Synthesis of 5‐(6‐Pyridazinone‐3‐yl)‐2‐Glycosylamino‐1,3,4‐Oxadiazoles

N‐Glycosyl‐2‐(1,4,5,6‐tetrahydropyridazin‐6‐one‐3‐carbonyl)‐hydrazinecarbothioamides 3a‐3g and N‐glycosyl‐2‐(1,6‐dihydropyridazin‐6‐one‐3‐carbonyl)‐hydrazinecarbothioamides 5a‐5g were prepared by the reaction of glycosyl isothiocyanates with the compounds 1,4,5,6‐tetrahydro‐3‐hydrozinecarbonyl‐6‐pyridazinone ( 1 ) and 1,6‐dihydro‐3‐hydrozinecarbonyl‐6‐pyridazinone ( 2 ). The terminal heterocyclic compounds 1,3,4‐oxadiazole derivatives were obtained from cyclization of compounds ( 3a‐3g ) and ( 5a‐5g ) by mercuric acetate. Their structures were confirmed by IR, ¹H NMR, MS and elemental analyses.     

8-羟基喹啉共轭连接芳香杂环化合物的合成、荧光性质及生物活性的研究

设计合成了4个8-羟基喹啉共轭联接芳香杂环化合物来研究它们在有机发光材料和荧光探针的潜在应用。用IR, 1H NMR, 13C NMR, MS, UV确认了这些新化合物的结构。测定了化合物1-4的荧光性质,发光衰变时间和量子产率,并用密度泛函方法研究了4个化合物的几何结构和荧光发射波长的关系。在调控骨髓间充质干细胞增殖以及清除DPPH自由基的活性测试结果表明,这些化合物具有促进小鼠骨髓间充质干细胞的增殖的活性及良好的抗氧化性。     

The Stability Constants of Some Benzo-15-Crown-5 And Naphtho-15-Crown-5 Derivatives

Abstract

The stability constants for the complexes of several benzo-15-crown-5 and naphtho-15-crown-5 derivatives containing various substituents in the aromatic ring have been determined in methanol. The potentiometric method with glass ion-selective electrodes has been employed. The stability constants have been compared to the selectivity coefficients (log k^pot _K,Na ) of membrane electrodes based on the mentioned compounds. No significant relationship has been stated.     

Regioselective synthesis of fused ring heterocyclic derivatives of ketene aminals and their biological activities

A regioselective and convenient methodology was developed to synthesize heterocyclic derivatives, bearing imidazole, piperidines, and azepines rings. The N-arylnitrones derived from 3-formylchromones were selected to react with heterocyclic ketene aminal to furnish the structurally attractive and pharmacologically important fused ring heterocycles. The N-arylnitrone moiety of 3-formylchromone was used to activate the formyl group for regioselective fused ring heterocycles synthesis, whereas, the effect of substituents at aryl functionality of nitrones were studied to improve the yield of target fused ring heterocyclic products. The synthesized compounds (10-12) were evaluated for their in vitro cytotoxic and antifungal influences. In cytotoxic (brine shrimp lethality) assay, compound 11e was found to be active with LD₅₀ = 4.1 × 10⁻⁶ μg/mL.     

Synthesis of 1,3,4‐Oxadiazoles and 1,3‐Thiazolidinones Containing 1,4,5,6‐Tetrahydro‐6‐pyridazinone

The reaction of 1,4,5,6‐tetrahydro‐6‐pyridazinone‐3‐carboxylic acid hydrazides ( 1 ) with aromatic aldehydes afforded 1,4,5,6‐tetrahydro‐6‐pyridazinone‐3‐carbonyl aromatic aldehyde hydrazones ( 2a‐2g ). Heterocyclic derivatives linked 1,3,4‐oxadiazole obtained by cyclocondensation of 2a‐2g with acetic anhydride in absolute ethanol, and 2a‐2g cyclized with mercaptoacetic acid in DMF in the presence of anhydrous ZnCl₂ afforded the 1,3‐thiazolidinone derivatives. The structures of the new compounds were established by elemental analyses, IR, ¹H NMR and MS spectral data.     

Synthesis,antimicrobial, and antioxidant activities of new pyridyl‐ and thiazolyl‐bearing carbohydrazides

A series of novel substituted (E)‐N′‐benzylidene‐4‐methyl‐2‐(2‐propylpyridin‐4‐yl)thiazole‐5‐carbohydrazide derivatives ( 6a‐l ) have been synthesized by following the multistep synthetic route starting from prothionamide. The resulting compounds were characterized via ¹H, ¹³C NMR, and HRMS spectral data. The synthesized carbohydrazides were evaluated for their in vitro antimicrobial and antioxidant activities. Tested molecules have displayed moderate to good growth inhibition activity. Among the screened compounds, 6b , 6e , 6j, and 6k are found to be the more promising antimicrobial agents. A 2,2‐diphenyl‐1‐picrylhydrazyl assay was used to test the antioxidant activity of the carbohydrazides. The carbohydrazide derivatives 6b and 6i have shown better free‐radical scavenging ability than the other investigated compounds.     

