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A synthesis of benzo[d]oxazoles by an N-deprotonation–O-SNAr cyclization sequence from anilide precursors is reported. Anilides derived from 2-fluorobenzaldehydes, activated toward SNAr ring closure by C5 electron-withdrawing groups, were prepared and subjected to deprotonation–cyclization using 2 equiv. of K2CO3 in anhydrous DMF. Following deprotonation at nitrogen, the delocalized anion cyclized from the amide oxygen to give high yields of benzo[d]oxazoles. The temperature required for the cyclization of benzanilides correlated with the potency of the C5 activating group on the SNAr acceptor ring with nitro (most potent) reacting at 90 °C (1 h), cyano reacting at 115 °C (1 h), methoxycarbonyl reacting at 120 °C (2 h), and trifluoromethyl (least potent) reacting at 130 °C (3 h). Acetanilides were more difficult to cyclize but generally required 4–6 h at these same temperatures for completion. Product purification was accomplished by recrystallization or chromatography. [ABSTRACT FROM AUTHOR]

Phenolic compounds have long captivated the interest of organic synthesis, particularly in their quest for selective hydroxylation of arenes using H2O as a hydroxyl source. However, the inherent high reactivity and low redox potential of phenols often lead to undesirable overoxidation byproducts. To address this challenge, herein, we develop an electrophotochemical approach, finetuning substrate oxidative potential and enabling para-selective hydroxylation of anilides. This method showcases versatility, accommodating a wide array of substrates, while revealing high regional selectivity and compatibility with diverse functional groups. Moreover, the protocol allows facile late-stage functionalization of biologically active molecules. Mechanistic investigations demonstrate the activation of anilides by the excited state photocatalyst, effectively decreasing their oxidative potential and enhancing regional selectivity during hydroxylation. By using this protocol, important drug molecules such as Paracetamol, Fenretinide, Practolol, and AM404 could be synthesized, demonstrating the applicability of this approach in drug synthesis and late-stage functionalization. Phenolic compounds have long captivated the interest of organic synthesis, particularly in their quest for selective hydroxylation of arenes using H2O as a hydroxyl source but the inherent high reactivity and low redox potential of phenols often lead to undesirable overoxidation byproducts. Here the authors develop an electrophotochemical approach, finetuning substrate oxidative potential and enabling para-selective hydroxylation of anilides. [ABSTRACT FROM AUTHOR]

The building of N-heterocyclic cores endures an influential area of research due to their ubiquitous presence in natural products, agrochemicals, and small bioactive molecules. Over the past two decades, the synthesis of N-heterocycles via C-H activation comes out as a dominating synthetic protocol in atom-economic manner. The creation of C-C/C-N bonds acts as a key determining step for the building of nitrogen-based heterocycles via direct C-H activation protocol, which could serve as a fascinating concept. In recent years, Group 9 (Co, Rh & Ir) transition metal emerged as a robust catalytic system for the development of valuable N-heterocyclic scaffolds among other transition metals due to their mild reaction conditions, high reactivity, and functional group tolerance. A diverse type of arenes such as anilines/anilides, benzamides, hydrazones, ketoximes, benzylamine, and N-aryl nitrones were subjected to the C-H bond activation for the annulation reaction. Moreover, unsaturated compounds such as alkyne and olefin as coupling partners are again the most used companions for the same purpose, i.e., formation of N-heterocycles. Therefore, this review centers on the up-to-date reports on N-heterocycles synthesis by implementing alkynes and olefins as coupling partners through Group 9 transition metals' catalysis. The methodologies will be based on the coupling of alkynes and olefin, which preferably react in an intermolecular fashion. The scope, limitation, and mechanistic investigation of the Group 9 metal-activated C-H functionalization for the access of N-containing heterocycles with unsaturated reacting partners are the primary focus of the current review. [ABSTRACT FROM AUTHOR]

