Synthetic Communications最新文献

英文中文

Indanone derivatives: Emerging frontiers in cancer therapy 吲哚酮衍生物：癌症治疗的新领域

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-18 DOI: 10.1080/00397911.2025.2530181

Dipanjan Karati (Conceptualization Writing – original draft) , Dhrubojyoti Sen (Conceptualization Supervision) , Beduin Mahanti (Supervision) , Souvik Roy (Conceptualization Supervision) , Swarupananda Mukherjee (Conceptualization)

Indanone has a wide range of biological and pharmacological applications. Growing awareness of its potential has sparked the creation of newer indanone derivatives as well as research into new synthetic techniques and their range of bioactivities. In the face of growing medication resistance and treatment failures, indanone derivatives have demonstrated encouraging antiproliferative actions against a variety of cancer cells, meeting the urgent need for novel therapeutic agents. A promising approach to drug development is the hybridization of indanone with other pharmacophores, which may help overcome drug resistance and enhance therapeutic efficacy. The increasing interest in this field is demonstrated by the several indanone-heterocycle hybrids that are presently undergoing clinical research. The review highlights indanone scaffolds’ anticancer potential and their significance as lead structures in the creation of novel, powerful therapeutic medicines.

吲哚酮具有广泛的生物学和药理学应用。越来越多的人意识到它的潜力，这激发了更新的吲哚酮衍生物的创造，以及对新的合成技术及其生物活性范围的研究。面对日益增长的耐药性和治疗失败，吲哚酮衍生物已显示出对多种癌细胞的抗增殖作用，满足了对新型治疗药物的迫切需求。吲哚酮与其他药物载体的杂交是一种很有前途的药物开发方法，可以帮助克服耐药性，提高治疗效果。目前正在进行临床研究的几种吲哚酮-杂环化合物证明了人们对这一领域日益增长的兴趣。这篇综述强调了吲哚酮支架的抗癌潜力，以及它们作为先导结构在开发新型强效治疗药物中的重要意义。

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引用次数: 0

Cycloaddition of sodium azide with 2-(methylsulfonyl)-3-(het)arylquinoxalines: A novel approach for the synthesis of 4-(het)aryltetrazolo[1,5-a]quinoxalines 叠氮化钠与2-（甲基磺酰基）-3-(het)芳基喹啉的环加成：合成4-(het)芳基四唑[1,5- A]喹啉的新方法

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-18 DOI: 10.1080/00397911.2025.2582181

Mallesha Nayaka Sahana (Methodology) , Kumar Kavya (Methodology) , Nagarakere C. Sandhya (Conceptualization) , Toreshettahally R. Swaroop (Writing – original draft Writing – review & editing) , Kempegowda Mantelingu (Supervision)

In this article, we report the synthesis of 4-(het)aryltetrazolo[1,5-a]quinoxalines by the cycloaddition of sodium azide with 2-(methylsulfonyl)-3-(het)arylquinoxalines in DMSO at room temperature. The substrate scope has been demonstrated in the presence of various electron donating and withdrawing groups. No need of heating, short reaction times and no formation of unwanted side products are the notable advantages of this method over reported methods. The plausible mechanism of formation of products is also presented.

本文报道了叠氮化钠与2-（甲基磺酰基）-3-（二甲基磺酰基）芳基喹啉在DMSO中室温环加成合成4-（二甲基磺酰基）芳基四唑[1,5-a]喹啉。在各种供电子和吸电子基团存在的情况下，衬底范围得到了证明。不需要加热，反应时间短，不形成不需要的副产物是该方法比报道的方法显着的优点。并提出了合理的产物形成机理。

引用次数: 0

New thieno[2,3-b]pyridine-based 1H-pyrazole hybrids attached to arylazo units: Synthesis of potential MRSA inhibitors 新型噻吩[2,3-b]吡啶基1h -吡唑杂化物：潜在MRSA抑制剂的合成

