Journal of Heterocyclic Chemistry最新文献

Mechanistic Study of N-t-Butyl Nitrone and Nitroethene (3 + 2) Cycloaddition: A Combined DFT, Docking, and ADMET Approach n -t-丁基硝基和亚硝基（3 + 2）环加成的机理研究：DFT、对接和ADMET联合方法

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-26 DOI: 10.1002/jhet.70064

Raad Nasrullah Salih, Muheb Algso, Haydar Mohammad-Salim

{"title":"Mechanistic Study of N-t-Butyl Nitrone and Nitroethene (3 + 2) Cycloaddition: A Combined DFT, Docking, and ADMET Approach","authors":"Raad Nasrullah Salih, Muheb Algso, Haydar Mohammad-Salim","doi":"10.1002/jhet.70064","DOIUrl":"https://doi.org/10.1002/jhet.70064","url":null,"abstract":"<div>\u0000 \u0000 In this study, the (3 + 2) cycloaddition 32CA reaction between N-t-butyl nitrone 1 and nitroethene 2 was comprehensively investigated using density functional theory (DFT), electron localization function (ELF), atoms-in-molecules (AIM) analysis, and ADMET profiling. The reaction paths were examined in terms of regio- and stereoisomeric outcomes, with four possible cycloadducts being characterized. DFT-based reactivity indices indicated a strong polar nature of the reaction, with the global electrophilicity index (ω) and nucleophilicity index (N) suggesting that nitroethene acts as a strong electrophile and the nitrone as a strong nucleophile. A significant global electron density transfer (GEDT) from the nitrone 1 to nitroethene 2 was observed at the transition states (0.19–0.23 e), confirming a polar character and forward electron density flux (FEDF). Topological analysis of ELF along the reaction coordinate revealed asynchronous one-step two-stage mechanisms, supported by the appearance of pseudoradical centers and disynaptic basin evolution. TSs were confirmed by intrinsic reaction coordinate (IRC) calculations. Molecular docking against the HPV-related 1MH1 protein and ADMET predictions demonstrated that compound 5 displayed the most favorable binding energy and drug-like properties. This integrated theoretical investigation offers new mechanistic insights and supports potential pharmacological applications of the synthesized nitroisoxazolidines.\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 10","pages":"1328-1343"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Catalyst-Free (3 + 2) Annulation of Morita–Baylis–Hillman Carbonates With Isoquinolines to Access Functionalized Pyrrolo[2,1-a]Isoquinolines Morita-Baylis-Hillman碳酸盐与异喹啉的无催化剂（3 + 2）环化以获得功能化吡咯[2,1-a]异喹啉

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-26 DOI: 10.1002/jhet.70080

Na-Na Zhao, Ya-Fei Li, Yue-Yao Ma, Xiao-Ran Wang, Yu Tang, Kai-Kai Wang, Aili Sun

{"title":"Catalyst-Free (3 + 2) Annulation of Morita–Baylis–Hillman Carbonates With Isoquinolines to Access Functionalized Pyrrolo[2,1-a]Isoquinolines","authors":"Na-Na Zhao, Ya-Fei Li, Yue-Yao Ma, Xiao-Ran Wang, Yu Tang, Kai-Kai Wang, Aili Sun","doi":"10.1002/jhet.70080","DOIUrl":"https://doi.org/10.1002/jhet.70080","url":null,"abstract":"<div>\u0000 \u0000 A divergent strategy has been developed for the reactions between Morita–Baylis–Hillman (MBH) carbonates and isoquinolines. When MBH carbonates, derived from o-acylamino-aryl aldehydes and acrylonitrile, were reacted with isoquinolines, the reaction proceeded via a (3 + 2) cycloaddition/aromatization pathway to afford a diverse array of completely aromatic pyrrolo[2,1-a]isoquinolines in moderate to good yields (51%–91%) with excellent chemo- and regioselectivity. In contrast, when the substrates were changed to MBH carbonates synthesized from o-acylamino-aryl aldehydes and methyl acrylate, and 3,4-dihydroisoquinolines were employed as reaction partners, the reaction underwent a formal (3 + 2) cycloaddition to provide pyrrolo[2,1-a]isoquinolines bearing two adjacent tertiary stereogenic centers in good yields (up to 93%) with excellent chemo-, regio-, and diastereoselectivity (all cases > 25:1 dr). Notably, these reactions proceeded under nearly identical reaction conditions, with no observable competitive side products.\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 10","pages":"1358-1368"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Water Extract of Onion Catalyzed Tandem CN and CC Bond Formation via Enaminone-Michael Addition-Intramolecular Cyclization: An Efficient Green Synthesis of Multi-Substituted Pyrrole Derivatives and Their Antioxidant Activity 洋葱水提物通过烯胺酮-迈克尔加成-分子内环化催化串联C -氨基和C -氨基键形成：一种高效的绿色合成多取代吡咯衍生物及其抗氧化活性

