Compounds 3a-e Research Articles

Synthesis and characterization of novel triazol compounds containing a thiophen ring as potential antifungal agents and the structure of 2-(2-hydroxy-2-p-tolyethyl)-5-(thiophen-2-ylmethyl)- 4-(4H-1,2,4-triazol-4-yl)-2H-1,2,4-triazol-3(4H)-one

A series of new 4-(3,5-disubstitue-4H-1,2,4-triazol-4-yl)- 5-(thiophen-2-yl-methyl)-2H-1,2,4-triazol-3(4H)-ones (3a-c) were obtained by reaction N'-1-ethoxy-2-thiophen-2-yl-ethylydene hydrazino carboxylic acid ethyl ester (1) and 4-amino-4H-1,2,4-triazoles (2). 4-(3,5-disubstitue-4H-1,2,4-triazol-4-yl)-2-(2-oxo-2-arylethyl)-5- (thiophen-2-yl-methyl)-2H-1,2,4-triazol-3(4H)-ones (4a-e) and ethyl 2-(4-(3,5-disubstitue-4H-1,2,4-triazol-4-yl)-5-oxo-3-(thiophen-2-ylmethyl)- 4,5-dihydro-1,2,4-triazol-1-yl)acetates (6a-c) were obtained by reaction of compounds 3 and bromoacetophenon derivatives and bromo ethylacetate, respectively. Compounds 5a-e were synthesized from the reaction of corresponding compounds 4a-e with NaBH_4. Compounds 7a-c were obtained by the reaction compounds 6 and LiAlH_4. Seventeen new compounds were synthesized and characterized by elemental analyses, IR, ^1H-NMR, and ^{13}C-NMR spectral data. The structure of compound 5d was inferred through IR, ^1H-, ^{13}C-NMR, elemental analyses, and X-ray spectral techniques. In addition, the newly synthesized chemicals were screened for their antibacterial and antifungal properties. Among the chemicals tested, 6a and 6b exhibited the highest degree of antifungal activity.

Synthesis of 3-(benzimidazol-2-yl-amino)-1-(4-bromophenyl)-2-thioxopyrimidin-4,6-dione analogs and their antimicrobial activity

3-(Benzimidazol-2-yl-amino)-5-(substituted benzylidene)-1-(4-bromophenyl)-2-thioxopyrimidin-4,6-dione (4a-e) and 5-(2-substituted phenylhydrazono)-3-(benzimidazol-2-yl-amino)-1-(4-bromophenyl)-2-thioxopyrimidine-4,6-dione (5a-c) were synthesized in three steps. Reaction of 2-hydrazinobenzimidazole (1) with 4-bromophenyl isothiocyanate gave 1-(benzimidazol-2-yl-amino)-4-(4-bromophenyl)thiosemicarbazide (2) which on cyclization with malonic acid in presence of acetyl chloride furnished 3-(benzimidazol-2-yl-amino)-1-(4-bromophenyl)-2-thioxopyrimidin-4,6-dione (3). Further, reaction of 3 with aryl aldehydes and diazonium salt of arylamines yielded desired compounds 4a-e and 5a-c in 52-72% yield. All the systhesized compounds have been characterized by spectral data's and they are screened for anti-microbial activity.

Regio- and Stereoselective 1,3-Dipolar Cycloaddition of C-Aryl-N-phenylnitrones over (E)-Arylidene-(2H)-indan-1-ones: Synthesis of Highly Substituted Novel Spiro-isoxazolidines

Synthesis of a series of novel spiro-isoxazolidines has been accomplished in good yields by regio- and diastereoselective 1,3-dipolar cycloaddition of (E)-2-arylidene-(2H)-indan-1-ones 1a-d to C-aryl-N-phenylnitrones 2e-h. The structure of the spiro-adducts 3ae-dh was elucidated by 1 H and 13 C NMR spectroscopy. The proposed regio- and stereochemistry of spiranic compounds 3ae and 3be has been corroborated by two single crystal X-ray crystallographic analyses and by means of DFT calculations.