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-18 DOI: 10.1080/00397911.2025.2584276

Ahmed A. M. Ahmed (Conceptualization Data curation Formal analysis Funding acquisition Investigation Methodology Project administration Resources Software Supervision Validation Visualization Writing – original draft Writing – review & editing) , Sherif M. H. Sanad (Conceptualization Data curation Formal analysis Investigation Methodology Project administration Resources Software Supervision Validation Visualization Writing – original draft Writing – review & editing) , Yasser A. El-Ossaily (Conceptualization Investigation Project administration Resources Validation) , Ahmed E. M. Mekky (Conceptualization Data curation Formal analysis Investigation Methodology Project administration Resources Software Supervision Validation Visualization Writing – original draft Writing – review & editing)

The goal of this work is to examine the impact of integrating arylazo units to the skeleton of thieno[2,3-b]pyridine-based 1H-pyrazoles on their MRSA inhibitory activity. Using a stoichiometric amount of p-toluenesulfonic acid (p-TSA), the new hybrids were obtained by reacting thieno[2,3-b]pyridine-based carbohydrazides with acetylacetone or its aryldiazenyl-containing derivatives. The protocol was carried out in refluxing ethanol for 3–8 h in the presence of three equivalents of p-TSA. Product 4e, connected to phenyldiazenyl and (4-methoxyphenyl)diazenyl units at thieno[2,3-b]pyridine-C5 and pyrazole-C4, respectively, demonstrates the highest antibacterial potency, which exceeds ciprofloxacin with MIC/MBC of 1.8/3.6 µM against S. aureus and E. coli. Moreover, it exceeds linezolid in efficacy with MIC/MBC of 1.8/7.3 µM against MRSA.

这项工作的目的是研究将芳基偶氮单元整合到噻吩[2,3-b]吡啶基1h -吡唑骨架上对其MRSA抑制活性的影响。利用化学计量量的对甲苯磺酸（p-TSA），由噻吩[2,3-b]吡啶基碳肼与乙酰丙酮或其含芳基二氮基衍生物反应得到新的杂化物。该方案在乙醇回流3-8小时，存在三等量的p-TSA。产物4e分别与噻吩[2,3-b]吡啶- c5和吡唑- c4上的苯基二氮基和（4-甲氧基苯基）二氮基连接，对金黄色葡萄球菌和大肠杆菌的抗菌效力最高，超过环丙沙星，MIC/MBC为1.8/3.6µM。此外，其对MRSA的MIC/MBC为1.8/7.3µM，其疗效超过利奈唑胺。

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引用次数: 0

Iodine/DMSO promoted C = C cleavage: a versatile access to 3,4,5-trisubstituted and fused 1,2,4-triazoles from arylidene meldrum’s acids 碘/DMSO促进C = C裂解：一种从芳基芳基酸中得到3,4,5-三取代和融合1,2,4-三唑的通用途径

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-18 DOI: 10.1080/00397911.2025.2581994

Durgarao Kantheti (Methodology) , Pawanjeet Kaur (Conceptualization) , Siddaiah Vidavalur (Conceptualization Formal analysis Supervision) , Kumari Yettula (Project administration) , Satishkumar Kotyada (Methodology)

Iodine/DMSO catalyzed an efficient methodology has been developed to access a library of 3,4,5-trisubstituted 1,2,4-triazoles and fused 1,2,4-triazoles from amidrazones and arylidene Meldrum’s acids via cleavage of carbon-carbon double bond. This method represents a new and simple way to prepare highly substituted 1,2,4-triazoles from easily available starting materials, inexpensive catalysts, and with good functional group tolerance in good to excellent yields.