The mechanism of acylamination of arenes with nitroalkanes in polyphosphoric acid has been clarified. The influence of the concentration of polyphosphoric acid, the structure of the starting compounds, and temperature on the result of the Beckmann rearrangement, which makes it possible to shift the reaction towards either benzamides or anilides, has been assessed. [ABSTRACT FROM AUTHOR]

A direct selenylation of N‐arylsulfonamides and anilides using environmentally friendly and readily available copper promoted assisted by amide is presented. This method provided convenient access for various selenylation reactions, demonstrating a wide range of substrates and strong tolerance to various functional groups. According to the selection of reaction substrates, products can be isolated to obtain a regioselectivity ortho‐, para‐, or unprecedented ortho, para‐diselenylation products. Such transformation was elucidated by a proposed copper‐promoted amide‐assisted radical mechanism. [ABSTRACT FROM AUTHOR]

Atropisomeric N-chloroamides were efficiently accessed by electrophilic halogenation of ortho-substituted secondary anilides. The stereodynamics of atropisomerism in these novel scaffolds was interrogated by detailed experimental and computational studies, revealing that racemization is correlated with amide isomerization. The stereoelectronic nature of the amide was shown to significantly influence racemization rates, with potentially important implications for other C-N atropisomeric scaffolds. [ABSTRACT FROM AUTHOR]

Many natural, biologically active compounds are stereogenic with a unique tridimensional structure that is on the origin of the specific interactions with the active binding site. This concept of chirality goes beyond chiral stereocenters, englobing also atropoisomerism related to a hindered rotation around an axis with the isolation of atropostable conformers at room temperature. Atropoisomerism is well-known in biaryls, however this phenomenon is encountered in many pharmaceutically relevant compounds such as heterobiaryl, diarylamines, benzamides and anilides. Currently four FDA-approved drugs are atropostable and many others are in clinical trials. It is also important to note that almost 30% of recent FDA-approved small molecules are "proatropisomeric" and interact with a target in a specific chiral conformation. Given this vivid interest in C--C but also C--N atropisomerically stable compounds, this account will detail the new atropoisomeric strategies we developed and their applications in the synthesis of relevant molecules and ligands. [ABSTRACT FROM AUTHOR]

Succinic acid diamides containing two pharmacophoric fragments, one of which is 2amino-pyrimidine, and the other, N-methylpiperazine, 2-aminopyrimidine, or substituted aniline moiety, were synthesized in two steps. The synthetic scheme included acylation of substituted (pyrimidin-2-ylamino)aniline or pyrimidin-2-amine with succinic anhydride and the subsequent acylation of another heterocyclic or aromatic amine with the resulting pyrimidine-substituted succinic acid monoamide. The key intermediate products in the synthesis are succinic acid anilides. The acylation heterocyclic or aromatic amines with substituted succinic acid monochloride or amidation of succinic acid benzotriazolyl ester gave the corresponding succinic acid diamides as potential inhibitors of enzymes mediating tumorigenic processes. [ABSTRACT FROM AUTHOR]

[Display omitted] Palladium complexes with inexpensive and available vicinal diamines can serve as catalysts for the reductive Heck-type cyclization. o -Bromo- N -(2-phenylallyl)anilides are converted into the corresponding 3-methyl-3-phenylindolines, the analogous cyclization occurred for 2-bromo-4-methylphenyl 2-phenylallyl ether and N -(2-bromophenyl)-2-phenylacrylamides. The use of (1 R ,2 R)- N , N' -dibenzylcyclohexane-1,2-diamine provides up to 35% ee of the indolines; this is the first case of asymmetric induction during the reductive Heck reaction involving diamine complexes. [ABSTRACT FROM AUTHOR]

Introducing amide functional groups under mild conditions has growing importance owing to the prevalence of such moiety in biologically active molecules. Herein, we disclose a mild protocol for the directed ruthenium‐catalyzed C−H aminocarbonylation with isocyanates as the amidating agents developed through high‐throughput experimentation (HTE). The redox‐neutral and base‐free reaction is guided by weakly Lewis basic functional groups, including anilides, lactams and carbamates to access anthranilamide derivatives. The synthetic utility of this transformation is reflected by large‐scale synthesis and late‐stage functionalization. [ABSTRACT FROM AUTHOR]

