Theoretical study of the vibrational spectra of the hydrogen-bonded systems between pyridine-3-carboxamide (nicotinamide) and DMSO

The vibrational characteristics (vibrational frequencies and infrared intensities) for the hydrogen-bonded systems of nicotinamide (NA(Z) and NA(E)) with dimethyl sulfoxide (DMSO) have been predicted using ab initio SCF/6-31G(d,p) and DFT (BLYP/6-311++G(d,p)) calculations. The changes in the vibrational characteristics from free monomers to a complex have been calculated. The ab initio and BLYP calculations show that the complexation between nicotinamide (NA(Z) and NA(E)) and DMSO leads to large red shifts of the stretching vibrations for the hydrogen-bonded N-H bonds of nicotinamide and very strong increase in their IR intensity. The results from the BLYP/6-311++G(d,p) calculations show that the predicted red shifts of the nu(s)(NH) and nu(as)(NH) vibrations for the complex NA(E)-DMSO (1:2) (Deltanu(as)(NH)=-186 cm(-1) and Deltanu(s)(NH)=-198 cm(-1)) are in better agreement with the experimentally measured. The magnitudes of the wavenumber shifts are indicative of strong NH...O hydrogen-bonded interactions in both complexes. The calculations predict an increase of the IR intensity of nu(s)(NH) and nu(as)(NH) vibrations in the complexes up to 14 times. Having in mind that in more cases the predicted changes in the vibrational characteristics for the complexes studied are very near, it could be concluded that both conformers of nicotinamide, Z-conformer and E-conformer, are present in the solution forming the hydrogen-bonded complexes with DMSO.     

Alkylation of pyridine-3,5-dicarboxamide and pyridine-3,5-dicarbonitriles by radical substitution

Structural modification of NAD(P) model compounds, N,N,N',N'-tetramethylpyridine-3,5-dicarboxamide ( 1 ), pyridine-3,5-dicarbonitrile ( 2 ), and 4-methylpyridine-3,5-dicarbonitrile ( 3 ), have been explored by the reaction with alkyl radicals such as the 1-adamantyl, tert-butyl, and isopropyl radicals. The alkyl substitutions of compounds 1 , 2 , and 3 with the 1-adamantyl and the tert-butyl radical gave both 2-mono and 2,6-disubstitution products, whereas the reaction of compound 2 with the isopropyl radical gave 2-mono 6c , 2,4-di 7c, 2,6-di 8c , and 2,4,6-trisubstitution 9c products.     

Two new potential optical materials: Co(II) and Ni(II) 3-fluorobenzoate complexes with pyridine-3-carboxamide

Two new complexes, [Co(3-fba)₂(na)₂(H₂O)₂] (1) and [Ni(3-fba)₂(na)₂(H₂O)₂] (2) (where 3-fba = 3-fluorobenzoate and na?=?pyridine-3-carboxamide, nicotinamide), were synthesized and characterized using different techniques (elemental analysis, FT-IR, UV-Vis spectrophotometer, single-crystal X-ray diffraction, fluorescence spectroscopy, and TGA/DTA analysis). X-ray structural analysis revealed that 1 and 2 are isostructural and exhibit distorted octahedral coordination geometry. In each molecule, metal atoms (Co⁺² and Ni⁺²) are linked by two 3-fluorobenzoate anions, two pyridine-3-carboxamide ligands, and two water molecules per formula unit. The 3-fluorobenzoate and pyridine-3-carboxamide are monodentate through a carboxylate oxygen atom and the nitrogen atom of the pyridine ring, respectively. UV-Vis results showed that the studied complexes have absorption edges similar to semiconductor structures. Namely, 1 and 2 indicated emission behaviors around 370?nm and 361?nm, respectively.     

