Acetamide Research Articles

Soluble Cocrystals of the Xanthine Oxidase Inhibitor Febuxostat

The synthesis and physicochemical characterization of febuxostat (FEB) cocrystals, a xanthine oxidase inhibitor, with pharmaceutically acceptable coformers, such as urea (URE), acetamide (ACT), nicotinamide (NIC), p-aminobenzoic acid (PABA), and saccharin (SAC) (all of 1:1 stoichiometry), are reported. X-ray crystal structures were determined for FEB drug and its cocrystals with URE, ACT, NIC, and PABA, whereas the SAC cocrystal was characterized by FT-IR-Raman, differential scanning calorimetry (DSC), 13C ss-NMR, and powder X-ray diffraction. The crystal structure of FEB has O–H···N hydrogen bonds (COOH···N≡C) instead of the expected acid–acid homodimer synthon. The cocrystal structures are sustained by the cyclic synthons acid–amide (FEB–URE, FEB–NIC) and acid–acid (FEB–PABA), while FEB–ACT has no distinct ring motif. The cocrystals exhibited a higher intrinsic dissolution rate (IDR) compared to FEB and good stability in accelerated ICH humidity conditions of 75% RH at 40 °C.

Synthesis of 6-hydrazino-3,4-dimethyl-1H-pyrazolo[3,4-d]pyrimidine and its application for the construction of a pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidine system

A new representative of heterocyclic hydrazines, viz., 6-hydrazino-3,4-dimethyl-1H-pyrazolo[3,4-d]pyrimidine (3) was synthesized from diacetyl ketene N,S-acetal. A condensation of hydrazine 3 with amide acetals or aldehydes and subsequent cyclization furnished pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidines, whose structure was confirmed by 1H, 13C, and 1H/15N HMBC NMR spectroscopy. Reactions of hydrazine 3 with acetylacetone, ethyl acetoacetate, diethyl malonate, and acetic anhydride were studied.

Influence of Spacer on Association Behavior and Thermodynamic Parameters of Dimeric Cationic Surfactants

AbstractNew dimeric surfactants [16‐s‐16, s: (CH2)4; CH2–COO–(CH2)2–OCO–CH2; CH2–COO–ISO–OCO–CH2 (ISO = d‐isorbide) and CH2–CONH–(CH2)2–NHCO–CH2] were synthesized and characterized (I–IV, respectively). The micellization behavior of dimeric surfactants with various spacers was studied by conductance/steady‐state fluorescence quenching (SSFQ) measurement and compared with the conventional surfactant (cetyltrimethylammoniumbromide, CTAB). The critical micelle concentration (CMC) values of several surfactants were found to be nearly the same by both techniques. Conductance measurements were used exclusively to obtain CMC and degree of dissociation (α) values at various temperatures, while SSFQ measurements were used to obtain a few CMC values (for comparison) and an aggregation number (Nagg). A decrease in CMC and Nagg values and an increase in α were observed for dimeric surfactants when compared with CTAB. CMC decreases and then increases with a continuous increase in temperature (U‐shaped behavior). The temperature of minimum CMC, Tm, was distinctly different for CTAB and the dimeric surfactants. Tm values were dependent on the nature of the spacer. The temperature dependence of CMC and α value was used to calculate the thermodynamic parameters of micelle formation for two classes of surfactant (conventional and dimeric). Enthalpy‐entropy compensation plots exhibited fair linearity except for IV. Compensation lines for spacers containing ester groups are parallel to one another. Micro‐polarity and apparent dielectric constant (εa) data suggest that the micellar environment felt by pyrene is similar to that of an alkanol with a 3–4 carbon chain.

Synthesis and Characterization of Nanocrystalline In2O3 and Its Efficacy as a Catalyst for the One Pot Synthesis of Amidoalkyl Naphthols

In2O3 nanopaticles were synthesized by glycine-nitrate combustion method. The synthesized In2O3 is characterized by the powder X-ray diffraction and transmission electron microscopy. The average crystallite size, as determined by Scherrer's formula, was found to be about 48 nm. A catalytic amount of In2O3 nanopaticles, were used for an efficient synthesis of amidoalkyl naphthols via multicomponent condensation of aryl aldehydes, β-naphthol, and urea or acetamide. In2O3 nanopaticles were found to be highly active for the transformation with excellent yield and purity of the product in a short reaction time.

