Search Results (14)

Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the treatment of hypertension, heart failure, and in the acute phase of myocardial infarction. Lisinopril [N²-[(1S)-1-car-boxy-3-phenylpropyl]-L-lysyl-L-proline], enalapril [(S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline] and ramipril [2-aza-bicyclo-[3.3.0]-octane-3-carboxylic acid] are all five-membered heterocycles and three of the most prevalent ACE inhibitors in clinical use worldwide. ACE inhibitor-induced angioedema (AE) is clinically characterized by self-limited edema of the dermis and subcutaneous lipid tissue, localized on face skin, oral mucosa and tongue in most cases. However, severe episodes of intestinal AE misdiagnosed as acute appendicitis and laryngeal AE requiring incubation have been reported. The pathophysiology of ACE inhibitor-induced angioedema is attributed to the accumulation of bradykinin, which is a potent vasodilator with proinflammatory activity that is normally degraded by angiotensin-converting enzyme (ACE) and aminopeptidase P; however, a small proportion of treated patients is affected. Given that patients do not respond to anti-H1 antihistamines and steroids, early clinical recognition and discontinuation of the ACE inhibitors are the treatments of choice for the long-term management of ACE inhibitor- induced angioedema. The search period of the present review was set up until November 2023, and its aim is to shed light on the broader context of ACE inhibitor-induced angioedema, exploring aspects such as clinical presentation, pathophysiology, and therapeutic considerations in this potentially life-threatening condition. The exploration of alternative drug options such as angiotensin II receptor blockers, the potential association of coadministration of DPP-4 inhibitors with ACE inhibitors, the presentation of angioedema and the significant clinical importance of this condition are also discussed. By focusing on the chemical structure of ACE inhibitors, specifically their nitrogen-based heterocycles—an attribute shared by over 880 drugs approved by the FDA within the pharmaceutical industry—this review emphasizes the pivotal role of nitrogen scaffolds in drug design and underscores their relevance in ACE inhibitor pharmacology. Full article

Diisocyanates are highly reactive compounds with two functional isocyanate groups. The exposure of diisocyanates is associated with severely adverse health effects, such as asthma, inflammation in the respiratory tract, and cancer. The hydrolysis product from diisocyanates to related diamines is also a potential carcinogen. Here, we developed an effective, accurate, and precise method for simultaneous determination of residual diisocyanates and related diamines in biodegradable mulch films, based on N-ethoxycarbonylation derivatization and gas chromatography-mass spectrometry. The method development included the optimization of ultrasonic hydrolysis and extraction, screening of N-ethoxycarbonylation conditions with ethyl chloroformate, evaluation of the diamines degradation, and analysis of the fragmentation mechanisms. Under the optimum experimental conditions, good linearity was observed with R² > 0.999. The extraction recoveries were found in the range of 93.9–101.2% with repeatabilities and reproducibilities in 0.89–8.12% and 2.12–10.56%, respectively. The limits of detection ranged from 0.0025 to 0.057 µg/mL. The developed method was applied to commercial polybutylene adipate co-terephthalate (PBAT) biodegradable mulch film samples for analysis of the diverse residual diisocyanates and related diamine additives. The components varied greatly among the sample from different origin. Overall, this study provides a reliable method for assessing safety in biodegradable mulch films. Full article

