Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• ]. Some rhodanine-based derivatives act as inhibitors of hepatitis C virus (HCV) protease [19], UDP-N-acetylmuramate/ʟ-alanine ligase [20], histidine decarboxylase [21], aldose/aldehyde reductase [22], fungal protein mannosyl transferase 1 (PMT1) [23], metallo β-lactamase [24], cathepsin D [25], JNK

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• class of interest in the search for new chemotherapeutic agents. They are known inhibitors of protein kinase C [40] and agonists of the GABA-type [41] and histamine-H3 receptors [42]. S-Allylic isothiouronium salts substituted with aliphatic groups have shown to combine high antitumor activity against

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• several potent pancreatic lipase inhibitors with nanomolar IC50 values [24], further supporting vibralactone as a promising lead compound warranting further investigation. Although vibralactone (6) is a relatively small natural product, its molecular structure features a unique 4/5-fused bicyclic β

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• molecules such as the huperzines have been discovered and advanced into human clinical trials as acetylcholinesterase inhibitors for treating Alzheimer’s disease [3]. Among the lycopodium family, complanadine A (1, Scheme 1) and its natural congeners such as complanadines B (2), D (3), and E (4) were

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• , as an attractive residue to design inhibitors with increased affinity towards this kinase as compared to the three other isoforms CLK1, CLK2, and CLK4. Based on this observation, we have been able to transform a molecule (DB18) previously established with a very low activity on CLK3 into a derivative

• as overexpression, is implicated in the pathogenesis of numerous deleterious diseases including nervous and inflammatory disorders as well as a number of malignancies [1][2][3]. Kinases are also known to be highly druggable by both allosteric and competitive inhibitors. As a consequence, protein

• kinases have become one of the most important drug targets: between a quarter to a third of the drug discovery efforts worldwide are focused on the discovery of new protein kinase inhibitors. More than 80 FDA-approved drugs that target about two dozen different protein kinases were discovered during the

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• ][2][3][4][5]. For example, triazole-fused 1,4-benzodiazepins are protease inhibitors [6] and part of drug molecules such as alprazolam [7], estazolam [8], and triazolam [9] (Figure 1). Tetrazole-containing functional materials have been developed as photographic sensitizers, diagnostic contrast

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• converts myristoylcholine into myristic acid and choline [120]. SC4A binds to the non-amphiphilic choline but not to the amphiphilic myristic acid, leading to the disassembly of the composite vesicles. Currently, the clinical treatment of Alzheimer's disease is mainly based on cholinesterase inhibitors

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• , the chemical synthesis of thiotrehalose analogs [116][117] provides a versatile tool for the construction of therapeutically relevant ligands or inhibitors of carbohydrate-specific innate immune receptors. Synthetic thiodigalactosides and their derivatives have been identified as selective inhibitors

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• as HIV inhibitors [14]. The imidazo[1,2-a]pyridine ring can be readily synthesized by the GBB reaction [10][15], while the isoquinolinone ring is commonly generated by a cyclative lactamization process. Performing a GBB reaction followed by an intramolecular amidation is a good approach for making

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• important role as building blocks for peptide synthesis [1][2][3][4][5], as organocatalysts [6][7][8][9][10] and as enzyme inhibitors [4][11][12][13]. The incorporation of such amino acids into peptides can, for example, influence peptide conformation, the binding affinity to receptors [14], as well as

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• anesthesia [14]. The imidazo[4,5-d][1,3]diazepine core is present in pentostatin and coformycin, which are naturally occurring N-nucleoside inhibitors of adenosine deaminase, known for their antibiotic and anticancer properties [15][16][17]. These examples highlight the importance of developing novel

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• Table 3 indicate that none of the candidates acted as substrates or inhibitors of CYP2D6, even though all were substrates for CYP3A4, suggesting potential metabolism via this pathway without any inhibitory effects. Excretion was assessed by examining total clearance, which is considered high when the

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• –inhibition assay. The measured results were systematically contextualized employing new reference compounds such as the respective homobivalent Man/Man glycocluster. An in-depth study comprising the analysis of the photochromic properties and the potential as inhibitors of bacterial adhesion of the synthetic

• UV–vis spectra of the two photoswitchable units. This design laid the basis for a robust switching cycle comprising the EManEGlc, the EManZGlc, and the ZManZGlc isomer of 1 [24]. In this contribution, we address the question of how the different isomers of 1 perform as inhibitors of bacterial

• potency as inhibitors of Man-specific bacterial adhesion investigated. Results and Discussion Synthesis For the preparation of the homobivalent glycocluster 6αMan3αMan 2, the known mannosyl thioacetate 7 [31] was prepared from the trichloroacetimidate 6 [32] and thioacetic acid in an α-selective reaction

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• motif has been exploited in the design of bioactive molecules [22][23] such as the histone deacetylase (HDAC) inhibitors 6 and 7 (Figure 2). The presence of the 1,2-difluoro moiety in 6 leads to greater potency and selectivity for certain HDAC isoforms, attributable to the higher polarity of the

• this was attributed to the partial tendency of this stereoisomer to adopt a bent alkyl chain. Another example of the use of the 1,2-difluoro moiety to influence the shape of an alkyl chain is seen in the HDAC inhibitors 16 and 17 (Figure 3) [29]. The threo-isomer 16 is found to be consistently more

