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Here we report the development of a concise and efficient synthetic protocol for the preparation of 1H-perimidin-2-amine derivatives that contain an N-(2,2,2-trichloroethyl)carboxamide substituent near the amino group. These compounds' synthesis method is based on the interaction of naphthalene-1,8-diamine with N-(2,2,2-trichloro-1-isothiocyanatoethyl)carboxamides under reflux in acetonitrile medium for 15 minutes. This transformation is likely to pass through the stage of formation of the intermediate thiourea, which further eliminates hydrogen sulfide, which is accompanied by the closure of the perimidine cycle. Using the developed protocol, we synthesized nine new 1H-perimidin-2-amine derivatives. The yield of synthesized compounds was 67-82%. IR,1H NMR,13C NMR, 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC spectroscopy data proved their structures. [ABSTRACT FROM AUTHOR]

We report herein a blue‐light‐promoted iron‐catalyzed reduction of carboxamides and carboxylic esters. Conducting the reaction under hydrosilylation conditions and blue light (2×24 W, 450–460 nm) in the presence of an iron(0) based pre‐catalyst, Fe(CO)4(IMes), amines and alcohols were obtained, respectively, notably at ambient conditions, whereas using white light, higher reaction temperatures up to 100 °C were required. Preliminary mechanism studies highlighted the crucial role of blue light not only to generate the catalytic active species, but also in some steps of the catalytic cycle. [ABSTRACT FROM AUTHOR]

The facile generation of the α‐acyloxy carboxamide radical is hereby reported for the first time, utilizing a photoredox catalyzed reaction of Passerini adducts synthesized using a 4‐formyl‐1,4‐dihydropyridine as the carbonyl component. This radical effectively engages in a Giese reaction with a range of olefins, ultimately leading to the synthesis of novel Passerini‐derived products not previously amenable to direct aldehyde‐based transformations. Consequently, the resulting strategy, developed both in batch and in flow, offers a promising opportunity to expand the chemical space accessible through the Passerini reaction, virtually incorporating “impossible” aldehydes. [ABSTRACT FROM AUTHOR]

A novel and highly efficient technique has been demonstrated for the transamidation of N-tert-butoxycarbonyl (N-Boc) activated secondary amides, as well as the direct amidation of esters with amines, resulting in the formation of amide bonds. This technique exhibits exceptional selectivity in cleaving N–C/O–C bonds and utilizes Co@NC as a highly efficient magnetic nano-catalyst. The method stands out for its solvent-free conditions, environmentally friendly catalyst, straightforward work-up, and the ability to easily reclaim (aided by an external magnet) and reuse the catalyst for up to five cycles without significant loss of catalytic activity, showcasing both novelty and efficiency. [ABSTRACT FROM AUTHOR]

A four-step synthesis of the natural product pseudane IX, starting from 3-oxododecanoic acid phenylamide and including only one chromatographic purification, was accomplished with an overall yield of 52%. The same synthetic sequence, but with a controlled partial reduction of a nitro group in the penultimate intermediate, led to the N-oxide of pseudane IX (NQNO). A shortened three-step variation of the synthesis allowed for the preparation of novel carboxamide analogs of the natural product. An agar diffusion assay against six different bacterial strains revealed significant antibacterial activity of the novel analogs against S. aureus at a concentration of 100 µg/mL. One of the novel compounds showed a remarkably broad spectrum of antibacterial activity, comparable to that of the positive control NQNO. [ABSTRACT FROM AUTHOR]

Many 1,2,4-triazole derivatives have high biological activity. They are of interest for scientific and practical human activity as potential drugs and pesticides. In this work, we report a synthesis of a series of new 3-amino-1,2,4-triazole derivatives containing an alkylamide moiety. It was found that the amidoalkylation of 3-amino-1,2,4-triazole N-(1,2,2,2-tetrachloroethyl)carboxamides in the presence of triethylamine occurred selectively at the endocyclic nitrogen atom N-1 with the formation of the corresponding N-(1-(5-amino-1H-1,2,4-triazol-1-yl)-2,2,2-trichloroethyl)carboxamides. The reaction products were isolated in 79–85% yields and characterized by 1H NMR and 13C NMR spectroscopy. To unambiguously establish the structure of the obtained compounds, we carried out X-ray diffraction analysis for N-(1-(5-amino-1H-1,2,4-triazol-1-yl)-2,2,2-trichloroethyl)-3-methylbutanamide. [ABSTRACT FROM AUTHOR]

In this work, we report the synthesis of a series of new 4H‐1,3,5‐oxadiazine derivatives. The method of their production is based on the dehydrosulfurization reaction of N‐(2,2,2‐trichloro‐1‐(3‐R‐thioureido)ethyl)carboxamides under the action of a mixture of iodine and triethylamine in DMF. A possible reaction mechanism has been proposed. The target products have been obtained in 58%–75% yield. The structure of the obtained compounds has been confirmed by 1H, 13C NMR, IR spectroscopy data, and x‐ray diffraction analysis carried out for 6‐(tert‐butyl)‐N‐phenyl‐4‐(trichloromethyl)‐4H‐1,3,5‐oxadiazin‐2‐amine. [ABSTRACT FROM AUTHOR]

Herein, we report the design, synthesis, and supramolecular behavior of 30 structurally diverse photoresponsive azobenzene molecular systems. To establish structure–property relationships, azobenzenes appended with N‐picolinyl and/or N‐benzyl groups tethered directly through carboxamides or via triazolylmethyl carboxamide linkages were explored. We have evaluated the photoswitching characteristics and thermal stability of the Z isomers through systematic studies. All the targets were also screened for their aggregation behavior and supramolecular aspects. Among all the derivatives, a few carboxamide‐based systems formed microcrystals upon aggregation, showing light responsiveness. In contrast, the derivatives tethered via triazolylmethyl carboxamide linkage exhibited hydrogel formation with excellent water‐absorbing capacity. All supramolecular aspects of the morphology of the microcrystal and hydrogel states and their stimuli‐responsiveness have been studied using spectroscopy and various microscopic techniques. [ABSTRACT FROM AUTHOR]

In continuation of our previous efforts for the development of potent small molecules against brain cancer, herein we synthesized seventeen new compounds and tested their anti-gliomapotential against established glioblastoma cell lines, namely, D54MG, U251, and LN-229 as well as patient derived cell lines (DB70 and DB93). Among them, the carboxamide derivatives, BT-851 and BT-892 were found to be the most active leads in comparison to our established hit compound BT#9.The SAR studies of our hit BT#9 compound resulted in the development of two new lead compounds by hit to lead strategy. The detailed biological studies are currently underway. The active compounds could possibly act as template for the future development of newer anti-glioma agents.