In this study, solvogels containing (2-((2-(ethoxycarbonyl)prop-2-en-1-yl)oxy)-ethyl) phosphonic acid (ECPA) and N,N′-diethyl-1,3-bis-(acrylamido)propane (BNEAA) as the crosslinker are synthesized by UV induced crosslinking photopolymerization in various solvents. The polymerization of the ECPA monomer is monitored by the conversion of double bonds with in situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The morphology of the networks is characterized by in situ photorheology, solid state NMR spectroscopy, and scanning electron microscopy (SEM) of the dried gels. It is demonstrated that the storage modulus is not only determined by the crosslinker content in the gel, but also by the solvent used for preparation. The networks turn out to be porous structures with G′ being governed by a rigid, phase-separated polymer phase rather than by entropic elasticity. The external and internal pK_a values of the poly(ECPA-co-BNEAA) gels were determined by titration with a specially designed method and compared to the calculated values. The polymer-immobilized phosphonic acid groups in the hydrogels induce buffering behavior into the system without using a dissolved buffer. The calcium accumulation in the gels is studied by means of a double diffusion cell filled with calcium ion-containing solutions. The successful accumulation of hydroxyapatite within the gels is shown by a combination of SEM, energy-dispersive X-ray spectroscopy (EDX) and wide-angle X-ray scattering (WAXS). Full article

An alternative Au(I)-catalyzed synthetic route to functionalized 1,2-dihydroquinolines is reported. This novel approach is based on the use of N-ethoxycarbonyl protected-N-propargylanilines as building blocks that rapidly undergo the IMHA reaction affording the 6-endo cyclization product in good to high yields. In the presence of N-ethoxycarbonyl-N-propargyl-meta-substituted anilines, the regiodivergent cyclization at the ortho-/para-position is achieved by the means of catalyst fine tuning. Full article

Due to their outstanding physicochemical properties, the next generation of the graphene family—graphene quantum dots (GQDs)—are at the cutting edge of nanotechnology development. GQDs generally possess many hydrophilic functionalities which allow their dispersibility in water but, on the other hand, could interfere with reactions that are mainly performed in organic solvents, as for cycloaddition reactions. We investigated the 1,3-dipolar cycloaddition (1,3-DCA) reactions of the C-ethoxycarbonyl N-methyl nitrone 1a and the newly synthesized C-diethoxyphosphorylpropilidene N-benzyl nitrone 1b with the surface of GQDs, affording the isoxazolidine cycloadducts isox-GQDs 2a and isox-GQDs 2b. Reactions were performed in mild and eco-friendly conditions, through the use of a natural deep eutectic solvent (NADES), free of chloride or any metal ions in its composition, and formed by the zwitterionic trimethylglycine as the -bond acceptor, and glycolic acid as the hydrogen-bond donor. The results reported in this study have for the first time proved the possibility of performing cycloaddition reactions directly to the p-cloud of the GQDs surface. The use of DES for the cycloaddition reactions on GQDs, other than to improve the solubility of reactants, has been shown to bring additional advantages because of the great affinity of these green solvents with aromatic systems. Full article

The development of the methods for amide bond formation is important for various uses in the laboratory and industrial applications. The compounds combined in their structures 1,4-dihydroisonicotinic acids and amino acids linked with an amide bond can be considered as “privileged structures” due to their broad range of biological activities. Herein, the formation of amide bond between 1,4-dihydroisonicotinic acid and l-methionine is reported. The coupling of l-methionine with pentafluorophenyl active ester of 1,4-dihydroisonicotinic acid appears to be a convenient and effective method for amide bond formation. Sodium N-(3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carbonyl)-l-methioninate has been successfully synthesized via a procedure where the key step is amide formation from 5-diethyl 4-(perfluorophenyl) 2,6-dimethyl-1,4-dihydropyridine-3,4,5-tricarboxylate and l-methionine. Sodium salt formation was performed to improve physicochemical properties, such as solubility of the l-methionine-derived 1,4-dihydroisonicotinamide. The obtained target compound was fully characterized by UV, IR, ¹H NMR, ¹³C NMR, MS, and microanalysis. Full article