在碘/DMSO催化下建立了一种高效的方法，通过碳-碳双键的裂解，获得了3,4,5-三取代1,2,4-三唑库，并从酰胺腙和芳基Meldrum酸中融合了1,2,4-三唑。该方法为制备高取代1,2,4-三唑提供了一种新的、简单的方法，原料容易获得，催化剂价格低廉，官能团耐受性好，收率高。

引用次数: 0

Novel pyrazole-clubbed pyrimidine conjugates as anti-cancer agents in MCF-7 cell line: Design, synthesis, DFT and ADME study 新型吡唑棒状嘧啶偶联物在MCF-7细胞系中的抗癌作用：设计、合成、DFT和ADME研究

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-18 DOI: 10.1080/00397911.2025.2582186

Jyoti Kuchhadiya (Data curation Formal analysis Methodology Resources Software Writing – original draft) , Jignesh Kamdar (Conceptualization Methodology Software Validation Writing – original draft Writing – review & editing) , Khushal M. Kapadiya (Conceptualization Data curation Project administration Supervision Validation)

The development of novel anti-cancer agents remains a critical area of research in the fight against cancer. In this study, a series of pyrazole-clubbed pyrimidine conjugates (5-amino-1-phenyl-3-(4-(pyrimidin-5-yl)phenyl)-1H-pyrazole-4-carbonitriles, (4a–4j) were synthesized via a one-pot reaction of 4-(pyrimidin-5-yl)benzaldehyde, various phenyl hydrazine, and malononitrile in ethanol, under mild conditions using sodium ascorbate as a reducing agent. The synthesized compounds were evaluated for their anti-cancer activity in MCF-7 cell line using docking studies on the EGFR tyrosine kinase domain and MTT assays. The compounds displayed promising cytotoxic effects with IC₅₀ values ranging from 3.56 ± 1.01 µM (for 4i) to 18.01 ± 0.70 µM (for 4c). Notably, compound 4a and 4i, featuring phenyl hydrazine and 2-fluoro phenyl hydrazine, exhibited an IC₅₀ of 4.10 ± 0.26 µM and 3.56 ± 1.01 µM, comparable to the standard anti-cancer drug Sunitinib (IC₅₀: 4.01 ± 0.04 µM). The docking scores of the compounds ranged from −8.6 to −9.9, indicating strong binding affinity with cancer-related molecular targets. DFT calculations and ADMET analyses identified compounds 4a and 4i as promising candidates due to their favorable molecular stability, electronic properties, and excellent pharmacokinetic and toxicity profiles. The results suggest that these pyrazole-pyrimidine conjugates hold significant potential as novel anti-cancer agents, especially in MCF-7 cell-line.

新型抗癌药物的开发仍然是对抗癌症研究的一个关键领域。本研究以抗坏血酸钠为还原剂，在温和条件下，以4-（嘧啶-5-基）苯甲醛、各种苯肼和丙二腈为原料，在乙醇中一锅反应合成了一系列吡唑-棒联嘧啶偶联物(5-氨基-1-苯基-3-（4-（嘧啶-5-基）苯基）- 1h -吡唑-4-羰基（4a-4j）。通过对EGFR酪氨酸激酶结构域和MTT的对接研究，对合成的化合物在MCF-7细胞系中的抗癌活性进行了评价。IC50值为3.56±1.01µM (4i) ~ 18.01±0.70µM （4c）。值得注意的是，含有苯基肼和2-氟苯基肼的化合物4a和4i的IC50分别为4.10±0.26µM和3.56±1.01µM，与标准抗癌药物舒尼替尼的IC50（4.01±0.04µM）相当。这些化合物的对接分数在−8.6到−9.9之间，表明它们与癌症相关的分子靶点有很强的结合亲和力。DFT计算和ADMET分析表明，化合物4a和4i具有良好的分子稳定性、电子特性、良好的药代动力学和毒性特征，是有希望的候选药物。结果表明，这些吡唑-嘧啶缀合物具有作为新型抗癌药物的巨大潜力，特别是在MCF-7细胞系中。

