Compounds 3a-e Research Articles

ChemInform Abstract: Simple Method for the Synthesis of Aryl(furfuryl)glyoxals.

Furan derivatives containing reactive functional groups are useful structural units for the synthesis of different classes of chemical compounds [1-6]. Even such simple furans as phenacylfurans [7] containing one carbonyl group can be used in the preparation of cyclopentenones [8] which are the basic structural fragments in prostaglandins. In this connection, the development of methods for the synthesis of novel, functionalized furan compounds is a current problem. To our surprise aryl(furfuryl)glyoxals (which might be expected to have interesting reactivity) have proved to be unknown compounds. In this work we report the synthesis of these aryl(furfuryl)glyoxals. A Knoevenagel condensation of the readily available phenacylazides 1a-d [9, 10] with the furfurals 2a,b gives the azidochalcones 3a-e [11]. Subsequent treatment with triethyl phosphite and hydrochloric acid gives the target compounds 4a-e.

Synthesis and Antimicrobial Activities of (4,5,6,7-Tetrahydro-1H-indazol- 2(3H)-yl)thiazole Derivatives

Synthesis, characterization and investigation of antimicrobial activities of ten novel tetrahydroindazolylthiazoles is presented. Their structures were determined using 1H and 13C NMR, FAB(+)-MS and HRMS analyses. Among the derivatives, compound 3f shows strong antibacterial activity against S. aureus ATCC 43300, S. aureus ATCC 25923, and S. epidermidis ATCC 12228 with MIC 7.81 µg/ml, and good activity against S. aureus ATCC 6538 with MIC 31.25 µg/ml. Compounds 3a-e and 3j show good antifungal activity with MIC values ranging from 31.25 µg/ml to 250 µg/ml.

Synthesis and druglikeness estimation of amide derivatives of 1-benzyltheobromine- 8-thioglycolic acid

Five-stage synthetic scheme for obtaining of N-substituted 1-benzyltheobromine-8- hioglicolacetamides was described. The intermediate compound 1-benzyl-8- romotheobromine was synthesized using aliquat 336 as phase transfer catalyst in very good yield. Five amide derivatives of 1-benzyltheobromine-8-thioglicolyc acid were obtained in yields of 61 to 81%. The structures of the studied compounds were established by FTIR, 1H NMR spectral data. In order to estimate the drug-likeness of compounds 7a-e, a theoretical calculation of some molecular descriptors was made using two approaches: the Lipinski`s Rule of Five limitations and the OSIRIS Property Explorer evaluation score. The comparison of the calculated results indicate that only one compound violates the Lipinski`s Rule of Five parameters - 7c, which makes it unsuitable for further structural optimizations. On the other hand compound 7e shows the highest drug like properties with Fragment Based Druglikeness score of 2.58 and total Drug score of 0.43 which are better than the same scores of parent compound theobromine.

Simple Method for the Synthesis of Aryl(Furfuryl)Glyoxals

Furan derivatives containing reactive functional groups are useful structural units for the synthesis of different classes of chemical compounds [1-6]. Even such simple furans as phenacylfurans [7] containing one carbonyl group can be used in the preparation of cyclopentenones [8] which are the basic structural fragments in prostaglandins. In this connection, the development of methods for the synthesis of novel, functionalized furan compounds is a current problem. To our surprise aryl(furfuryl)glyoxals (which might be expected to have interesting reactivity) have proved to be unknown compounds. In this work we report the synthesis of these aryl(furfuryl)glyoxals. A Knoevenagel condensation of the readily available phenacylazides 1a-d [9, 10] with the furfurals 2a,b gives the azidochalcones 3a-e [11]. Subsequent treatment with triethyl phosphite and hydrochloric acid gives the target compounds 4a-e.

