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U-47,700 is a synthetic opioid that emerged on the novel psychoactive substance market a few years ago. After incorporating the substance into the urine UPLC-TOF-MS screening used in post-mortem toxicology, the drug was detected in 10 autopsy cases within routine case work. In all cases, the cause of death was accidental poisoning by U-47,700 alone or in combination with other psychoactive substances. The concentration of U-47,700 in the blood samples ranged between 0.15-2.0 mg/L with a median of 0.30 mg/L. In one of the cases with a U-47,700 concentration of 0.27 mg/L, no other psychoactive substances were detected. The stored TOF-MS analytical data from the year preceding the incorporation of U-47,700 into the screening was reprocessed in order to search for more positive cases. The data-independent acquisition of the original screening allowed for retrospective re-analysis of the full-scan data without additional experiments on the actual sample. The retrospective data-analysis revealed two additional cases positive for U-47,700. The first mention of U-47,700 on a Finnish internet discussion forum was in March 2015. After having been detected in several death cases, the drug was put under national control in November 2016 and the last fatality occurred in 2017. The toxic lifespan of U-47,700 thus lasted for approximately 2 years in Finland. Forensic and clinical laboratories need to rapidly adjust their screening procedures in order to adapt to the continuously expanding field of novel psychoactive substances. Retrospective data-analysis is a practical tool for monitoring the emergence of new substances onto the market. [ABSTRACT FROM AUTHOR]

Thrimurtulu et al. recently reported unprecedented cobalt-catalyzed annulation of allenes with benzamide (N. Thrimurtulu, A. Dey, D. Maiti, C. M. R. Volla, Angew. Chem., Int. Ed., 2016, 55, 12361-12365). In this reaction, the substituent on the allene controls the regioselectivity for the formation of either dihydroisoquinolin-1(2H)-one or isoquinolin-1(2H)-one. In the present study, density functional theory calculations were performed to investigate the detailed reaction mechanism and the origin of the experimentally observed regioselectivity. A systematic search shows that the electronic and steric effects of the substituent on the allene determine which of the two allene insertions is followed, and thus determine the regioselectivity. The bulky diphenylphosphonate and two phenyl substituents of the allenylphosphonate and diarylallene favor C1vC2 insertion, which eventually leads to the formation of isoquinolin-1(2H)-one. In contrast, for the arylallene, which has a relatively electron-rich C2vC3 bond, C2vC3 insertion is favored and eventually leads to the formation of dihydroisoquinolin-1(2H)-one. The calculations also explain why annulation rather than hydroarylation of benzamide with allenylphosphonate occurs with a cobalt catalyst. [ABSTRACT FROM AUTHOR]

We report herein the design, synthesis and antimycobacterial activity of 3,5-dinitrobenzamide derivatives containing fused ring moieties. Results reveal that many of the target compounds have considerable in vitro antitubercular activity. Especially, N -((2-(4-fluorophenyl)/ N -((2-(3-fluorobenzyl)-1,2,3,4-tetrahydroisoquilin-6-yl)methyl)-3,5-dinitrobenzamides 18a and 20e exhibit potent MIC values of 0.056–0.078 μg/mL against both drug-sensitive Mycobacterium tuberculosis (MTB) H37Rv strain and two clinically isolated multidrug-resistant MTB (MDR-MTB) strains, opening a new direction for further SAR studies. [ABSTRACT FROM AUTHOR]

An efficient and convenient ligand-free, rhodium-catalyzed ortho-C(sp2)–H amidation of benzaldehydes with dioxazolones using H2O as the key promoter is described. Using this protocol, a wide range of benzaldehyde substrates were selectively amidated in good to excellent yields with broad functional group compatibility. KIE experiments revealed that the C–H bond activation was likely the rate-limiting step. In addition, computational studies indicated that the catalyst precursor interacted with water and dioxazolones to generate the active catalytic species. Notably, the practicality and efficacy of this method were illustrated by a late-stage amidation of an estrone-derived molecule and further transformations of the amidated product. [ABSTRACT FROM AUTHOR]