Catalytic C–H/N–H cross-coupling is considered an ideal strategy for accessing anilines and their derivatives, but its synthetic execution remains extremely challenging, especially when the exclusion of external oxidants is desired. Reported herein is a photoelectrocatalytic method for the preparation of anilides through the C–H/N–H coupling of arenes and carbamates, which employs DDQ as a molecular catalyst. The reactions are conducted in a simple undivided cell with visible-light irradiation and without any need for external chemical oxidants. In addition, the reactions employ arenes as a limiting agent and are compatible with benzene and halogenated benzenes. [ABSTRACT FROM AUTHOR]

Anilides are often found in pharmaceuticals and active ingredients in crop protection. Although of great interest, the atom‐ and step economic formation of the amide bond between a less nucleophilic aniline with an acid or ester remains still a major challenge. Herein, we report an aminolysis of aromatic and alkyl esters with anilines catalyzed by a readily available catalytic system comprising of an earth‐abundant Mn‐salt in combination with an inexpensive base. [ABSTRACT FROM AUTHOR]

Axial chirality is an interesting stereoisomeric phenomenon in organic chemistry and a key structural feature of several organic compounds. Atropisomers such as biaryls, anilides and diaryl ethers are one type of axially chiral compounds, whose axial chirality is resulted from rotationally blocked single bond. Allenes, spiranes and alkylidenecycloalkanes are another type of axially chiral compounds and their axial chirality come from the perpendicular geometry of two pairs of substituents. The axial chirality in atropisomers, allenes and spiranes has been widely investigated and well developed, while the similar chirality in alkylidene‐cyclic molecules gained very limited attentions. This concept focuses on summarizing recent advances of axial chirality in alkylidene‐cyclic molecules and arouses the research interests to this promising field. [ABSTRACT FROM AUTHOR]

Iron (Fe) is an essential element for all organisms. Fe deficiency can limit plant production and cause anaemia in humans. The improvement of Fe homoeostasis could resolve both problems. Fe homoeostasis in Aegilops tauschii , the D genome donor of bread wheat, is not fully understood. Here, we analysed physiological traits in 42 accessions of Ae. tauschii associated with Fe homoeostasis, i.e. mugineic acid family phytosiderophores (MAs), phenylamides, SPAD values and metal concentrations. All traits showed diversity, suggesting the presence of candidate genes in the Ae. tauschii accessions, which could improve Fe homoeostasis in bread wheat. All accessions mainly produced and secreted mainly 2′-deoxymugineic acid among MAs, but eight of them secreted unknown products from their roots under Fe deficiency. It was revealed that 15 kinds of phenylamides and 2 kinds of bread wheat phytoalexins were produced in Fe-deficient roots of Ae. tauschii. Multivariate and principal component analyses showed that chlorophyll content was correlated with shoot Fe concentration. Genome-wide association study analysis associated several genomic markers with the variations in each trait analysed. Our results suggest that Ae. tauschii has alleles that could improve Fe homoeostasis to generate Fe-deficiency-tolerant or Fe-biofortified bread wheat. [ABSTRACT FROM AUTHOR]