Double C?H Functionalization in Sequential Order: Direct Synthesis of Polycyclic Compounds by a Palladium‐Catalyzed C?H Alkenylation–Arylation Cascade

Palladium‐catalyzed cascade C? H alkenylation and arylation provides convenient access to polycyclic aromatic compounds. Treatment of 3‐bromoaniline derivatives bearing a bromocinnamyl group on the nitrogen atom with a catalytic amount of [Pd(OAc)₂] and PCy₃?HBF₄ in the presence of Cs₂CO₃ in dioxane affords naphthalene‐fused indole derivatives in good yields. This double cyclization reaction is also applicable to heterocyclic substrates, giving fused indoles containing a heteroaromatic ring such as dibenzofuran, dibenzothiophene, carbazole, indole, or benzofuran through heterocyclic C? H arylation. When using a 2,6‐unsubstituted aniline derivative, the first C? H arylation preferentially proceeds at the more hindered position of the aniline ring.     

Synthesis of new annulated pyridazine derivatives and studying their antioxidant and antimicrobial activities

Benzil was reacted with cyanoacetohydrazide under microwave irradiation to give 3-oxo-5,6-diphenyl-2,3-dihydropyridazine-4-carbonitrile 1 which used as starting material for the synthesis of new heterocyclic compounds. Chlorination of pyridazinone 1 with POCl₃ afforded the chloro-pyridazine derivative 3, which then condensed with 2-aminothiazole or hydrazine hydrate to produce 3,4-diphenyl-5H-thiazolo[3′,2′:1,2]pyrimido[4,5-c]pyridazin-5-one 5 or 3-hydrazinyl-5,6-diphenylpyridazine-4-carbonitrile 6, respectively. New Schiff bases were obtained by condensation reactions of compound 6 with different aldehydes. On the other hand, compound 6 reacted with different carbon electrophiles naming acetyl acetone, diethyl malonate, and phenyl isothiocyanate producing new pyarazolo-pyridazine derivatives 11, 12, and 14, respectively. Chemical structures of all newly synthesized compounds were confirmed on the basis of spectral data and had been screened for antimicrobial and antioxidant activity.     

Synthesis and Biological Study of Some 4-oxo-Thiazolidine Derivatives of 2-Aminothiazole

Conventional and microwave assisted synthesis of new series of N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐5‐(substituted benzylidene)‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 5a–5m have been developed. The cycloaddition reaction of thioglycolic acid with N‐{2‐(substituted benzylidenehydrazino)‐ethyl}‐2‐aminothiazole 3a–3m in the presence of anhydrous ZnCl₂ afforded new heterocyclic compounds N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 4a–4m . The later product on treatment with several selected substituted aromatic aldehydes in the presence of C₂H₅ONa undergoes Knoevenagel reaction to yield 5a–5m . The structures of compounds 1 , 2 , 3a–3m , 4a–4m and 5a–5m were confirmed by IR, ¹H NMR, ¹³C NMR, FAB‐Mass and chemical analysis. All above compounds were screened for their antimicrobial activities against some selected bacteria and fungi and antituberculosis study against M. tuberculosis.     

Synthesis and pancreatic lipase inhibitory activities of some 1,2,4-triazol-5(3)-one derivatives

In this study, starting from 4-amino-5-(4-chlorobenzyl)-2,4-dihydro-3H-1,2,4-triazole-3-one ( 1 ), the 4-Amino-5-(4-chlorobenzyl)-2-undecyl-2,4-dihydro-3H-1,2,4-triazol-3-one ( 2 ) was first synthesized and this compound was converted to Schiff base derivatives ( 3a-e ). In the second step of the study, the 2-[3-(4-chlorobenzyl)-5-oxo-1-undecyl-1,5-dihydro-4H-1,2,4-triazole-4-yl]-acetohydrazide ( 6 ), which was used as a key product in the synthesis of many heterocyclic compounds was synthesized in four steps, and then this compound was converted into methylidene acetohydrazide ( 7a-e ), thiosemicarbazide ( 8a-e ), and 1,2,4-triazole-5-thione ( 9a-e ) derivatives. Also, in the last part of the study, 1,2,4-triazole-5-thione derivatives were changed into Mannich bases ( 10a-b ) bearing a 4-phenylpiperazine ring. These new compounds were tested with regard to pancreatic lipase (PL) inhibition activity, and compound 3b , 3d , 7d , 8d , and 9d showed a considerable anti-lipase activity at various concentrations. The activity of compounds 7b (IC₅₀ = 1.45 ± 0.12 μM) was the highest in terms of IC₅₀, comparable to that of orlistat, a well-known PL inhibitor used as an antiobesity drug.     