An efficient Pd(0)-catalyzed alkylarylation of N-alkyl-Nmethacryloylbenzamides with alkyl iodides for the synthesis of isoquinoline- 1,3-diones is described. A highlight of the method is its excellent functional-group tolerance. Mechanistic investigations suggest that a radical addition/cyclization process is probably involved in the sequences. [ABSTRACT FROM AUTHOR]

Three benzamide hydrated derivatives as para-methyl-N-(3-pyridyl)benzamide monohydrate (I) or Mpm · H2O; N-(3-fluorophenyl)-4- pyridylcarboxamide monohydrate (II) or NpmF · H2O and para-chloro-N-(3-pyridyl)benzamide dihydrate (III) or Clpm · 2H2O are obtained from a series of crystallization experiments using a range of solvents to obtain polymorphs and solvates (hydrates). Most of the crystallization experiment attempts did not provide hydrates and yielded the starting parent crystalline materials. However, from the experiments, two benzamides, Mpm as a monohydrate and Clpm as a dihydrate were isolated and together with a carboxamide monohydrate as NpmF · H2O are reported herein. The water molecules play a key role in crystal structure formation using classical hydrogen bonding via amide N-H···OH2, O- H···Npyridine and O-H···O=C interactions. They compensate for the excess of strong hydrogen bonding acceptors over donors in the benzamide/pyridinecarboxamide molecules, by participating as O-H hydrogen bond donors twice and usually as an O acceptor once. In the Clpm dihydrate, both water molecules form hydrogen bonded chains along the a-axis direction. The lack of hydrate formation in the majority of related benzamides is presumably related to the relative hydrophobicity of these compounds. [ABSTRACT FROM AUTHOR]

Ten new 2(4-hydroxy-3-benzoyl) benzamide-5-phenyl-1,3,4-oxadiazole derivatives ( 10a–j ) were synthesized by coupling 3-benzoyl-4-hydroxybenzoic acid ( 5) with 2-amino-5-phenyl-1,3,4-oxadiazoles ( 9a–j ). The structures of these compounds were confirmed by IR, 1 H, 13 C NMR, and mass spectra, and also by elemental analyses. The anti-inflammatory activity of the compounds 10a–j were investigated by screening them against human red blood cells (HRBC) in-vitro . The results reveal that among this series, compound 10j with hydroxy substituent, particularly at the ortho position of the phenyl ring attached to the 5th carbon atom of the oxadiazole ring possess significant membrane stabilizing activity in comparison with the control. Further , in-vivo chick chorioallantoic membrane (CAM) and rat corneal anti-angiogenesis assays were performed to assess the effect of compound 10j on endothelial cell migration. This confirmed that compound 10j inhibits the proliferation of endothelial cells. Anti-inflammatory studies detected the amelioration of carrageen induced rat hind paw edema. Further in-vivo and in-silico approaches revealed the inhibition of inflammatory marker enzyme cyclooxygenase-2 (Cox-2) and myleoperoxidase (MPO). The study reports that the compound 10j effectively act against the inflammatory mediated anti-angiogenic disorders which could be translated into a new drug in future. [ABSTRACT FROM AUTHOR]

The equilibrium ( r e ) molecular structure of thiobenzamide along with r h1 structure has been determined in gas phase using gas electron-diffraction (GED) at about 127 °C and quantum-chemical calculations (QC). Rovibrational distance corrections to the thermal averaged GED structure have been computed with anharmonic force constants obtained at the MP2/cc-pVTZ level of theory. According to the results of GED and QC thiobenzamide exists as mixture of two non-planar enantiomers of C 1 symmetry. The selected equilibrium geometrical parameters of thiobenzamide ( r e , Å and ∠ e , deg) are the following: (C S) = 1.641(4), (C N) = 1.352(2), (C C) = 1.478(9), (C C) av  = 1.395(2), CCN = 114.7(5), CCS = 123.4(5), C2C1C7S = 31(4), C6C1C7N = 29(4). The structure of thiobenzamide in the gas phase is markedly different to that in the literature for the single crystal. The differences between the gas and the solid structures are ascribed to the presence of intermolecular hydrogen bonding in the solid phase. [ABSTRACT FROM AUTHOR]

