Journal of Heterocyclic Chemistry最新文献

{"title":"One-Pot Sequential Four-Component Reaction for the Synthesis of Novel Dihydro Oxaphospholo Pyrazole 2-Oxides in Acetic Acid Medium","authors":"Mingshu Wu,&nbsp;Zhengfan Sun,&nbsp;Rui Ning,&nbsp;Ziwen Yan,&nbsp;Junying Ma,&nbsp;Siqi Fan","doi":"10.1002/jhet.4946","DOIUrl":"https://doi.org/10.1002/jhet.4946","url":null,"abstract":"<div>\u0000 \u0000 <p>A four-component one-pot sequential approach to five-membered oxaphosphaheterocycles have developed. The method involves in situ generation of methylpyrazolin-5-one from ethyl acetoacetate and phenyl hydrazine. Further, a sequential reaction of methylpyrazolin-5-one with various aromatic aldehydes and phenyl dichloro phosphine afforded dihydro oxaphospholo pyrazole 2-oxide derivatives.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 3","pages":"316-321"},"PeriodicalIF":2.0,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555136","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}

{"title":"Design, Synthesis, Antiproliferative Screening, and In Silico Studies of Some Pyridinyl-Pyrimidine Candidates","authors":"Ali H. Abdelrahman,&nbsp;Mohammad E. Azab,&nbsp;Mohamed A. Hegazy,&nbsp;Ahmed Labena,&nbsp;Sayed K. Ramadan","doi":"10.1002/jhet.4945","DOIUrl":"https://doi.org/10.1002/jhet.4945","url":null,"abstract":"<div>\u0000 \u0000 <p>Using pyrimidinethione, a new series of pyridinyl-pyrimidine candidates was prepared by reacting with diverse carbon-centered electrophiles like hydrazonoyl chloride, <i>N</i>-arylchloroacetamide, ethyl chloroacetate, and enaminone derivatives. Some heteroannulated compounds, such as triazolopyrimidine and thiazolopyrimidine derivatives were obtained. The mass fragmentation pathways were investigated by the electron impact mass spectrometry (EI-MS), and the molecular ion peaks (M^+.) were recorded at different intensities. The in vitro antiproliferative efficacy of the prepared compounds against MCF7 and HCT116 cancer cell lines showed the highest potency of pyrimidinethione <b>2</b>, triazolopyrimidine <b>4</b>, and thiazolopyrimidine <b>10</b>. Also, in silico studies were performed to recognize these findings. A molecular docking simulation towards the EGFR enzyme showed the best docking score of thiazolopyrimidine <b>10</b> through H-bonding and hydrophobic interactions in comparison to the interactions of co-crystallized ligand and doxorubicin. With DFT calculations, compound <b>10</b> exhibited the lowest energy gap and the highest softness. Among ADME simulation, compounds <b>7</b>, <b>8</b>, <b>9</b>, and <b>11</b> exhibited desirable lead-likeness. It is hoped that this work may affect advancing new effective antiproliferative agents.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 3","pages":"303-315"},"PeriodicalIF":2.0,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555135","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}

{"title":"Synthesis and Characterization of Benzo[6,7]Cyclohepta[1,2-b]Pyrazolo[4,3-e]Pyridines","authors":"Zeinab A. Abdallah,&nbsp;Ahmed M. Abdelfattah,&nbsp;Ahmed A. M. Ahmed","doi":"10.1002/jhet.4943","DOIUrl":"https://doi.org/10.1002/jhet.4943","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, a novel ring system, benzo[6,7]cyclohepta[1,2-<i>b</i>]pyrazolo[4,3-<i>e</i>]pyridin-9-amines was efficiently synthesized. For that, 4-(aryl)-2-thioxo-2,5,6,7-tetrahydro-1<i>H</i>-benzo[6,7]cyclohepta[1,2-<i>b</i>]pyridine-3-carbonitriles were chosen as valuable intermediates. These synthons were reacted with the respective hydrazonyl chlorides in ethanol in the presence of triethylamine. The reaction was stirred at 50°C for 1–1.5 to afford a novel series of 2-oxo-<i>N</i>-phenylpropanehydrazonothioates in 82%–89% yields. Heating of the previous hydrazonothioates in an ethanolic sodium ethanolate solution under reflux for 2–3 h yielded a novel series of 8,11-diphenyl-5,6,7,11-tetrahydrobenzo[6,7]cyclohepta[1,2-<i>b</i>]pyrazolo[4,3-<i>e</i>]pyridin-9-amines in 77%–86% yields. The structures of the novel products were elucidated by elemental-analyses and spectral data.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 3","pages":"285-293"},"PeriodicalIF":2.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555164","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}