Isocyanate diinsertion into the N–H bond of the 2-pyridylamino ligand of organolanthanides

[Cp2LnNHPy]2 (Py = 2-pyridyl) (1a-e) react with phenyl isocyanate to form the N-H diinsertion products Cp2Ln[eta2:eta1-PyNCON(Ph)CONHPh](THF) (Ln = Yb (3a), Er (3b), Y (3c), Dy (3d), Gd (3e)). It has been proven that nPr2NH can abstract one PhNCO unit from 3c to form Cp2Y[eta3-OC(NHPh)NPy] (2c) and nPr2NHCONHPh (4), representing a rare example of selective release of a functional group of ligands in organolanthanide chemistry. Hydrolysis of 2c gives the organic nitrogen-containing product PyNHCONHPh (5). Moreover, 3c can also be obtained by the reaction of 2c with PhNCO. These results demonstrate that the diinsertion of PhN=C=O into the N-H bond of coordinated amino ligands might proceed in a stepwise manner. All the compounds were characterized by elemental analysis and spectroscopic properties. The structures of compounds 3a-e and 4 are also determined through X-ray single-crystal diffraction analysis.

Synthesis of chiral N-(2-(1-oxophthalazin-2(1H)-yl) ethanoyl)-α-amino acid derivatives as antitumor agents

A series of chiral α-amino acid derivatives conjugated with 1-oxophthalazine moiety 5a-e were synthesized by coupling of various L-acylated amino acid derivatives with 2-(1-oxophthalazin- 2(1H)-yl)acetic acid in the presence of 1-hydroxybenzotriazole (HOBt) and N,N`- dicyclohexylcarbodiimide (DCC) as coupling reagent. Alternatively, compounds 5a-e were prepared by the reaction of the corresponding aizde 4, via the azide-coupling method, with L- acylated amino acid derivatives. The peptide esters 5a-d were converted into their corresponding amides 6a-d by treating with methanolic ammonia. Moreover, 5a was boiled with hydrazine hydrate to afford the corresponding hydrazide 7. Finally, the dipeptides 8a-c were prepared by coupling of 5a with the appropriate L-amino acid methyl ester. The synthesized compounds were tested against Caucasian breast adenocarcinoma MCF7 cell line.

Microwave Assisted Synthesis of Novel 1,2,3,4‐Tetrahydrocarbazolyl thiazolidin‐4‐ones and Azetidin‐2‐ones and its Biological Behavior

A new family of 1,2,3,4 – tetrahydrocarbazolyl thiazolidin‐4‐ones (4a-e) and 1,2,3,4–tetrahydrocarbazolyl azetidin‐2‐ones (5a-e) were individually derived using N‐[(α‐substituted bezylidenehydrazino) acetyl] ‐1,2,3,4‐tetra‐hydrocarbazoles 3a-e by cyclization with thioglycolic acid and chloro‐ acetylchloride respectively. The compounds (3a-e) were prepared by condensation of N‐(hydrazinoacetyl) 1,2,3,4‐tetrahydrocarbazole (2) with a series of aldehydes. The compound 2 was obtained by the hydrazinolysis of N‐(chloroacetyl)‐1,2,3,4‐tetrahydrocarbazole (1). These products were characterized by IR, NMR, MASS spectra and by elemental analysis. All the titled compounds (4a-e) and 5(a-e) were screened for antibacterial and antifungal activities.

Studies on the synthesis and fluorescent properties of long-chained 2-(5-alkyl-1, 3, 4-oxadiazol-2-yl)-3H-benzo[f]chromen-3-ones

The synthesis and fluorescent properties of some new benzocoumaryl heterocyclic molecules are presented. Condensation of 2-hydroxy-1-naphthaldehyde with diethyl malonate in the presence of catalytic amount of piperidine in ethanol affords benzocoumarin-3-ethyl carboxylate 2 in fairly good yield (90%). Further the compound 2 on treatment with hydrazine hydrate afforded compound 3 with excellent yield (95%). Thus compounds 4a-e have been obtained by direct cyclization of 3 with various fatty acids in the presence of POCl3. The structures of all newly synthesized compounds were confirmed by IR, 1 H NMR, 13 C NMR and UPLC-Mass spectral data. Fluorescent experimental results revealed remarkable photoluminescence properties. Luminescent properties of all newly synthesized compounds were determined and observed that they exhibited strong blue-green fluorescent properties. The fluorescence spectral properties of compounds 4a-e are similar to each other and the Stoke's shift ranges from 54 to 59 nm. Both the absorption and fluorescence maxima of the benzocoumarin-oxadiazole compounds showed good bathochromic shift.

