Aminomethyl Derivatives Research Articles

Synthesis, antimicrobial activity and docking study of some novel 4-(4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino derivatives carrying biologically active sulfonamide moiety

A new series of 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(substituted)benzenesulfonamide 3–17, monosubstituted 2-((4-((4-aminophenyl)sulfonyl)phenyl)amino)methylene 18, and its disubstituted derivative 19 were synthesized from the starting material 2-((dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione 2. The crystal structures of compounds 2, 7 and 13 were reported by us through X-ray crystallography. All the prepared compounds were evaluated for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Clostridium sporogenes), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli), and antifungal activity against Aspergillus fumigatus, Penicillium chrysogenum, Fusarium oxysporum, Candida albicans. The synthesized compounds displayed interesting antimicrobial activity. Compounds 4 and 12 were the most potent in this study and displayed higher activity compared to the reference drugs, with MIC value of 3.9–31.3μg/mL against a panel of Gram-positive, Gram-negative bacteria and fungi. Molecular modeling was performed inside the active site of dihydropteroate synthase. The synthesized compounds showed similar orientation and binding interactions to that of the co-crystallized ligand inside the binding pocket.

Synthesis and membrane-protective activity of 2,6-diisobornylphenol derivatives with N- and O-containing fragments at position 4

Two series of new amide derivatives containing 2,6-diisobornylphenol moiety were synthesized based on 3,5-diisobornyl-4-hydroxybenzoic acid and 4-butylaminomethyl-2,6-diisobornylphenol. Toxicity, membrane-protective (MP) and antioxidant (AO) activity of the obtained compounds were evaluated using red blood cells of laboratory mice as the test object. The tests demonstrated the absence of hemolytic activity for all the synthesized derivatives and the presence of high MP and AO activity under conditions of acute H2O2-induced oxidative stress for (3,5-diisobornyl-4-hydroxyphenyl)(morpholino)methanone and N-n-butyl-N-(3,5-diisobornyl-4-hydroxybenzyl)acetamide. A comparison of the data of the newly obtained compounds and those of described earlier 2,6-diisobornylphenol derivatives with N- and O-containing fragments at position 4 (alkoxymethyl, carboxy, and aminomethyl derivatives) led to a conclusion that the most promising for further studies of pharmacological activity are compounds containing methoxycarbonyl, methoxymethyl, ethoxymethyl, morpholinomethyl, di-n-butylaminomethyl, (azepan-1-yl)methyl, or N-acetyl-N-alkylaminomethyl function, which provide low toxicity and high MP and AO activity.

Reductive Amination as an Aminomethylation Method for Isoflavone Ring B

The possibility of introducing a substituted aminomethyl group into ring B of an isoflavone via reductive amination was studied. Several novel 2′-aminomethyl derivatives of natural 7-hydroxy-3′,5′ -dimethoxyisoflavone and its 7-O-methoxy derivative were synthesized.

Inverse electron demand Diels–Alder reactions with aminomethyl derivatives of 3-arylhydroxycoumarins

The reactivity of Mannich bases derived from 6- and 7-hydroxycoumarins was studied in inverse electron demand Diels–Alder reactions with enamines. The reactions were shown to proceed by a cycloaddition mechanism followed by transformation of hemiaminals and resulted in the formation of heterocyclic pyrano[2,3-a]xanthene, pyrano[2,3-b]xanthene, and pyrano[3,2-b]xanthene.

Oxa-Pictet–Spengler reaction as key step in the synthesis of novel σ receptor ligands with 2-benzopyran structure

The Oxa-Pictet–Spengler reaction of methyl 3-hydroxy-4-phenylbutanoate (8) was explored to obtain novel σ receptor ligands. 1-Acyl protected piperidone ketals 10 and 11 reacted with phenylethanol 8 to yield spirocyclic compounds. Aliphatic aldehyde acetals 19 provided 1,3-disubstituted 2-benzopyrans 20 with high cis-diastereoselectivity. The intramolecular Oxa-Pictet–Spengler reaction of 24 led to the tricyclic compound 25. The spirocyclic compounds 18 show high σ1 affinity (Ki 20–26nM) and σ1/σ2 selectivity (>9-fold), when a large substituent (n-octyl, benzyl, phenylpropyl) is attached to the piperidine N-atom. Opening of the piperidine ring to yield aminoethyl (22, 23) or aminomethyl derivatives (21) resulted in reduced σ1 affinity and σ1/σ2 selectivity.