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-26 DOI: 10.1002/jhet.70077

Loganathan Selvaraj, Rajendran Eswaran, Santhiya Ramasamy, Seenivasa Perumal Muthu

{"title":"Water Extract of Onion Catalyzed Tandem CN and CC Bond Formation via Enaminone-Michael Addition-Intramolecular Cyclization: An Efficient Green Synthesis of Multi-Substituted Pyrrole Derivatives and Their Antioxidant Activity","authors":"Loganathan Selvaraj, Rajendran Eswaran, Santhiya Ramasamy, Seenivasa Perumal Muthu","doi":"10.1002/jhet.70077","DOIUrl":"https://doi.org/10.1002/jhet.70077","url":null,"abstract":"<div>\u0000 \u0000 An efficient tandem reaction method catalyzed by aqueous onion extract comprising enaminone formation followed by Michael addition-cyclization is disclosed by 1,3-diketone 1, primary amine 2, and β-nitroalkene 3. In this work, diverse structures of enaminones and β-nitroalkenes 3 were involved to produce various multi-substituted pyrroles 6 in excellent yields (up to 97%). The structure of compound 6d was confirmed by single-crystal X-ray diffraction. This method has been applicable for a broad range of substrates and good functional group tolerance. Further, this proposed methodology has added advantages such as a simple, short reaction time, easy workup procedure, and environmentally benign manner. The in vitro antioxidant activity studies of the produced compounds, 6a–6y, were examined. When compared to 6e–6g, 6l, 6m, 6q, 6r, 6t, and 6u, the compounds such as 6h, 6i, 6j, 6k, and 6x have shown excellent IC50 value with standard (1.80 × 10−4 M). In addition, compound 6h has demonstrated exceptional IC50 value (1.58 × 10−4 M) among the synthesized compounds.\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 10","pages":"1344-1357"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent Advances in the Pharmacological Applications of 1,3,4-Oxadiazole Derivatives: A Comprehensive Review 1,3,4-恶二唑衍生物药理应用研究进展综述

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-24 DOI: 10.1002/jhet.70022

Navilehal Raheem Mallika Banu, Basavarajappa Pushpa, Mallikarjuna Pushpa

{"title":"Recent Advances in the Pharmacological Applications of 1,3,4-Oxadiazole Derivatives: A Comprehensive Review","authors":"Navilehal Raheem Mallika Banu, Basavarajappa Pushpa, Mallikarjuna Pushpa","doi":"10.1002/jhet.70022","DOIUrl":"https://doi.org/10.1002/jhet.70022","url":null,"abstract":"<div>\u0000 \u0000 Oxadiazoles have gathered significant courtesy in recent years due to their diverse pharmacological activities and synthetic versatility. Despite the extensive selection of heterocyclic derivatives, 1,3,4-oxadiazole has been essential to medical chemistry. Many synthesized compounds containing the oxadiazole nucleus are employed in antibacterial, antifungal, analgesic, anticonvulsant, HIV activity, antiinflammatory, plant growth-promoting agents, and herbicidal characteristics that have been investigated for derivatives of 1,3,4-oxadiazole, which have been essential in the development of pharmaceutically significant compounds. Inspired by these findings, scientists from all around the world are working to synthesize novel heterocycles with an oxadiazole moiety in the hopes of enhancing their medicinal and biological potential. The insights presented aim to act as a valuable resource for researchers and chemists involved in the synthesis of novel therapeutic representatives based on 1,3,4-oxadiazole scaffolds. In an effort to generate fresh ideas for the creation of more potent and less hazardous 1,3,4-oxadiazole-based scaffolds, ideally, this review would be very beneficial.\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 10","pages":"1301-1327"},"PeriodicalIF":2.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of Alpha-Acyloxy-(1,2,5-Oxadiazole-2-Oxide) Carboxamides via Passerini Multicomponent Reaction. Evaluation of Nitric Oxide-Releasing and Anti-Proliferative Properties 通过Passerini多组分反应合成α -酰基-（1,2,5-恶二唑-2-氧化物）羧酰胺。一氧化氮释放和抗增殖性能的评价

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-20 DOI: 10.1002/jhet.70062

Nicolas S. Anjos, Gustavo S. Sant’Ana, João Vitor C. Santos, Caroline Alves, Ana Caroline S. Teodoro, Paulo Vinicius de Sousa, Hugo P. Monteiro, Luiz S. Longo Jr