Synthesis and antimicrobial activity of some oxazaphosphinine oxides

A new family of phosphorus heterocycle, namely 2-substituted 3-[4-(2-oxo-3,4-dihydro-2λ 5 benzo[e][1,3,2]oxazaphosphinin-3-yl)phenyl]-3,4-dihydrobenzo[e][1,3,2]oxazaphosphinin-2oxides (5a–j) has been synthesized by the condensation of 2-[[4-(2-hydroxy-benzylamino)phenylamino]methyl]phenol (1) with phosphorus oxychloride in presence of triethylamine in dry tetrahydrofuran, followed by the reaction with various phenols 3a–j. Alternatively, some of these compounds 5a-e were prepared by the cyclocondensation of 1 with aryl phosphorodichloridates 4a–e. All title compounds were characterized by elemental and spectral analyses. Their antimicrobial activity was also evaluated.

Synthesis, Acidity and Antioxidant Properties of Some Novel 3,4-disubstituted-4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives

3-Alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2a-g reacted with4-diethylaminobenzaldehyde to afford the corresponding 3-alkyl(aryl)-4-(4-diethyl-aminobenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3a-g. The acetylation reactions of compounds 3a-e were investigated and compounds 4a-e were thus obtained. The new compounds were characterized using IR, 1H-NMR, 13C-NMR, UV and MS spectral data. In addition, the newly synthesized compounds 3a-g were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as isopropyl alcohol, tert-butyl alcohol, acetone and N,N-dimethylformamide (DMF), and the half-neutralization potential values and the corresponding pKa values were determined for all cases. Moreover, 3 and 4 type compounds were also screened for their antioxidant activities.

Synthesis and antimicrobial, antifungal and anthelmintic activities of 3h-1,5-benzodiazepine derivatives

The diazonium salt of 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide in the presence of sodium hydroxide was condensed with different ?-diketones/?-ketoesters, 3a-e, to obtain new ?-diketones/?-ketoesters, 4a-e. The ?-diketones/?-ketoesters 4a-e were condensed with o-phenylenediamine (o-PDA) in presence of p-toluenesulfonic acid/SiO2 to give biologically active 3H-1,5-benzodiazepines, 5a-e. All the newly synthesized compounds were characterized by elemental analysis and spectral studies. The compounds 5a-e were screened for their antimicrobial, antifungal and anthelmintic activities.

Synthesis and Biological Evaluation of 2-amino-3-(3, 4, 5-trimethoxyphenylsulfonyl)-5-aryl thiophenes as a New Class of Antitubulin Agents

Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. Bioisosteres are substituents or groups that have chemical or physical similarities and that produce broadly similar biological effects. The sulfone moiety is recognized as a nonclassical bioisostere for replacement of the carbonyl group. When sulfonyl derivatives 5a-e were compared with carbonyl compounds 4a-e, the sulfone substitution dramatically decreased the antiproliferative activity of the series.

Synthesis and bioactivity of some new 2-substituted-3,4-dihydro-1-(9H- carbazol-4-yloxy)methyl-3-[2-(2-methoxyphenoxy)ethyl]-1,3,2 λ5-oxazaphosphole 2-oxides, sulfides and selenides

Novel 2-substituted-3,4-dihydro-1-(9H-carbazol-4-yloxy)methyl-3-(2-(2-methoxyphenoxy) ethyl)-1,3,2λ 5 -oxazaphosphole 2-oxides (3a-e) were synthesized by condensation of 1-(9H- carbazol-4-yloxy)-3-(2-(2-methoxy phenoxy)ethylamino)propan-2-ol (1) (carvedilol) with dichlorides of aryl phosphorodichloridates / N,N-bis(2-chloroethyl)phosphoramidic dichloride (2a-e) in the presence of triethylamine at 40 to 45 °C. The other title compounds (6a-c, and 6d-f) were prepared in two steps. In the first step, dichlorophenylphosphine/ethyl phosphorodichloridite was reacted with 1 in the presence of Et3N to give the corresponding P(III) intermediates (5a,b) in N2 atmosphere. In the second step, 5a,b were treated with H2O2, S or Se to convert them to the corresponding P(V) state (6a-c, 6d-f). Compounds 3a-e, 6a-f were screened for antifungal and antibacterial activity. Most of these compounds exhibited moderate activity.