• ][79]. For example, consider the diastereoisomeric BACE-1 inhibitors 40 and 41 (Figure 6). The preferred ring pucker for each of 40, 41 positions the C–F bond in an axial position, allowing nO → σ*C–F hyperconjugation. The shape adopted by diastereoisomer 41, with a pseudoaxial orientation of the

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• [9]. Pyrazolobenzothiazines have also been synthesized and explored as p38α MAPK inhibitors [35]. In 2015, Sabatini and co-workers synthesized a novel series of pyrazolobenzothiazines and identified as new generation anti-inflammatory agents. Two of these compounds are reported with an IC50 of 0.5 µM

• complex as the amide coupling agent with thionyl chloride [38] (Figure 1C). Recently, benzothiazine scaffolds of phenyl acetamides were synthesized as potent inhibitors for ureolytic infections [39] (Figure 1D). Saccharine (a sweetener) was reported to be a potent carbonic anhydrase inhibitor (CAI) by

• /cancer and other CAs (I, II). Non-selective inhibitors may have certain adverse effects so selective CAIs are worthier and more valuable [57]. Results of hCA inhibition assays are listed in Table 3. It was observed that the dialkylated pyrazolobenzothiazines 7i–n failed to inhibit any of the four

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• reasonably concluded that farinosones D (1) and A (2) hold significant potential as biofilm inhibitors because of their ability to inhibit biofilm formation at very low concentrations, suggesting their value in early-stage therapeutic applications against S. aureus infections. Experimental General

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• whether the reaction proceeded through a free radical mechanism, different free radical inhibitors were added to the reaction (reaction 7, Scheme 5). The addition of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) resulted in complete inhibition of the reaction, while BHT (2,6-di-tert-butyl-4-methylphenol

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• aeruginosa biofilm inhibitors and antibiotic enhancers. Large-scale extraction and isolation studies resulted in the discovery of four new and minor natural products, ianthelliformisamines D–G (4–7) and the known steroid, aplysterol (8). Compounds 4–7 were fully characterised following 1D/2D NMR, MS and UV

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• , the tetrahydropyridazines, six-atom nitrogenous heterocycles, are found in various bioactive molecules such as influenza virus neuraminidase inhibitors, GABA type A receptor modulators, and regulators of progesterone receptor or cannabinoid CB1 receptor antagonists (Figure 1) [6][7][8][9]. This

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• inhibitors, and their effects were investigated using the Amplex-Red® kit in C. elegans. Individuals exposed to compounds 2a, 2b, 2c, 2d, 2e, and 2f at a concentration of 1 mM were analyzed for AChE activity in their extracts. The results revealed significant inhibition of AChE levels, with compound 2e

• a multicomponent reaction to obtain SIRT2 inhibitors (Scheme 12). The authors suggest a Knoevenagel condensation approach between isatin derivatives and ethyl cyanoacetate, followed by a Michael addition with C–H activated carbonyl compounds and intramolecular cyclization [50]. They synthesized 45

• ]. The most potential β-amiloyd aggregation inhibitors generated by Galante et al. [37]. Best pyrazine-based MTDLs synthesized by Madhav et al. [40]. Most active 1,4-dihydropyridines developed by Malek et al. [43]. Best CDH-based MTDLs as AChE inhibitors synthesized by Malek et al. [46]. SIRT2 activity

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• assessed as inhibitors of galectin-9 and were found to exhibit selectivity and potency against galectin-9. In 2021, Chen and colleagues developed a method to synthesize naproxen-containing diaryliodonium salts 67 using naproxen methyl ester 65 and ArI(OH)OTs 66, activated by trimethylsilyl

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• myelocytic leukemia [5][6][7]. Indirubin, a red isomer of indigo, is an ingredient of indigo naturalis active against various cancers. Since the 1990s, we are witnessing a renaissance of the chemistry of indirubins because of their activity as potent inhibitors of several kinases, such as GSK-3β and CDK’s [8

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• compounds 4a–e and 5a–e to CYP51 and to evaluate which of these molecules could act as inhibitors of the enzyme. As mentioned above, CYP51 inhibitors contain a heterocyclic nitrogen atom that forms a coordination bond with haem iron. Therefore, only those compounds that could form such a bond according to

• tetrahydroimidazo[1,2-a]pyrimidine favors the inhibitory activity of this class of compounds, whereas the position of the substituent on the C-6 atom disrupts it. Furthermore, only the (S)-isomers of the compounds under consideration are expected to be potent inhibitors of CYP51. The analysis of the interaction

• probable reaction path of the interaction was suggested. Based on the docking data, N-aryl(alkyl)-7-oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidin-5-carboxamides as (S)-isomers were shown to be potent inhibitors of CYP51. These results allow us to consider these compounds as potential CYP51 inhibitor

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• pyridone and thiazolopyridone derivatives. This work is interesting from the point of view that it involved the emerging technique of “chemical editing”. The pyridone and thiazolopyridone derivatives were the most promising inhibitors, with IC50 values below 90 µM. Marques et al. described the synthesis of

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fact, several inhibitors of the β-site amyloyd β A4 precursor protein cleaving enzyme (BACE1), which is involved in the production of β-amyloid, and fluoroalkene analogs of dipeptidyl peptidase-4 inhibitors have previously been reported [2][3]. These inhibitors possess higher drug efficacies than their