N-substituted Aminomethyl Research Articles

Synthesis and Characterization of New N-Substituted Aminomethyl Compounds Based on Dimedone as Promising Antimicrobial Agents

Synthesis and Characterization of New N-Substituted Aminomethyl Compounds Based on Dimedone as Promising Antimicrobial Agents

Synthesis and antioxidant properties of N-substituted aminomethyl derivatives of 2-isobornylphenol

Synthesis and antioxidant properties of N-substituted aminomethyl derivatives of 2-isobornylphenol

Synthesis of 6-aryl-7-arylazo-4-(N-substituted aminomethyl)-2H-thiazolo-[3, 2-a]-1, 3, 5-triazino-2-thiones as Antiviral Agents

2-amino-4-aryl thiazole was diazotised with different aromatic amines to give 2-amino-4-aryl-5-arylazo thiazoles. These compounds were refluxed with ammonium thiocyanate and chloroacetyl chloride in acetone to afford N1-chloroacetyl-N3-(4-aryl-5-arylazothiazol-2-yl)-thioureas. These thioureas were cyclized in presence of POCl3 and PCl5 to give 6-aryl-7-arylazo-4-chloromethyl-2H-thiazolo-[3, 2-a]-1, 3, 5-triazino-2-thiones. These compounds were reacted with secondary amines in methanol to give title compounds 6-aryl-7-arylazo-4-(N-substituted aminomethyl)-2H-thiazolo-[3,2-a-]1,3,5-triazino-2-thiones.Antiviral nature of these compounds was studied against Ranikhet Disease Virus (RDV), Vaccinia Virus (VV) and Sunnhemp Rosette Virus (SRV). Some of these compounds have been found to be active against RDV and Vaccinia Virus.

Permeability of novel 4′-N-substituted (aminomethyl) benzoate-7-substituted nicotinic acid ester derivatives of scutellarein in Caco-2 cells and in an in vitro model of the blood-brain barrier

A series of 4′-N-substituted (aminomethyl) benzoate-7-substituted nicotinic acid ester derivatives of scutellarein was designed and synthesized. Evaluation of physiochemical properties showed that the newly designed compounds had greater chemical stability and aqueous solubility than scutellarin or scutellarein. The permeabilities (P app AP to BL) of compounds 7b and 7e in Caco-2 cells were 5.9-fold and 3.7-fold higher than that of scutellarin, and 3.7-fold and 2.4-fold higher than that of scutellarein. The permeabilities (P app AP to BL) of compounds 7b and 7e in an in vitro model of the blood–brain barrier were 9.7-fold and 5.9-fold higher than that of scutellarin, and 9.2-fold and 5.6-fold higher than that of scutellarein.

Radical aminomethylation of imines.

Taking advantage of the high level of performance of N-alkoxycarbonyl-imines, we achieved the first example of addition of the aminomethyl radical to imine. The reaction efficiency depended on the structure of the radical precursor, whether it is an iodide or a xanthate, and an electron-withdrawing group on the nitrogen atom of the radical. This reaction allows direct introduction of an N-substituted aminomethyl group onto imine to provide 1,2-diamine as well as the short-step synthesis of ICI-199,441.

ChemInform Abstract: Efficient Synthesis of 2,3‐Disubstituted‐1,3‐benzoxazines by Chlorotrimethylsilane‐Mediated Aza‐Acetalizations of Aromatic Aldehydes.

AbstractTmsCl is found to be an effective and green Lewis acid catalyst for the aza‐acetalization of aromatic aldehydes with 2‐(N‐substituted aminomethyl)phenols.

Macrocyclic arylopeptoids – a novel type of cyclic N-alkylated aromatic oligoamides forming nanotubular assemblies

The head-to-tail conversion of linear arylopeptoids (oligomeric N-substituted aminomethyl benzamides) into the derived novel macrocycles has enabled the first X-ray structures of arylopeptoid constructs and the identification of well-defined architectures in solution.

Design and synthesis of new N-substituted amino methyl-[1,2,3] triazolyl moieties of fluoroquinolones as antibacterial agents

A series of twenty new N-substituted amino methyl-[1,2,3] triazolyl derivatives at C-7 position of fluoroquinolones were designed and synthesized through multistep synthesis. The synthesized compounds were characterized by 1H NMR, 13C NMR, ESI–MS, and IR. The antibacterial activities of these new fluoroquinolones were evaluated using a standard broth micro dilution technique. Out of the twenty derivatives, aryl substituted amino derivatives (6m to 6q) exhibited very good potency in inhibiting the growth of Methicillin-sensitive Staphylococcus aureus (MSSA), Methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-Resistant Enterococcus faecalis (VRE faecalis) (MIC: 0.25–4.00 μg/mL) as compared to the marketed drugs Linezolid and Ciprofloxacin.