Amide derivatives have gained considerable attention because of their extensive range of biological activities and pharmaceutical applications. The current paper presents the synthesis of N, N′ -(ethane-1,2-diyl) bis (3-methylbenzamide), ( I ), its molecular and crystal structure and an evaluation of its likely biological activity, including cytotoxicity (LD 50 = 37.21 μg/ml) and antileishmanial activity (IC 50 = 5.77 μg/ml). Moreover, a docking simulation was used to determine the possible interaction sites of the compound (I) with TryR, an enzyme involved in the redox metabolism of the leishmania parasite. Docking computations demonstrate that the compound established prominent binding interactions with the key residues of the TryR and possess the potential to effectively inhibit the catalytic activities of the enzyme. Thus the results suggest that this compound can serve as a potential scaffold for the treatment of leishmaniasis and deserves further development. [ABSTRACT FROM AUTHOR]

The organic materials, N-methyl–N-aryl benzamides were synthesized from benzoylation of N-methyl-4-nitrobenzenamine (MNBA) using suitably substituted benzoyl chlorides. The products were purified by recrystallization and their single crystal were grown by a slow evaporation technique. The crystals were characterized by FTIR, UV–Vis–NIR, 1 H & 13 C NMR, and single & powder X-ray diffraction. Thermal stability of the crystals was studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Dielectric and NLO properties of MNPB, FMNPB and MMNPB crystals were studied. The second harmonic generation (SHG) has been confirmed by the Kurtz powder test for all these crystals and the SHG efficiency of MMNPB crystal was found to be 2.25 times higher than that of KDP crystal. [ABSTRACT FROM AUTHOR]

The present study deals with the synthesis of two new compounds namely, benzamide – 2-chloro-4-nitrobenzoic acid (BENCNBA) and anthranilic acid–2-chloro-4-nitrobenzoic acid (AACNBA) using solid phase reactions. The phase diagram studies revealed that formation of the investigated compounds occurs in 1:1 molar ratio. The synthesized compounds were characterized using several spectral techniques such as FT-IR, 1 H and 13 C NMR, UV–Vis, powder X-ray diffraction (PXRD). Single crystal XRD (SCXRD) study showed that both BENCNBA and AACNBA compounds crystallize in triclinic crystal system with P-1 space group. Further, the presence of intermolecular hydrogen bonding between the constituent components was also supported by single crystal X-ray diffraction (SCXRD) method. Heat of mixing, entropy of fusion, roughness parameter, interfacial energy and excess thermodynamic functions have also been computed using the enthalpy of fusion values derived from differential scanning calorimeter (DSC) study. The inhibition effect of BENCNBA and AACNBA on the mild steel corrosion in hydrochloric acid solution was tested using electrochemical methods. Electrochemical impedance spectroscopy (EIS) study revealed that both BENCNBA and AACNBA behaved as interface corrosion inhibitors and showed maximum inhibition efficiencies of 95.71% and 96.42%, respectively at 400 ppm (1.23 × 10 −3 M) concentration. Potentiodynamic polarization (PDP) measurements suggested that BENCNBA and AACNBA acted as mixed type corrosion inhibitors. EIS and PDP results showed that BENCNBA and AACNBA act as efficient corrosion inhibitors for mild steel and their inhibition efficiencies enhances on increasing their concentrations. [ABSTRACT FROM AUTHOR]

An overexpression of the transmembrane ATP-binding cassette transporter G2 (ABCG2, BCRP) in cancer tissues is supposed to play a role in the multidrug resistance (MDR) of tumors resulting in an inefficient chemotherapy. Therefore, co-administration of selective and non-toxic ABCG2 inhibitors is a promising strategy for improving the efficacy of chemotherapy by blocking ABCG2-mediated export of the cytostatic drugs. In the present study, we designed a small library of 38 novel compounds containing a heteroaryl-phenyl scaffold possessing several (bioisosteric) moieties, and twelve new precursors. We investigated the library for ABCG2 inhibition, for the selectivity against MDR-involved efflux pump ABCB1 (P-gp) and for toxicity. Structure activity relationship (SAR) studies revealed that, at least a phenylheteroaryl-phenylamide scaffold is necessary for observing an ABCG2 inhibition. 4-Methoxy- N- (2-(2-(6-methoxypyridin - 3-yl)-2 H- tetrazol-5-yl)phenyl)benzamide ( 43 ) exhibited a high potency (IC 50  = 61 nM)), selectivity, low intrinsic toxicity and reversed the ABCG2-mediated drug resistance in presence of only 0.1 μM. [ABSTRACT FROM AUTHOR]