An organocatalyzed three‐component protocol using diazoacetonitrile to access a wide range of cyanopyrazole derivatives is reported here. This strategy, which proceeds through a piperidine‐catalyzed Knoevenagel condensation/formal [3+2] cycloaddition/dehydrocyanation sequence, provides an efficient route to construct dicyanopyrazoles from aldehydes, malononitrile, and diazoacetonitrile regioselectively. Interestingly, by engaging cyanoacetate and cyanoacetamide in this protocol, we could achieve cyanopyrazole esters and carboxamides. [ABSTRACT FROM AUTHOR]

The nature of protecting group chemistry necessitates a deprotection step to restore the initially blocked functionality prior to further transformation. As this aspect of protecting group manipulation inevitably adds to the step count of any synthetic sequence, the development of methods enabling simultaneous deprotection and functionalization ("deprotective functionalization"—distinct from "deprotection followed by functionalization") is appealing, as it has the potential to improve efficiency and streamline synthetic routes. Herein, we report a deprotective functionalization of the newly introduced Nms‐amides guided by density functional theory (DFT) analysis, which exploits the inherent Nms reactivity. Mechanistic studies further substantiate and help rationalize the exquisite reactivity of Nms‐amides, as other commonly used protecting groups are shown not to exhibit the same reactivity patterns. The practicality of this approach was ultimately demonstrated in selected case studies. [ABSTRACT FROM AUTHOR]

This work presents the design, synthesis and biological activity of novel N-substituted benzimidazole carboxamides bearing either a variable number of methoxy and/or hydroxy groups. The targeted carboxamides were designed to investigate the influence of the number of methoxy and/or hydroxy groups, the type of substituent placed on the N atom of the benzimidazole core and the type of substituent placed on the benzimidazole core on biological activity. The most promising derivatives with pronounced antiproliferative activity proved to be N-methyl-substituted derivatives with hydroxyl and methoxy groups at the phenyl ring and cyano groups on the benzimidazole nuclei with selective activity against the MCF-7 cell line (IC50 = 3.1 μM). In addition, the cyano-substituted derivatives 10 and 11 showed strong antiproliferative activity against the tested cells (IC50 = 1.2–5.3 μM). Several tested compounds showed significantly improved antioxidative activity in all three methods compared to standard BHT. In addition, the antioxidative activity of 9, 10, 32 and 36 in the cells generally confirmed their antioxidant ability demonstrated in vitro. However, their antiproliferative activity was not related to their ability to inhibit oxidative stress nor to their ability to induce it. Compound 8 with two hydroxy and one methoxy group on the phenyl ring showed the strongest antibacterial activity against the Gram-positive strain E. faecalis (MIC = 8 μM). [ABSTRACT FROM AUTHOR]

The advancement of sustainable chemistry and changes in the economy are strongly intertwined. Reaction time, cost savings, moderate temperatures, and generation of the fewest byproducts are frequently achieved by using catalytic processes. Herein, we report the C−H olefination of imidazo[1,2a] pyridine carboxamides with various acrylates in the presence of Pd (OAc)2 with O2 as the oxidant in aqueous ethanol rather than using non‐ecofriendly solvents. The C−H activation features most user‐friendly reaction conditions, excellent yield as well as plenty substrate scope and applicable for C−H deuteriation of the corresponding heteroarenes with D2O. Experimental mechanistic studies indicate that C−H activation step succeeded after formation of tetra coordinated square planer Pd‐substrate adduct. [ABSTRACT FROM AUTHOR]

A series of novel carboxamide compounds containing benzoxazole motif was synthesized through multiple steps, including electrophilic substitution, cyclization, reduction and amide formation. These processes utilized ortho-aminophenol and heptafluoro-2-iodopropane as starting materials. The structures of these compounds (4a–4r) were characterized by 1H NMR, 13C NMR, and HRMS. Bioassay results revealed that most of these compounds exhibited significant insecticidal activity against Mythimna separata at 500 mg/L. Among them, compound 6-chloro-N-(4-methoxy-3-(6-(perfluoropropan-2-yl)benzo[d]oxazol-2-yl)phenyl)-N-methylnicotinamide (4r) possessed the highest activity, even at 4 mg/L. Molecular docking predicted the binding modes of 4r. These novel carboxamide compounds containing benzoxazole motifs offer valuable insights for designing insecticidal compounds targeting GABA receptors, aiming to control lepidopteran pests effectively. [ABSTRACT FROM AUTHOR]