Efficient Peptide Coupling Involving Sterically Hindered Amino Acids

Hindered amino acids have been introduced into peptide chains by coupling N-(Cbz- and Fmoc-alpha-aminoacyl)benzotriazoles with amino acids, wherein at least one of the components was sterically hindered, to provide compounds 3a-e, (3c +3 c'), 5a-d, (5a + 5a'), 6a-c, (6b + 6b'), 8a-c, 9a-e, 10a-d, and (10a + 10a') in isolated yields of 41-95% with complete retention of chirality as evidenced by NMR and HPLC analysis. The benzotriazole activation methodology is a new route for the synthesis of sterically hindered peptides. (Note: compound numbers written within brackets represent diastereomeric mixtures or racemates; compound numbers without brackets represent enantiomers.).

Microwave-Assisted Dehydrosulfurization: An Efficient, Solvent-Free Synthesis of 5-(1-Adamantyl)-2-arylamino-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles

A fast and efficient microwave-assisted synthesis of 2-arylamino-5-(1-adamantyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles is described. The reaction of 3-(l-adamantyl)-5-mercapto-l,2,4-triazole (2) with arylisothiocyanates in DMF at room temperature yielded the corresponding N,N'-disubstituted thioureas (3a-e) in high yields. Compounds (3a-e) were desulfurized via microwave irradiation for 5 min to yield the corresponding 5-(l-adamantyl)-2-arylamino-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles (4a-e). Compounds (4a-e) were also prepared in good yields via microwave irradiation of a mixture of (2) and the corresponding arylisothiocyanates for 8 minutes. Attempted preparation of the aliphatic analogues (6a-e) via microwave irradiation was unsuccessful, they were obtained in poor yields via prolonged heating of compound (2) with the corresponding aliphatic isothiocyanate in DMF. Compounds (6a-e) were independently obtained in good yields via the reaction of (2) with cyanogen bromide to yield the 2-amino analogue (7) that was subsequently reacted with the corresponding aliphatic halide.

Synthesis and anticonvulsant activities ofN-Cbz-α-aminoglutarimidooxy carboxylate derivatives

Previous studies on the anticonvulsant activity of N-Cbz-alpha-aminoglutarimides have shown that the derivatives of N-Cbz-alpha-amino-N-alkoxy glutarimide have significant anticonvulsant activity. In addition, their anticonvulsant activities are dependent on the presence of N-alkoxy groups. Based on these results, a series of N-Cbz-alpha-amino-glutarimidooxy carboxylates derivatives (3a-e) were synthesized in moderate yield using a known synthetic procedure. Their anticonvulsant activities were evaluated using the maximal electroshock seizure (MES) test, the pentylene tetrazole induced seizure (PTZ) test, and the strychinine (Str) threshold test with the ultimate aim of developing more active anticonvulsants. None of the compounds (3a-e) tested showed anticonvulsant activity in the MES and PTZ test. However, all the compounds tested exhibited significant anticonvulsant activity in the Str. test. The most active compound in the Str. test was the methyl ester of N-Cbz-alpha-amino-glutarimidooxy acetic acid 3a (ED50 = 42.9 mg/kg).