Synthesis of thiophene-linked pyrimidopyrimidines as pharmaceutical leads

Thiophene-substituted chalcones were cyclised with guanidine in the presence of potassium hydroxide to get 4-substituted-6-thiophenopyrimidines 2a–e which were then refluxed with acetylacetone to obtain pyrimidopyrimidines 3a–e. Compounds 2a–e were also refluxed with ethylacetoacetate to afford pyirmidopyirimidines 4a–e which on refluxing with POCl3 in presence of DMF produced compounds 5a–e. Nucleophilic substitution reactions on 5a-e were carried out with aniline to obtain 6a-e. The structures of the newly synthesised compounds have been confirmed by elemental analysis and spectral studies. Some selected compounds have been screened for antibacterial and analgesic activities. Thiophene-substituted chalcones were cyclised with guanidine to obtain 4-substituted-6-thiophenopyrimidines 2a-e which were refluxed with acetylacetone to obtain pyrimidopyrimidines 3a-e. Compounds 2a-e were refluxed with ethylacetoacetate to afford pyirmidopyirimidines 4a-e which on refluxing with POCl3 in presence of DMF produced compounds 5a-e. Nucleophilic substitution reactions on 5a-e produced compounds 6a-e.

Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs.

Design, Synthesis and Cytotoxicity Evaluation of New 2-Aryl-5, 6-Dihydropyrrolo[2, 1-a]Isoquinoline Derivatives as Topoisomerase Inhibitors.

Two set of 2-aryl-5, 6-dihydropyrrolo [2,1-a] isoquinolines were designed and synthesized to evaluate their biological activities as topoisomerase inhibitors. Cytotoxic activity of the synthesized compounds 4a-e and 7a-d was assessed against several human cancer cell lines, including MCF-7 (breast cancer cell), HepG2 (liver hepatocellular cells), A549 (adenocarcinomic human alveolar basal epithelial cells), T47D (Human ductal breast epithelial tumor cell line) and Hela (Human cervix cancer). According to our results, HepG2 seems to be the most sensitive cell line for these compounds with mean IC50 values ranging from 4.25 to 70.05 μM. Our results indicated that compound 7b exhibited the best potency against the tested cell lines. These results also suggest that pyrroloisoquinoline moiety constitutes a suitable scaffold to design new anti-proliferative agents.

Benzofuran-morpholinomethyl-pyrazoline hybrids as a new class of vasorelaxant agents: synthesis and quantitative structure-activity relationship study.

The benzofuran-morpholinomethyl-pyrazoline hybrids 4a-e, 5a-e and 6a-j were synthesized via reaction of α,β-unsaturated carbonyl compounds 3a-e with hydrazine hydrate, semicarbazide or thiosemicarbazide. Applying the Mannich reaction to 5-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-4-methoxybenzofuran-6-ols 7a-e with morpholine hydrochloride and paraformaldehyde afforded positional isomeric 7-morpholinomethyl derivatives 4a-e and N-morpholinomethyl derivatives 8a-e. All the synthesized compounds showed significant vasodilatation properties in isolated thoracic aortic rings of rats precontracted using the standard norepinephrine hydrochloride technique. Compounds 3d, 3e, 5a-c, 6b, 6c, 6f, 6h and 6i exhibited activity (IC50 0.3185-0.4577 mM) superior to that of prazocin (IC50 0.487 mM), while 5d, 6j and 8c showed comparable activity (IC50 0.4789-0.4951 mM). The quantitative structure-activity relationship study revealed a correlation between the observed vasorelaxant activities of the newly synthesized compounds and their different physicochemical parameters, especially solubility, in addition to structure connectivity and energetic quantities calculated from stored three dimensional (3D) conformations. Absorption, distribution, metabolism and elimination (ADME) evaluation showed good agreement with the biological results obtained.

Synthesis and biological evaluation of novel β-hydroxy benzimidazolyl sulfone fluoroquinolones by selective oxidation using ammonium molybdate catalysed H2O2