Introduction: 3-(2-butyl-5-chloro-1H-imidazole-4-yl)-N-[4-methoxy-3-(trifluoromethyl)phenyl]-4,5- dihydro-1,2-oxazole-5-carboxamide is new antirheumatic drug. It is necessary to identify and synthesize the biotransformation products for its complete pharmacokinetic study. Material and Methods: A biotransformation study was carried out by intraperitoneal administration of the drug to Wistar rats and Soviet Chinchilla breed rabbits. Animal blood sampling was performed before the injection and 0.5 h, 1 h, 2 h, 4 h, 24 h after the injection of the investigated compound. The samples were immediately centrifuged for plasma separation. Urine was simultaneously collected from rats before the administration and at intervals of 0-2 h, 2-4 h, 4-6 h, 6-24 h after administration, faeces -- before administration and at intervals of 0-12 h and 12-24 h after administration. The samples were analyzed by HPLC-MS/MS after immediate preparation by adding acetonitrile. Results and Discussion: 3-(2-butyl-5-chloro-1H-imidazole-4-yl)-4,5-dihydro-1,2-oxazole-5-carboxylic acid and 4-methoxy-3-(trifluoromethyl)aniline -- hydrolysis products of the active substance were found during the analysis of plasma, urine and fecal samples. The 4,5-dihydro-1,2-oxazole-5-carboxylic acid derivative has been synthesized. The second metabolite is a raw material for production of active pharmaceutical substance. During comparative tests, no significant difference between the retention times, ratio areas of chromatographic peaks at the main MRM-transitions and mass spectra of these metabolites on chromatograms of standard and animal samples was found, which indicates the correct identification of biotransformation products. Conclusion: The studied drug undergoes biotransformation by hydrolysis to form two main metabolites: 3- (2-butyl-5-chloro-1H-imidazole-4-yl)-4,5-dihydro-1,2-oxazole-5-carboxylic acid and 4-methoxy-3- (trifluoromethyl)aniline. The structure of the metabolites was confirmed by comparison with the synthesized standard samples using HPLC-MS/MS. [ABSTRACT FROM AUTHOR]

[Display omitted] Iodocyclization of N -(2-alkenylphenyl)carboxamides with acetoxybenziodoxolone/NaI system gives 4-iodomethyl- 4 H -3,1-benzoxazines with high efficiency. The process is triggered by the oxidation of NaI with acetoxybenziodo- xolone to afford iodine cation which is added to alkene moiety to form iodonium species, and the ultimate intra- molecular nucleophilic addition generates the final products. [ABSTRACT FROM AUTHOR]

Bicyclo[1.1.1]pentane (BCP) carboxamides are prepared from the direct addition of [1.1.1]propellane with semicarbazides in the presence of iron(II) phthalocyanine {Fe(Pc)} and tert‐butyl hydroperoxide (TBHP) in moderate to good yields. BCP ketones are also obtained under similar conditions in moderate yields. This protocol provides a straightforward one‐step access to BCP carboxamides, synthesis of which requires multiple chemical steps in previous reports. [ABSTRACT FROM AUTHOR]

Tridentate bis(carboxamide) pincers are key ligands used in catalysis, investigational medicinal inorganic compounds, and materials science. This study examined the atropisomerism of a group of bis(carboxamide) pincers with C2 symmetry to elucidate their physical, chemical, and structural behaviour, paving the way for the application of their metal complexes in different fields. One of the five compounds structurally elucidated by X-ray crystallography, 1c, has a pair of intramolecularly constrained isoquinoline ring substituents and crystallized enantiomerically pure in a chiral Sohncke space group. PM6 calculations of the 3-D potential energy surface for the main atropisomerisation reaction coordinate of 1c indicated that the lowest-energy conformer (atropisomer) has the isoquinoline rings canted out-of-plane by almost +30° and −30° relative to the central pyridine ring. The X-ray structure of 1c is located close to this energy minimum. Circular dichroism (CD) spectroscopy on bulk solid samples confirmed the presence of an excess population of one enantiomer (C2-symmetric atropisomer), most notably for compounds 1c, 1e, and 1f. CD spectra could be recorded for all compounds in solution, similarly reflecting an excess population of one atropisomer. The experimental spectra were confirmed by TD-DFT simulations at the CAM-B3LYP/def2-tzvp level of theory. We conclude that the present group of ligands are worthy of further investigation as chelating agents for metal ions with applications in chiral catalysis or biology. [ABSTRACT FROM AUTHOR]

The design and synthesis of new chemical entities (NCEs) with suitable physicochemical properties are playing a key role in medicinal research areas. Hence, we have designed and synthesized the 10 diverse scaffolds by rightly selecting the quinoline and pyrazine to articulate carboxamide derivatives in a single‐step process with maximum conversation in a shorter time through diverse studies of Ugi multi‐component reaction. Molecular docking studies against FMS‐like tyrosine kinase‐3 (FLT3) provided well‐clustered solutions for the binding modes of these molecules and shed light on the key structural features governing the binding affinity. Two carboxamides derivatives with 3,4,5‐trimethoxy, and chloro substituents showed comparable potency in Leukemia cell lines and medium efficacy in Breast and Melanoma cancer. These results suggest that pyrazine and quinoline‐based carboxamides may be prominent as new anti‐cancer agents in chemotherapy. Additionally, in silico analysis was employed to predict the comprehensive physicochemical ADME profile (absorption, distribution, metabolism, and excretion) of the carboxamide derivatives which was proven drug‐like properties. [ABSTRACT FROM AUTHOR]

Cyanide represents a persistent threat for accidental or malicious misuse due to easy conversion into a toxic gas and access to large quantities through several industries. The high safety index of hydroxocobalamin is a cornerstone quality as a cyanide scavenger. Unfortunately, intravenous infusion of hydroxocobalamin limits the utility in a mass casualty setting. We previously reported platinum(II) [Pt(II)] complexes with trans-directing sulfur ligands as an efficacious alternative to hydroxocobalamin when delivered by a bolus intramuscular (IM) injection in mice and rabbits. Thus, to enable Pt(II) as an alternative to hydroxocobalamin, a high safety factor is needed. The objective is to maintain efficacy and mitigate the risk of nephrotoxicity. Platinum amino acid complexes with the ability to form 5- or 6-membered rings and possessing either carboxylates or carboxamides are evaluated in vitro for cyanide scavenging. In vivo efficacy wa s evaluated in the zebrafish and mice cyanide exposure models. In addition, Pt(II) complex toxicity and pharmacokinetics were evaluated in a cyanide naive Sprague Dawley model. Doses for toxicity are escalated to 5× from the efficacious dose in mice using a body surface area adjustment. The results show the carboxamide ligands display a time and pH dependence on cyanide scavenging in vitro and efficacy in vivo. Additionally, exchanging the carboxylate for carboxamide showed reduced indications of renal injury. A pharmacokinetic analysis of the larger bidentate complexes displayed rapid absorption by IM administration and having similar plasma exposure. These findings point to the importance of pH and ligand structures for methionine carboxamide complexes with Pt(II). [ABSTRACT FROM AUTHOR]