Synthesis and Biological Evaluation of 2-(2-Deoxy-β-D-ribofuranosyl)pyridine-4-carboxamide

A new protected 2-deoxy-D -ribose derivative, 5-O-[(tert-butyl)diphenylsilyl]-2-deoxy-3,4-O- isopropylidene-aldehydo-D -ribose ( 5 ), was synthesized starting from 2-deoxy-D -ribose. This compound was coupled with 2-lithio-4-(4,5-dihydro-4,4-dimethyloxazol-2-yl)pyridine giving a D /L -glycero-mixture 7 of 5-O-[(tert-butyl)diphenylsilyl]-2-deoxy-1-C-[4-(4,5 -dihydro-4,4-dimethyloxazol-2-yl)pyridin-2-yl]-3,4-O-isopropylidene- D -erythro-pentitol. The mixture 7 was 1-O-mesylated with methanesulfonyl chloride and subsequently treated with CF₃COOH/H₂O and ammonia to afford the α/β-D -anomers 10 of 2-(2-deoxy-D -ribofuranosyl)pyridine-4-carboxamide. Both anomers were purified and separated by HPLC and identified by NMR and DCI-MS. Anomer β-D - 10 was evaluated against a series of tumor-cell lines and a variety of viral strains. No antitumor or antiviral activity was observed.     

氮-[双(2-吡啶)甲基]吡啶-2-甲酰胺金属配合物的热力学稳定性研究

利用简单步骤合成了酰胺类配体氮-[双(2-吡啶)甲基]吡啶-2-甲酰胺(L),在25℃,I=0.1mol/LKNO₃的30%乙醇-水溶液中用pH滴定法测定了其与不同金属离子组成的二元和三元配合物的稳定常数,结合单晶结构讨论了物种的可能构型,并比较了配体与Cu()和Fe()形成配合物的热力学稳定性差异,发现此配体在三元体系中存在线性自由能关系.     

(S)-N-取代-1,2,3,4-四氢异喹啉-3-甲酰胺催化直接不对称Aldol反应研究

本文研究了以(S) -N-取代-1,2,3,4-四氢异喹啉-3-甲酰胺衍生物的有机小分子催化剂催化不对称Aldol反应,得到高达92%收率和57%的ee值.     

Coordination compounds of N-(2-aminophenyl)- and N-(3-aminophenyl)pyridine-2′-carboxamide with cobalt(II) and cobalt(III). The nature of amide deprotonation induced by cobalt(III) in acidicpH

New complexes of the general formulae CoL ₂ X·nH₂O (X=Cl, Br, I, NCS, NO₃ andn=0, 1, 2 or 3), Co₂ L ₂ X ₃·EtOH (X=Cl, Br, I, NCS), Co(DH)X ₂ (X=NCS, NO₃) and Co(DH)₂ X ₂ (X=NCS, I) have been prepared, whereLH=N-(2-aminophenyl)pyridine-2-carboxamide andDH=N-(3-aminophenyl)pyridine-2-carboxamide. The compounds were characterized by X-ray powder patterns, conductivity measurements, thermogravimetric analysis, magnetic properties as well as by IR, ligand field and¹H-NMR spectroscopy. In the presence of oxygen,LH undergoes a cobalt(III) ion promoted amide hydrogen ionization in thepH region 4–6.

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Koordinationsverbindungen von N-(2-aminophenyl)- und N-(3-aminophenyl)pyridin-2-carboxamid mit Cobalt(II) und Cobalt(III). Die Natur der Deprotonierung von Amiden induziert von Cobalt(III) in saurem Medium

Zusammenfassung Neue Komplexe der allgemeinen Formeln CoL ₂ X·nH₂O (X=Cl, Br, I, NCS, NO₃ undn=0, 1, 2, 3), Co₂ L ₂ X ₃·EtOH (X=Cl, Br, I, NCS), Co(DH)X ₂ (X=NCS, NO₃) und Co(DH)₂ X ₂ (X=NCS, I) wurden dargestellt mit LH=N-(2-aminophenyl)pyridin-2-carboxamid undDH=N-(3-aminophenyl)pyridin-2-carboxamid. Die Verbindungen wurden mittels Röntgenstrukturanalyse, Leitfähigkeitsmessungen, thermogravimetrischen Analysen, magnetischen Eigenschaften sowie mit IR-, Ligandenfeld- und¹H-NMR-Spektroskopie charakterisiert. In Gegenwart von Sauerstoff unterliegtLH einer Cobalt(III)ion-induzierten Amidwasserstoffionisierung impH-Bereich 4–6.