Novel 2-(E)-substituted benzylidene-6-(N-substituted aminomethyl)cyclohexanones and cyclohexanols as analgesic and anti-inflammatory agents

Twenty-two new 2-(E)-substituted benzylidene-6-(N-substituted aminomethyl)cyclohexanones (6a–6j) and cyclohexanols (7a–7l) were designed and synthesized. Target compounds were obtained through Stork enamine, Mannich, and Grignard reactions taking cyclohexanone as starting material. The structures were confirmed by the application of IR, 1H NMR, MS, and HR-MS data. The analgesic activities were evaluated by acetic acid-induced writhing test and hot plate method. The anti-inflammatory activities were assayed by xylene-induced ear swelling and carrageenan-induced paw edema in mice model. All tested compounds showed analgesic and anti-inflammatory capacities in oral administration. Some compounds (6a, 6c, 6h, 6i, 7c, 7h, and 7i) displayed the moderate analgesic activity compared with positive control ibuprofen, and some compounds (6a, 6b, 6d, 6h, 7a, and 7d) exhibited more anti-inflammatory activity than ibuprofen. Among them, compound 6a could be a potential nonsteroidal anti-inflammatory agent with significant analgesic activities and remarkable anti-inflammatory activities. Further research is being conducted.

Synthesis and Fungicidal Activity of Novel 2,3-Disubstituted-1,3-benzoxazines

A series of new 2,3-disubstituted-3,4-dihydro-2H-1,3-benzoxazines were prepared in moderate to excellent yields by aza-acetalizations of aromatic aldehydes with 2-(N-substituted aminomethyl)phenols in the presence of TMSCl. Their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. The fungicidal activities of the target compounds were preliminarily evaluated, and some compounds exhibited good activity against Rhizoctonia solani.

Improved solid-phase synthesis and study of arylopeptoids with conformation-directing side chains

The development of an improved methodology for iterative solid-phase synthesis of para- and meta-arylopeptoids (oligomeric N-substituted aminomethyl benzamides) using benzoyl chloride building blocks is described. This methodology has enabled the synthesis of arylopeptoids with tert-butyl and phenyl side chains, which allows for complete control over the amide conformation: the tert-butyl results in a 100% cis amide conformation while the phenyl side chain results in a 100% trans amide conformation. The method has furthermore enabled the first synthesis and preliminary conformational studies of arylopeptoids bearing (S)-N-(1-phenylethyl) side chains.

Efficient and versatile COMU-mediated solid-phase submonomer synthesis of arylopeptoids (oligomeric N-substituted aminomethyl benzamides)

The development of a highly efficient methodology for solid-phase synthesis of para- and meta-arylopeptoids (oligomeric N-substituted aminomethyl benzamides) with free acids or free amides at the C-terminus is described. The arylopeptoids were synthesised by means of a convenient submonomer protocol in which the arylopeptoid residues were created in an iterative manner on the growing chain using an acylation-substitution cycle. The uronium salt COMU was found to be the most efficient reagent for ensuring fast and clean couplings of the benzoic acid building blocks.

Secondary–secondary diamine catalysts for the enantioselective Michael addition of cyclic ketones to nitroalkenes

Secondary–secondary diamines derived from S-proline are efficient catalysts for the ketone–nitroalkene Michael addition reaction. The stereoselectivity of the Michael addition is dependant on the p K a of the N-substituted aminomethyl pendant in these diamines. N′-Aryl aminomethyl pyrrolidines provide γ-nitroketones with moderate to good enantiomeric excess (65–92%). Removal of the hydrogen-bond donor group by N-methylation results in a dramatic reduction of enantioselectivity (average ee 6%).

Synthesis, cytostatic and anti-HCV activity of 6-( N-substituted aminomethyl)-, 6-( O-substituted hydroxymethyl)- and 6-( S-substituted sulfanylmethyl)purine nucleosides

An efficient and facile synthesis of a large series of diverse 6-( N-substituted aminomethyl)-, 6-( O-substituted hydroxymethyl)- and 6-( S-substituted sulfanylmethyl)purine nucleosides (55 examples of both ribo- and 2′-deoxyribonucleosides), aimed at identifying novel homologues of natural nucleosides, was developed. The key transformation involved nucleophilic substitutions of Tol-protected 6-(mesyloxymethyl)purine nucleosides by primary or secondary amines, alcoholates or thiolates. While the 2′-deoxyribonucleosides were inactive, the ribonucleosides exerted considerable cytostatic effects and some anti-HCV activity with low selectivity.

A Short and Convenient Synthesis of 3-Aminomethyl-5-imino-8-nitro-2,3-dihydroimidazo[1,2-a]pyridines

A two-step synthesis of 3-(N-substituted aminomethyl)-5-(N-substituted imino)-2,3-dihydro-imidazo[1,2-a]pyridines is reported. Starting from 3-bromomethyl-5-chloro-2,3-dihydroimidazo[1,2-a]pyridine, the synthesis comprises two consecutive reactions with primary amines. The products are derived from a three-dimensional molecular scaffold and may therefore be useful in medicinal chemistry in the search for small molecules that can adapt optimally to the three-dimensional binding sites of biological targets. The present synthesis is also particularly suitable for the preparation of combinatorial libraries since primary amines are commercially available in great structural diversity. Moreover, the second step is selective for primary amines, which means that secondary amino groups can be introduced into the products without the need for protection.