Plant diseases caused by pathogenic fungi or oomycetes seriously affect crop growth and the quality and yield of products. A series of novel 1,2,4-triazole derivatives containing carboxamide fragments based on amide fragments widely used in fungicides and the commercialized mefentrifluconazole were designed and synthesized. Their antifungal activities were evaluated against seven kinds of phytopathogenic fungi/oomycete. Results showed that most compounds had similar or better antifungal activities compared to mefentrifluconazole's inhibitory activity against Physalospora piricola, especially compound 6h (92%), which possessed outstanding activity. Compound 6h (EC50 = 13.095 μg/mL) showed a better effect than that of mefentrifluconazole (EC50 = 39.516 μg/mL). Compound 5j (90%) displayed outstanding anti-oomycete activity against Phytophthora capsici, with an EC50 value of 17.362 μg/mL, far superior to that of mefentrifluconazole (EC50 = 75.433 μg/mL). The result of molecular docking showed that compounds 5j and 6h possessed a stronger affinity for 14α-demethylase (CYP51). This study provides a new approach to expanding the fungicidal spectrum of 1,2,4-triazole derivatives. [ABSTRACT FROM AUTHOR]

The organocatalytic enolization of 2‐arylacetamides, followed by an enantioselective intramolecular conjugate addition to tethered 2,5‐cyclohexadienones, yielding 3D fused N‐heterocycles, is described. The transformation represents the first strong activating group‐free activation of carboxamides via α‐C−H deprotonation in a metal‐free, catalytic, and enantioselective reaction, and is achieved by employing a bifunctional iminophosphorane (BIMP) superbase. [ABSTRACT FROM AUTHOR]

A single-site Fe(III) carboxamide complex, [Fe(HbpH) (Cl) 2 ] (1), (HbpH‾ = N,N′-Bis(picolinoyl)hydrazine) anion), was synthesized and used as the electrocatalyst of water oxidation reaction. Complex 1 catalyzes the oxidation of water to O 2 at the pH of 8 in phosphate buffer solution with the onset of a catalytic wave at about 0.45 V versus RHE with the turnover frequency (TOF) of 5.8 s−1 at room temperature. The stability of the catalyst in water oxidation processes by electrochemical and UV–vis measurements, demonstrated the realistic molecular electrocatalysis of 1. Differential pulse voltammetry (DPV) of 1 in different pH values showed the dependency of oxidation potential to the pH of the environment, establishing the fact that the catalytic cycle involves the proton-coupled electron transfer (PCET) process. Density functional theory (DFT) calculations on the mechanism of water oxidation process of 1 shows that the oxygen evolution reaction is carried out through the water nucleophilic attack (WNA) to the metal center ion, resulted to the formation of FeIV(O) species. Also, DFT calculations showed that the formation of an O–O bond proceeds through the interaction two molecular mechanism (I2M), which compete with the WNA mechanism following from experimental analysis. The electroactivity of the metal centre and carboxamide ligand and the ability of the ligand to stabilize the high oxidation numbers of the metal-ion centre during the oxidation process, provide different oxidation pathways for an OER process. • Synthesis of carboxamide Fe(III) complex using ionic liquid as an environmentally benign reaction medium. • Electrocatalytic studies of the [Fe(HbpH) (Cl) 2 ] (1) in the OER process. • TOF values of 5.8 mol of hydrogen in each mole of catalyst per second for the catalyst 1. • The I2M mechanism competes with the WNA mechanism investigation using DFT calculations in OER process. [ABSTRACT FROM AUTHOR]

A nickel-catalyzed hydrogen isotope exchange has been developed with acetone-d6 as the deuterium source. The reaction showed an improved kinetic feature of H/D exchange under the assistance of 2-pyridones, efficiently affording regioselective labeled aryl and alkyl carboxamides. [ABSTRACT FROM AUTHOR]

Borane-pyridine acts as an efficient (5 mol%) liquid catalyst, providing improved solubility for the direct amidation of a wide range of aromatic and aliphatic carboxylic acids and amines to form secondary and tertiary carboxamides. Tolerance of potentially incompatible halo, nitro, and alkene functionalities has been demonstrated. [ABSTRACT FROM AUTHOR]

In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone–carboxamide compounds 3h and 3s, which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC50 = 10 μM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity (3g: IC50 = 27.5 μM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e: IC50 = 52 μM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode. [ABSTRACT FROM AUTHOR]

Succinate dehydrogenase (SDH, EC 1.3.5.1) is one of the most promising targets for fungicide development and has attracted great attention worldwide. However, existing commercial fungicides targeting SDH have led to the increasingly prominent problem of pathogen resistance, so it is necessary to develop new fungicides. Herein, we used a structure-based molecular design strategy to design and synthesize a series of novel SDHI fungicides containing an N-(alkoxy)diphenyl ether carboxamide skeleton. The mycelial growth inhibition experiment showed that compound M15 exhibited a very good control effect against four plant pathogens, with inhibition rates of more than 60% at a dose of 50 μg/mL. A structure–activity relationship study found that N-O-benzyl-substituted derivatives showed better antifungal activity than others, especially the introduction of a halogen on the benzyl. Furthermore, the molecular docking results suggested that π–π interactions with Trp35 and hydrogen bonds with Tyr33 and Trp173 were crucial interaction sites when inhibitors bound to SDH. Morphological observation of mycelium revealed that M15 could inhibit the growth of mycelia. Moreover, in vivo and in vitro tests showed that M15 not only inhibited the enzyme activity of SDH but also effectively protected rice from damage due to R. solani infection, with a result close to that of the control at a concentration of 200 μg/mL. Thus, the N-(alkoxy)diphenyl ether carboxamide skeleton is a new starting point for the discovery of new SDH inhibitors and is worthy of further investigation. [ABSTRACT FROM AUTHOR]