Background: The increasing distribution of Substandard and Falsified Medical Products is a well-known health risk. The quantity of these medicines sent to consumers is not known, and it can only be accurately estimated with a specific sample collection study. These consignments ordered via mail from illegal online sources pose a great health risk on the population. Methods: We used an observation-based cross-sectional study in order to obtain accurate data regarding the number of medicinal shipments from dubious origin. We collected data on-site to assess the number of Substandard and Falsified Medical Products arrived in Hungary via postal services in 2020. Results: The therapeutic category (according to the Anatomical Therapeutic Chemical Classification (ATC) system of the WHO) of the most frequently shipped products contained active ingredients for treating erectile dysfunction. These substances were sildenafil (G04BE03), tadalafil (G04BE08), and other analgesics and antipyretics, such as anilides (N02BE). In 2020 we estimated that the real Defined Daily Dose of SFMP was 1.2 DDD per 1000 inhabitants per day. This value is equivalent to one third of Hungary's opioid analgesic use. We also calculated that the average exposure was approximately 4 ampoules per day and 40 oral preparations per day (without DDD value) for 1000 people in Hungary. Conclusions: This study accurately estimates the number of consignments received by post containing Substandard and Falsified Medical Products, and determines the quantity per 1000 persons per day expressed in DDD. This parameter may be used as a benchmark that helps more detailed research in the future. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify and characterise different classes of bioactive compounds from freeze-dried red goji berries (RGB) grown in Serbia, using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC Q-ToF MS). In addition, this study aims to demonstrate the importance of applying the advanced UHPLC Q-ToF MS technique in the identification of various biocompounds. The analysis showed the presence of 28 phenolic compounds, 3 organic acids, and 26 phenylamides. The 2- O -β- d -glucopyranosyl- l -ascorbic acid (AA-2 β G) was identified by UHPLC Q-ToF MS and quantified by standardised UHPLC-DAD method. Most of the compounds detected were derivatives of caffeic acid and ferulic acid, followed by quercetin derivatives. Among the phenylamides, several glucosylated caffeoyl and/or dihydrocaffeoyl derivatives of spermidine and spermine were characterized, confirming their recent characterization. Some glycosylated/non-glycosylated putrescine derivatives and caffeoyl-dihydrocaffeoyl-feruloyl spermidines were identified in goji berriesfor the first time. Their tentative structures and fragmentations were proposed. • Different classes of bioactive compounds from Lycium barbarum L. were analysed. • UHPLC Q-ToF MS untargeted analysis was used for the detection bioactive compounds. • Glycosides of phenolic acids and quercetin were the most frequently identified. • The AA-2βG was identified and quantified in freeze-dried goji berry. • Various glycosylated and non-glycosylated goji phenylamides have been identified. [ABSTRACT FROM AUTHOR]

Direct amidation of carboxylic acids with poorly nucleophilic amines such as anilines is a notorious challenge in organic chemistry. Previously reported methodologies for direct amidation tend to report none or just a few examples with simple anilines, which generally react at temperatures over 100 °C. To address this challenge and develop a mild and direct dehydrative anilide synthesis, herein a series of novel boronic acids with a biphenyl scaffold were prepared based on a design concept of bifunctional activation. The optimal thioether‐substituted biphenylboronic acid, 1e, exhibits good reactivity in promoting the amidation reaction of various anilines at 85 °C in fluorobenzene, including halogenated anilines, electron‐rich and electron‐deficient anilines, and the heterocyclic 6‐aminoquinoline. Variations of the aliphatic carboxylic acid are possible, affording the corresponding anilides in good yields. The efficiency and recyclability of boronic acid 1e were demonstrated on a gram‐scale amidation reaction. [ABSTRACT FROM AUTHOR]

The intestinal bile acid carrier ASBT ( SLC10A2 ), the hepatic bile acid carrier NTCP ( SLC10A1 ), and the steroid sulfate carrier SOAT ( SLC10A6 ), all members of the solute carrier family SLC10, are established drug targets. The ASBT inhibitors odevixibat, maralixibat, and elobixibat are used to treat intrahepatic cholestasis, cholestatic pruritus, and obstipation. The peptide drug bulevirtide blocks binding of the hepatitis B and D viruses to NTCP and thereby inhibits the virus's entry into hepatocytes. Experimental SOAT inhibitors have antiproliferative effects on hormone-dependent breast cancer cells. The phenylsulfonylamino-benzanilide S1647 is an inhibitor of ASBT and SOAT. The present study aimed to comparatively analyze a set of newly synthesized and commercially available S1647 derivatives for their transport inhibition against ASBT, NTCP, and SOAT. Structure-activity relationships were systematically analyzed regarding potency and target specificity to elucidate whether this compound class is worth being further developed in preclinical studies for pharmacological ASBT, NTCP, and/or SOAT inhibition.