哒嗪酮类α1-肾上腺素受体拮抗剂的合成和生物活性研究

将苯(氧)乙胺和苯氧烷胺类α₁-肾上腺素受体拮抗剂中的苯(氧)乙胺、苯氧烷胺片段引入哒嗪酮类化合物中, 设计、合成了30个新的含哒嗪酮环的α₁-肾上腺素受体拮抗剂. 所有新化合物的结构均经¹H NMR, IR, HRMS确证. 生物活性测试表明28个目标物对α₁-肾上腺素受体有较好的拮抗作用(pA₂＞6.00), 化合物6o, 6p, 6q, 6v, 6x, 6y, 10c, 10d的pA₂值＞7.00.     

Synthesis,Characterization, and Structure of Quinoline‐based Benzimidazole Derivatives

Quinoline‐based benzimidazole compounds have been successfully synthesized and characterized by various spectroscopic techniques like FT‐IR, ¹H NMR, ¹³C NMR, and mass spectral analysis, and the structures have been authenticated by single crystal X‐ray diffraction method. Here, we report an economical, mild, and efficient procedure that involves condensation of 8‐hydroxyquinoline‐2‐carbaldehyde with various diamines as substrates to give bis‐imines. A systematic study towards both aliphatic and aromatic bis‐imines has been conducted to investigate the ring‐closure reaction that generates the benzimidazole moiety in the heterocyclic compounds discussed in this study. Aliphatic bis‐imines does not undergo cyclization; however, the bis‐imines derived from o‐phenylenediamine and derivatives generates heterocyclic compounds with benzimidazole moiety. In contrast to synthetic procedures reported earlier for benzimidazoles, the reaction conditions herein reported are simpler. Path for reactions holds initial condensation with one equivalent of 8‐hydroxyquinoline‐2‐carbaldehyde to form mono‐imine followed by immediate intramolecular ring closure. The subsequent nupleophilic attack to another equivalent of 8‐hydroxyquinoline‐2‐carbaldehyde and migration of hydride generates the benzimidazole moiety and the active methylene group. The ─CH₂ group was confirmed from ¹H and ¹³C NMR, wherein the two hydrogens appeared at around 6.40–6.52 ppm and the carbon center appeared at 51.54–51.77 ppm. The single crystal X‐ray diffraction also confirmed the formation of benzimidazole moiety and the active methylene group in the heterocyclic compounds discussed in this study.     

An Easy Access to Construct Some New Fused 1,2,4‐Triazines with Ring Junction Nitrogen Systems and Their Biological Evaluation

The chemical reactivity of 4‐amino‐6‐benzyl‐3‐mercapto‐1,2,4‐triazine‐5(4H )‐one ( 1 ) towards various aliphatic or/and mono and bis aromatic carboxylic acid derivatives to give the corresponding fused heterocyclic systems, 1,3,4‐thiadiazoles 4 , 5 , 6 , which incorporating 1,2,4‐triazine moiety was achieved. Moreover, compound 1 was subjected to reaction either with halo acetic acids or bromo ester to afford the respective fused nitrogen ring junction systems, thiadiazole 2 and 3 or thiadiazine 7 . However, while the tetracyclic ring system 9 was furnished through condensation reaction of isatine with triazine 1 . In addition, some of the new synthesized compounds were evaluated as an antioxidant and antitumor agents.     

An Easy Access to Construct Some Fused 1,2,4‐Triazines with Ring Junction Nitrogen Systems and Their Biological Evaluation

The chemical reactivity of 4‐amino‐6‐benzyl‐3‐mercapto‐1,2,4‐triazine‐5(4H )‐one ( 1 ) towards various aliphatic or/and mono and bis aromatic carboxylic acid derivatives to give the corresponding fused heterocyclic systems, 1,3,4‐thiadiazoles 4 , 5 , 6 , which incorporating 1,2,4‐triazine nucleus was achieved. Moreover, compound 1 was subjected to react either with halo acetic acids or bromo ester to afford the respective fused nitrogen ring junction systems, thiadiazole 2 and 3 , or thiadiazine 7 . However, the tetracyclic ring system 9 was furnished through condensation reaction of isatine with triazine 1 . In addition, some of the new synthesized compounds were evaluated as an antioxidant and antitumor agents.     