Synthon polymorphs of sulfacetamide–acetamide cocrystal based on N–H⋯OS and N–H⋯OC hydrogen bonding

A rare case of polymorphism in SO2–NH–CO containing molecules is reported in the 1 : 1 cocrystal of sulfacetamide (SACT) and acetamide (ACT). The R44(16) ring motif in polymorph 1 is assembled via N–H⋯OS and N–H⋯OC H-bonds whereas a similar hydrogen-bonded ring motif made of N–H⋯OC H-bonds only is present in form 2.

Synthesis and SAR studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off-target kinase selectivity

The structure–activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. The SAR of the acetic acid amides was explored and the effect of substitution on enzyme inhibition as well as mechanism-based cell activity was studied. Additionally, several of the more potent inhibitors were screened for their off-target kinase selectivity.

Use of polarizability and chemical hardness to locate the transition state and the potential energy curve for double proton transfer reaction: A DFT based study

Density functional theory (DFT) based calculations on a series of double and single proton-transfer reactions e.g. formamide (FA), acetamide (AA) and trifluoro acetamide (TFA) dimmers are performed to understand the potential energy surfaces during proton transfer processes. Apart from using the N–H distances as proton transfer co-ordinate we have computed the variations in polarizations and chemical hardnesses of the species involved to locate the transition state structures during the double proton transfer reactions. The average polarizability (αav) and the chemical hardness (η) show their optimum value at the same N–H distance and it corresponds to the transition state for all the three titled complexes. The maximum polarizability and minimum chemical hardness at the transition state (TS) are due to maximal charge separation at TS. We observe that computation of maximum polarizability and minimum chemical hardness along the reaction co-ordinate are the easiest way to locate the transition state during the proton transfer processes.

Ionization energy and electron affinity of oligoglycines: a CAM-B3LYP density functional theory study

Long-range corrected CAM-B3LYP density functional theory level with the polarized and diffuse 6-31+G* basis set has been used to compute delta self-consistent field (ΔSCF) vertical ionization energies (VIE) and electron affinities (VEA) of single-chain oligoglycines (H2N–(CH2–CO–NH) n –CH2COOH, n = 1–9) in the α-helix and β-strand conformations. For all the investigated oligopeptides VIE (α-helix) VIE (β-strand), owing to the cooperative effects of the –N–H···O=C– intramolecular hydrogen bonds in the α-helices. The VIE–VEA band gap for β-strands is predicted to be greater than that of the corresponding α-helices. In the limit of the polymer, the conductivity of the α-helix is predicted to be ca. double that of the β-strand. The α-helix-based materials are potentially more efficient single-chain conductors than β-strands.

Examining the robustness of a theophylline cocrystal during grinding with additives

The robustness of theophylline-p-hydroxybenzoic acid cocrystal (TP·pHBA) while grinding with additives in the solid state was evaluated through a series of solvent-drop grinding experiments with coformers containing various functional groups. Powder X-ray diffraction was used to qualitatively analyse the powders after grinding and identify the species present. The TP·pHBA cocrystal was found to be robust in the presence of benzoic acid (BA), p-nitrobenzoic acid (pNBA), p-(N,N-dimethylamino)benzoic acid (dMABA), m-hydroxybenzoic acid (mHBA), p-nitrophenol (pNP), hydroquinone (HDQ) and benzamide (BZA), but it disintegrates in the presence of salicylic acid (SA), 3,5-dinitrobenzoic acid (dNBA), acetamide (ACA) and melamine (MLM).

Mesoporous SBA-15 modified with manganese pyrazolylpyridine complexes for the catalytic epoxidation of terminal alkenes

A manganese-based hybrid mesoporous material (denoted as 5) was synthesized by covalent grafting of [Mn II( 1) 2](OAc) 2 ( 3) ( 1 = [3-(2-pyridyl)pyrazol-1-yl]acetic acid amide) onto the surface of SBA-15, and characterized by means of XRD, N 2 adsorption–desorption, FT-IR, Raman, EPR and UV–vis spectroscopic techniques. Catalytic tests showed that 5 could act as an efficient heterogeneous catalyst for the epoxidation of a wide range of alkenes (including terminal ones) under mild reaction conditions when peracids (e.g., meta-chloroperbenzoic acid) are used as oxidants. Moreover, the catalytic performance of 5 is solvent-dependent, it exhibits higher catalytic activity and selectivity to epoxides when the reaction is carried out in aprotic solvent like CH 3CN. UV–vis and electrochemical measurements revealed that high-valent Mn species are easily formed during the reaction course, when meta-chloroperbenzoic acid is used as oxidant and CH 3CN is used as solvent, being probably the main reason for the high activity of 5 and its selectivity toward epoxide formation.