The synthesis of biaryl amides, which are prevalent motifs in bioactive molecules, often necessitates lengthy and inefficient procedures. To address these limitations, catalytic C-H activation protocols have emerged, enabling the direct ortho-arylation of aryl amides. However, these protocols often suffer from issues such as lack of selectivity, reliance on stoichiometric oxidants, and the requirement for excess reagents and harsh reaction conditions. To overcome these challenges, we present a novel and highly selective protocol for the ortho-arylation of N-aryl amides and ureas. The high selectivity originates from the directed installation of BBr3 to form a boracycle, which then undergoes cross-coupling with an aryl halide. Our method offers significant advantages, including mild reaction conditions, excellent site-specificity, and scalability. The protocol demonstrates broad compatibility with a diverse range of readily accessible functionalized anilides and aryl iodides, as evidenced by 55 successful examples yielding products in the 30-95% range. Furthermore, our methodology surpasses conventional approaches by facilitating the one-pot selective diagonal diarylation of dianilides. This capability unlocks the construction of previously unattainable diagonal aryl systems, which serve as valuable precursors for the synthesis of diagonal tetraarylbenzenediamines and N-doped fulminene, two crucial compound classes in materials science., (© 2024 Wiley‐VCH GmbH.)

Stem cell-based therapies show promise for clinically addressing circumferential tracheal defects (CTD) through tissue engineering. However, creating a tissue-engineered tracheal tube possesses a healthy cartilage matrix and intact tube structure remains a challenge. A solution lies in the use of an injectable hydrogel with shape adaptability and chondrogenic capacity, serving as a practical and dependable platform for tubular tracheal cartilage regeneration. In this study, we developed an injectable hydrogel using modified natural polymers-hydrazide-grafted gelatin (Gelatin-ADH) and aldehyde-modified hyaluronic acid with sulfated groups (HA-CHO-SO 3 ) via Schiff Base interaction. Additionally, aldehyde-modified β-cyclodextrin (β-CD-CHO) was introduced into the network during hydrogel formation. The negative sulfated groups and hydrophobic cavities of β-cyclodextrin facilitated the efficient encapsulation and sustained release of transforming growth factor-β1 (TGF-β1) and kartogenin (KGN) within our hydrogel. This synergistically promoted the chondrogenesis of loaded bone marrow stem cells (BMSCs). Subsequently, we employed this TGF-β1, KGN, and BMSCs loaded hydrogel to form a cartilage ring. This ring was then assembled into an engineered tracheal cartilage tube using our previously reported ring-to-tube strategy. Our results demonstrated that the engineered tracheal cartilage tube effectively repaired CTD in a rabbit model. Hence, this study introduces a novel hydrogel with significant clinical application potential for tracheal tissue engineering., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Metastatic non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with a poor prognosis and is treated with immunotherapy (IO)-based combinations according to the clear cell renal cell carcinoma. Tyrosine-kinase inhibitors (TKIs), such as cabozantinib and axitinib, are commonly used as the 2nd line therapy after 1st line IO combination therapy, but their efficacy as 2nd line TKI therapy for nccRCC is unknown. In this study, we performed a retrospective multicenter analysis of nccRCC patients who were previously treated with IO combination therapy and received 2nd line TKIs., Methods: Among 254 patients enrolled in the Japanese multicenter retrospective study, 52 patients with nccRCC histology who received second-line TKIs were included in this study. Progression-free survival and overall survival (OS) from 2nd line TKIs were analyzed by log-rank test and Cox-proportional hazard model. Objective response rate (ORR) of 2nd line TKIs were analyzed., Results: The 1-year PFS and OS rates were 25.0% (95% CI = 13.1-36.8) and 63.8% (95% CI, 48.0-75.9), respectively. No patients had a complete response, 11 had a partial response, and 18 had stable disease. ORR was 21.1%. IMDC poor risk and sunitinib as the 2nd line therapy were significantly associated with poor PFS., Conclusion: The 2nd-line TKI was effective for a small group of nccRCC patients previously treated with IO combination therapy, although this study was retrospectively analyzed with a small number of cases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. LIBRETTO-001 is a registrational phase I/II, single-arm, open-label study of selpercatinib in patients with RET (REarranged during Transfection)-activated cancers (ClinicalTrials.gov identifier: NCT03157128). We present long-term safety and efficacy from LIBRETTO-001 in patients with RET -mutant medullary thyroid cancer (MTC; n = 324) and RET fusion-positive thyroid cancer encompassing different histological subtypes (TC; n = 66). At the data cutoff of January 2023, the objective response rate was 82.5% among patients with cabozantinib/vandetanib-naïve MTC and 95.8% among patients with treatment-naïve TC. At a median follow-up time of 42.4 and 44.0 months in patients with cabozantinib/vandetanib-naïve and pretreated MTC, the median progression-free survival (PFS) was not reached and 41.4 months, respectively. At a median follow-up time of 24.9 and 30.4 months in patients with treatment-naïve and pretreated TC, the median PFS was not reached and 27.4 months, respectively. Three-year PFS rates were 75.2% and 87.3% among patients with cabozantinib/vandetanib-naïve MTC and treatment-naïve TC, respectively. Median PFS was similar to median duration of response for each patient group. The safety profile of selpercatinib was consistent with previous reports. With an additional follow-up of 37 months and 228 more patients from the last disclosure, selpercatinib continued to provide durable and robust responses in treatment-naïve and previously treated patients with RET -mutant MTC and RET fusion-positive TC.