The Cp*Co(III) C−H allylation of (hetero)arenes with allyl aryl ethers has been developed using an amide as directing group (24 examples). DFT calculations have shed light on the mechanistic course and reactivity pattern, showing that strong electron releasing groups favour the reaction by reducing the activation barrier of the rate‐determining C−H activation step. However, the steric strain can increase the energy of the migratory insertion step to the point of completely preventing the reaction, as in the case of the 3,5‐dimethylbenzamide. The obtained allylated compounds have been transformed into a variety of interesting heterocyclic and carbocyclic structures, such as isoquinolones and isochromanones. [ABSTRACT FROM AUTHOR]

According to the recent studies bezylcarboxamide fragment attached to the thiophene ring of thieno[2,3-d]pyrimidine is beneficial for antimicrobial activity of the compounds. Therefore we focused our efforts on constructing of the simple molecules such as N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides to get deeper insight into their antimicrobial activity. As the optimal procedure for preparation of target compounds we choose 1,1'-carbonyldiimidazole promoted interaction of 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid with the series of substituted benzyl amines. The obtained amides showed good activity against the strains of S. aureus and B. subtilis, which was higher for the derivative without substituents in benzene ring or the compounds with small substituents like methyl or methoxyl groups in the para-position of the benzene ring. Docking studies showed that despite the good values of the scoring functions, the conformational analysis of the ligands' poses in the active site revealed their ability for only partial inhibition of TrmD of P. aeruginosa. [ABSTRACT FROM AUTHOR]

A wide range of polyaryl compounds (π‐extended biaryls) including terphenyls, tetraphenyls, pentaphenyls, and hexaphenyls were assembled in a single operation of Pd(II)‐catalyzed C−H coupling of biaryl carboxamides and iodobiaryls. Traditionally, cross‐coupling protocols involving organometallic reagents were employed to assemble the core structure of π‐extended biaryls (polyphenylenes or polyaryls). The pre‐assembling of organometallic reagents is a limitation in investigations pertaining to the aryl‐aryl cross‐coupling reactions affording polyaryls (polyphenylenes). We report the application of Pd(II)‐catalyzed bidentate directing group (DG)‐aided C−H arylation method for constructing polyaryl motifs (π‐extended biaryls) using biaryl‐based carboxamides and iodobiaryls as the coupling partners in a single operation. The current investigation on the bidentate DG‐aided C−H arylation of biaryl carboxamides with iodobiaryls is expected to serve as a useful route to enrich the library of π‐extended biaryls (polyphenylenes or polyaryls). [ABSTRACT FROM AUTHOR]

[Display omitted] Isosteric replacement of the oxadiazole ring by amide bond in the structure of new non-β-lactam antibiotics led to compounds with higher activity against Gram-positive pathogens of ESKAPE panel. A series of 17 compounds were synthesized by acylation of 4-(4-fluorophenoxy)aniline with various amino acids. The spirocyclic derivative with 6-methylsulfonyl-2,6-diazaspiro[3.4]octane moiety showed excellent minimum inhibitory concentrations of 0.093–0.75 μg ml−1 against a number of methicillin-resistant Staphylococcus aureus strains. [ABSTRACT FROM AUTHOR]

Despite remarkable successes in linear and branched vinyl (hetero) arene synthesis, regiodivergent C−H olefination with a single catalytic system has remained underdeveloped. Overcoming this limitation, a Pd/MPAA‐catalyzed regiodivergent C−H olefination of imidazo[1,2a] pyridine carboxamides with unactivated terminal alkenes to generate branched and linear olefinated products depending upon the electronic nature of alkenes is reported herein. Moreover, this protocol can be applied for C−H deuteriation of the corresponding heteroarenes with D2O as deuterium source. Preliminary experimental studies combined with computational investigations (DFT studies) suggest that regiodivergent olefination can be controlled by olefin insertion and β‐hydride elimination steps. [ABSTRACT FROM AUTHOR]

Direct synthesis of Pyridine-2,6-dicarboxylic a-+cid bis-(3-hydroxy phenyl)]amide, (Pydca), chelating ligand was applied for Th(IV) extraction from Abu Rusheid Ore Sample, South Eastern Desert, Egypt, between latitudes 24° 37ʹ 16ʹʹ N and longitudes 34° 46 ʹ 35 ʹʹ E and far from the Red Sea coast by about 42 km west, using poly phosphoric acid catalyst (PPA). The synthesis of new amide via direct condensation of organic acid and aromatic amine was performed in DMF at 100°C. The immediate condensation reaction led to construct the carboxamide derivative in one easy step dismantling the hard activation, halogenation, step resulting in a good yield production. This cross-coupling reaction appears simple, convenient and has a wide scope of activities. This protocol could be extended to industrial large-scale production processes. Experimental measurements have been optimised such as diluent type, pH, contact time, initial Th(IV) concentration, temperature, pydca conc., co-existing ions and stripping agents. It was found that a maximum value of Th(IV) retention (0.86 × 10−3 mol/L) is observed with 0.015 mol/L pydca/CCl4 chelating ligand at room temperature. From kinetic aspects, it was found that Th(IV) extraction follows the pseudo-first order kinetic model. The thermodynamic parameters, ΔS, ΔH and ΔG were also evaluated indicating an endothermic and spontaneous extraction process with increasing the randomness of the extraction system. Th(IV) can be completely back extracted from the loaded pydca chelating ligand using 0.5 M HNO3, 1 M H2SO4 and 1 M HCl. Finally, the optimised factors have been applied for Th(IV) recovery from Abu Rusheid Ore Sample, South Eastern Desert, Egypt, producing a thorium oxide concentrate with Th(IV) content of 81.43% with a purity of 92.67%. [ABSTRACT FROM AUTHOR]