{"title":"Design, Synthesis, and Fungicidal Activities of Novel Strobilurin Derivatives Containing a Substituted 1,3,4-Oxadiazole Moiety","authors":"Wenliang Zhang,&nbsp;Hongtao Wang,&nbsp;Xiaohua Du","doi":"10.1002/jhet.4944","DOIUrl":"https://doi.org/10.1002/jhet.4944","url":null,"abstract":"<div>\u0000 \u0000 <p>To explore novel structures of strobilurin fungicides, a series of novel strobilurin derivatives featuring a substituted 1,3,4-oxadiazole in the side chain were synthesized using an intermediate derivatization method and characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). The reactions involved in the synthesis process include hydrazine hydrolysis, cyclization, nucleophilic substitution reactions. The raw materials required for these reactions are readily available, and the procedures involved in the reaction process are straightforward. The fungicidal activities of the compounds were tested using the inhibition zone method. The inhibition rate of compound <b>5f</b> on <i>Magnaporthe oryzae</i> was 81.8% at a concentration of 3.125 mg/L, and the EC₅₀ value (0.3045 mg/L) was better than superior to that of kresoxim-methyl (0.5247 mg/L).</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 3","pages":"294-302"},"PeriodicalIF":2.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555184","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}

{"title":"Selective Electrophile-Promoted Cyclization Reactions of Lapachol and Evaluation of Bioactive Naphthoquinones Against Cancer Cell Lines","authors":"Irene Nadege Omdim,&nbsp;Kenneth Oben Eyong,&nbsp;Blandine Marlysse Wache Ouahouo,&nbsp;Herve Landry Ketsemen,&nbsp;Thomas Werner,&nbsp;Michael Hermann K. Kamdem,&nbsp;Derek Tantoh Ndinteh,&nbsp;Gabriel Ngosong Folefoc,&nbsp;Abhinav Rajkumar,&nbsp;Kayla Morales,&nbsp;Joseph Taube,&nbsp;Sundarababu Baskaran","doi":"10.1002/jhet.4935","DOIUrl":"https://doi.org/10.1002/jhet.4935","url":null,"abstract":"<div>\u0000 \u0000 <p>Cyclic ether-fused tricyclic naphthoquinones are major pharmacophores because of their biological activities. The methodology of construction is either by inter or intra-molecular cyclization of functionalized naphthoquinones. This reaction includes a wide range of reagents from classical Brønsted to Lewis acids. The choice of appropriate reagent and reaction conditions against the substrate is the key to accomplishing the regio- and/or stereo-selective synthesis of these compounds, though it seems difficult at first glance to decide how because numerous numbers of actual examples have been presented. To have a deeper insight into the mechanism of cyclization under acid conditions, lapachol <b>1</b> was subjected to electrophilic entities: Brønsted acids (H₂SO₄, HCl, H₃PO₄, HNO₃, HCOOH, CH₃COOH, HOOCCH₂COOH), Lewis acids (AlCl₃, FeCl₃, ZnCl₂) nitrogenous cations (NO⁺, NO²⁺), carbocation (CH₃CO⁺), neutral polarized molecules (CH₃COCl, CH₃COOCH₃), neutral polarizable molecules (Br₂, I₂), oxidant promoted cyclization (DDQ, CAN, Peroxides), and reaction conditions. A series of Naphthoquinones based on the Isoprenyl-1,4-naphthoquinone (Lapachol), naphtho[1,2-b]furan-4,5-dione (nor β-lapachone), naphtho[2,3-b]pyran-5,10-dione (α-lapachone), naphtho[1,2-b]pyran-5,6-dione (β-lapachone), and naphtho[2,3-b]furan-4,9-dione (2-acetyl furonaphthoquinone) skeletons were selectively synthesized. By looking at our result, there are characteristic trends of cyclized adducts depending on which reagents were used. The synthesized compounds were evaluated for their biological activity against the MDA-MB-231 breast cancer, HT-29 MTX colon cancer, and non-transformed mammary epithelial cell lines at concentrations of 1 μM, 10 μM, and 100 μM. The result indicated that lapachol and β-lapachone skeletons were the most active at 10 μM and 100 μM especially 3-hydroxy-β-lapachone <b>8</b> with interesting growth stimulatory effect on cancer cell lines, but not the non-transformed cells.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 3","pages":"259-273"},"PeriodicalIF":2.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555126","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}

{"title":"Synthesis of Photochromic Lactone-Fused Naphthopyrans With Extended Visible Light Absorption","authors":"Nuno Ferreira,&nbsp;Céu M. Sousa,&nbsp;Paulo J. Coelho","doi":"10.1002/jhet.4940","DOIUrl":"https://doi.org/10.1002/jhet.4940","url":null,"abstract":"<div>\u0000 \u0000 <p>The synthesis of new photochromic lactone-fused naphthopyrans substituted with arylethenyl groups is discussed. Brief exposure of solutions of these colorless compounds to the UV light results in the generation of intense hues, which spontaneously return to the uncolored state within seconds after removing the light source. As anticipated, introducing the ethenyl bonds caused a bathochromic shift in the absorption spectrum of the opened colored photoisomers, however, due to non-uniform absorption across the visible spectrum, the perceived color ranged from red to brownish-red.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 3","pages":"274-284"},"PeriodicalIF":2.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555127","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}