     

Kinetics and mechanism of aqua ligand substitution reactions from cis-diaqua-bis(bipyridine)ruthenium(II) ion by pyridine-2-aldoxime in aqueous medium

Summary The kinetic behaviour of cis-[Ru(bipy)₂(H₂O)₂]²⁺ towards the anating ligand pyridine-2-aldoxime as a function of temperature, ligand concentration, substrate complex concentration and pH is reported and the rate expression Rate = k ₁ k ₂[Ru(bipy)₂(H₂O)₂]²⁺ [LL]/(k _-1 + k ₂[LL]) is established where k ₁ is the water dissociation rate constant for the slow step, k _-1 is the rate constant for the aquation, k ₂ is the ligand-capturing rate constant of the five-coordinate intermediate [Ru(bipy)₂(H₂O)]²⁺ and LL is pyridine-2-aldoxime. The reaction is pH-dependent in the pH range 3.65–5.50. The enthalpy and entropy of activation were obtained using Eyring plots. The results are in conformity with a dissociative mechanism.     

Simultaneous micro-determination of nicotinamide and its major metabolites, N1-methyl-2-pyridone-5-carboxamide and N1-methyl-4-pyridone-3-carboxamide, by high-performance liquid chromatography

A simultaneous micro-determination of nicotinamide and its major metabolites, N1-methyl-2-pyridone-5-carboxamide (2-py) and N1-methyl-4-pyridone-3-carboxamide (4-py) by high-performance liquid chromatography is described. The method employs a 7-ODS-L (250 mm X 4.6 mm I.D., particle size 7 microns) column eluted with 10 mM potassium dihydrogenphosphate-acetonitrile (96:4, v/v; pH adjusted to 3.0 by the addition of concentrated phosphoric acid) at a flow-rate of 1.0 ml/min. The UV detector was set at 260 nm. The detection limits for nicotinamide, 2-py and 4-py were 10 pmol (1.22 ng), 2 pmol (304 pg) and 2 pmol (304 pg), respectively, at a signal-to-noise ratio 5:1. Isonicotinamide was used as an internal standard. The technique was applied to the analysis of rat and human urines. The total analysis time was ca. 15 min.     

Nucleophilic substitution of hydrogen (3-H) in quinoxalone by arylamines

When quinoxalone is heated with aromatic amines in acetic acid in the presence of ammonium nitrate, a hydrogen undergoes nucleophilic substitution to give the corresponding 3-(4′-aminophenyl)quinoxalones.     

