Sulfonylureas as Dual Acting Agents — Synthesis and Biological Activity

2‐Amino‐5‐aryl/alkyl‐1,3,4‐thiadiazoles 3a‐e were used as intermediates in the synthesis of some 1,3‐substituted urea derivatives 5a‐o to evaluate their antidiabetic activity as well as antibacterial activity. The obtained compounds exhibited marginal activity against the animal models and the selected microorganisms.     

Microwave Irradiation Promoted Synthesis of Aryloxy Acetic Acids

Several aryloxy acetic acids were synthesized under microwave irradiation. The factors, which affect the reaction, were investigated and optimized. It was revealed that the best yields(92. 7%--97.4%) were obtained when the molar ratio of the reactants was n(ArOH) : n(NaOH) : n(CICH2CO2H) = 1：2.5： 1.2 with microwave irradiation power of 640 W for 65--85 s.     

Synthesis of Novel Isothionucleosides as Potential Antiviral Agents

The synthesis of novel isothionucleosides is described. The thioether moiety was prepared via a highly regioselective opening of chiral thiirane 9 with vinylmagnesium bromide.     

Synthesis of Some Novel Heterocycles Bearing Thiadiazoles as Potent Anti‐inflammatory and Analgesic Agents

2‐Bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole derivative was synthesized and reacted with a number of heterocyclic amines to give a series of fused imidazole derivatives. Also, reaction of 2‐bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole with o‐phenylene diamine and 2‐aminothiophenol yielded the respective products. Moreover, reaction of 2‐bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole with thiourea, thiosemicarbazide, thiocarbahydrazide gave the respective thiazoles. The structures of all the novel products were elucidated on the basis of elemental analysis and spectral data. In addition, the biological activity of the newly synthesized compounds was evaluated, and the results obtained indicate their potency as anti‐inflammatory, analgesic, and anti‐ulcer agents. The binding mechanism of the most active compounds was studied using MOE to analyze the molecular interactions.     

Novel Analogues of a-Terthienyl, Thienyl 1, 3, 4-Thia(oxa)diazoles as Potential Photoactivated Insecticides: Synthesis and Bioactivity

a-Terthienyl (aT) is a phototoxic compound originated from the marigold Tagetes eretra1. The aT and its analogues have been widely used for photodynamic killing of insects, in photodynamic therapy for dermatophytes, and in human immunodeficiency virus (HIV)2. The phototoxicity of aT and its derivatives are attributed to their triplet states that easily generate a reactive oxygen species (ROS). Many of the biomolecules and enzymes are targets of these ROS, such as DNA in vitro and in v…     

Synthesis of Novel 1,3,5-Trisubstituted Pyrazoles as Potential Hypoglycemic Agents

A novel series of 1,3,5-trisubstituted pyrazoles was synthesized. Thus, ethyl 2,4-dioxo-6-phenylhex-5-enoate (I) was condensed with phenylhydrazine to afford 3-ethoxycarbonyl-1-phenyl-5-styrylpyrazole (II) which on fusion with hydrazine hydrate gave the corresponding acid hydrazide (III). Reaction of III with the appropriate isothiocyanate yielded the disubstituted thiosemicarbazides (IVa-e) which were cyclized into thiotriazoles (Va-e), thiadiazoles (Vla-e) and oxadiazoles (VIIa-). The structure of the newly synthesized compounds was elucidated by elemental analyses, IR and ¹H NMR spectra.     

Synthesis of Some New Fused and Binary 1,3,4‐Thiadiazoles as Potential Antitumor and Antioxidant Agents

Annulations of 2‐amino‐1,3,4‐thiadiazole ( 1 ) with α,β‐unsaturated carbonyl compounds 2 , 5 , and 9 afforded thiadiazolo[3,2‐a]pyrimidin 3 , benzamide 7 , and bis‐pyrazole derivative 11 . Cyclization of benzamide 7 with POCl₃ gave binary imidazole derivative 8 . Moreover, alkylation of 1 with 2‐bromo‐1‐(2H‐chromen‐3‐yl) ethanone ( 9 ) followed by cyclization gave imidazo[2,1‐b]‐1,3,4‐thiadiazole derivative 15 . Multicomponent reaction of 1 with heterocyclic and/or aromatic aldehyde and thioglycolic acid afforded the corresponding thiazolidinones 17 and 19 . Finally, a one‐pot synthesis of 1 with isatin and thiosemicarbazide furnished the spirotriazole 20 . The newly synthesized compounds were evaluated as antitumor agents.     