Purpose: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control tyrosine kinase inhibitor designed to selectively and potently inhibit the CSF1 receptor., Patients and Methods: This first-in-human, multicenter, open-label phase I/II study of vimseltinib in patients with malignant solid tumors (N = 37) or TGCT not amenable to surgery (N = 32) followed a pharmacologically guided 3 + 3 study design (NCT03069469). The primary objectives were to assess safety and tolerability, determine the recommended phase II dose, and characterize the pharmacokinetics; exploratory objectives included pharmacodynamics and efficacy., Results: Vimseltinib was well tolerated; the majority of non-laboratory treatment-emergent adverse events were of grade 1/2 severity. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The recommended phase II dose was determined to be 30 mg twice weekly (no loading dose), and vimseltinib plasma exposure increased with the dose. In patients with TGCT, the median treatment duration was 25.1 months (range, 0.7-46.9), and the objective response rate as assessed by independent radiological review using RECIST version 1.1 was 72%., Conclusions: Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT not amenable to surgery., (©2024 The Authors; Published by the American Association for Cancer Research.)

Intervertebral disc degeneration is a clinical disease that reduces the quality of patient's life. The degeneration usually initiates in the nucleus pulposus (NP), hence the use of hydrogels represents a promising therapeutic approach. However, the viscoelastic nature of hydrogel and its ability to provide biomimetic architecture and biochemical cues influence the regeneration capability. This study focused on tuning the physical nature of a glycosaminoglycan hydrogel (κ-carrageenan) as well as the release kinetics of a chondrogenic factor (kartogenin - KGN) through physical cross-linking. For this, κ-carrageenan was cross linked with 2.5 % and 5 % potassium chloride (KCl) for 15 and 30 min and loaded with KGN molecule at 50 μM and 100 μM. The tight network structure with low water retention and degradation property was seen in hydrogel cross-linked with increased KCl concentration and time. However, optimal degradation along with NP mimicking viscoelastic nature was exhibited by 5 wt% KCl treated hydrogel (H3 hydrogel). All hydrogel groups exhibited burst KGN release at 24 h followed by a sustained release for 5 days. However, hydrogel cross-linked with 5 wt% KCl enhanced chondrogenic differentiation, mainly at lower KGN dose. In summary, this study shows the potential application of biomimetic KGN laden carrageenan hydrogel in NP regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The initial randomized, double-blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study., Methods: Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological-BICR). The primary endpoint for this subgroup analysis was CNS progression-free survival (PFS)., Results: Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological-BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17-0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11-0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed., Conclusions: These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases., Trial Registration: ClinicalTrials.gov number, NCT03849768., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)