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引用次数: 0

Sodium hydride induced condensation of methyl ketones with S-methyl O-phenyl carbonodithioate: a regiospecific synthesis of β-oxodithioesters 氢化钠诱导甲基酮与s -邻苯基碳二硫酸甲酯缩合：β-氧二硫酯的区域特异性合成

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-02 DOI: 10.1080/00397911.2025.2564411

Amogh R. Kulkarni (Methodology) , Mahesha Kumaraswamy (Funding acquisition) , Turuvekere K. Chaitra (Funding acquisition) , Doddahosur M. Gurudatt (Funding acquisition) , Kanchugarakoppal S. Rangappa (Supervision) , Toreshettahally R. Swaroop (Supervision Writing – original draft) , Basappa Basappa (Supervision)

In this article, we disclose a regiospecific condensation of methyl ketones with S-methyl O-phenyl carbonodithioate in the presence of sodium hydride in DMF for the synthesis of β-oxodithioesters. The present method is easy and efficient with respect to yield and substrate scope. A probable mechanism of formation of β-oxodithioesters is also given. Our approach overcomes limitations such as commercially discontinued substrates, difficulties in preparing thionating substrates, lengthy synthetic steps and requirement of high temperatures.

在本文中，我们揭示了甲基酮与s -甲基o -苯基碳酸二硫酸酯在DMF中氢化钠存在下的区域特异性缩合反应，以合成β-氧二硫酯。本方法在产率和衬底范围方面简便有效。还给出了β-氧二硫酯的可能形成机理。我们的方法克服了一些限制，如商业上停产的底物，制备硫代基物的困难，漫长的合成步骤和高温的要求。

引用次数: 0

Advances in the development of potent heterocyclic anticancer agents: a critical review 强效杂环抗癌药物的研究进展

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-02 DOI: 10.1080/00397911.2025.2529464

Soukhyarani Gopal Nayak (Conceptualization Data curation Formal analysis Funding acquisition Investigation Writing – original draft Writing – review & editing) , Vishwa B. Das (Resources Writing – review & editing) , Vinuta Kamat (Writing – review & editing) , Venuprasad K. D. (Writing – review & editing)

Background

Cancer remains one of the leading causes of death worldwide. Several factors contribute to the development of cancer. Current cancer treatments primarily involve chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapies such as kinase inhibitors. While these treatments have been used for various types of cancer, they often fall short of providing a complete cure. The limitations of existing treatments include inherent drug resistance, systemic toxicity, severe side effects, low efficacy, and poor solubility. These challenges underscore the need for new therapeutic approaches.

Objective

1. Identification of new targets and development of more effective drugs
2. Overcoming drug resistance and minimizing toxicity and side effects
3. Improving drug solubility and bioavailability

Methods and Results

One promising avenue is the development of heterocyclic-based anticancer agents. These compounds, have demonstrated potential in preclinical and clinical studies. This study aims to review the latest advancements in heterocyclic anticancer agents and examine the structure-activity relationships (SAR) of the most potent compounds, shedding light on how modifications to their chemical structures can enhance their anticancer efficacy and minimize side effects.

Conclusion

The development of anticancer agents has made significant strides in recent years, with numerous compounds demonstrating promising potential in preclinical and clinical studies.

癌症仍然是世界范围内死亡的主要原因之一。有几个因素导致癌症的发生。目前的癌症治疗主要包括化疗、放疗、手术、免疫治疗和激酶抑制剂等靶向治疗。虽然这些治疗方法已用于各种类型的癌症，但它们往往不能完全治愈。现有治疗方法的局限性包括固有的耐药、全身毒性、严重的副作用、低疗效和溶解度差。这些挑战强调了对新的治疗方法的需求。新靶点的确定和更有效药物的开发克服耐药性，减少毒副作用。提高药物的溶解度和生物利用度方法与结果杂环类抗癌药物的开发是一条很有前途的途径。这些化合物已在临床前和临床研究中显示出潜力。本文综述了杂环抗癌药物的最新研究进展，并对其中最有效的化合物的构效关系（SAR）进行了研究，揭示了如何通过改变其化学结构来提高其抗癌效果和减少副作用。结论近年来抗癌药物的开发取得了长足的进步，许多化合物在临床前和临床研究中显示出良好的潜力。