Synthesis of aminomethyl derivatives of 5-substituted-3-(prop-2-ynyl)dihydrofuran-2(3H)-ones

Abstract An easy approach for the synthesis of various 5-substituted-3-(prop-2-ynyl)dihydrofuran-2(3H)-ones is described. As a method of choice, Mannich aminomethylation of terminal alkynes is adopted. The reaction works well with acyclic and cyclic secondary amines and provides the desired products, with good to very good yields.

Synthesis, Characterization and Antimicrobial Evaluation of Schiff’s Base and Aryl Aminomethyl Derivatives

Schiff’s bases are obtained on heating an aldehydes with aromatic amine in presence of glacial acetic acid. These are the compounds containing characteristic –HC=N– group. Aryl amino methyl derivatives of heterocyclic compounds to synthesize by selective reduction of schiff’s bases (imine group) with sodiumborohydride in controlled experimental condition. Schiff’s base of N-Aryl-1-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]methanimines & Aryl amines of N-Aryl-1-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]methanamines were prepared. Their chemical structures were confirmed by means of IR, NMR, Mass data and by elemental analysis. All of the synthesized compounds were tested for their antibacterial and antifungal activity.

Synthesis, Characterization and Antimicrobial Evaluation of Schiff’s Base and Aryl Aminomethyl Derivatives

Schiff’s bases are obtained on heating an aldehydes with aromatic amine in presence of glacial acetic acid. These are the compounds containing characteristic –HC=N– group. Aryl amino methyl derivatives of heterocyclic compounds to synthesize by selective reduction of schiff’s bases (imine group) with sodiumborohydride in controlled experimental condition. Schiff’s base of N-Aryl-1-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]methanimines & Aryl amines of N-Aryl-1-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]methanamines were prepared. Their chemical structures were confirmed by means of IR, NMR, Mass data and by elemental analysis. All of the synthesized compounds were tested for their antibacterial and antifungal activity.

Synthesis of New Arylmethylene Derivatives of Resorcinarene via the Catalyzed Mannich Reaction

The C-arylation of Mannich base is used to obtain a series of new arylmethylene resorcinarene derivatives. Initially, aminomethyl derivative as the intermediate is formed in the Mannich reaction of resorcinarene with iminodiacetic acid. Next, activated aromatic rings act as a nucleophile in the reaction with this Mannich base and the arylmethylene derivatives of resorcinarene are prepared. The mixture of isomeric products is obtained for monosubstituted phenyl rings. Reaction with a suitably substituted phenyl ring gives one main product in good yields.

5,5`-BÜTAN-1,4-DIILBIS [4-ALLIL-2-({4-[3 (TRIFLOROMETIL) FENIL] PIPERAZIN-1-IL} METIL)-2,4-DIHIDRO-3H-1,2,4-TRIAZOL-3-TIYON BİLEŞİĞİNİN FARELERİN BÖBREK, KARACİĞER VE SERUMLARINDAKİ MDA VE VİTAMİN DÜZEYLERİNE ETKİSİ

The 1,2,4-triazole along with its derivatives were reported to exhibit various pharmacological activities [1]. 1,2,4-triazole moieties have been incorporated into a wide variety of therapeutically interesting drug candidates, including anti-inflammatories, CNS stimulants, sedatives, anti-anxiety compounds, antimicrobial agents, as well as anti-mycotic ones such as fluconazole, intraconazole andvoriconazole [2]. As previously reported, Aminomethyl derivatives were synthesized. In this study, the effects of newly synthesized bis1,2,4-triazole containing aminomethyl derivatives on the level of malondialdehyde(MDA)and antioxidant vitamins (A,E,C) of the serum, liver and kidney of rats have been investigated. In addition, level of malondialdehyde (MDA) and vitamins (A,E,C) has been determined by HPLC [3]. Most of the compounds showed satisfactory performance when compared to the control group [4]

Synthesis, structure, photo- and electroluminescent properties of zinc(II) complexes with aminomethylene derivatives of 1-phenyl-3-methyl-4-formylpyrazol-5-one and 3- and 6-aminoquinolines

