Amide Ethyl Research Articles

Hydroxyethylamide substituted triterpenoic acids hold good cytotoxicity for human tumor cells

Pentacyclic triterpenoic acids, betulinic acid, platanic acid, oleanolic acid and ursolic acid, were acetylated and subsequently converted into mono-, bis- and tris(hydroxyl)ethyl amides. While parent compounds are of none or minor cytotoxicity, these amides showed EC50 values even in low μM concentration for a variety of different human tumor cell lines. Especially a bis(hydroxyethyl)amide 12 derived from oleanolic acid held an EC50 = 7.7 μM for A375 melanoma cells while being less cytotoxic for non-malignant fibroblasts NIH 3 T3 (EC50 > 30 μM). Several of these amides were converted into their corresponding sulfamates. While these sulfamates held no inhibitory activity for the enzyme carbonic anhydrase II, the highest cytotoxicity was observed for a betulinic acid derived sulfamate 17 with an EC50 = 4.9 μM for A375 melanoma cells.

Synthesis of N-hydroxycinnamoyl amide derivatives and evaluation of their anti-oxidative and anti-tyrosinase activities

Twelve N-hydroxycinnamoyl amino acid amide ethyl esters (CAES) were synthesized by using l-amino acid ethyl ester hydrochloride and corresponding cinnamic acid (ferulic acid, acetylferulic acid and caffeic acid) as raw materials in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide-hydrochloride (EDC) and 1-hydroxybenzotriene (HOBt). The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities of CAES were evaluated. The anti-tyrosinase activities of N-feruloyl amino acid ethyl esters and the hydroxyl (OH) free radical scavenging activities of N-caffeoyl amino acid ethyl esters were also examined. DPPH free radical scavenging activity was shown in all CAES, of which N-caffeoyl amino acid ethyl esters demonstrated higher radical scavenging activity than N-feruloyl amide derivatives, and (E) -N-(caffeic acid)-l-glycinate ethyl ester (c5) had the strongest ability to scavenge free radicals with an IC50 value of 18.6 µM. The acetylferuloyl amino acid esters exhibited the highest tyrosinase inhibition activity among the tested amides.

A conceptual framework for the development of iridium(iii) complex-based electrogenerated chemiluminescence labels.

Translation of the highly promising electrogenerated chemiluminescence (ECL) properties of Ir(iii) complexes (with tri-n-propylamine (TPrA) as a co-reactant) into a new generation of ECL labels for ligand binding assays necessitates the introduction of functionality suitable for bioconjugation. Modification of the ligands, however, can affect not only the photophysical and electrochemical properties of the complex, but also the reaction pathways available to generate light. Through a combined theoretical and experimental study, we reveal the limitations of conventional approaches to the design of electrochemiluminophores and introduce a new class of ECL label, [Ir(C^N)2(pt-TOxT-Sq)]+ (where C^N is a range of possible cyclometalating ligands, and pt-TOxT-Sq is a pyridyltriazole ligand with trioxatridecane chain and squarate amide ethyl ester), which outperformed commercial Ir(iii) complex labels in two commonly used assay formats. Predicted limits on the redox potentials and emission wavelengths of Ir(iii) complexes capable of generating ECL via the dominant pathway applicable in microbead supported ECL assays were experimentally verified by measuring the ECL intensities of the parent luminophores at different applied potentials, and comparing the ECL responses for the corresponding labels under assay conditions. This study provides a framework to tailor ECL labels for specific assay conditions and a fundamental understanding of the ECL pathways that will underpin exploration of new luminophores and co-reactants.

Properties of the Amide Bond Involving Proline 4,5‐methanologues: an Experimental and Theoretical Study

AbstractHerein we disclose a combined experimental and theoretical study on the conformational properties of amide bonds involving diastereomeric 4,5‐methano‐L‐proline congeners as N‐acetyl ethyl esters and dimeric amide ethyl esters as substrates for cyclization to diketopiperazines. The results are discussed in light of density functional theory calculations aimed at delineating the importance of the n→π* stabilization of the trans‐amide conformations. The transitions states for the cyclization of diastereomeric 4,5‐methano‐L‐proline ethyl esters to diketopiperazines were calculated and correlated to the experimental studies.