An efficient method for preparation of substituted 6H-isoindolo[2,1- a ]indol-6-ones ( 2 ) that are important structural components of a vast array of naturally occurring and pharmacologically active compounds, has been developed by the palladium-catalyzed intramolecular cycloaminocarbonylation of 2 -(1H-indol-2-yl)phenyl tosylates with CO. Significantly, the intermolecular aminocarbonylation products 2 -(1H-indol-2-yl)benzamides are formed when an excess of amine is used in this reaction system. Alternatively, 2 -(1H-indol-2-yl)benzamides can also be synthesized by the in situ aminolysis of 2 . Furthermore, treatment of 2 with hydrosilane in the presence of KOH gave the unprecedented reducing products 2 -(-1H-indol-2-yl)benzyl alcohols in 75–86% yields. These results demonstrate that 6H-isoindolo[2,1- a ]indol-6-ones are versatile substrates for further synthetic elaboration. [ABSTRACT FROM AUTHOR]

A novel series of substituted benzamide derivatives bearing a 1,2,3-triazole moiety were designed and synthesized by click chemistry. Human dihydroorotate dehydrogenase inhibition assay was used to evaluate the synthesized compounds as potent hDHODH inhibitors. Most compounds showed moderate to significant potency, accompanied with a suitable clogD 7.4 value and compounds 4d , 4o , and 5j effectively inhibited the activity of hDHODH with IC 50 values of 2.1, 2.1 and 1.5 μM, respectively. Compound 4o also effectively suppressed proliferation of the activated PBMCs. The study of structure-activity relationships also revealed that a suitable substitution on para-position of terminal phenyl ring was crucial for high activity. Together, the most promising compound 4o might serve as a novel hDHODH inhibitors for further investigation. [ABSTRACT FROM AUTHOR]

The design, synthesis, and structure activity relationships of the novel class of pyrazolylethylbenzamide orexin receptor 1-selective antagonists are described. Further derivatization of the prototype dual orexin receptor 1/2 antagonist lead ( 1 ) by installing a ( S )-methyl group into the ethyl linker moiety between the pyrazole ring and benzamide resulted in an increase of the antagonist potency against orexin receptor 1/2 receptors. Optimization of the benzamide and pyrazole parts of compounds 2 and 9b led to the identification of N -ethyl-5-fluoro- N -{(2 S )-1-[5-(4-fluorophenyl)-2 H -tetrazol-2-yl]propan-2-yl}-2-(pyrimidin-2-yl)benzamide ( 24 ), which exhibited excellent antagonistic activity against orexin receptor 1 with an IC 50 of 2.01 nM and a 265-fold selectivity for orexin receptor 1 over orexin receptor 2. [ABSTRACT FROM AUTHOR]

A sulfonamidebenzamide series was assessed for anti-kinetoplastid parasite activity based on structural similarity to the antiparasitic drug, nifurtimox. Through structure-activity optimization, derivatives with limited mammalian cell toxicity and increased potency toward African trypanosomes and Leishmania promastigotes were developed. Compound 22 had the best potency against the trypanosome (EC 50 = 0.010 μM) while several compounds showed ∼10-fold less potency against Leishmania promastigotes without impacting mammalian cells (EC 50 > 25 μM). While the chemotype originated from an unrelated optimization program aimed at selectively activating an apoptotic pathway in mammalian cancer cells, our preliminary results suggest that a distinct mechanism of action from that observed in mammalian cells is responsible for the promising activity observed in parasites. [ABSTRACT FROM AUTHOR]