Synthesis and evaluation of 6-methylene-bridged uracil derivatives. Part 1: Discovery of novel orally active inhibitors of human thymidine phosphorylase

A series of novel 6-methylene-bridged uracil derivatives have been prepared as inhibitors of human thymidine phosphorylase (TP). To enhance the in vivo antitumor activity of fluorinated pyrimidine 2′-deoxyribonucleosides such as 2′-deoxy-5-(trifluoromethyl)uridine (F 3dThd), a potent TP inhibitor preventing their degradation to an inactive compound, has become a target of medicinal chemistry. We present here the synthesis and evaluation of novel human TP inhibitors. Introduction of an N-substituted aminomethyl side chain at the 6-position of 5-chlorouracil has improved water solubility and enhanced inhibitory activity compared with the known TP inhibitor, 6-amino-5-chlorouracil. Compound 42 was reasonably well absorbed in mice after oral administration. When combined with F 3dThd, compound 42 exerted its TP inhibitory potency by increasing the maximum plasma concentrations of the former as evidenced in experiments with monkeys. Positive changes in pharmacokinetic profile were accompanied by the enhanced in vivo antitumor activity of this combination when compared to F 3dThd alone, in mice bearing human tumor xenografts. Both biochemical and pharmacological effects appeared to fit the concept as anticipated.

Synthesis of New Chiral 1,2-Disubstituted Ferrocenes

Synthesis of six chiral 1,2-disubstituted ferrocene derivatives is described starting from (S)-{[2-(methoxymethyl)pyrrolidin-1-yl]methyl}ferrocene (2) and {[N-((1R,2S)-methoxy-1-methyl-2-phenethyl)-N-methylamino]methyl}ferrocene (3). Oxidation of the (N-substituted aminomethyl)ferrocenes with active MnO2 furnished the corresponding 2-substituted ferrocenecarbaldehydes.

Synthesis of mono- and bis(aminomethyl)dioxanes fromN-[3-(2-chloroethoxy)-2-hydroxypropyl]sulfamates

N-Substituted aminomethyl- and 2,5-bis(aminomethyl)-1,4-dioxanes were prepared by cyclization of the corresponding potassiumN-[3-(2-chloroethoxy)-2-hydroxypropyl]sulfamates under the action of an alkaline agent followed by alcoholysis of the resulting sulfamic acids.

Crystal and molecular structure of protonated ( N-propyl)-aminomethyl ferrocene, a proton-sensitive redox-responsive fragment

In order to rule out any possible ‘chelat’ iron-proton interaction which could be responsible for the dramatic changes observed in the Fe 1/Fe redox potential on proton addition in a series of N-substituted aminomethyl ferrocenes ( 4a-d), we report the results of electrochemical titration experiments with strong acids on the free amines in protic and aprotic solvents and the X-ray diffraction structure of (ferrocenyl-methyl) propylammonium p-toluenesulfonate, [ 4aH[OTs]. Crystals of [ 4aH][OTs] are orthorhombic, space group P2 12 12 1, with a=11.919(2), b=21.313(3), c=8.246(2) A ̊ , Z=4 . The conformation of the FcCH 2NH 2C 3H 7 cation, which prevents any intramolecular iron-proton interaction, seems imposed by the intermolecular NH⋯O hydrogen bonds that the amino H atoms form with oxygen atoms from p-toluenesulfonate anions.

Potential Antimalarials. XVI. 4'-Chloro-3-[7″-chloro(and trifluoromethyl)quinolin-4″-yl]amino-5-(substituted amino)methylbiphenyl-4-ols and 4'-Bromo(and 3'-trifluoromethyl)-3-(substituted amino)methyl-5-(7″-trifluoromethylquinolin-4″-yl)aminobiphenyl-2-ols

Twenty-four mono-Mannich bases of the general formulae 4'-chloro-3-[7″-chloro(and trifluoro-methyl)quinolin-4'-yl]amino-5-(substituted amino)methylbiphenyl-4-ols and 4'-bromo(and 3'- trifluoromethyl-3(substituted amino)methyl-5(7″-trifluoromethylquinolin-4″-yl) aminobiphenyl-2-ols have been prepared by condensation of the 4-chloro heterocycle with 5-amino-3-(N-substituted amino)methyl-4'-chlorobiphenyl-4-ols or 5-amino-3-(N-substituted amino)methyl- 4'-bromo(or 3'-trifluoromethyl)biphenyl-2-ols. The antimalarial activity of these products in in vitro tests against Plasmodium falciparum reveals many with IC50 values of 50-100 nM ( chloroquine 20-40 nM ). The biphenyl-2-ols were more active than comparable biphenyl-4-ols.