Biocompatible hydrogelators based on bile acid ethyl amides

Four novel bile acid ethyl amides were synthetized using a well-known method. All the four compounds were characterized by IR, SEM, and X-ray crystal analyses. In addition, the cytotoxicity of the compounds was tested. Two of the prepared compounds formed organogels. Lithocholic acid derivative 1 formed hydrogels as 1% and 2% (w/v) in four different aqueous solutions. This is very intriguing regarding possible uses in biomedicine.

Study on Corrosion Scale Inhibitor for Blast Furnace Gas TRT System

Cyclohexylamine, morphine, ethanolamine, propiolic alcohol, seventeen alkenyl amide ethyl imidazoline, water depolymerization malaya acid anhydride, etc were chosen as the raw material of corrosion scale inhibitor in view of corrosion scaling reason and characteristic of blast furnace top gas pressure recovery turbine unit. The optimized formula of corrosion inhibitor have been obtained through orthogonal experiment. Corrosion and scale inhibitor performance were evaluated respectively by static weight-loss method, dynamic weight-loss method and calcium carbonate deposition. The results show that when these components are reasonable distributed, the corrosion effect is satisfied. When water depolymerization malaya acid anhydride is combined with the corrosion inhibitor, the corrosion and scale inhibition efficiency of composite inhibitor are more than 90%. Simulation blast furnace gas is adopted in dynamic simulation experiment, the corrosion inhibition efficiency is over 92%.

ChemInform Abstract: HBF4·OEt2 as a Mild and Versatile Reagent for the Ritter Amidation of Olefins: A Facile Synthesis of Secondary Amides.

Abstract A variety of alkenes undergo smooth amidation with nitriles in the presence of HBF4·OEt2 at room temperature under mild conditions to afford the corresponding secondary amides in good to excellent yields. This is a highly efficient method for the preparation of α-aryl ethyl amides especially from vinyl arenes without any side reactions such as olefin polymerization. The use of readily available and easy to handle reagent HBF4·OEt2 makes this method simple, convenient, and practical.

HBF 4·OEt 2 as a mild and versatile reagent for the Ritter amidation of olefins: a facile synthesis of secondary amides

A variety of alkenes undergo smooth amidation with nitriles in the presence of HBF 4·OEt 2 at room temperature under mild conditions to afford the corresponding secondary amides in good to excellent yields. This is a highly efficient method for the preparation of α-aryl ethyl amides especially from vinyl arenes without any side reactions such as olefin polymerization. The use of readily available and easy to handle reagent HBF 4·OEt 2 makes this method simple, convenient, and practical.

An EIS study of the effect of the pedant group in imidazolines as corrosion inhibitors for carbon steel in CO2 environments

AbstractElectrochemical impedance spectroscopy (EIS) measurements were carried out to study the corrosion inhibition of carbon steel in 3 % NaCl with and without diesel saturated with CO2 at 50 °C. The inhibitors examined were hydroxyethyl (HEI‐18), amino ethyl (AEI‐18), and amide ethyl imidazolines (AMEI‐18). When the oily phase, i.e diesel, is absent, the inhibition efficiency of the imidazolines is low, around 80 %. It was found, however, that the inhibition dramatically increased with the presence of the oily phase, because the imidazolines are able to act as both emulsifiers and corrosion inhibitors. Experimental results showed an increase in the film resistance (Rf), charge transfer resistance (Rct), capacitance of the film and the capacitance of the double layer values with the addition of inhibitor in presence of the oily phase also in several orders of magnitude. The most effective inhibitor in presence of diesel is a solution of AMEI‐18, as the oily phase is carried to the surface also. This is due to the presence of two large alkyl groups than the only chain present in the HEI‐18 and AEI‐18 imidazolines with better hydrophobic properties associated with the formation of a protective film that reduces drastically the corrosion process. The effects of the interaction of inhibitors with hydrocarbons and the correlation on the performance of inhibitor films have been examined.

Esters and amides of 2,3-dimethoxy-8,9-methylenedioxy-benzo[ i]phenanthridine-12-carboxylic acid: Potent cytotoxic and topoisomerase I-targeting agents

