Aminomethyl Derivatives Research Articles

Tailoring a Bacteriochlorin Building Block with Cationic, Amphipathic, or Lipophilic Substituents

Bacteriochlorins are attractive candidates for photodynamic therapy (PDT) of diverse medical indications owing to their strong absorption in the near-infrared (NIR) region, but their use has been stymied by lack of access to stable, synthetically malleable molecules. To overcome these limitations, a synthetic free base 3,13-dibromobacteriochlorin (BC-Br(3)Br(13)) has been exploited as a building block in the synthesis of diverse bacteriochlorins via Pd-mediated coupling reactions (Sonogashira, Suzuki, and reductive carbonylation). Each bacteriochlorin is stable to adventitious dehydrogenation by virtue of the presence of a geminal dimethyl group in each pyrroline ring. The target bacteriochlorins bear cationic, lipophilic, or amphipathic substituents at the 3- and 13- (beta-pyrrolic) positions. A dicarboxybacteriochlorin was converted to amide derivatives via the intermediate diacid chloride. A diformylbacteriochlorin was subjected to reductive amination to give aminomethyl derivatives. A set of 3,5-disubstituted aryl groups bearing lipophilic or amphipathic groups was introduced via Suzuki coupling. Altogether 22 free base bacteriochlorins have been prepared. Eight aminoalkylbacteriochlorins were quaternized with methyl iodide at two or four amine sites per molecule, which resulted in water solubility. Each bacteriochlorin exhibits a Q(y) absorption band in the range of 720-772 nm. The ability to introduce a wide variety of peripheral functional groups makes these bacteriochlorins attractive candidates for diverse applications in photomedicine including PDT in the NIR region.

Synthesis of New Polysubstituted Pyrrolidinones with Potential Biological Activity

The reaction of succinic anhydride and N-benzylidene-benzylamine gave rise to the corresponding substituted trans-5-oxopyrrolidine-3-carboxylic acid, which was transformed stereoselectively into two series of compounds. The first one consists of carboxamides, and the second one includes aminomethyl derivatives. The compounds prepared incorporate both a pyrrolidinone part and other nitrogen containing heterocyclic fragments of pharmacological interest.

Antioxidant properties of sulfides derived from 2-propylphenol and of their aminomethyl derivatives

Antioxidant properties of sulfides derived from 2-propylphenol and of their aminomethyl derivatives were studied in a model reaction of cumene oxidation. The kinetic parameters of the reactions of these compounds with cumylperoxy radicals and cumyl hydroperoxide were determined.

Aminomethyl derivatives of furancarboxylic acids in the Paal-Knorr reaction

Aminomethyl derivatives of furancarboxylic acids react with 1,4-dicarbonyl compounds under Paal-Knorr reaction conditions to form the pyrrole ring. It is found that α-aminomethyl derivatives of furancarboxylic acids react faster than their β analogs. The carboxy group adjacent to the aminomethyl fragment decelerates the process.

Synthesis of symmetrical amino and aminomethyl derivatives of Tröger's base via Pd-catalyzed C–C and C–N bond formation

In this paper, we report the synthesis of amino and aminomethyl derivatives of Tröger's base (±)- 1 and (±)- 2. The key steps in the synthesis of (±)- 1 and (±)- 2 are Pd-catalyzed amination and cyanation, respectively, of the easily accessible dihalo derivatives (±)- 3. These compounds are important intermediates in the synthesis of new ligands and building blocks for H-bonded supramolecular architectures.

Designing nanoporous crystalline materials by self-assembly: 2D hydrogen-bonded networks from upper rim calix[4]arene diamide derivatives

The self-assembly properties in the solid state of tectons derived from the reaction of calix[4]arene aminomethyl derivatives with a carboxylic acid or a protected amino acid are described, along with their conformational properties in solution. The X-ray crystal structures show that these compounds self-assemble in the lattice through a network of hydrogen-bonds between the amide groups, which overall results in infinite nanotubes formed by the calixarene aromatic cavities. Small changes in the upper rim substituents do not disturb the basic self-assembly motif which appears general and quite useful for controlling crystal growth by design and obtaining novel nanoporous crystalline materials.

New TRANS/CIS tetrahydroisoquinolines. 3. [1,3]‐oxazolo‐[3,2‐B]‐tetrahydroisoquinolinones having an angular aryl substituent

Abstractmagnified imageThe parent compound 5‐oxo‐10a‐phenyl‐2,3,10,10a‐tetrahydro‐5H‐[1,3]‐oxazolo‐[3,2‐b]‐isoquinoline‐10‐carboxylic acid (5) was prepared in large scale and a good yield by reaction between homophthalic anhydride (3) and 4,5‐dihydro‐2‐phenyl‐1,3‐oxazole (4). Thus, the closure of the isoquinoline ring and fusion of the 1,3‐oxazol ring occur in one step. Trans configuration was assumed for the product. The parent acid 5 was converted in four steps to the target aminomethyl derivatives 9a‐1. The latter contain four features that make them interesting from pharmaceutical point of view.