Herein, we present the first metallomacrocyclic Mn(II) complexes as efficient catalysts for the transfer hydrogenation of ketones. The dinuclear Mn(II) complexes [Mn2(L1–L4)2Cl2] (Mn1–Mn4), were synthesised in good yields by reacting MnCl2 ⋅ 4H2O with the ligands N,N′‐(1,4‐phenylene)dipicolinamide (L1), N,N′‐(1,2‐phenylene)dipicolinamide (L2), N,N′‐(4‐methoxy‐1,2‐phenylene)dipicolinamide (L3) and N,N′‐(4,5‐dimethyl‐1,2‐phenylene)dipicolinamide (L4). Structural characterization of the resulting Mn(II) complexes was achieved using FT‐IR spectroscopy, mass spectrometry, magnetic moment measurements, elemental analysis, and single‐crystal X‐ray diffraction for Mn2. The solid‐state structure of complex Mn2 reveals a dinuclear Mn(II) core, in which the metal coordination sphere consists of two bidentate, K2(N−O) bridging L2 units and two chlorido ligands to give a distorted octahedral geometry. The Mn(II) complexes (Mn1–Mn4) were quite active catalysts for the transfer hydrogenation of ketones displaying turnover numbers (TON) of up to 2633, which is comparable to those of well‐established Mn(I) catalysts. The new Mn(II) complexes also efficiently hydrogenated a number of aromatic, heterocyclic, functionalized and aliphatic ketones. More significantly, cheaper, and readily available hydrogen sources like ethanol also gave decent catalytic activities in the transfer hydrogenation reactions. [ABSTRACT FROM AUTHOR]

As part of our continuous efforts to discover novel c-Met inhibitors as antitumor agents, four series of thiazole/thiadiazole carboxamide-derived analogues were designed, synthesised, and evaluated for the in vitro activity against c-Met and four human cancer cell lines. After five cycles of optimisation on structure–activity relationship, compound 51am was found to be the most promising inhibitor in both biochemical and cellular assays. Moreover, 51am exhibited potency against several c-Met mutants. Mechanistically, 51am not only induced cell cycle arrest and apoptosis in MKN-45 cells but also inhibited c-Met phosphorylation in the cell and cell-free systems. It also exhibited a good pharmacokinetic profile in BALB/c mice. Furthermore, the binding mode of 51am with both c-Met and VEGFR-2 provided novel insights for the discovery of selective c-Met inhibitors. Taken together, these results indicate that 51am could be an antitumor candidate meriting further development. [ABSTRACT FROM AUTHOR]

Highly enantio‐ and diastereoselective (Ipc)2BOTf mediated aldol reactions of morpholine carboxamides are described. A wide variety of α‐substituted N‐acyl morpholine carboxamides were successfully employed, including α‐bromo, α‐chloro, α‐vinyl and para‐methoxyphenyl morpholine carboxamides which provided the corresponding aldol products in moderate to excellent yields, and generally with high enantio‐ and diastereoselectivities. [ABSTRACT FROM AUTHOR]

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC 50 : 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC 50 : 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development. A class of novel AXL inhibitors has been discovered, in which compound 59 exhibited potent AXL inhibition, high kinase selectivity and significant in vivo anti-tumor efficacy with desirable pharmacokinetic profile. [Display omitted] [ABSTRACT FROM AUTHOR]

This contribution described the chemoselective reduction of secondary carboxamides to aldimines. To perform such challenging transformation, we reported a catalyzed hydrosilylation using Fe(CO)4(IMes) [IMes=1,3‐bis (2,4,6‐trimethylphenyl) imidazol‐2‐ylidene] as the catalyst, diphenylsilane as the reductant under UV irradiation (350 nm) at room temperature for 16 h. Aldimines were then obtained, after a basic quench, in 32–83 % isolated yields. This transformation was unprecedented at iron. [ABSTRACT FROM AUTHOR]

Seven-coordinate rhenium oxo complexes supported by a tetradentate bipyridine carboxamide/carboxamidate ligand are reported. The neutral dicarboxamide H2Phbpy-da ligand initially coordinates in an L4 (ONNO) fashion to an octahedral rhenium oxo precursor, yielding a seven-coordinate rhenium oxo complex. Subsequent deprotonation generates a new oxo complex featuring the dianionic (L2X2) carboxamidate (NNNN) form of the ligand. Computational studies provide insight into the relative stability of possible linkage isomers upon deprotonation. Structural studies and molecular orbital theory are employed to rationalize the relative isomer stability and provide insight into the rhenium–oxo bond order. [ABSTRACT FROM AUTHOR]

5-Arylisoxazolyl- and 4,5-dichloroisothiazolyl-3-carboxamides were synthesized based on trichlorethylene and its dimer. The prepared carboxamides were used for the synthesis of azanediylbisisoxazolyl(isothiazolyl)carboxamides and bis(azolyl)carboxamides. The new polynitrogen ligands form palladium complexes LPdCl2, which exhibit high catalytic activity in cross-coupling reactions in water media in organic solvent-free conditions. [ABSTRACT FROM AUTHOR]

Naegleria fowleri is a free-living thermophilic flagellate amoeba that causes a rare but life-threatening infection called primary amoebic meningoencephalitis (PAM), with a very high fatality rate. Herein, the anti-amoebic potential of carboxamide derivatives possessing sulfonyl or sulfamoyl moiety was assessed against pathogenic N. fowleri using amoebicidal, cytotoxicity and cytopathogenicity assays. The results from amoebicidal experiments showed that derivatives dramatically reduced N. fowleri viability. Selected derivatives demonstrated IC50 values at lower concentrations; 1j showed IC50 at 24.65 μM, while 1k inhibited 50% amoebae growth at 23.31 μM. Compounds with significant amoebicidal effects demonstrated limited cytotoxicity against human cerebral microvascular endothelial cells. Finally, some derivatives mitigated N. fowleri-instigated host cell death. Ultimately, this study demonstrated that 1j and 1k exhibited potent anti-amoebic activity and ought to be looked at in future studies for the development of therapeutic anti-amoebic pharmaceuticals. Further investigation is required to determine the clinical relevance of our findings. [ABSTRACT FROM AUTHOR]