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引用次数: 0

Dual action of novel 5-nitroguaiacol-based hydrazones: Targeting aldolase-a and inducing apoptosis in lung cancer 新型5-硝基愈创木酚腙的双重作用：靶向醛缩酶a并诱导肺癌细胞凋亡

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-02 DOI: 10.1080/00397911.2025.2568472

Mürvet Tümenci (Formal analysis Funding acquisition Investigation Methodology Resources Validation Visualization Writing – original draft) , Burçin İrem Abas (Investigation Methodology Validation Visualization Writing – original draft Writing – review & editing) , Bensu Kozan (Data curation Formal analysis Methodology Resources Validation Visualization Writing – original draft Writing – review & editing) , Özge Çevik (Conceptualization Formal analysis Methodology Validation Visualization Writing – original draft Writing – review & editing) , Necla Kulabaş (Investigation Methodology Resources Software Validation Writing – original draft Writing – review & editing) , Faika Başoğlu (Software Validation Visualization Writing – original draft Writing – review & editing) , Sevil Şenkardeş (Conceptualization Data curation Funding acquisition Investigation Methodology Project administration Supervision Writing – original draft Writing – review & editing)

Building upon previous research on hydrazone-bearing aryloxyacetic acid derivatives, a novel series of 5-nitroguaiacol-based hydrazones (3a–l) was synthesized and characterized spectroscopically. Their in vitro cytotoxic effects were evaluated against human non-small cell lung cancer (A549) and normal bronchial epithelial cell lines (BEAS-2B) using the MTT assay. Compounds 3d and 3k exhibited selective and potent cytotoxicity (IC₅₀ = 10.24 µM and 4.99 µM, respectively) and strong aldolase A (ALDOA) inhibition at 10 µM (89.89% and 75.19%). Further mechanistic studies revealed that both compounds decreased HIF-1α expression and modulated apoptotic pathways by upregulating Bax and downregulating Bcl-2 protein levels. Molecular docking studies supported the experimental findings, demonstrating significant interactions of 3d and 3k with key residues in ALDOA, Bax, and Bcl-2, suggesting a dual mechanism involving glycolysis inhibition and apoptosis induction. These results indicate that 3d and 3k are promising lead compounds for targeted lung cancer therapy.

在前人对含腙芳氧乙酸衍生物研究的基础上，合成了一系列新的5-硝基愈创木酚基腙（3a-l）并对其进行了光谱表征。采用MTT法评价其对人非小细胞肺癌（A549）和正常支气管上皮细胞系（BEAS-2B）的体外细胞毒作用。化合物3d和3k具有选择性和强的细胞毒性（IC50分别为10.24µM和4.99µM），并且在10µM时具有很强的醛缩酶A （ALDOA）抑制作用（89.89%和75.19%）。进一步的机制研究表明，这两种化合物通过上调Bax和下调Bcl-2蛋白水平来降低HIF-1α的表达并调节凋亡途径。分子对接研究支持了实验结果，发现3d和3k与ALDOA、Bax和Bcl-2中的关键残基有显著的相互作用，提示其存在抑制糖酵解和诱导细胞凋亡的双重机制。这些结果表明，3d和3k是有希望用于靶向肺癌治疗的先导化合物。

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引用次数: 0

Pseudo-seven-component double Ugi reaction with 2,2’-(hexane-1,6-diylbis(oxy))dibenzaldehyde for the synthesis of bis- carboxamides 伪七组分双Ugi与2,2 ' -（己烷-1,6-二基双（氧））二苯甲醛反应合成双羧胺