The sensory characteristics and volatile compounds that affect consumers’ acceptance of rice liquors were investigated. A total of 80 consumers evaluated 12 yakju samples and descriptive analysis by 11 trained panelists was conducted. Solvent-assisted flavor evaporation-gas chromatography-mass spectrometry analysis also was conducted revealing 120 volatile compounds in the yakju samples. Sensory attributes (n = 31) except appearance attributes were used for principal component analysis (PCA). As results, fruit odor (apple, hawthorn, omija, and pineapple odor) and flower odor (chrysanthemum, pine, and peppermint odor) were placed on the positive side of PC1 whereas persimmon vinegar odor, bitter taste, alcohol flavor, stinging and coating mouthfeel were located on the negative side of PC1. The yakju samples were mainly characterized by their alcohol content and supplementary ingredients. Sensory descriptors (n = 31; except appearance attributes and p > 0.05) and volatile compounds (n = 30; p > 0.5 correlation coefficient with overall acceptance) were chosen for multiple factor analysis (MFA). The MFA correlation map showed that ethyl propanoate, ethyl-2-hydroxy-2-methylbutanoate, methyl 2-furoate, γ-butyrolactone, 4-ethoxycarbonyl-γ-butyrolactone, hawthorn odor, apple flavor, grape flavor, and sweet taste were positively correlated with young consumers’ overall acceptance. Additionally, negative correlation with overall acceptance was found in 1,3-butanediol, 2,3-butanediol, and 1,1-diethoxy-3-methylbutane. Full article

Novel ether thionocarbamates, O-butoxy isopropyl-N-ethoxycarbonyl thionocarbamate (BIPECTC) and O-(2-butoxy-1-methylethoxy) isopropyl-N-ethoxycarbonyl thionocarbamate (BMIPECTC), were synthesized in this study. Their collecting efficiencies in the flotation of chalcopyrite were investigated using flotation tests, adsorption measurements, ultraviolet spectra (UV) and Fourier transform-infrared spectroscopy (FT-IR) and density functional theory (DFT) calculations. The synthesized ether thionocarbamates showed better frothing properties than methyl-isobutyl-carbinol (MIBC) and stronger affinity to chalcopyrite compared with O-isopropyl-N-ethyl thionocarbamate (IPETC) and O-isobutyl-N-ethoxycarbonyl thionocarbamate (IBECTC). UV spectra analysis showed that the ether thionocarbamates react with Cu²⁺, with the exception of Fe²⁺, Ni²⁺, Zn²⁺ and Pb²⁺. Additionally, it was further confirmed by FTIR spectra that a chemical reaction occurs between copper ion and BIPECTC and BMIPECTC. The adsorption capacity measurements revealed that chalcopyrite exhibits good adsorption ability for ether thionocarbamates at an approximate pH of 8–10, which agrees with the flotation tests. The quantum chemistry calculation results indicated that the ether thionocarbamates exhibit stronger collecting ability for copper mineral in terms of frontier molecular orbital analysis, binding model simulation with copper ions and the molecular hydrophobicity compared with IPETC and IBECTC. The computational results are in very good agreement with the experimental results. Full article

A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives 1a,b as starting materials. Treatment of 1a,b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to afford the thioamides 4a,b, which was reacted with methyl iodide to obtain methylated products 5a,b. Cyclocondensation of 4a,b with chloroacetone 6 and phenacyl chloride 7 gave the corresponding thiophene derivatives 9a–c. Reaction of 4a,b with C-acetyl-N- arylhydrazonoyl chlorides 14a and 14b in boiling EtOH in the presence of triethylamine, afforded the corresponding 1,3,4-thiadiazoline derivatives 16a–d. The thioamides 4a,b were reacted with C-ethoxycarbonyl-N-arylhydrazonoyl chlorides 18a,b which afforded 1,3,4-thiadiazoline derivatives 19a–d. The benzosuberones 1a,b were treated with 3-mercaptopropanoic acid to give compounds 21a,b, which were cyclized to tricyclic thiopyran-4(5H)-one derivatives 22a,b. The latter compounds 22a,b were reacted with 3-mercaptopropanoic acid to give compounds 23a,b, which were cyclized tetracyclic ring systems 24a,b. Finally, compounds 24a,b were oxidized using hydrogen peroxide under reflux conditions to afford the oxidized form of the novel tetracyclic heterogeneous ring systems 25a,b. The newly synthesized compounds were screened for antimicrobial activities. The structures of new compounds were characterized by ¹H-NMR, ¹³C-NMR, IR, and EI-MS. Full article