The combination of two neutral CHON reagents, a lipophilic phenanthroline dicarboxamide and a hydrophilic diglycolamide, resulted in a synergistic separation of adjacent light lanthanides in nitrate medium as the ligands present a reversed lanthanide selectivity. Separation factors higher than 7 were obtained for the pair Pr/Nd, which is one of the highest values reported in the literature. [ABSTRACT FROM AUTHOR]

Sulfonamide-based carboxamide drugs have multiple active sites that confers them with a variety of chemical and pharmacological activities. The combination of structural functionalities has been established to be vital in the drug discovery process. The synthesis of novel, nontoxic, cheap and effective anti-parasitic analogues is a trending aspect of pharmaceutical and medicinal chemistry research. In this research, the synthesis, characterization, and density functional theory (DFT) investigation of the reactivity and anti-trypanosomal simulation of benzenesulphonamide-based carboxamide derivatives was carried out for 2-[N-(benzenesulfonyl)-1-phenylformamido]-N-(4-nitrophenyl)acetamide(BPNA), 2-[N-(benzenesulfonyl)-1-phenylformamido]-N-(4-nitrophenyl)-3-phenylpropanamide (BPNPP), 2-[N-(benzenesulfonyl)-1-phenylformamido]-3-(1H-indol-2-yl)-N-(4-nitrophenyl)propenamide (BPINP) and 2-[N-(benzenesulfonyl)-1-phenylformamido]-4-methyl-N-(4-nitrophenyl)pentanamide (BPMNP) following an environmentally friendly zinc chloride catalyst mediated synthesis. The lower value of the HOMO-LUMO energy gap (2.9756 eV) observed for BPMNP indicated its higher chemical and biological activity. The global electrophilicity index (ω), which is related to chemical hardness and chemical potential in line with other global descriptors showed that the order of reactivity is BPMNP > BPINP > BPNPP > BPNA. The NBO analysis showed that σ → σ*, σ* →π*, π → π*, and π* → π* transitions were observed in all the compounds while σ → σ* and π* → π* showed the lowest and the highest stabilization energy, respectively. From the molecular docking analysis, BPMNP again, showed the most stable binding energy of − 9.6 kcal/mol and bond length of 1.99 Å, evidently performing better than the standard drug with binding energy and bond length of −7.6 kcal/mol and 2.89 Å, respectively. The binding energy obtained was observed to follow a decreasing order as thus; BPMNP > BPINP > BPNA > BPNPP which strongly indicates alkane-substituted benzenesulphonamide carboxamides especially BPINP and BPMNP possess potent curative properties against trypanosomiasis. [ABSTRACT FROM AUTHOR]

(N-Alkyloxalamido)-amino acid amides 9–12 exhibit excellent gelation capacities toward some lipophilic solvents as well as toward the commercial fuels, petrol and diesel. Gelator 10 exhibits an excellent phase-selective gelation (PSG) ability and also possesses the highest gelation capacity toward petrol and diesel known to date, with minimum gelation concentration (MGC) values (%, w/v) as low as 0.012 and 0.015, respectively. The self-assembly motif of 10 in petrol and toluene gel fibres is determined from xerogel X-ray powder diffraction (XRPD) data via the simulated annealing procedure (SA) implemented in the EXPO2014 program and refined using the Rietveld method. The elucidated motif is strongly supported by the NMR (NOE and variable temperature) study of 10 toluene-d8 gel. It is shown that the triple unidirectional hydrogen bonding between gelator molecules involving oxalamide and carboxamide groups, together with their very low solubility, results in the formation of gel fibres of a very high aspect ratio (d = 10–30 nm, l = 0.6–1.3 μm), resulting in the as-yet unprecedented capacity of gelling commercial fuels. Rheological measurements performed at low concentrations of 10 confirmed the strength of the self-assembled network with the desired thixotropic properties that are advantageous for multiple applications. Instantaneous phase-selective gelation was obtained at room temperature through the addition of the 10 solution to the biphasic mixture of diesel and water in which the carrier solvent was congealed along with the diesel phase. The superior gelling properties and PSG ability of 10 may be used for the development of more efficient marine and surface oil spill recovery and waste water treatment technologies as well as the development of safer fuel storage and transport technologies. [ABSTRACT FROM AUTHOR]

This study presents the synthesis, characterization, and antimicrobial efficacy of a novel pyrazoline carboxamide heterocyclic compound. Synthesized through a two-step process, involving the formation of an α,β-unsaturated ketone and subsequent conversion into a pyrazoline carboxamide derivative, the compound's structure and functional groups were confirmed using FT-IR, 1H NMR, and DEPT-135 techniques. The compound demonstrated high purity and yield, displaying significant inhibitory zones against microorganisms, notably Listeria monocytogenes (14.2 ± 0.0 mm to 16.8 ± 1.3 mm) and Candida albicans (10.9 ± 0.6 mm to 17.8 ± 1.5 mm). Evaluation of drug-likeness and toxicity highlighted its potential for drug development. Molecular docking studies indicated strong binding affinities to key antimicrobial target proteins, including DNA gyrase, penicillin-binding protein, and C. albicans sterol 14-a-demethylase. Molecular dynamics simulations revealed the compound's structural flexibility. These results make this new compound a candidate for further exploration in drug development, highlighting its potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Forensic toxicology laboratories often encounter casework backlogs, which raise concerns for drug stability that can be affected by long storage times, temperature and preservatives, or the lack thereof. The focus of this research was to evaluate the impact of these factors on the stability of 17 synthetic cannabinoids (SCs) in human whole blood and 10 associated metabolites in human urine. The fortified biological specimens were stored under room temperature (20°C), refrigerator (4°C) and freezer (–20°C) conditions for a period of 52 weeks. Preservatives included potassium oxalate, sodium ethylenediaminetetraacetic acid and sodium fluoride. Extraction of analytes was conducted using supported liquid extraction and analyzed using a liquid chromatograph-tandem mass spectrometer. Under all three storage conditions, the majority of urine metabolites were stable up to 9 weeks. All analytes in frozen sodium fluoride–preserved blood were stable at 21–52 weeks with the exception of APP-PICA. Analytes in the blood that were stable up to 52 weeks in the freezer generally had a core structure of a carbonyl substituent on a pyrazole or pyrrole with surrounding nonpolar groups. In contrast, compounds with two adjacent polar carbonyl functional groups experienced degradation at ≤1 week under ambient temperature and refrigeration. 5-Fluoropentyl analogs, XLR11 and 5-fluoro ADB-PINACA, in comparison to their counterpart analytes, UR144 and ADB-PINACA, were unstable at earlier time points under all temperatures. Based on these data, forensic blood evidence suggesting the presence of SC compounds is recommended to be frozen with sodium fluoride and potassium oxalate preservatives for optimal quantitative results. [ABSTRACT FROM AUTHOR]