Synthesis and antimicrobial activity of succinimido(2-aryl-4-oxo-3-{[(quinolin-8-yloxy)acetyl]amino}-1,3-thiazolidin-5-yl)acetates

Hydroxyquinoline 1 reacts with ethyl chloroacetate in the presence of anhydrous K2CO3 to produce ethyl (quinolin-8-yloxy)acetate 2. Treatment of 2 with hydrazine hydrate forms 2- (quinolin-8-yloxy)acetohydrazide 3, which on condensation with various aldehydes 4a-e gives N'-{((1Z)-arylmethylene)-2-(quinolin-8-yloxy)}acetohydrazides 5a-e. These, on cyclization with mercaptosuccinic acid, yield (2-aryl-4-oxo-3-{((quinolin-8-yloxy)acetyl)amino}-1,3-thiazolidin- 5-yl) acetic acids 6a-e. Compounds 6a-e are further converted into acid chloride derivatives 7a- e by reaction with thionyl chloride. Subsequent treatment of 7a-e with N-hydroxysuccinimide in the presence of TEA furnishes the title compounds 8a-e. Antibacterial and antifungal activities of the final compounds have been evaluated and all the compounds have shown significant inhibition of bacterial and fungal growth.

6-Aryl-8H-indeno[1,2-d]thiazol-2-ylamines: A1 Adenosine Receptor Agonist Allosteric Enhancers Having Improved Potency

Allosteric enhancers (AEs) of the A(1) adenosine receptor (A(1)AR) have potential as drugs for treating neurological, cardiovascular, and renal diseases. This report describes the synthesis and evaluation of a series of 6-aryl-8H-indeno[1,2-d]thiazol-2-ylamines that exhibited AE activity at the A(1)AR. Palladium-mediated condensation of arylboronic acids with 5-bromoindan-1-one generated arylindanones 2a-aj for iodine-catalyzed condensation with thiourea, generating 2-aminothiazolium salts 3a-aj. Binding studies using membranes from cells stably expressing human A(1)ARs, A(2A)ARs, or A(3)ARs evaluated AE activity and receptor subtype selectivity. The EC(50) of the AE activities of compounds 3m-o, 3x, and 3ae were 2.2, 1.5, 0.9, 1.0, and 3.0 muM, respectively, substantially lower than that of the well characterized 2-amino-3-aroylthiophene (PD 81,723), >10 microM. The new compounds also have substantially higher maximal AE activity. These compounds had no AE activity at the A(2A)AR and only minimal activity at the A(3)AR.

Síntese, toxicidade frente a Artemia salina Leach e avaliação da atividade antimicrobiana de 1,2,4-oxadiazóis-3,5-difenilclorados

The known oxadiazoles 3,5-bis-(phenyl)-1,2,4-oxadiazole (3a); the 3-(4-chlorophenyl)-5-phenyl-1,2,4-oxadiazole (3b); and the new 3,5-diphenylchlorinated-1,2,4-oxadiazoles 3c-e were synthesized from the reaction of benzamidoximes with an appropriated acid chloride and cyclisation of the resulting O-acylbenzamidoxime intermediate. The compounds synthesized were characterized on the basis of their IR, NMR (1D and 2D) and mass spectral data. Compounds 3a-e were evaluated for their antimicrobial activity and for their toxicity towards brine shrimp (Artemia salina Leach).

Discovery of Novel Phenolic Antioxidants as Inhibitors of Vascular Cell Adhesion Molecule-1 Expression for Use in Chronic Inflammatory Diseases

Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of leukocytes to endothelial cells and is implicated in many inflammatory conditions. Since part of the signal transduction pathway that regulates the activation of VCAM-1 expression is redox-sensitive, compounds with antioxidant properties may have inhibitory effects on VCAM-1 expression. Novel phenolic compounds have been designed and synthesized starting from probucol (1). Many of these compounds demonstrated potent inhibitory effects on cytokine-induced VCAM-1 expression and displayed potent antioxidant effects in vitro. Some of these derivatives (4o, 4p, 4w, and 4x) inhibited lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 from human peripheral blood mononuclear cells (hPBMCs) in a concentration-dependent manner in vitro and showed antiinflammatory effects in an animal model. Compounds 4ad and 4ae are currently in clinical trials for the treatment of rheumatoid arthritis (RA) and prevention of chronic organ transplant rejection, respectively.

Facile One‐Pot Microwave Induced Solvent‐Free Synthesis and Antifungal Antitubercular Screening of Spiro [1,5]‐Benzothiazepin‐2,3′[3′H]indol‐2[1′H]‐ones.

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