The Synthesis of Epiboxidine and Related Analogues as Potential Pharmacological Agents

Methyl epiboxidine‐N‐carboxylate ( 8 ) was synthesized from 7 under reductive Heck conditions (Scheme 2). The C? C coupling of the new epiboxidine analog 9 with aryl and heteroaryl halides gave by hydroarylation C‐aryl, N‐(3‐methylisoxazol‐5‐yl)‐substituted tricyclic imides 10a – 10f (Table). The [3+2] cycloaddition of 9 with nitrile oxides yielded the bridged dihydroisoxazole derivatives 11a – 11d with potential biological activity (Scheme 4).     

Design,Synthesis of Novel Thiourea and Pyrimidine Derivatives as Potential Antitumor Agents

1,3‐Bis‐(arylidene)thiourea derivatives ( 11a‐c ) were prepared by reacting thiourea ( 9 ) with bezaldehyde, p‐chlorobenzaldehyde or p‐anisaldehyde ( 10a‐c ) respectively. Further reaction of ( 11b ) with acetyl acetone, ethyl acetoacetate, malononitrile and acetic anhydride gave tetrahydropyrimidine‐2‐thiones ( 12‐14 ) and 1,3‐diacetyl thiourea ( 15 ). Compound ( 11b ) reacted with chloroacetyl chloride to give the corresponding pyrimidin‐4‐one derivative ( 16 ). Reaction of ( 12‐14 ) with acetic acid in aqueous sodium nitrite yielded the corresponding oxime derivatives ( 17‐19 ). The triazole ( 20 ) was achieved via refluxing of ( 19 ) in dimethylformamide. Reaction of ( 16 ) with mercaptoacetyl chloride gave the sulfanyl‐acetic acid ( 21 ) which afforded the dihydrazinyl ( 22 ) up on treatment with hydrazine hydrate. Newly synthesized compounds ware characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR and mass spectra). The investigated compounds were screened for their cytotoxicity, i.e. compounds 19 , 20 and 22 exhibited highly potential antitumor activity.     

Synthesis and Biological Evaluation of Novel Benzoxaboroles as Potential Antimicrobial and Anticancer Agents

Several novel benzoxaborole derivatives were synthesized starting from 2‐formylphenylboronic acid utilizing Baylis–Hillman reaction, Barbier allylation, Passerini reaction, and aldol reaction protocols as the key step. All the synthesized benzoxaboroles have been evaluated for their antibacterial, antifungal, and anticancer activities.     

Synthesis of Some Newer Analogues of 4‐Hydroxyphenyl Acetic Acid as Potent Anti‐Inflammatory Agents

A series of 1,3,4‐oxadiazole and 1,2,4‐triazole derivatives of 4‐hydroxyphenyl acetic acid have been synthesized and evaluated for their anti‐inflammatory activity by carrageenan induced rat paw edema method. The compounds, which showed good anti‐inflammatory activity, were screened for their ulcerogenic and lipid peroxidation activities.     

Synthesis of New Branched Hydrazones as Potential Hole-transporting Materials

A new class of branched hydrazones has been prepared by the reaction of N-2,3-epoxypropylated N-phenylhydrazones containing photoconductive groups with 2,5-dimercapto-1,3,4-thiadiazole in the presence of the catalyst triethylamine.     