The exceptional topoisomerase I-targeting activity and antitumor activity of 5-(2- N, N-dimethylamino)ethyl-8,9-dimethoxy-2,3-methylenedioxy-5 H-dibenzo[ c, h][1,6]naphthyridin-6-one (ARC-111, topovale) prompted studies on similarly substituted benzo[ i]phenanthridine-12-carboxylic ester and amide derivatives. Among the benzo[ i]phenanthridine-12-carboxylic esters evaluated, the 2-( N, N-dimethylamino)ethyl, 2-( N, N-dimethylamino)-1-methylethyl, and 2-( N, N-dimethylamino)-1,1-dimethylethyl esters possessed similar cytotoxicity, ranging from 30 to 55 nM in RPMI8402 and KB3-1 cells. Several of the carboxamide derivatives possess potent topoisomerase I-targeting activity and cytotoxicity. The 2-( N, N-dimethylamino)ethyl, 2-( N, N-diethylamino)ethyl, and 2-(pyrrolidin-1-yl)ethyl amides were among the more cytotoxic benzo[ i]phenanthridine-12-carboxylic derivatives, with IC 50 values ranging from 0.4 to 5.0 nM in RPMI8402 and KB3-1 cells.

Chronobiotic activity of N-[2-(2,7-dimethoxyfluoren-9-yl)ethyl]-propanamide. Synthesis and melatonergic pharmacology of fluoren-9-ylethyl amides

A series of fluoren-9-yl ethyl amides ( 2) were synthesized and evaluated for human melatonin MT 1 and MT 2 receptor binding. N-[2-(2,7-dimethoxyfluoren-9-yl)ethyl]propanamide ( 2b) was selected and evaluated in functional assays measuring intrinsic activity at the human MT 1 and MT 2 receptors and demonstrated full agonism at both receptors. The chronobiotic properties of 2b were demonstrated in both acute and chronic rat models where 2b produced an acute phase advance of 32 min at 1 mg/kg and chronically entrained free-running rats with a mean effective dose of 0.23 mg/kg. Compound 2b is significantly less efficacious than melatonin in constricting human coronary artery.

Tetracarbonyl Systems: VII. Reactions of 1,3,4,6-Tetracarbonyl Compounds with o-Aminothiophenol in the Synthesis of Regioisomeric 3(2)-Aroylmethylene-1,4-benzothiazin-2(3)ones

In reaction of 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones with o-aminothiophenol (3Z)-3-aroylmethylene-3,4-dihydro-2H-1,4-benzothiazin-2-ones were obtained in a preparative yield. In solution of the latter compounds an enamine-imine tautomerism was observed. In reaction of ethyl esters or amides of 2-substituted 6-aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic acids with the o-aminothiophenol regioisomeric 2-aroylmethylene-2H-1,4-benzothiazin-3(4H)-ones were formed.

Selective sensing of zinc ions with a novel magnetic resonance imaging contrast agent†

Light-based microscope imaging techniques using fluorescence sensor molecules suffer from photobleaching and light scattering, but magnetic resonance imaging (MRI) can provide three-dimensional imaging without these problems. Recently, “smart” MRI contrast agents which modulate the access of water to a chelated gadolinium (Gd3+) ion in the presence or absence of a specific trigger have been reported. Zinc (Zn2+) is an essential component of many enzymes, transcription factors and synaptic vesicles in excitatory nerve terminals, so imaging of chelatable Zn2+ is of interest. We have designed and synthesized the Gd3+ DTPA bisamide complex 7a as a Zn2+-sensitive MRI contrast agent. Compound 7a shows a dose-dependent change in the R1 relaxivity in the presence of Zn2+. We investigated this relaxation behavior, and for this purpose we also synthesized the Gd3+ DTPA amide ethyl ester complex 7b. It was shown that binding between 7a and Zn2+ caused a change in the relaxation time. Moreover, 7a had high selectivity for Zn2+ against Ca2+ and Mg2+. Compound 7a may have practical problems for in vivo usage, since the R1 relaxivity is reduced with increased Zn2+ concentration. However, this report demonstrates new approaches to the design and synthesis of Gd3+ complexes with R1 values that change with variation in Zn2+ concentration.

Purification, characterization, crystallization and preliminary X-ray diffraction of acuthrombin-B, a thrombin-like enzyme from Agkistrodon acutus venom.