Synthesis of new β-hydroxy benzimidazolyl sulfides (4a-e) and β-hydroxy benzimidazolyl sulfones (5a-e) containing 7-piperazine fluoroquinolones have been described and evaluated for their antimicrobial activity. Benzoxazine fluoroquinolone carboxylic acid, 1, on reaction with piperazine in presence of triethylamine in acetonitrile under reflux resulted 7-piperazine bezoxazole fluoroquinolone, 2. The latter is reacted with epichlorohydrine in presence of NaOH in acetone yielded corresponding N -substituted epoxide, 3, with retained chirality, which on treatment with 5-substituted-2-mercaptobenzimidazoles given the corresponding β-hydroxy bezimidazolyl sulfides (4a-e). Further compounds 4a-e on treatment with H 2 O 2 and ammonium molybdate in dichloromethane yielded the β-hydroxy bezimidazolyl sulfones, 5a-e. The antimicrobial activity of newly synthesized compounds along with levofloxacin (reference drug) were evaluated against different microorganisms and found many of the evaluated compounds have been exhibited remarkable activity.

Tacrine–Flurbiprofen Hybrids as Multifunctional Drug Candidates for the Treatment of Alzheimer's Disease

Five tacrine-flurbiprofen hybrid compounds (3a-e) were synthesized as multi-target-directed compounds for the treatment of Alzheimer's disease. Compared to tacrine, two compounds (3d and 3e) showed better acetylcholinesterase (AChE) inhibitory activity and others (3b-e) better or the same butyrylcholinesterase (BuChE) inhibitory activity. Notably, 3d showed a mixed-type inhibitory action for AChE, indicating a "dual-binding site action" of both toward the catalytic active site (CAS) and the peripheral anionic site (PAS), whereas for BuChE, a competitive inhibitory action was observed. Furthermore, a cell-based assay on amyloid-β inhibition demonstrated that the selected target compound 3d effectively inhibits the formation of amyloid-β in vitro.

Synthesis and Antibacterial Activity of 4‐Aryl‐2‐(1‐substituted ethylidene)thiazoles

(E)-4-Aryl-2-[2-(1-substituted ethylidene)hydrazinyl]thiazoles and (Z)-3-substituted-4-aryl-2-[(E)-(1-phenylethylidene)hydrazono]-2,3-dihydrothiazoles were synthesized by the reaction of (substituted ethylidene)hydrazinecarbothioamides with ω-bromoacetophenones. The characterization of this new class of compounds was performed using different spectroscopic tools. The structure of (Z)-3-benzyl-4-(4-bromophenyl)-2-[(E)-(1-phenylethylidene)hydrazono]-2,3-dihydrothiazole 6e was unambiguously confirmed by single-crystal X-ray crystallography. Compounds 5a-e, 5i, 6e, 6g, and 6i were screened for their in vitro antibacterial activity against different strains of microorganisms; most of the tested compounds exhibited promising antibacterial activity against some organisms compared to ciprofloxacin and sulbactam penicillin. Compounds 5e, 5i, 6e, 6g, and 6i exhibited several-fold significant antibacterial activity against the Gram-positive bacteria Staphylococcus aureus, better than ciprofloxacin, with minimum inhibitory concentration values ranging from 0.05 to 0.4 µg/mL. The rest of the tested compounds gave significant antibacterial activities against different Gram-negative bacterial strains.

Synthesis and Antimicrobial Screening of Some Novel 2-(2-Chloroquinolin-3-yl)-3-(1-phenylamine)-1,3-thiazolidin-4-ones

Chloro-3-formylquinoline derivative (1) on treatment with phenyl hydrazine (2) yields Schiff's bases 2-(2-chloroquinolin-3-yl)methylene-2-phenyl hydrazine (3a-e). Compound 3a-e on treatment with thioglycollic acid and catalytic quantity of ZnCl 2 in methanol yields the title compounds 4a-e. The newly synthesized compounds 4a-e have been screened for their antibacterial and antifungal activities and their chemical structures have been elucidated by IR, NMR spectral data. Some of them exhibited significant antifungal activity.

