,2-dichloroethane as solvent,triphe-nylphosphine as reducer,and triethylamine as catalyst,n(I):n(II):n(triphenylphosphine)51.0:1.0:1.0,the product was obtained at room temperature in 98.1%yield.The purity of the product without further purification is 98.7%determined by HPLC method.This procedure could be a suitable alternative to the traditional processes because of its easy handling,high yield and low cost.

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats

Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.

A Novel Luminescent Tetranuclear-copper(Ⅰ) Complex with Cavities Formed through Hydrogen Bonds

The solvothermal reaction of CuI with 5-amino-2-benzimidazolethiol in acetonitrile condition affords complex [Cuz（5-amino-2-benzimidazolethiol）2]2 which has been characterized by elemental analysis, infrared spectrum and single-crystal X-ray diffraction analysis. Crystal data for C28H24N12S4Cu4： monoclinic, space group C2/c with a = 15.970（5）, b = 12.365（4）, c = 16.293（5） A, fl = 91.977（6）°, V = 3215.5（18）, Z = 4, Mr= 910.99, Dc= 1.882 g/cm3 , F（000） = 1824, p = 2.913 mm-1, λ（MoKa） = 0.71073A, T= 293（2） K, the final R = 0.0527 and wR = 0.1342. X-ray diffraction analysis revealed that the title complex exhibits a l D channel constructed from tetranuclear-copper（I） motifs connected by hydrogen bonds and shows strong photoluminescence in the solid state at room temperature.

Syntheses, Characterization and Biological Activity of Novel Thiazoylazo Dye and Its Coordination Compounds

The present work describes the synthesis of a novel heterocyclic azo dye by general diazonization of 2-amino-4,5-dimethylthiazole followed by the diazo- coupling of the resulting diazonium ion with 5-methyl-2-(propan-2-yl)phenol to obtain ligand L. This was characterized using Fourier-transformed infrared and electronic spectrophotometry. Ligand L was further coordinated with five metal ions, M:L, 1:2 [M = Cu(II), Mn(II), Zn(II), Ni(II) and Co(II)]. The coordination compounds obtained were characterized by electronic, IR spectrophotometry, magnetic susceptibility and percentage metal analyses. The results obtained suggested that a thiazoylazo dye was obtained as ligand L. It was proposed that two molecules of the solvent coordinated to the metal ion in addition with the ligands to give an octahedral geometry for copper(II), manganese(II) and nickel(II) complexes. On the other hand, square planar geometry was suggested for zinc(II) and cobalt(II) complexes. The anti-infla- mmatory activity of the ligand and coordination compounds was evaluated using four in vitro-based assays viz: xanthine oxidase and lipoxygenase inhibition assay, membrane stability and protein denaturation assay. The synthesized compounds generally exhibited good anti-inflammatory activity in all the assays carried out. However, the reference standards, in this instance, were more effective in the case of xanthine oxidase, lipoxygenase and protein denaturation inhibitory assays. For the membrane stability study, the coordination compounds and ligand L elicited more potent anti-inflammatory activity than the standard drug.

Improved microwave-assisted catalyst-free synthesis of9-aryl-5,9-dihydropyrimido[4,5-d][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-dione derivatives

Agreen regioselective synthesis of some new and known 9-aryl-5,9-dihydropyrimido[4,5-d][l,2,4]triazolo[1,5-a]pyrimidine-6,8（4H,7H）-diones has been described via the microwave-assisted one-pot reaction of 3-amino-1H-1,2,4-triazoles,aromatic aldehydes and barbituric acids under solvent- and catalyst-free conditions.This operationally simple procedure is less laborious and provides a better scope than previously reported procedures.