Acuthrombin-B, a thrombin-like enzyme from Agkistrodon acutus venom, has been isolated and purified to homogeneity by ion-exchange chromatography on DEAE-Sepharose, gel filtration on Sephacryl S-100 and fast performance liquid chromatography on DEAE-8HR. The protease is an acid protein (pI 6.0) consisting of two non-identical polypeptide chains (14.4 and 16 kDa) and there is no disulfide bond between the subunits. Its molecular weight is 27 kDa as estimated by gel filtration on Sephacryl S-100. The protease has arginine-esterase activity and hydrolyzes synthetic substrates such as p-toluenesulfonyl arginine methyl ester and alpha-N-benzoyl-L-arginine amide ethyl ester, and shows clotting activity with human fibrinogen, rabbit citrated plasma and human citrated plasma in vitro. The specific activity with human fibrinogen was estimated to be 230 NIH units mg-1. The protease is considered as a serine-type protease and contains metal ion(s) to some extent, as indicated by the fact that its clotting and arginine-esterase activities could be completely inhibited by PMSF and partially inhibited by the chelating agent EDTA, while the thrombin inhibitor heparin had no effect on its clotting activity towards rabbit citrated plasma. Acuthrombin-B crystals with a resolution limit of 2.06 A were obtained by conventional hanging-drop vapour diffusion. The crystals belong to space group P21 with unit-cell parameters a = 34.97, b = 53.58, c = 67.88 A, beta = 98.89 degrees and contain one molecule per asymmetric unit.

The use of methoxy acetoxy esters significantly enhances reaction rates in the lipase-catalyzed preparation of enantiopure 1-(4-chloro phenyl) ethyl amines

In this paper we report on the lipase-catalyzed preparation of enantiopure amines. Hydrolysis of two different ( R, S)-[1-(4-chlorophenyl)] ethyl amides was best performed in phosphate buffer, resulting in conversions ∼48% and optical purities of the ( S)-product >99% ee. Similar optical purities and conversions were found in the R-selective acylation of the ( R, S)-amine using two different acyl donors in t-butylmethyl ether. The reaction rate was significantly enhanced using methoxy acetoxy acid derivatives either as leaving group in the hydrolysis of the ( R, S)-amide or as ethyl ester in the acylation of the ( R, S)-amine. In all reactions studied, immobilized lipase from Candida antarctica B gave the best results.

New 4(5H)-oxazolonium perchlorate derivatives

The condensation of 2,3-dimethyl-4(5H)-oxazolonium salts with ethyl orthoformate and amides of 5-substituted 2-furancarboxylic acids gives the corresponding products derived by modification of the methyl group at C(2), 2-formylmethylene-4-oxazolidinone and 2-furoylaminoethenyl-4(5H)-oxazolanium perchlorates.

Enzymatically catalyzed synthesis of oxytocin fragments 1-6 and 7-9

Papain, α-chymotrypsin, thermolysin and elastase were utilized in the synthesis of peptide bonds of the protected oxytocin nonapeptide, except the S-benzylcysteine-proline bond. Amino groups were protected with benzyloxycarbonyl or tert-butyloxycarbonyl groups, carboxy groups as ethyl ester, phenylhydrazides or amides. The cysteine sulfhydryl group was blocked with the benzyl group whereas the tyrosine hydroxyl was unprotected. Most of the fragments were synthesized in satisfactory yields using an equimolar ratio of both reaction components and minimal (experimentally determined) amount of the given enzyme.

The Preparation of Protoheme Mono-N-[5-(2-methyl-1-imidazolyl)pentyl]amide and Its Oxygenation

Abstract Iron(II)protoporphyrin IX N-[5-(2-methyl-1-imidazolyl)pentyl]amide ethyl ester (1) and its derivatives (2–4) were prepared. They predominantly form pentacoordinate heme complexes in organic and aqueous solutions, based on their 2-methylimidazole-ligand and spacer N-pentylamide groups. Oxygen adducts of 1–4 were rapidly formed on exposure to oxygen in N,N-dimethylformamide (DMF) at −30 °C, and their life-times were more than 30 min.

Synthesis and properties of 3-substituted 2h-1,2,4-benzothiadiazine 1,1-dioxides

The ethyl ester and amides of 2H-1,2,4-benzothiadiazine-3-carboxylic acid 1,1-dioxide were obtained by reaction of 2-aminobenzenesulfonamide with diethyl oxalate or oxamic acid esters in the presence of sodium methoxide. The hydrolysis, animation, and hydrazinolysis of the ester were studied.

Investigations in the field of pyridinenarboxylic acids II. Gas-liquid chromatography of carboxylic acids of the pyridine series and their amides

1. The synthesis of ethyl esters and amides ofα-picolinic, nicotinic, isonicotinic, quinolinic, isocinchomeronic, and dipicolinic acids was developed. 2. A gas-liquid Chromatographie analysis of pyridinecarboxylic acids in the form of their ethyl esters, and that of the amides of pyridinecarboxylic acids in the form of their nitriles by preliminary rapid phosgenization of the amides of the corresponding nitriles, was developed.