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-02 DOI: 10.1080/00397911.2025.2572083

Afagh Banifereydani (Data curation Validation Writing – original draft) , Hossein Nasr-Isfahani (Conceptualization Methodology Project administration Resources Supervision Visualization Writing – review & editing) , Mohammad Bakherad (Conceptualization Investigation Methodology) , Afshin Sarvary (Data curation Formal analysis Validation Writing – review & editing)

A pseudo seven component double Ugi reaction of isocyanide, aniline, benzoic acid, and 2,2’-(hexane-1,6-diylbis(oxy)) dibenzaldehyde in MeOH solvent under reflux has been reported. This pseudo-seven-component reaction under mild reaction conditions led to the synthesis of pharmaceutically important and structurally interesting bis- carboxamide products. The reaction with tert-butyl isocyanide is diastereoselective (5a–h), while with cyclohexyl isocyanide the diastereoselectiveness depends to the substitution on the benzoic acid. Benzoic acid with electron-donating substituents leads to diastereoselectiveness (5i–k), and with benzoic acid with electron-withdrawing substituents each pair of diastereomers is formed (5l–r). Numerous analytical methods, including ¹H-NMR,¹³C-NMR, and FT-IR, are used to validate the chemical structures of the products.

报道了异氰化物、苯胺、苯甲酸和2,2 ' -（己烷-1,6-二基双（氧））二苯甲醛在甲醇溶剂回流下的伪七组分双Ugi反应。这种伪七组分反应在温和的反应条件下合成了具有重要药理意义和结构意义的双羧胺产品。与异氰酸叔丁基的反应具有非对映选择性（5a-h），而与环己基异氰酸的反应具有非对映选择性，取决于对苯甲酸的取代。具有供电子取代基的苯甲酸形成非对映体选择性（5i-k），具有吸电子取代基的苯甲酸形成每对非对映体（5l-r）。许多分析方法，包括1H-NMR，13C-NMR和FT-IR，被用来验证产品的化学结构。

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引用次数: 0

Synthesis of a N-Fmoc dibenzyl pyrazolyl phosphonate protected τ-phosphohistidine building block for Fmoc SPPS N-Fmoc二苄基吡唑膦酸酯保护τ-磷酸组氨酸的合成

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications

Pub Date : 2025-10-02 DOI: 10.1080/00397911.2025.2568479

Mehul V. Makwana (Conceptualization Data curation Formal analysis Investigation Validation Writing – original draft Writing – review & editing) , Richard F. W. Jackson (Conceptualization Formal analysis Funding acquisition Investigation Methodology Project administration Resources Supervision Validation Writing – review & editing) , Richmond Muimo (Conceptualization Formal analysis Funding acquisition Investigation Project administration Resources Supervision Writing – review & editing)

Stable phosphohistidine (pHis) analogues which can be incorporated into peptides are valuable tools for the study of pHis in a biological context. The phosphopyrazolyl side chain has proved useful in the generation of selective τ-pHis antibodies. To allow potential incorporation of the phosphopyrazolyl side chain to peptides a N-Fmoc dibenzyl pyrazole phosphonate building block 3 was synthesized. N-Fmoc dibenzyl pyrazole phosphonate 3 was accessible in four synthetic steps using the Hirao cross coupling reaction via a P-aryl bond formation, and Vederas Boc-β-lactone 11 opening reaction to give the protected amino acid.

稳定的磷酸组氨酸（pHis）类似物可以被纳入多肽，是在生物学背景下研究pHis的有价值的工具。磷酸吡唑基侧链已被证明在产生选择性τ-pHis抗体中是有用的。为了使磷酸吡唑侧链可能与肽结合，合成了N-Fmoc二苄基吡唑膦酸酯构建块3。N-Fmoc二苄基吡唑膦酸盐3通过Hirao交叉偶联反应和Vederas Boc-β-内酯11打开反应得到。

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