Aminomethyl derivatives of 2,4-di-α-methylbenzylphenol as multifunctional additives for lubricating oils

The results of study of the aminomethyl derivatives of 2,4-di-α-methylbenzylphenol as antioxidant, antiwear, and antimicrobial additives for lubricating oils are described. It was found that their antioxidant and antibacterial efficiency depend to a certain extent on the nature of the substituent on the nitrogen atom.

Synthesis of 3-Hydroxy-6-Methyl- and 3-Hydroxy-2-(2-phenylethyl)pyridines and Their Sulfur-Containing Amino and Hydroxymethyl Derivatives

The aminomethylation of 3-hydroxy-6-methyl- and 3-hydroxy-2-(2-phenylethyl)pyridines by secondary amines has been investigated. It was shown that like 2-alkyl-3-hydroxypyridine aminomethylation is directed primarily to position 6 and then 4 of the pyridine ring. On heating the aminomethyl derivatives of 3-hydroxy-6-methyl- and 3-hydroxy-2-(2-phenylethyl)pyridines with acetic anhydride the corresponding acetoxy derivatives were obtained, which were converted on heating with hydrochloric or hydrobromic acids into hydroxy and bromomethyl derivatives. Isothioureidomethyl and benzimidazolylthiomethyl derivatives were synthesized by heating the bromomethyl-substituted derivative with thiourea or with 2-mercaptobenzimidazole. The structures of compounds were confirmed by data of 1H NMR spectra.

3-Aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3- f]indole-5,10-dione for circumvention of anticancer drug resistance

A series of 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3- f]indole-5,10-dione was synthesized by Mannich reaction or by the transamination of 3-dimethylaminomethyl 4,11-dihydroxy- or 4,11-dimethoxynaphtho[2,3- f]indole-5,10-dione. The potency of novel derivatives was tested on a National Cancer Institute panel of 60 human tumor cell lines as well as in cells with genetically defined determinants of cytotoxic drug resistance, P-glycoprotein (Pgp) expression, and p53 inactivation. Mannich derivatives of 4,11-dihydroxynaphtho[2,3- f]indole-5,10-dione with an additional amino function in their side chain, demonstrated equal cytotoxicity against the parental K562 leukemia cells and their Pgp-positive subline, whereas the latter showed ∼7-fold resistance to adriamycin, a Pgp transported drug. 3-(1-Piperazinyl)methyl and 3-(quinuclidin-3-yl)aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3- f]indole-5,10-dione killed HCT116 colon carcinoma cells (carrying wild type p53) and their p53-null variant within the similar range of concentrations. We conclude that Mannich modification of 4,11-dihydroxynaphtho[2,3- f]indole-5,10-dione, especially when cyclic diamine (e.g., piperazine, quinuclidine) is used, confers an important feature to the resulting compounds, namely, the potency for tumor cells otherwise resistant to a variety of anticancer drugs.

Synthesis of a Novel Heterocyclic System: 7‐Methyl‐3‐methylthio‐7,8‐dihydro[1,2,4]triazolo[3,4‐f][1,2,4]triazine.

During a study of triazoles and related condensed heterocycles [1], we synthesized 7-methyl-3methylthio-7,8-dihydro[1,2,4]triazolo[3,4-f][1,2,4]triazine (5), which is a previously unknown heterocyclic system. The amino alcohol 2 obtained by methylation of thione 1 is converted to the chlorinated derivative 3, and then to the methylamino derivative 4. Compound 5 is obtained by condensation of the latter with ethyl orthoformate. In its IR spectrum, there were no vibrational bands for the amino groups, but in the H NMR spectrum we observed a signal from the methine proton at 7.11 ppm.

Functionalized 2,5‐Disubstituted Benzazepines: Stereoselective Synthesis of 3‐Methyl‐5‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine‐2‐carbonitrile and Related Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

N2‐Benzyl‐N1‐(1‐ (1‐naphthyl)ethyl)‐3‐phenylpropane‐1,2‐diamines and Conformationally Restrained Indole Analogues: Development of Calindol as a New Calcimimetic Acting at the Calcium Sensing Receptor.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Fluorescence quenching of 1-methylaminopyrene near gold nanoparticles: size regime dependence of the small metallic particles

Gold nanoparticles of variable sizes have been exploited to study their influence on the emission behavior of methylamino derivative of pyrene. The probe molecules adsorbed onto the metallic surfaces suffer strong quenching of their fluorescence and the rate of quenching efficiency with particle size is different for two different size regimes. The size regime dependence of the particles on the fluorescence quenching process have been rationalized in view of the dependence of surface area on the size of the particles. The mechanism of fluorescence quenching on the gold surfaces has been treated in the light of electron and energy-transfer processes.