Thermodynamic contributions of peptide backbone unit from water to biocompatible ionic liquids at T = 298.15 K

To quantify the biomolecular interactions of protein functional groups with biocompatible ionic liquids (ILs), transfer free energies ( Δ G tr ′ ) of model compounds from water to aqueous ILs solutions have been determined from the solubility measurements, as a function of ILs concentration at T = 298.15 K under atmospheric pressure. The aqueous systems investigated contain amino acids of zwitterionic glycine peptides: glycine (Gly), diglycine (Gly 2), and cyclic glycylglycine (c(GG)) with ILs of diethylammonium acetate ([Et 2NH][CH 3COO], DEAA), triethylammonium acetate ([Et 3NH][CH 3COO], TEAA), and trimethylammonium acetate ([Me 3NH][CH 3COO], TMAA). It was found that the solubility of model compounds in aqueous IL solutions decreases with increasing IL concentration (salting-out effect). We observed positive values of Δ G tr ′ for Gly, Gly 2, and c(GG) from water to ILs, indicating that the interactions between ILs and protein surface are unfavourable, which leads to stabilization of the native structure of amino acids. Moreover, our experimental data is used to determine transfer free energies ( Δ g tr ′ ) of the peptide backbone unit (–CH 2C ONH–) from water to IL solutions. These results explicitly elucidate that all alkyl ammonium ILs acted as stabilizers for tested model compounds through the exclusion of ILs from surface of model compounds and also reflect the effect of alkyl chain on the stability of protein model compounds. To obtain the mechanism events of the ILs role in enhancing the stability of the model compounds structure, we further studied the UV–vis spectrum analysis.

Stereoselective total synthesis of (+)-licochalcone E

The synthesis of (+)-licochalcone E (1) was accomplished for the first time in 13 steps from aryl bromide (6) with 8% overall yield. Palladium-catalyzed Negishi-Reformatsky coupling reaction of compound 6 with ethyl 2-(tributylstannyl)acetate provided the aryl acetic ester (5), which was converted to aryl acetamide (4) via mixed anhydride formation. Chiral auxiliarymediated methylation of the (S)-4-benzyl-2-oxazolidinone-derived aryl acetamide (4) provided the key asymmetric benzylic methyl group in compound 1.

Thermal property measurement and heat transfer analysis of acetamide and acetamide/expanded graphite composite phase change material for solar heat storage

As a phase change material (PCM), acetamide (AC) can be a potential candidate for energy storage application in the active solar systems. Its utilization is however hampered by poor thermal conductivity. In this work, AC/expanded graphite (EG) composite PCM with 10 wt% (mass fraction) EG as the effective heat transfer promoter was prepared; its thermal properties were studied and compared with those of pure AC. Transient hot-wire tests showed that the addition of 10 wt% EG led to about five-fold increase in thermal conductivity. Investigations using a differential scanning calorimeter revealed that the melting/freezing points shifted from 66.95/42.46 °C for pure AC to 65.91/65.52 °C for AC/EG composite, and the latent heat decreased from 194.92 to 163.71 kJ kg −1. In addition, heat storage and retrieval tests in a latent thermal energy storage unit showed that the heat storage and retrieval durations were reduced by 45% and 78%, respectively. Further numerical investigations demonstrated that the less improvement in heat transfer rate during the storage process could be attributed to the weakened natural convection in liquid (melted) AC because of the presence of EG.

Effect of lacosamide on expression of Nav1.8 in dorsal root ganglia in a rat model of chronic neuropathic pain

Objective To investigate the effect of lacosamide on expression of Nav1 .8 in dorsal root ganglia (DRG) in a rat model of chronic neuropathic pain.Methods Thirty-six female specific-pathogen-free (SPF)SD rats were randomly assigned into 3 groups ( n = 12 each): sham operation group (group S), model group (group M) and lacosamide group (group L) . Chronic neuropathic pain was produced by insertion of a small stainless steel rod (4.00 mm in length and 0.63 mm in diameter) into the L, intervertebral foramen in the rat, producing a chronic steady compression of the DRG in M and L groups. The mechanical threshold was measured 2 days before operation and on the 2, 4, 6, 7, 8, 9 and 10 days after operation (T0-7 ) . Intraperitoneal lacosamide 20mg/kg (in normal saline 0.5 ml) was injected at T4-7, twice a day in S and L groups. In group M, normal saline 0.5 ml was injected at T4-7 twice a day and the mechanical threshold was measured after the last administration everyday . The L, DRG on the operated side was removed after measurement of pain threshold to detect the expression of Na, 1.8 mRNA and protein by RT-PCR and immuno-histochemistry respectively. Results Compared with group S, the mechanical pain threshold was significantly decreased at T1-7 and the expression of Navl .8 mRNA and protein was up-regulated in M and L groups ( P < 0.05) . Compared with group M, the mechanical pain threshold was significantly increased at T4-7 and the expression of Nav 1.8 mRNA and protein was down-regulated in group L ( P < 0.05) . Conclusion The mechanism by which lacosamide reduces chronic neuropathic pain is related to the down-regulation of the expression of Nav 1.8 in rat DRG. Key words: Acetamides; Sodium channels; Ganglia, spinal; Neuralgia