Analytical high-performance liquid chromatographic enantioseparation of 1-(4-chlorobenzhydryl) piperazine benzamide derivatives was accomplished on different chiral stationary phases. The enantiomers of the compounds were resolved by normal-phase chromatography on silica-based amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H), cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and cellulose tris(4-methylbenzoate) (Chiralcel OJ) columns with mobile phases consisting of mixtures of n-hexane and ethanol in different proportions (90: 10, 80: 20). The mobile phase and the chiral stationary phase were varied to achieve the best resolution. The effect of the concentration of ethanol in the mobile phase was studied. The resolution obtained on the three columns was significant. [ABSTRACT FROM AUTHOR]

Herein we report for the first time a series of 2-benzamido -N -(2-oxo-4-(methyl/trifluoromethyl)-2 H -chromen-7-yl) benzamide 3a – f and substituted quinazolin-4(3 H )-ones and 2 H -benzo[e][1,2,4]thiadiazin-3(4 H )-one 1,1-dioxides ( 5 , 6 , 8 and 10a – c ) as selective inhibitors of the tumor associated hCA IX and XII isoforms. Among the compounds reported the trifluoromethyl derivative 3d resulted the most potent against these CA isoforms with K I s of 10.9 and 6.7 nM. [ABSTRACT FROM AUTHOR]

The title compound crystallizes in monoclinic crystal system, with space group P21/c. The compound exhibits intermolecular interactions of the types N–H⋯N, C–H⋯O, and C–H⋯π; intramolecular interactions of the type N–H⋯N. The intercontacts are also studied using Hirshfeld surface analysis. The compound showed no remarkable antibacterial activity when screened against two gram-negative and two gram-positive bacteria. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the clinical efficacy of depigmentation through the dual inhibition of tyrosinase and melanogenesis. Topics covered include the effects of various substituent groups at the 5-position of N-benzylbenzamide and the main factor that results in a high degree of efficacy, an illustration of the general synthesis of substituted N-benzylbenzamides, and the anti-melanogenic and tyrosinase inhibitory activities of benzamide 3.

An unprecedented and convenient synthetic approach to 2,3-dihydro-1 H -isoindol-1-one (isoindolinone) derivatives has been developed. The key and final step of the method is the reaction of N -alkyl- N -( o -bromobenzyl)benzamides with butyllithium in THF at −78 °C. The corresponding 2-alkyl-3-aryl-2,3-dihydro-1 H -isoindol-1-ones were produced in moderate-to-fair yields, probably via oxidation of the initially formed corresponding 2 H -isoindole derivatives with air during workup. [ABSTRACT FROM AUTHOR]

N-(2-Acylaryl)benzamides and analogous N-substituted furan-2-, thiophene-2-, and cyclopropane-carboxamides in the systems EtONa-EtOH, EtONa-THF, and t-BuOK- t-BuOH undergo Camps cyclization to 2-aryl-, 2-hetaryl-, and 2-cyclopropylquinolin-4(1 H)-ones with high yields. The same substrates in the system t-BuOK (5 equiv)-THF are converted mainly to the corresponding N-(2-hydroxyaryl) amides as a result of oxidative transformation of the acyl fragment into hydroxy group. [ABSTRACT FROM AUTHOR]

A novel aromatic chiral dicarboxylic acid, 5-[4-(2-tetrabromophthalimidylpropanoylamino)benzoylamino]isophthalic acid was synthesized in three steps in high yield and purity starting from tetrabromophthalic anhydride and l-alanine. A series of new soluble, thermally stable and optically active polyamides (PA)s having pendent tetrabromophthalimide, flexible asymmetrical and benzamide groups with flame retardancy properties have been successfully prepared using triphenyl phosphite/pyridine in the presence of calcium chloride and N-methyl-2-pyrrolidone (NMP). The resulting new polymers were obtained in good yields, inherent viscosities ranging between 0.36 and 0.63 dL g and were characterized with FT-IR, H NMR, specific rotation and thermogravimetric analysis techniques. Bulky pendent groups of the polymer chains disturb interchain and intrachain interactions and make these polymers readily soluble in various solvents, such as NMP, N,N-dimethylacetamide, dimethyl sulfoxide, and N,N-dimethylformamide. The resulting PAs were thermally stable, with 10 % weight loss recorded at 432 and 478 °C in the nitrogen atmosphere. In addition, due to existence of chiral center and optical activity of these polymers, they have potential to be utilized as chiral stationary phase in chromatography technique for the separation of racemic mixtures. [ABSTRACT FROM AUTHOR]