An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite

Our recent studies identified a novel pathway of nicotinamide metabolism that involves 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) and demonstrated its endothelial cytotoxic effect. This study tested the effects of 4PYR and its metabolites in experimental models of breast cancer. Mice were divided into groups: 4T1 (injected with mammary 4T1 cancer cells), 4T1 + 4PYR (4PYR-treated 4T1 mice), and control, maintained for 2 or 21 days. Lung metastasis and endothelial function were analyzed together with blood nucleotides (including 4PYR), plasma amino acids, nicotinamide metabolites, and vascular ectoenzymes of nucleotide catabolism. 4PYR metabolism was also evaluated in cultured 4T1, MDA-MB-231, MCF-7, and T47D cells. An increase in blood 4PYR in 4T1 mice was observed at 2 days. 4PYR and its metabolites were noticed after 21 days in 4T1 only. Higher blood 4PYR was linked with more lung metastases in 4T1 + 4PYR vs. 4T1. Decreased L-arginine, higher asymmetric dimethyl-L-arginine, and higher vascular ecto-adenosine deaminase were observed in 4T1 + 4PYR vs. 4T1 and control. Vascular relaxation caused by flow-dependent endothelial activation in 4PYR-treated mice was significantly lower than in control. The permeability of 4PYR-treated endothelial cells was increased. Decreased nicotinamide but enhanced nicotinamide metabolites were noticed in 4T1 vs. control. Reduced N-methylnicotinamide and a further increase in Met2PY were observed in 4T1 + 4PYR vs. 4T1 and control. In cultured breast cancer cells, estrogen and progesterone receptor antagonists inhibited the production of 4PYR metabolites. 4PYR formation is accelerated in cancer and induces metabolic disturbances that may affect cancer progression and, especially, metastasis, probably through impaired endothelial homeostasis. 4PYR may be considered a new oncometabolite.Subject terms: Mechanisms of disease, Pathogenesis, Breast cancer     

Efficient Synthesis of 3-(4-Carboxyphenyl)pyridine-2,6-dicarboxylic Acid

Russian Journal of Organic Chemistry - An efficient synthetic approach to 3-(4-carboxyphenyl)pyridine-2,6-dicarboxylic acid has been developed on the basis of “1,2,4-triazine”...     

Synthesis of highly functionalized 2(1H)-pyrazinone 3-carboxamide scaffolds

Synthesis of highly functionalized 2(1H)-pyrazinone 3-carboxamide derivatives is reported. A one-pot, two-step process including the base-mediated reaction of N,N-disubstituted aminoacetonitrile derivatives 18 with 3,5-dihalo-2(1H)-pyrazinones 1 afforded substituted aminoacetonitrile pyrazinone derivative 19, which on subsequent oxidation followed by transamidation of the resulting intermediate with primary or secondary amines gave the corresponding highly functionalized 2(1H)-pyrazinone 3-carboxamide derivatives 21.     

Enhanced bioaccesibility of selective PDE4 inhibitor N-(3,4-dihydro-2h-1,5-benzodioxepin-7-yl) pyridine-4-carboxamide using polyamidoamine dendrimer

The aim of this study was to improve the aqueous solubility of highly hydrophobic but selective PDE4 inhibitor N-(3,4-dihydro-2h-1,5-benzodioxepin-7-yl) pyridine-4-carboxamide by associating it with polyamidoamine dendrimer. The PAMAM dendrimer restraining ethylenediamine core synthesized by a divergent approach was utilized for encapsulation. The solubility of conjugates was evaluated on the basis of concentration and generation of the dendrimer, pH of the solution, and temperature. The phase solubility diagram confirmed an increase in aqueous solubility of drug with increase in dendrimer concentration with respect to pH in the order 9.0 > 7.0 > 4.0. Moreover, values of thermodynamic parameters such as negative value of ΔH^o, positive value of ΔS^o and ΔG^o reflects an exothermic complexation, presence of number of particles and spontaneity of the complexation. Overall, investigations validate the enhancement in solubility of drug after complexation with polyamidoamine dendrimer which further confirmed promising bioactivity of the drug-dendrimer conjugates.     

3-(3-吲哚基)-5-吡唑甲酰胺的合成及抑菌活性

本文以3-乙酰吲哚、草酸二乙酯、水合肼等为原料,经缩合、环化、水解反应制备3-(3-吲哚基)吡唑-5-甲酸,后者再与苄胺或2-苯乙胺在EDC-BTOH催化下合成了一系列N-取代苄基-3-(3-吲哚基)吡唑-5-甲酰胺和N-(2-取代苯基乙基)-3-(3-吲哚基)吡唑-5-甲酰胺。采用平板计数法测试了化合物对大肠杆菌和金黄色葡萄球菌的抑制活性,结果表明,在浓度为80 μg/mL时部分化合物有较高的抑菌活性。