Two high-speed countercurrent chromatography (HSCCC) modes were compared by separation of major alkaloids from crude extract of Picrasma quassioides. The conventional HSCCC separation was performed with a two-phase solvent system composed of petroleum ether–ethyl acetate–methanol–water (5:5:4.5:5.5, v/v/v/v) with 200 mg loading. pH-Zone-refining CCC was performed with two-phase solvent system composed of petroleum ether–ethyl acetate–n-butanol–water (3:2:7:9, v/v/v/v) where triethylamine (10 mM) was added to the upper organic stationary phase and hydrochloric acid (5 mM) was added to the lower aqueous phase with 2 g loading. From 2 g of crude extract, 87 mg of 5-methoxycanthin-6-one (a), 38 mg of 1-methoxy-β-carboline (b), 134 mg of 1-ethyl-4,8-dimethoxy-β-carboline (c), 74 mg of 1-ethoxycarbonyl-β-carboline (d), 56 mg of 1-vinyl-4,8-dimethoxy-β-carboline (e) and 26 mg of 1-vinyl-4-dimethoxy-β-carboline (f) were obtained with purities of over 97.0%. The results indicated that pH-zone-refining CCC is an excellent separations tool at the multigram level. Full article

A series of novel polyfunctionalized acyclic and heterocyclic dye precursors and their respective azo (hydrazone) counterpart dyes and dye precursors based on conjugate enaminones and/or enaminonitrile moieties were synthesized. The dyes and their precursors are based on 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide, 2-ethoxycarbonyl-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide or 2-phenylcarbamoyl-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide systems as precursors. The latter compounds were used to synthesize polyfunctional thiophene-, thiazole-, pyrazole, pyridine-, pyrimidine-, oxazine-, as well as acyclic moieties. The dyes and dye precursors were characterized by elemental analysis and spectral methods. All dyes and their precursors were screened in vitro and evaluated for both their antibacterial and antifungal activities. MIC data of the novel dye systems and their respective precursors showed significant antimicrobial activity against most tested organisms. Some compounds exhibited comparable or even higher efficiency than selected standards. Dyes were applied at 5% depth for disperse dyeing of nylon, acetate and polyester fabrics. Their spectral characteristics and fastness properties were measured and evaluated. Full article

The reaction of 5-(1-adamantyl)-4-amino-3-mercapto-1,2,4-triazole (5) with various aromatic aldehydes in ethanol or acetic acid yielded the corresponding 4-arylideneamino derivatives 6a–v. Treatment of the 4-(2,6-difluoro- and dichlorobenzylideneamino) derivatives 6o and 6q with 1-substituted piperazines, and formaldehyde solution in ethanol afforded good yields of the corresponding 5-(1-adamantyl)-4-(2,6-dihalobenzylideneamino-2-(4-substituted-1-piperazinylmethyl)-1,2,4-triazoline-3-thiones 7a–p. 5-(1-Adamantyl)-4-arylideneamino-2-(4-ethoxycarbonyl-1-piperidylmethyl)-1,2,4-triazoline-3-thiones 8a–n, were similarly prepared via the reaction of the corresponding arylideneamino derivative with ethyl 4-piperidinecarboxylate and formaldehyde solution in ethanol. Compounds 6a–v, 7a–p and 8a–n were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives showed good or moderate activities, particularly against the tested Gram-positive bacteria. In addition, the in vivo anti-inflammatory activity of 21 compounds was determined using the carrageenan-induced paw oedema method in rats. Compounds 7d, 7g, 7i, 7j, 7l, 8c, 8e and 8l showed good or moderate dose-dependent activity in this area. Full article