The compound, 2-methyl-N-((4-methylpyridin-2-yl)carbamothioyl)benzamide was derived from ortho-toluylchloride and 2-amino-4-picoline. It was fully crystallised and characterised on the basis of elemental analysis, X-ray crystallography and spectroscopic techniques namely infra-red, Uv-Vis and nuclear magnetic resonance. The melting point was in the range of 164.9°C-165.8°C. The Fourier transform infrared (FTIR) analysis shows the following vibrational frequencies for ν(N-H), ν(C=O), ν(C-N) and ν(C=S) at 3237 cm-1, 1683 cm-1, 1329 cm-1 and 1154 cm-1 respectively. 1H NMR results showed chemical shifts at 9.140 ppm and 12.983 ppm for the two N-H protons. Single crystal X-ray diffraction studies on the compound showed it to be a rigid molecule due to the presence of internal hydrogen bonding. The compound shows antibacterial activity towards gram positive and gram negative bacteria. [ABSTRACT FROM AUTHOR]

Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thio)carbamates were investigated using Ellman's method for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). O-Aromatic (thio)carbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 μM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thio)carbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)-phenyl]benzamide, 2-hydroxy-N-phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenyl)carbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 μM), while 2-(phenylcarbamoyl)phenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 μM). Results from molecular docking studies suggest that carbamate compounds, especially N,Ndiphenyl substituted representatives with considerable portion of aromatic moieties may work as non-covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization. [ABSTRACT FROM AUTHOR]

In this work, the structure of a novel 3-acetoxy-2-methyl- N -(4-methoxyphenyl) benzamide, was analyzed both experimentally and theoretically using three methods, X-ray single crystal diffraction technique, IR spectroscopy, and quantum chemical computation. The X-ray diffraction analysis indicates that 3-acetoxy-2-methyl- N -(4-methoxyphenyl) benzamide molecula crystallizes in a triclinic system (space group P−1) and the calculated lattice constants are, a = 5.1205 ± 0.0004 Å, b = 9.8598 ± 0.0008 Å, c = 15.3398 ± 0.0013 Å, α = 80.79(7)°, β = 83.142(6)°, γ = 85.411(6)°, and Z = 2. In addition, the molecular geometry and vibrational frequencies of the title compound in ground state have been calculated using density functional theory (DFT) at B3LYP level 6-31G+(d,p) basis set. The geometrical parameters of the title compound obtained from XRD studies are good in agreement with the calculated values. The electronic properties, such as HOMO and LUMO energies and thermodynamic properties were calculated with DFT (using B3LYP/6-31G+(d,p) basis set) approach. To estimate the chemical reactivity of the molecule, the molecular electrostatic potential (MEP) surface map of the title molecule and PES scan were investigated with theoretical calculations at the B3LYP/6-31+G(d,p) and B3LYP/3-21G levels, respectively. Antioxidant properties are determined using DPPH free radical scavenging test. [ABSTRACT FROM AUTHOR]

Preclinical experiments and clinical observations suggest the potential effectiveness of selective 5-HT 1F receptor agonists in migraine. Identifying compounds with enhanced selectivity is crucial to assess its therapeutic value. Replacement of the indole nucleus in 2 (LY334370) with a monocyclic phenyl ketone moiety generated potent and more selective 5-HT 1F receptor agonists. Focused SAR studies around this central phenyl ring demonstrated that the electrostatic and steric interactions of the substituent with both the amide CONH group and the ketone C O group play pivotal roles in affecting the adopted conformation and thus the 5-HT 1F receptor selectivity. Computational studies confirmed the observed results and provide a useful tool in the understanding of the conformational requirements for 5-HT 1F receptor agonist activity and selectivity. Through this effort, the 2-F-phenyl and N -2-pyridyl series were also identified as potent and selective 5-HT 1F receptor agonists. [ABSTRACT FROM AUTHOR]

We report the development of a novel series of saccharin-based N -hydroxybenzamides as histone deacetylases inhibitors. Among them, 6j exhibited potent HDACs inhibitory activity against Hela nuclear extract. Further biological evaluation found 6i showed similar antiproliferative activities in vitro compared with the approved SAHA. [ABSTRACT FROM AUTHOR]