The para‐selective fluorination reaction of anilides using electrochemically generated hypervalent ArIF2 is reported, with Et3N ⋅ 5HF serving as fluoride source and as supporting electrolyte. This electrochemical reaction is characterized by a simple set‐up, easy scalability and affords a broad variety of fluorinated anilides from easily accessible anilides in good yields up to 86 %. [ABSTRACT FROM AUTHOR]

Here described a copper‐catalyzed direct chlorination and bromination of anilides in the presence of N‐fluorobenzenesulfonimide as oxidant. This protocol shows excellent regioselectivity and mono‐substitution with inexpensive KCl or NaBr as the halogen source and industrially friendly solvent. [ABSTRACT FROM AUTHOR]

Metalation of 2,4,6-triphenylphenylamine (H2N-C6H2-2,4,6-Ph3, 1a) and 4-methyl-2,6-bis(diphenylmethyl)aniline (2,6-bis(diphenylmethyl)-p-toluidine, H2N-C6H2-4-Me-2,6-(CHPh2)2, 2a) with dibutylmagnesium and Ae[N(SiMe3)2]2 with a stoichiometric 1 : 2 ratio in THF at room temperature yields the corresponding primary anilides [(thf)nAe{N(H)-C6H2-2,4,6-Ph3}2] (Ae/n = Mg/2 (1b), Ca/2 (1c), Sr/3 (1d), and Ba/3 (1e)) and [(thf)nAe{N(H)-C6H2-4-Me-2,6-(CHPh2)2}2] (Ae/n = Mg/2 (2b), Ca/3 (2c) and Sr/2 (2d)), respectively. The 1 : 1 reaction of Mg(n/sBu)2 and MgPh2 with 2a leads to the formation of heteroleptic [(thf)2Mg(R){N(H)-C6H2-4-Me-2,6-(CHPh2)2}] (R = n/sBu (2bBu), Ph (2bPh)). At 50 °C, the strontium complex 2d liberates one equivalent of 2avia intramolecular deprotonation of the triarylmethyl functionality yielding dinuclear [(thf)2Sr{N(H)-C6H2-4-Me-2-(CPh2)-6-(CHPh2)2}]2 (2d′). The barium compound is significantly more reactive and regardless of applied stoichiometry the isotypic barium congener [(thf)2Ba{N(H)-C6H2-4-Me-2-(CPh2)-6-(CHPh2)2}]2 (2e′) forms. The molecular structures of 1c, 2d, 2d′, and 2e′ are stabilized by metal-phenyl π-interactions. [ABSTRACT FROM AUTHOR]

Summary: The exploitation of phenolic compounds in different fields has motivated researchers to explore eco‐friendly and efficient extraction techniques. This study aimed to comparatively reveal that green extraction techniques (microwave‐ and ultrasound‐assisted) are alternative to conventional extraction (maceration and magnetic stirring) with positive impact on the phenolic content, antioxidant activity, and bioactive profile of bee pollen extracts. The highest total phenolic and flavonoid content was reached using the microwave‐assisted technique (MAE) with equivalent values of 28 and 8 mg g−1, with magnetic stirring and maceration showing a lower value. The composition profile of the extracts revealed the presence of twenty‐six bioactive compounds, including thirteen phenolics and thirteen phenylamides. Although the extraction technique had little impact on the chemical diversity, the amount of bioactive compounds raised significantly with the use of the green extraction techniques, with gains between 40% and 60% for phenolics and up to 200% for phenylamides. The radical scavenging activity and the reducing power of the extracts confirmed that bee pollens are potent antioxidant source, with the most bioactive extracts corresponding to green extraction techniques. Consequently, all findings recommend the use of MAE as the technique most effective for the extraction of bioactive compounds from naturally encapsulated structures such as bee pollen. [ABSTRACT FROM AUTHOR]