Synthesis of Thiazole Derivatives and Evaluation of Their Antiamoebic Activity and Cytotoxicity

Five ethyl (5-alkyl-2-amino-1,3-thiazol-4-yl) acetates (designated compounds 4a-e) incorporating octyl, decyl, dodecyl, tetradecyl, and hexadecyl alkyl chains, respectively, were prepared by reacting 4-alkyl-4-bromo-3-oxobutyric acid ethyl esters (3a-e) with thiourea in dried acetonitrile. Compounds 3a-e were synthesized by reacting alkylated ethyl acetoacetates with bromine. The newly synthesized compounds were characterized by mass spectrometry, NMR, and elemental analysis. Compounds 4a-c demonstrated good in vitro antiamoebic activity against Acanthamoeba polyphaga exposed to 10 mg L(-1) for 6 h at 28 °C. Compound 4b showed the highest antiamoebic activity among the tested compounds, comparable to that of chlorhexidine dihydrochloride (CHX), decreasing the number of viable cells to below the detection limit of 1 cell mL(-1). The activity of compounds 4a and 4c was similar to that of the commercial antifungal agent fluconazole (Flu). The cytotoxic and hemolytic activity of the compounds was assayed against human neonate dermal fibroblasts and sheep erythrocytes, respectively. Compounds 4a-c were less cytotoxic than Flu and CHX. Our results suggest that compound 4b, which is composed of a 2-amino-thiazole attached to a decyl group and an ethyl ester moiety, is a particularly safe and effective alternative amoebicidal agent.

A Facile Synthesis of Arylazonicotinates for Dyeing Polyester Fabrics under Microwave Irradiation and Their Biological Activity Profiles

A as textile dyes and the fastness properties of the dyed samples were measured. Most of the dyed fabrics tested displayed very good washing and perspiration fastness and series of 2-hydroxy- and 2-amino-6-substituted-5-arylazonicotinate monoazo compounds 7a–e and 9a–c were prepared via condensation of 3-oxo-3-substituted-2-arylhydrazonals 2a–e with active methylene nitriles 3a–d using microwave irradiation as an energy source. These substances were then tested moderate light fastness. Finally, the biological activity of the synthesized compounds against Gram positive bacteria, Gram negative bacteria and yeast were evaluated.

Synthesis and Biological Activity Evaluation of Some Binuclear Metal Complexes of Cu(II) and Zn(II) with Tridentate Schiff Base Ligands

A few kinds of new Schiff bases were synthesized by reaction of 2-aminophenol and corresponding synthesized azo compounds 3a-e. Further reaction of these Schiff bases 4a-e with transition metal salts as Cu(II) and Zn(II) gave corresponding binuclear complexes 5a-e and 6a-e. The antibacterial activity of prepared complexes was investigated against Staphylococcus aureus and Escherichia coli bacteria. The results for some compounds revealed a moderate to good inhibition against Staphylococcus aureus compared with penicillin zone of inhibition.

Analgesic, antibacterial and antiviral activities of 2-(5-alkyl-1,3,4-oxadiazol-2-yl)-3 H -benzo [f] chromen-3-ones

A novel series of 2-(5-alkyl-1,3,4-oxadiazol-2-yl)-3H-benzo[f]chromen-3-ones (4a-e) have been evaluated for analgesic, antibacterial and antiviral activities. Analgesic activity was carried out using acetic acid-induced writhing method in Swiss albino male mice. The antibacterial activity was performed against Gram-positive and Gram-negative clinical strains by agar well diffusion method. The in vitro antiviral activity was carried out against camelpox and buffalopox viruses. The analgesic activity exhibited by the compounds 4a, 4c and 4d were found to be more significant compared to the standard. The bacterial activity was determined by the inhibition of growth of the organism by the drugs at different concentrations. All the compounds showed significant activity when compared with the drug ciprofloxacin. The in vitro antiviral activity of the compound 4b tested against camelpox and buffalopox viruses revealed no activity when tested at concentrations of 250 μg. The compound 4b did not alter the titres of both the viruses and the titres remain, respectively, 106.5 TCID50 and 106.74 TCID50 per ml for camelpox vaccine virus and buffalopox vaccine virus. However, the compounds 4a-e showed significant analgesic and antibacterial activities.