Here we report the investigation of diazabicycloalkane cores as potential new scaffolds for the development of novel analogues of the previously reported diazatricyclodecane selective delta (δ) opioid agonists, as conformationally constrained homologues of the reference δ agonist (+)-4-[(α R )-α((2 S ,5 R )-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N , N -diethylbenzamide (SNC80). In particular, we have simplified the diazatricyclodecane motif of δ opioid agonist prototype 1a with bridged bicyclic cores. 3,6-diazabicyclo[3.1.1]heptane, 3,8-diazabicyclo[3.2.1]octane, 3,9-diazabicyclo[3.3.1]nonane, 3,9-diazabicyclo[4.2.1]nonane, and 3,10-diazabicyclo[4.3.1]decane were adopted as core motifs of the novel derivatives. The compounds were synthesized and biologically assayed as racemic ( 3 – 5 ) or diastereoisomeric ( 6 , 7 ) mixtures. All the novel compounds 3 – 7 showed δ agonism behaviour and remarkable affinity to δ receptors. Amongst the novel derivatives, 3,8-diazabicyclo[3.2.1]octane based compound 4 evidenced improved δ affinity and selectivity relative to SNC80. [ABSTRACT FROM AUTHOR]

The fragmentations of argentinated N-allylbenzamides have been exhaustively studied through collision-induced dissociation and through deuterium labeling. The intriguing elimination of AgOH is certified as the consequence of intramolecular cyclization between terminal olefin and carbonyl carbon following proton transfer to carbonyl oxygen, rather than simple enolization of amide. Linear free energy correlations and density functional theory (DFT) calculations were performed to understand the competitive relationship between AgOH loss and AgH loss, which results from the 1,2-elimination of α-hydrogen (to the amido nitrogen) with the silver. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The standard molar energies of combustion of 2-nitrobenzamide, 3-nitrobenzamide and 4-nitrobenzamide were determined with an isoperibolic, static-bomb, combustion calorimeter. From the combustion results, the standard molar enthalpies of combustion and formation for these compounds in the condensed phase at T = 298.15 K were derived. Subsequently, to determine the enthalpies of sublimation, the vapour pressure data as a function of the temperature for the compounds under investigation were estimated using thermogravimetry by applying Langmuir’s equation, and the enthalpies of vaporisation were derived. Standard enthalpies of fusion were measured by differential scanning calorimetry then added to those of vaporisation to obtain reliable results for the enthalpy of sublimation. From the combustion and sublimation data, the gas phase enthalpies of formation were determined to be (−138.9 ± 3.5) kJ · mol −1 , (−122.9 ± 2.9) kJ · mol −1 and (−108.5 ± 3.7) kJ · mol −1 for the ortho , meta and para isomers of nitrobenzamide, respectively. The meaning of these results with regard to the enthalpic stability of these molecular structures is discussed herein. [ABSTRACT FROM AUTHOR]

Abstract: Two series of N-alkyl, N-alkoxy, and N-hydroxy bisguanidines derived from the N-phenylbenzamide and 1,3-diphenylurea scaffolds were synthesised in three steps from the corresponding 4-amino-N-(4-aminophenyl)benzamide and 1,3-bis(4-aminophenyl)urea, respectively. All of the new compounds were evaluated in vitro against T. b. rhodesiense (STIB900) trypomastigotes and Plasmodium falciparum NF54 parasites (erythrocytic stage). N-alkoxy and N-hydroxy derivatives showed weak micromolar range IC50 values against T. b. rhodesiense and P. falciparum whereas the N-alkyl analogues displayed submicromolar and low nanomolar IC50 values against P. falciparum and Trypanosoma brucei, respectively. Two compounds, 4-(2-ethylguanidino)-N-(4-(2-ethylguanidino)phenyl)benzamide dihydrochloride (7b) and 4-(2-isopropylguanidino)-N-(4-(2-isopropylguanidino)phenyl)benzamide dihydrochloride (7c), which showed favourable drug-like properties and in vivo efficacy (100% cures) in the STIB900 mouse model of acute human African trypanosomiasis represent interesting leads for further in vivo studies. The binding of these compounds to AT-rich DNA was confirmed by surface plasmon resonance (SPR) biosensor experiments. [Copyright &y& Elsevier]