Formation of Hydroxyapatite Whiskers by Hydrothermal Homogeneous Precipitation Using Acetamide

Well‐crystallized, compositionally homogeneous HA whiskers with uniform morphology and high aspect ratio were successfully prepared by hydrothermal homogeneous precipitation from aqueous solution using acetamide (AA). The product had a mean length of 116 μm and an aspect ratio of 102. The nucleation and crystal growth of such whiskers were studied by quenching the solution from various temperatures. It was found that the nuclei could be formed at about 120°C, while stable and well‐grown whisker‐like precipitation only occurred above 140°C. The product had the same crystallographic characteristics as normal HA crystals. No other phase than HA was detected. Compared with widely used wet chemical routes, the slow hydrolysis of AA provided a stable and continuous growth environment with a low degree of supersaturation, facilitating rapid growth of long HA whiskers directly from a hydrothermal solution, free of any interference from other phases. The whiskers showed spiral growth, with preferential c‐axis orientation.

Synthesis of N-(3-Cyano-7-ethoxy-1,4-dihydro-4-oxoquinolin-6-yl)acetamide

Synthesis of N-(3-Cyano-7-ethoxy-1,4-dihydro-4-oxoquinolin-6-yl)acetamide

Amide acetals in the synthesis of pyridothienopyrimidines

Methyl 3-amino-4-arylaminothieno[2,3-b]pyridine-2-carboxylates containing various substituents in the benzene ring were synthesized by the Thorpe-Ziegler reaction of 4-arylamino-2-chloropyridine-3-carbonitriles with methyl thioglycolates. The influence of the substituent in the benzene ring, acetal structure, the solvent and the process temperature on the reactions of obtained compounds with amide acetals was studied. It was established that reactions with dimethylacetamide dimethylacetal in toluene smoothly results in amidine derivatives, viz., methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2-carboxylates, regardless of the substituent in the benzene ring. Analogous reaction of p-fluoroderivative with dimethylacetamide dimethylacetal in refluxing anhydrous ethanol leads to intramolecular cyclocondensation to produce substituted pyridothienopyrimidines, viz., 5H-1-thia-3,5,8-triazaacenaphthenes, in good yields. Amidine derivatives were the major products in the case of the coupling of aminothienopyridines with dimethylformamide dimethylacetal under the same conditions. A new approach to the synthesis of substituted pyridothienopyrimidines, viz., 3H-1-thia-3,5,8-triazaacenaphthylenes, based on the prolonged heating of methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2-carboxylates in the excess of acetic anhydride was elaborated. Putative mechanisms of the processes concerned are given.

ChemInform Abstract: Synthesis and Antimicrobial Evaluation of Some New 2‐(6‐Oxo‐5,6‐dihydro[1,3]thiazolo [3,2‐b]‐2‐aryloxymethyl‐1,2,4‐triazol‐5‐yl)‐N‐arylacetamides.

AbstractA series of arylacetamides (III) (20 examples) is synthesized by condensing triazole‐3‐thiol (I) with various N‐phenylmaleimides (II).

ChemInform Abstract: Amide Acetal Claisen Rearrangement in the Synthesis of Mesembrane Alkaloids.

The synthesis of primary and secondary allylic alcohols (differing in the degree of steric hindrance) and of amide acetals (achiral and chiral) is reported. These compounds were used as substrates in the amide acetal Claisen rearrangement, and the effect of Lewis acids on the stereoselectivity of the reaction was studied. The rearrangement products have been applied to the synthesis of the mesembrane alkaloids (–)-mesembranone, rac-O-methyljoubertiamine and joubertiamine.

ChemInform Abstract: Acetals of Lactams and Acid Amides. Part 60. N- and O-Alkylation of 5-Oxo-5,6,7,8-tetrahydrocarbostyril Derivatives. Synthesis of Isoxazolo(5,4-f)- and Pyrazolo(3,4-f)quinolines.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.