Two new isatin derivatives: 1‐benzyl‐4,5,6‐trimethoxyindoline‐2,3‐dione and 1‐benzyl‐5‐fluoroindoline‐2,3‐dione

Isatin (1H‐indole‐2,3‐dione) derivatives represent synthetically useful substrates which can be used to prepare a broad range of heterocyclic compounds. In the title compounds, C₁₈H₁₇NO₅, (I), and C₁₅H₁₀FNO₂, (II), the isatin ring systems are planar and form a dihedral angle of 73.04 (7)° in (I) and 76.82 (11)° in (II) with the benzyl groups. The bicyclic scaffolds in both compounds are almost superimposable, with an r.m.s. deviation of 0.061 Å. The crystal structures of both derivatives are stabilized by C—H...O interactions. These contacts generate an R¹₂(7) ring motif in (I) and a C(7) chain motif in (II).     

Synthesis and anti-inflammatory activity of N′-substituted 2-[2-(diarylmethylene)hydrazinyl]-5,5-dimethyl-4-oxohex-2-enehydrazides

New N′-substituted 2-(2-(diarylmethylene)hydrazinyl)-5,5-dimethyl-4-oxohex-2-enehydrazides were synthesized by the ring opening reaction of 3-diarylmethylenehydrazono-5-tert-butyl-3H-furan-2-ones under the action of aliphatic, aromatic, and heterocyclic acid hydrazides. The structures of the obtained compounds were confirmed by ¹H and ¹³C NMR spectroscopy, IR spectroscopy, and elemental analysis. Their anti-inflammatory activity was studied.

     

Pyridazine derivatives. XIX: Functionalization studies at the 5 position in the 6-phenyl-3(2H)-pyridazinone system

A series of 6-phenyl-3(2H)-pyridazinones bearing different substitution at the 5 position of the pyridazinone ring were prepared in the search for new platelet aggregation inhibitors. The structure of the final compounds was determined on the basis of spectroscopics methods.     

TiO2–SiO2 Catalyzed Eco‐friendly Synthesis and Antioxidant Activity of Benzopyrano[2,3‐d]pyrimidine Derivatives

A cost‐effective and eco‐friendly synthesis of benzopyrano[2,3‐d ]pyrimidine derivatives has been developed via three component one‐pot tandem approach by condensing different salicylaldehydes and secondary amines with malononitrile in the presence of TiO₂–SiO₂ catalyst at 80°C under solvent‐free conditions. Mild experimental conditions, reusability of the catalyst, and cost effectiveness are the merits of this procedure. Compounds 4g , 4h , and 4i bearing 2‐OMe group on the hydroxyphenyl group linked to the central carbon present in between the two nitrogen atoms of the pyrimidine ring were found to exhibit good antioxidant activity while other compounds have moderate antioxidant activity.     

Chemo-and stereoselectivity of the reaction of aromatic aldehydes with triphenylphosphine and trichloroacetic acid derivatives

Aromatic aldehydes react with triphenylphosphine and ethyl trichloroacetate or trichloroacetonitrile to give the corresponding benzylidene dichlorides or α-chlorocinnamic acid derivatives. The chemo-and regioselectivity of these reactions depend on both the substituent in the aromatic ring and reaction conditions. The product configuration was determined on the basis of the coupling constants ² J _CH and ³ J _CH in the ¹³C NMR spectra.     

Antiproliferative,Cytotoxic, and Apoptotic Effects of New Benzimidazole Derivatives Bearing Hydrazone Moiety

In order to take the advantages of the anticancer properties of benzimidazoles and hydrazones, we synthesized new 4‐(5‐chloro‐1H‐benzimidazol‐2‐yl)‐benzoic acid benzylidene hydrazide derivatives ( 3a–3t ) and evaluated their anticancer activity against A549 (human lung adenocarcinoma) and MCF‐7 (human breast adenocarcinoma) cells. The structures of the compounds ( 3a–3t ) were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, mass spectroscopy, and elemental analyses. Antiproliferative activities of the compounds were evaluated using MTT assay, BrdU method, and flow cytometric analysis. In addition, with purpose of determining selectivity the cytotoxic activities of the final compounds were screened against healthy NIH3T3 cell line (mouse vembryonic fibroblast cells). Among the tested compounds 3e and 3f showed significant cytotoxic activity against A549 and MCF‐7 cancer cells with an IC₅₀ value of 0.0316 μM. Furthermore, compound 3p showed remarkable cytotoxic activity against MCF‐7 comparing with standard drug cisplatin. Annexin V‐FITC assay also suggested that this compounds induced cell death by apoptosis.