Quinolyl-3-pyrazole (I) and quinolyl-6-pyrazole (II) azomethines have been used as precursors to novel zinc complexes (III, IV, correspondingly) that have been synthesized and thoroughly investigated by IR, UV–vis, NMR 1H spectroscopy. The atomic structure of the complexes was determined by quantum-chemical calculations (DFT-optimization of the molecules geometry). The results obtained were compared with quantitative characteristics of the local atomic environment of zinc ions derived from Zn K-edge EXAFS. Theoretical and experimental data on the bond lengths within the metal coordination sites are in a good agreement. Bands in experimental UV–vis spectra have been assigned based on computational results. Photo- and electroluminescent properties of zinc complexes have been investigated. The photoluminescence maximum occurs around λ=478nm for both compounds. Prototypes of electroluminescent devices utilizing the complexes as active media were designed and tested. The device with III as the electroluminescent layer shows a luminance of 800Cd/m2 at 10V with conversion efficiency of 0.5Lm/W, whereas the device with IV as the electroluminescent layer demonstrates somewhat lower characteristics, viz., 200Cd/m2 at 13V.

Advances in chemistry of chromone aminomethyl derivatives

Chromones play an important role in the design and discovery of new pharmacologically active compounds. A large volume of reports dedicated to synthesis and study of properties of nitrogen-containing chromone derivatives show important role of chromone alkaloid-like compounds. The present review covers achievements in the field of synthesis of chromone aminomethyl derivatives as one of perspective scaffolds.

Synthesis and biological evaluation of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one and its aminomethyl derivatives

Aminomethyl derivatives of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one, designed as new cytotoxins, were synthesized and evaluated in terms of their cytotoxic activities. The compounds have low CC50 values in the low micromolar range against HL-60 neoplasms and HSC-2, HSC-3 and HSC-4 carcinoma cells. In general, the average CC50 values of these compounds were higher towards HGF, HPC and HPLF non-malignant cells, which reveals the tumour-selectivity of these aminomethyl derivatives, Mannich bases. Using specific concentrations of compounds 4 and 6 caused cleavage of PARP1 in HSC-2 cells but not HGF cells, which may be a contributing factor to cytotoxicities and the tumour-selectivities.

CHEMISTRY OF 3-HETARYLCOUMARINS. 3. SYNTHESIS AND AMINOMETHYLATION OF 7'-HYDROXY-3,4'-BICOUMARINS

An improved procedure for the synthesis of 7′-hydroxy-3,4′-bicoumarins has been developed. Their 8′-aminomethyl derivatives were obtained by interaction with aminals. Authors: M. S. Frasinyuk, S. P. Bondarenko, and V. P. Khilya. English Translation in Chemistry of Heterocyclic Compounds , 2012, 48 (3), pp 422-426 http://link.springer.com/article/10.1007/s10593-012-1009-z

SYNTHESIS AND PROPERTIES OF 4-(3-AMINOTHIENO[2,3- b ]PYRIDIN-2-YL)COUMARINS

Substituted 4-[(3-cyanopyridin-2-yl)thiomethyl]coumarins have been synthesized by the alkylation of 2-mercapto-4,6-dimethylnicotinonitrile with 4-chloromethylcoumarins. Substituted 4-(3-amino-thieno[2,3- b ]pyridin-2-yl)coumarins have been obtained by a subsequent intramolecular condensation of the methylene and cyano groups. 6 H -Chromeno[4,3- d ]thieno[3,2- b :5,4- b ']dipyridin-6-ones were isolated as a result of the interaction of these compounds with aldehydes, and their aminomethyl derivatives were synthesized. Authors: S. V. Gorelov, S. P. Bondarenko, and M. S. Frasinyuk. English Translation in Chemistry of Heterocyclic Compounds , 2012, 48 (6), pp 955-962 http://link.springer.com/article/10.1007/s10593-012-1083-2

Synthesis of Aminomethyl Derivatives of Chrysin

Aminomethylation of chrysin through the action of aminals was studied. 6,8-Bis-substituted chrysin derivatives were synthesized.

Studies on the interactions of bioactive quinone avarone and its methylamino derivatives with calf thymus DNA

The interactions of avarone, a quinone from the marine sponge Dysideaavara, and the methylamino derivatives of avarone (2), 3′-(methylamino)avarone (3) and 4′-(methylamino)avarone (4) with calf thymus DNA (CT-DNA) were studied. Agarose gel electrophoreticanalysis showed that binding of the quinones quenched fluorescence of ethidium bromide (EB). The extent of fluorescence quenching of intercalator EB by competitive displacement from EB–CT-DNA system and of groove binder Hoechst 33258 (H) from H–CT-DNA system with the quinones was analyzed by fluorescence spectroscopy. The obtained results demonstrated that the quinones reduced binding of both the intercalator EB and the minor groove binder H, indicating possible degradation of DNA. The substituent on the quinone moiety determined the extent of DNA damaging effect of the quinone, which was the most extensive with 3′-(methylamino)avarone and the least extensive with its regioisomer 4′-(methylamino)avarone. The results were confirmed by the observed hyperchromic effects in UV–visible spectra measured after interactions of the derivatives with CT-DNA.