Highlights: [•] It provides the ability of the B3LYP/6-31G** computational method. [•] Prediction of most stable structure and structural properties were done. [•] The complete vibrational assignment and spectroscopic analysis have been carried out. [•] The research shows the presence of intramolecular interaction in the title compound. [•] It explains a good correlation between the experimental and theoretical data. [ABSTRACT FROM AUTHOR]

A simple analytical method was developed and validated to determine fluopicolide residues in grapes and soil using the “Quick, Easy, Cheap, Effective, Rugged and Safe” approach followed by gas chromatography-mass spectrometry in the selected ion monitoring mode. Fluopicolide residues were extracted from grape and soil samples with acetonitrile, and the extracts were cleaned up by dispersive solid-phase extraction with primary secondary amine sorbent. The limit of quantification was 0.02 mg kg−1with grape and soil samples spiked at three levels, and recoveries were from 95% to 101% and 94% to 101% with relative standard deviations from 0.2% to 4.4%. The method is less expensive and safer than existing analytical methods for grapes and soil. [ABSTRACT FROM PUBLISHER]

The lack of robust and tunable chiral versions of cyclopentadienyl (Cp) ligands hampers progress in the development of catalytic asymmetric versions of a myriad of reactions catalyzed by this ubiquitous ligand. Herein, we describe of a class of chiral Cp ligands with tunable steric parameters. Coordinated to transition metals, the ligand creates a well-defined chiral pocket, able to imprint its chirality onto the metal. The corresponding Rh complexes are shown to be excellent catalysts for enantioselective allylation of N-methoxybenzamides via directed C-H functionalizations at very mild conditions. The obtained enantioselectivities are excellent and demonstrate the viability of chiral Cp complexes as selective transition metal catalysts. [ABSTRACT FROM AUTHOR]

Histone deacetylase (HDAC) inhibitors have received considerable attention as potential therapeutics for a variety of cancers and neurological disorders. Recent publications on a class of pimelic diphenylamide HDAC inhibitors have highlighted their promise in the treatment of the neurodegenerative diseases Friedreich's ataxia and Huntington's disease, based on efficacy in cell and mouse models. These studies' authors have proposed that the unique action of these compounds compared to hydroxamic acid-based HDAC inhibitors results from their unusual slow-on/slow-off kinetics of binding, preferentially to HDAC3, resulting in a distinctive pharmacological profile and reduced toxicity. Here, we evaluate the HDAC subtype selectivity, cellular activity, absorption, distribution, metabolism and excretion (ADME) properties, as well as the central pharmacodynamic profile of one such compound, HDACi 4b, previously described to show efficacy in vivo in the R6/2 mouse model of Huntington's disease. Based on our data reported here, we conclude that while the in vitro selectivity and binding mode are largely in agreement with previous reports, the physicochemical properties, metabolic and pglycoprotein (Pgp) substrate liability of HDACi 4b render this compound suboptimal to investigate central Class I HDAC inhibition in vivo in mouse per oral administration. A drug administration regimen using HDACi 4b dissolved in drinking water was used in the previous proof of concept study, casting doubt on the validation of CNS HDAC3 inhibition as a target for the treatment of Huntington's disease. We highlight physicochemical stability and metabolic issues with 4b that are likely intrinsic liabilities of the benzamide chemotype in general. [ABSTRACT FROM AUTHOR]

A surprising methylation of C(sp3)-H bonds in aliphatic amides and of C(sp2)-H bonds in benzamides with phenyltrimethylammonium iodide as methyl source is reported. [ABSTRACT FROM AUTHOR]

A highly para-selective oxidative coupling of monosubstituted arenes with benzamides affords biaryl carboxamides efficiently under mild conditions. [ABSTRACT FROM AUTHOR]

Optimized conditions to favor the intermolecular metal-catalyzed transformation over the intramolecular ring closure of 2-iodoanilides are presented. [ABSTRACT FROM AUTHOR]