{"title":"Synthesis of Alpha-Acyloxy-(1,2,5-Oxadiazole-2-Oxide) Carboxamides via Passerini Multicomponent Reaction. Evaluation of Nitric Oxide-Releasing and Anti-Proliferative Properties","authors":"Nicolas S. Anjos, Gustavo S. Sant’Ana, João Vitor C. Santos, Caroline Alves, Ana Caroline S. Teodoro, Paulo Vinicius de Sousa, Hugo P. Monteiro, Luiz S. Longo Jr","doi":"10.1002/jhet.70062","DOIUrl":"https://doi.org/10.1002/jhet.70062","url":null,"abstract":"High intracellular levels of nitric oxide (NO) lead to cytotoxic effects against tumor cells. In this context, organic compounds containing the 1,2,5-oxadiazole-2-oxide (furoxan) scaffold play an important role as exogenous NO donors under physiological conditions and, therefore, may act as potential antitumor agents. Multicomponent reactions are considered useful synthetic tools for the rapid and efficient construction of structurally diverse organic compounds, such as furoxan hybrid molecules. Herein, we report the Passerini multicomponent reaction applied to the synthesis of nitric oxide-releasing furoxan based α-acyloxy carboxamides as well as their NO release capacity and anti-proliferative activity. A total of 23 α-acyloxy-(1,2,5-oxadiazole-2-oxide) carboxamides were synthesized using the Passerini reaction under microwave heating, in moderate to excellent yields (67%–95%). The quantification of nitric oxide release demonstrated that all compounds were capable of releasing NO within the range of 0.8–7.4 μM. In vitro anti-proliferative assays were carried out with mama (MCF-7), melanoma (SK-MEL-28), and prostate (LNCaP) cancer cell lines, as well as normal cell line (HUVEC). Compounds 21 and 22 showed moderate anti-proliferative activity (IC50 = 95.5 and 66.6 μM, respectively) against LNCaP cells. This study demonstrated the potential of α-acyloxy-(1,2,5-oxadiazole-2-oxide) carboxamides as a promising class of compounds to be explored for antitumor activity.","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 10","pages":"1285-1292"},"PeriodicalIF":2.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jhet.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145196925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Influence of Benzothiophene C2-Substituents in Palladium-Catalyzed Direct C3-Arylation 苯并噻吩取代基对钯催化的直接c3 -芳基化反应的影响

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-19 DOI: 10.1002/jhet.70056

Imane Idris-Halli, Norman Le Floch, Fazia Derridj, Henri Doucet

引用次数: 0

Recent Development in Synthesis and Anticonvulsant Activity of Promising Schiff Base Derivatives 希夫碱衍生物的合成及抗惊厥活性研究进展

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-19 DOI: 10.1002/jhet.70073

Check Princewill Ngu, Rakesh Sahu, Kamal Shah, Deepika Paliwal, Ashok Kumar Sah, Bhupendra G. Prajapati

{"title":"Recent Development in Synthesis and Anticonvulsant Activity of Promising Schiff Base Derivatives","authors":"Check Princewill Ngu, Rakesh Sahu, Kamal Shah, Deepika Paliwal, Ashok Kumar Sah, Bhupendra G. Prajapati","doi":"10.1002/jhet.70073","DOIUrl":"https://doi.org/10.1002/jhet.70073","url":null,"abstract":"<div>\u0000 \u0000 One of the most common neurological conditions in the world, epilepsy, increases a person's risk of dying young by three times when compared to the general population. This has led to the development of new antiepileptic drugs, although safety and potency are concerns. Additionally, Schiff base derivatives (commonly referred to as imines or azomethines) are a significant player in the medical treatment of epilepsy. Apart from being essential linkers and intermediates, this adaptable moiety also acts as a basic scaffold in the building of compounds with biological activity. Numerous Schiff base derivatives have been shown to regulate and cure neurological illnesses by blocking enzymes, receptors, and other targets. To cure epilepsy, researchers are concentrating on creating novel derivatives based on Schiff bases since they serve as a linker for various pharmacophores. Thus, this study sheds light on the current therapeutic expansion of derivatives based on Schiff bases as well as their synthesis schemes, all of which will assist researchers in creating effective prospective antiepileptic medications with advantageous pharmacological action.\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 10","pages":"1264-1284"},"PeriodicalIF":2.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145196899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Strategies for the Synthesis of Alkylated Coumarins Using Various Alkyl Radical Precursors 利用各种烷基自由基前体合成烷基香豆素的策略

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-19 DOI: 10.1002/jhet.70079

Md. Belal

引用次数: 0

A Green Approach for the Synthesis of 5,6-Dihydropyrimido[4,5-d]Pyrimidines From N-Uracil Amidines in Water 水中n -尿嘧啶脒合成5,6-二氢嘧啶[4,5-d]嘧啶的绿色方法

IF 2 3区化学

Journal of Heterocyclic Chemistry Pub Date : 2025-08-18 DOI: 10.1002/jhet.70063

Samir Debnath, Pradip Debnath, Utpal Ch. De

引用次数: 0

Synthesis of Substituted Dithiazolo[4,5-b:5′,4′-e] Pyridine-2,6-Diamines Based on the Interaction of 2,4-Diaminothiazole With Aldehydes 基于2,4-二氨基噻唑与醛相互作用的取代二噻唑[4,5-b:5′，4′-e]吡啶-2,6-二胺的合成