Synthesis and Anti Tuberculostatic Activity of Novel 1,3,4‐Oxadiazole Derivatives

A series of novel 2,5‐disubstituted 1,3,4‐oxadiazole derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis H₃₇Rv. The result of the antimycobacterial activity tests revealed that 2‐(2‐naphthyloxymethyl)‐5‐phenoxymethyl‐1,3,4‐oxadiazole ( IVd ) exhibited > 90% inhibition at MIC ?6.25.     

The Synthesis and Antimicrobial Screening of Some Novel AZA-Imidoxy Compounds as Potential Chemotherapeutic Agents

Some novel azaimidoxy compounds viz. 2-{[(4-chlorophenyl)diazenyl]oxy}-1H-isoindole-1,3-(2H)-dione (Va), and 1-{[1-naphthyldiazenyl]oxy}pyrrolidine-2,5-dione (IVc), etc. have been synthesized by a simple diazotization reaction followed by a coupling with 2-hydroxy-1H-isoindole-1,3(2H)-dione (III)/1-hydroxypyrrolidine-2,5-dione (II) of corresponding aromatic primary amine derivatives at a suitable pH. A similar reaction with a [1,3]thiazolo[4,5-b]pyridin-2-amine (VIII) lead us to some interesting results variable with a pH. The structure of all synthesized compounds has been established by IR, ¹H NMR, and mass studies. These compounds have been screened for antimicrobial activities in order to evaluate the possibility of the derivatives to be used as potential chemotherapeutic agents.     

Facile Synthesis of Novel Amino Acids Derivatives as Potential Antibacterial Agents using Sustainable Materials

Following the principles of green chemistry, cardanol derivatives have been used as renewable, low‐cost, and available natural starting materials to construct a variety of protected and unprotected amino acids derivatives. The reaction of cardanol derivatives with different phthaloylamino acids including glycine, alanine, phenylalanine, and valine in the presence N,N'‐ dicyclohexylcarbodiimide (DCC ) as coupling reagent afforded high yields of the target compounds. Deprotection of phthaloylamino acids derivatives was achieved by heating with hydrazine hydrate. The chemical structures of all products were confirmed by spectral data (IR , MS , ¹H NMR , ¹³C NMR ) and elemental analyses. Antibacterial evaluation of the synthesized products was performed, which exhibited potent to weak activity in comparison with a standard drug.     

Design,Synthesis and Pharmacological Evaluation of Novel 4-Phenoxyquinoline Derivatives as Potential Antitumor Agents

A series of novel 4-phenoxyquinoline derivatives containing 3-amino-2-cyano-acrylamide framework was designed and synthesized, and the in vitro cytotoxic activities of them against five cancer cell lines(HT-29, H460, A549, MKN-45, and U87MG) were evaluated. Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines as compared with Foretinib. The studies of their preliminary structure-activity relationships(SARs) indicate that the compounds containing methyl groups, especially methyl groups at 4-position of the phenyl ring(moiety B) are more effective. Among them, compound 36 shows the most potent antitumor activities with IC₅₀ values of 0.04, 0.09, 0.67, 0.39 and 1.10 μmol/L against HT-29, H460, A549, MKN-45 and U87MG cell lines, respectively.     

Synthesis,Biological Evaluation and Molecular Docking of Novel Phenylpyrimidine Derivatives as Potential Anticancer Agents

Based on our previous researches, a novel phenylpyrimidine pharmacophore model was proposed and fifteen derivatives were synthesized and characterized by means of spectroscopy methods. The inhibitory effects of them were screened against HeLa cell line by virtue of MTT assay in vitro. The results indicate some of the phenylpyrimidine derivatives exhibit potent biological activities. Among them, compounds 6g and 6h exhibit the best activity at half maximal inhibitory concentrations of 1.5 and 2.8 μmol/L, respectively. These compounds also exhibit good activities against HepG2 cell line and MCF-7 cell line. FLT-3 kinase was screened as the most potent molecular target. Computational docking between compound 6g and FLT-3 was carried out to interpret the binding mode. The results show phenylpyrimidine derivatives have effective antitumor activities, which provides a base for further research of them as antitumor agents.