Synthesis and Stereochemistry of exo‐4‐Aminomethyltetracyclo [6.2.1.13,6.02,7]dodec‐9‐ene.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Emission Behavior of 1-Methylaminopyrene in Aqueous Solution of Anionic Surfactants

A new fluorescent probe, methylamino derivative of pyrene, has been considered to characterize the concentration dependent emission behavior of an aqueous solution of anionic surfactants, viz., SDS, DSS, and SDBS. It was found that the emission of the probe is uniquely sensitive to the changes in surfactant (anionic) concentration due to the functional group effect of the probe over the parent moiety, pyrene. Here, 1-methylaminopyrene (MAP) showed significant quenching of emission well below the critical micellar concentration (cmc) of the surfactant. Excimer emission of the probe due to the formation of premicellar aggregates of the surfactant solutions at a concentration close to but below the cmc and again an enhanced emission of the probe above the cmc were observed as a consequence of definite MAP-surfactant interactions. These observations assisted the possible quantification ofsurfactant concentrations and their chain length dependent premicellar aggregate formations. Significant monomer emission in relation to probe distribution in micelle was analytically authenticated. Dynamic light scattering (DLS) studies revealed the incorporation of the probe molecules in the micellar core. The fluorophore emission showed nonlinear behavior when the surfactant concentration was far above the cmc. Abrupt changes in the emission characteristics in relation to the micellar concentration led to the determination of the cmc of the surfactants.

Aminomethylation of 2- and 3-(Diethoxyphosphorylmethyl)furans

Dimethyl(methylene)ammonium chloride reacts with 2-, 3-(diethoxyphosphorylmethyl)furansby the free α position of the furan ring to give the corresponding aminomethyl derivatives. 2,5-Disubstitutedfurans do not enter this reaction.

N2-Benzyl- N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and conformationally restrained indole analogues: development of calindol as a new calcimimetic acting at the calcium sensing receptor

The synthesis and calcimimetic activities of two new families of compounds are described. The most active derivatives of the first family, N 2-(2-chloro-(or 4-fluoro-)benzyl)- N 1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamine ( 4b and 4d, respectively, tested at 10 μM) produced 98 ± 6% and 95 ± 4%, respectively, of the maximal stimulation of [ 3H]inositol phosphates production obtained by 10 mM Ca 2+ in CHO cells expressing the rat calcium sensing receptor (CaSR). The second family of calcimimetics was obtained by conformationally restraining the compounds of type 4 to provide the 2-aminomethyl derivatives 5. One of these compounds, ( R)-2-[ N-(1-(1-naphthyl)ethyl)aminomethyl]indole (( R)- 5a, calindol), displayed improved calcimimetic activity compared to 4b and 4d as well as stereoselectivity. In the presence of 2 mM Ca 2+, calindol stimulated [ 3H]inositol phosphates accumulation with an EC 50 of 1.0 ± 0.1 or 0.31 ± 0.05 μM in cells expressing the rat or the human CaSR, respectively. The calcimimetic activities of these novel compounds were shown to be due to a specific interaction with the CaSR.

Spectral Luminescent Properties of Metal Chelates on the Basis of Aminomethylene Derivatives of 5-Pyrazolethione

The absorption and luminescence of bisbidentate complexes of aminomethylene derivatives of 5-pyrazolethione with Zn2+, Cd2+, Hg2+, and Pb2+ in dilute solutions in hydrocarbons and 95% ethanol are determined by the structure of the ligand in the complexes. In the Zn2+, Cd2+, and Hg2+ complexes, N···→M coordination is realized, whereas in the Pb2+ complexes, S··· → M. In the Zn-Cd-Hg series, a heavy-atom effect is revealed, which stimulates exclusively radiationless transitions involving the S1 and T states.

Functionalized 2,5-Disubstituted Benzazepines: Stereoselective Synthesis of 3-Methyl-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-2-carbonitrile and Related Derivatives

A stereoselective synthesis of 2-carbonitrile and 2-aminomethyl-substituted 5-phenylbenzazepine derivatives was developed starting from [4-hydroxy-3-(methyloxy)phenyl]acetic acid. The key step in the synthesis is a stereoselective addition of cyanide to 3-methyl-1-phenyl-2,3-dihydro-1H-3-benzazepine (4) to give a 15:1 trans/cis mixture of 2-carbonitrile-5-phenyl benzazepine dia­stereomers 5a/5b in 83% yield. The stereochemistry of the major product was deduced by 1H NMR NOESY analysis. The carbonitrile diastereomers could be separated and further manipulated by reduction to the corresponding aminomethyl derivatives 3a and 3b in a stereoselective manner. The aminomethyl benzazepine template 3 has potential to serve as a handle for the synthesis of a variety of derivatives modified at the 2-position of the benzazepine scaffold, as illustrated by an acylation of the primary amine of 3 ­followed by mild deprotection of the 7-phenol functionality.