Synthesis and Evaluation of Analgesic/ Anti-inflammatory and Antimicrobial Activities of 3-Substituted-1,2,4-triazole-5-thiones

In this study, the synthesis of a novel series of Mannich bases of 5-mercapto-3-aryl-1,2,4-triazoles is described. The structures attributed to compounds la-5e were elucidated using IR and 1H-NMR spectroscopic techniques besides elemental analysis. The formation of 1-aminomethyl-3-substituted-1,2,4-triazole-5-thiones - not the isomeric 3-substituted-4-aminomethyl-1,2,4-triazole-5-thiones was unambiguously confirmed by X-ray crystallographic analysis of 1c. The compounds were examined for their in vivo anti-inflammatory and analgesic activity in two different bioassays, namely carrageenan-induced hind paw edema and p-benzoquinone-induced abdominal constriction tests in mice, respectively. In addition, the ulcerogenic effects of the compounds were determined. Among the tested derivatives most promising results were obtained for the compounds bearing a nonsubstituted phenyl group at C-3 position of the triazole ring (1a-e). The compounds were also evaluated for their in vitro antimicrobial activity against a series of gram positive bacteria [Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212)], gram negative bacteria [Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853)] and yeast-like microorganisms [Candida albicans (ATCC 90028), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019)]. One series of the examined compounds (3a-e) exhibited better antibacterial activity especially against gram positive bacteria than against gram negative bacteria. Compounds 2c, 3b, and 3e were found to be more effective against C. parapsilosis compared with the other derivatives (MIC: 16 microg/mL).

DNA binding and anticancer activity of naphthalimides with 4-hydroxyl-alkylamine side chains at different lengths

A series of novel naphthalimide derivatives modified with various hydroxyl-alkylamines at 4-position have been synthesized. Their DNA binding properties were investigated by UV-Vis, fluoescence, and circular dichroism (CD) spectroscopies and thermal denaturation. The results showed that compounds 3a-e as the DNA intercalator exhibited middle binding affinities with Ct-DNA. The anticancer activities of 3a-e were preliminarily evaluated, compounds 3c and 3e exhibited potent anticancer activities against Bel-7402 cell line with IC(50) values of 5.57 and 9.17μM, respectively. More interestingly, enhancement of the fluorescence emission was found in the complexes of 3a-e with Ct-DNA, especially for 3c. This would make these compounds as potential DNA staining agents.

New N-aryloxy-phthalimide derivatives. Synthesis, physico-chemical properties, and QSPR studies

Abstract Starting from N-hydroxyphthalimide 1 and the reactive fluoro- or chloro-nitroaryl derivatives 2, 3 and 4a-e (2-chloro-3,5-dinitropyridine; 3, NBD-chloride; 4a, 1-fluoro-2,4-dinitrobenzene; 4b, picryl chloride; 4c, 4-chloro-3,5-dinitrobenzotrifluoride; 4d, 2-chloro-3,5- dinitrobenzotrifluoride; 4e, 4-chloro-3,5-dinitrobenzoic acid) the corresponding N-(2-nitroaryloxy)-phthalimide derivatives 5a-e, or 6 and 7 were obtained and characterized by IR, UV-Vis 1H-NMR and 13C-NMR spectroscopy. The TLC behavior and the hydrophobicity of these derivatives have been experimentally evaluated by RM0 parameters (using RP-TLC). The experimental RM0 parameters were compared with the calculated partition coefficient, log P. A QSPR study was also performed to establish possible correlations between the structure and physical properties (λmax and RM0) of compounds 5a-e, 6, and 7.

Synthesis and Spectral Properties of Novel Thionaphtoquinone Dyes

2,3-Dichloro-1,4-naphtoquinone 1 compound was reacted with octadecanethiol 2 in two different mole ratio. Compound 3 was obtained from the reaction of 1 and 2 in 1:2 mole/mole ratio. Compounds 7 and 8 were obtained from reaction of 1 and 2 in 1:1 mole/mole ratio and known compound 9 was synthesized as by-product in this reaction. Novel compounds 5a-e were obtained from reaction of 1 and related thiols 4a-e. Known compounds 6c and 6e were synthesized as by-product in this reaction. The structures of the compounds were characterized by elemental analysis, UV-vis, FTIR, 1 H-NMR, 13 C-NMR and Mass spectroscopies.