QSAR and pharmacophore approach on substituted imidazole derivatives as angiotensin II receptor antagonists

A QSAR analyses of 32 aminomethyl and acylaminomethyl substituents derivatives were carried out to interpret the relationship between structural properties and angiotensin II AT1 receptor activity. Two-dimensional (2D-QSAR), Group-based (G-QSAR), 3D-QSAR, and pharmacophore mapping studies were performed using partial least square and k-nearest neighbor methodology coupled with various feature selection methods, viz. stepwise, genetic algorithm, and simulated annealing (SA) to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The activity contributions of whole compounds and their substituents were determined from regression equation. The statistically significant best 2D-QSAR model 1 having r 2 = 0.8754 and q 2 = 0.7231 with $$ {\text{pred}}\_r^{ 2} = \, 0. 8 3 8 9 $$ was developed by GA-PLS with the descriptors like SdssCcount, SssNHcount and SaaaCcount. The best Group-based QSAR model-5 having r 2 = 0.7516 and q 2 = 0.6714 with $$ {\text{pred}}\_r^{ 2} = \, 0. 7 3 0 9 $$ was developed by GA-PLS. The 2D-QSAR results agreed with those from the Group based QSAR model and suggested the structural features of SssOE-index, Mol.Wt and SssNHE-index functionality that would enhance the antihypertensive activity of the imidazole derivatives in this series. The results of two-dimensional, Group-based QSAR showed that a combination of topological indices, hydrophobic properties, and auto-correlation descriptors of different atomic properties could be explored to design potent antihypertensive agents. The k-nearest neighbor approach was used to generate three-dimensional quantitative structure–activity relationship (3D-QSAR) models for these sets of molecules. The present study is an attempt in this direction seeking for the development and comparison of QSAR models of substituted imidazoles by different feature selection methods, which ultimately establishes the superiority of the GA-based models. Statistically genetic algorithm (GA) selection k-nearest neighbor (GA-kNN-MFA) model with respect to both the internal (q 2 = 0.7856) as well as external (pred_r 2 = 0.8193) model validation and correctly predicts the activity of calculated 78.56 % and calculated 81.93 % for the training and test set, respectively. Continuing with the series of substituted imidazoles derivatives, chemical feature-based pharmacophore models with lowest RMSD value (0.1397 A), consisting of one aromatic carbon center, two hydrogen bond acceptor, and one hydrogen bond donor features, was developed. The information rendered by 2D-QSAR, Group-based QSAR, k-nearest neighbor, and pharmacophore identification models may lead to a better understanding of structural requirements of antihypertensive agents and can help in the design of novel potent molecules.

Synthesis and Biological Activities of Some Novel Aminomethyl Derivatives of 5,5′-Butane-1,4-diyl-bis[4-allyl-2,4-dihydro-3H-1,2,4-triazole-3-thiones

A series of aminomethyl containing 5,5 �-Butane-1,4-diyl-bis(4-allyl-2,4-dihydro-3H-1,2,4- triazole-3-thiones were prepared under conventional cyclic condensation. The structures of newly synthesized compounds were established based on analytical and spectral studies. Further these compounds were evaluated for their antioxidant, antifungal and antibacterial activities. Most of the compounds showed good activity when compared with standard.

Synthesis and biological activities of some novel aminomethyl derivatives of 4-substituted-5-(2-thienyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones

A novel series of compounds were synthesized by cyclic condensation reaction of substituted isothiocyanate (2a–c) with 2-thiophenecarboxylic acid hydrazide (1) in the presence of ethyl alcohol, to obtain intermediate thiosemicarbazides (3a–c), which were further treated with sodium hydroxide in the presence of ethanol to obtain triazole derivatives (4a–c). The latter were refluxed with substituted secondary amines and formaldehyde for 6–10 h to afford Mannich bases (5a–k). The synthesized compounds were characterized on the basis of their spectral (IR, 13C and 1H NMR) data and evaluated for biological activities. Some of the compounds were found to exhibit significant antimicrobial and antioxidant activity.