5-Chloro-N-((2-oxo-3-(4-(3-oxomorpholino) phenyl) oxazolidin-5-yl) methyl) thiophene-2-carboxamide derivatives were synthesized in a simple and efficient approach using 2-(oxiran-2-ylmethyl) isoindoline-1, 3-dione, 4-(4-aminophenyl) morpholin-3-one, and 5-chlorothiophene-2-carbonyl chloride by stepwise synthesis. Three compounds 3, 4 and 7 were designed, prepared, and screened for anticancer activity against HeLa, MCF- 7, A-549 and K-562 and antibacterial activities against Gram +ve and Gram -ve strains. The carboxamide moieties proved to be capable for the development of new anticancer and anti-bacterial agents. Docking studies carried out on target receptors caspase-3 HeLa cell line and Staphylococcus aureus DNA-Gyrase also supported the anticancer and antimicrobial activity of compounds 3, 4 and 7. [ABSTRACT FROM AUTHOR]

Using ab-initio molecular simulations we have detected an asymmetric vibrational activation effect in N-methyl acetamide. The effect is generated by a favorable disposition of the orthogonal σ–π system present in the carboxamide moiety of N-methyl acetamide, so when the CO site is perturbed, it generates a charge oscillation in the molecule which produces a general vibrational activation in the molecule. Meanwhile, the NH bond stretching does not generate a charge oscillation precluding the vibrational molecular activation which traps the vibrational energy in this specific site of the carboxamide moiety of the N-methyl acetamide molecule. [ABSTRACT FROM AUTHOR]

Background: Succinate dehydrogenase inhibitors (SDHIs) emerging in fungicide markets are widely used in crop protection. Currently, the structural modification focusing on a structurally diverse 'core' moiety (aryl) of SDHIs is being gradually identified as one of the innovative strategies for developing novel, highly effective and low resistant fungicides. Results: By optimization of lead compound SCU2028, 30 novel aromatic carboxamides Ia‐o and IIa‐o without a pyrazol group were designed, synthesized and characterized by 1H NMR, 13C NMR and high resolution mass spectrum (HRMS). In vitro antifungal activities showed that most of the compounds Ia‐o and IIa‐o exhibited good antifungal activities against Rhizoctonia solani. Among them, compounds Ic and IIc (EC50 = 0.02 mg/L), with the 2‐chloro‐3‐pyridyl moiety, and compounds Io (EC50 = 0.03 mg/L) and IIo (EC50 = 0.02 mg/L), with the 4‐methyl‐2‐trifluoromethylthiazolyl moiety, all exhibited the equivalent antifungal activities against R. solani with compound SCU2028 (EC50 = 0.03 mg/L) and bixafen (EC50 = 0.04 mg/L). Additionally, in pot tests, compound IIc (EC50 = 3.63 mg/L) also had higher antifungal activity against R. solani than compound SCU2028 (EC50 = 7.63 mg/L). Furthermore, in vitro inhibitory activity against fungal SDH showed the inhibitory ability of compound IIc was equivalent with that of compound SCU2028, and molecular dynamics simulation of the SDH–compound IIc complex suggested that compound IIc could strongly bind to and interact with the binding site of SDH. Conclusion: Novel aromatic carboxamides without a pyrazol group have potential as a class of SDHIs, and the strategy of replacing the pyrazol group with another aryl in the 'core' moiety might offer an alternative option in discovery of SDHI fungicides. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The structural investigation of twin chiral carboxamide compounds synthesized by slow-evaporation style, namely Ch-1 [(S)-N-(1-phenylethyl)thiophene-2-carboxamide (Ch-1S) & (R)-N-(1-phenylethyl)thiophene-2-carboxamide (Ch-1R)] and Ch-2 [(S)-N-(1-phenylethyl)furan-2-carboxamide (Ch-2S) & (R)-N-(1-phenylethyl)furan-2-carboxamide (Ch-2R) were described by X-ray analysis and the chiral compounds crystallized like isomers with little discrepancies in lattice parameters. The synthesized chiral compounds were characterized via FT-IR, UV–visible, NMR, and mass spectroscopic techniques. The chirality of the compound was confirmed by the absolute structure parameter and specific rotation values. The perceptible inter- and intra-molecular connections of twin chiral were analyzed by Hirshfeld surface (HS) analysis with respective 2D Fingerprint (2D-FP) plots which gave the contacts contribution rate. N–H⋅⋅⋅O inter- and intra-molecular contact is chiefly answerable for crystal stuffing in both chiral. By employing the DFT computation, the chemical electronic characteristics such as energies of molecular orbitals (FMO), electrostatic potential (MESP), and Mullican's charge/atom (MAC) were characterized. The binding affinities of the chiral have been hypothesized with target CDC7-kinase inhibitor by performing docking studies (MDOC). The dynamic simulation (MDS) was prescribed to confirm the molecular stability of the chiral with the calculation of binding free energy (BFE). [ABSTRACT FROM AUTHOR]