{"title":"Synthesis and Cancer Cell Cytotoxicity of 6-, 7-, or 8-Substituted 2-(Hetero)aryl-4-(4-(Hetero)aryl-2-Oxobut-3-en-1-Ylidene)Benzothiazepanes","authors":"Katarina Magdalenic,&nbsp;Donatien Morillon,&nbsp;Steven De Jonghe,&nbsp;Leentje Persoons,&nbsp;Dominique Schols,&nbsp;Kristof Van Hecke,&nbsp;Charlotte Grootaert,&nbsp;John Van Camp,&nbsp;Matthias D'hooghe","doi":"10.1002/jhet.4936","DOIUrl":"https://doi.org/10.1002/jhet.4936","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer chemotherapy is continuously challenged by serious complications like pronounced side effects and multidrug resistance (MDR). Natural products, such as curcumin, offer promising alternatives due to their diverse biological applications and low toxicity. However, curcumin's clinical utility is limited by poor bioavailability, rapid metabolism, and non-specific (PAINS) activity. Building on previous findings, this study explored the structural modification of curcumin-inspired benzothiazepane derivatives in an attempt to enhance their therapeutic potential through modifications of the two peripheral (hetero)aromatic rings and the benzothiazepane scaffold. In this way, eight new 2-(hetero)aryl-4-(4-(hetero)aryl-2-oxobut-3-en-1-ylidene)benzothiazepanes and two 4-thiobutan-2-one “double Michael addition” derivatives were synthesized and tested for cytotoxicity against a panel of eight cancer cell lines. The screening results indicated that bis-(4-hydroxyphenyl) analogs bearing a chlorinated benzothiazepane ring exhibited the highest potency and broad-spectrum activity at the low micromolar range. Bis-substitutions with 3-pyridinyl and 2-furyl groups showed less potent but more specific activity profiles, potentially reducing PAINS effects. 2-Aminothiophenol-derived double Michael addition products demonstrated increased broad-spectrum activity, highlighting the importance of the free aniline amino group for targeted effects. This study underscores the potential of benzothiazepane derivatives as viable cancer cell cytotoxic agents and provides useful insights for future optimization and evaluation.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 2","pages":"249-256"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379995","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}

{"title":"N-Carbamimidoyl-2,2,2-Trifluoro-N′-Arylacetimidamides as Important Intermediates for the Synthesis of 3-Amino-4-Aryl-5-(Trifluoromethyl)-1H-1,2,4-Triazoles","authors":"Salimeh Abdinasab,&nbsp;Ali Darehkordi,&nbsp;Alireza Abbasi","doi":"10.1002/jhet.4934","DOIUrl":"https://doi.org/10.1002/jhet.4934","url":null,"abstract":"<div>\u0000 \u0000 <p>A novel series of N-carbamimidoyl-2,2,2-trifluoro-N′-arylacetimidamides (3a–j) have been prepared via condensation of 2,2,2-trifuoroacetimidoyl chlorides with guanidine in the presence Na and in dry EtOH solvent at ambient temperature. Then, these key intermediates were applied for the synthesized of 3-amino-4-aryl-5-(trifluoromethyl)-1H-1,2,4-triazoles (4a–j) under oxidative cyclization reaction in the presence of KI/I₂ as an oxidant system and DMSO solvent. The target compounds were produced in high yields and without the need for isolation.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 2","pages":"240-248"},"PeriodicalIF":2.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380934","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}

{"title":"Synthesis of 5-Aryltetrahydrobenzazepines","authors":"Naveenkumar Thoti,&nbsp;Deepika Gupta,&nbsp;Heera Lal,&nbsp;Indrapal Singh Aidhen","doi":"10.1002/jhet.4932","DOIUrl":"https://doi.org/10.1002/jhet.4932","url":null,"abstract":"<div>\u0000 \u0000 <p>Envisaging 5-aryltetrahydrobenzazepinone and 5-aryltetrahydrobenzazepines as conformationally locked potential B⁰AT1 inhibitors, a convenient synthetic route has been developed for their access. The synthetic route banks on using the Schmidt reaction for quick access to symmetrical/unsymmetrical 5-aryltetrahydrobenzazepinone and 5-aryltetrahydrobenzazepines.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 2","pages":"219-239"},"PeriodicalIF":2.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381032","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}

{"title":"One-Pot, Multicomponent Synthesis of 1,3-Oxazin-One and Evaluation of Their Potential Antioxidant Activities","authors":"Phitovili Sumi,&nbsp;Betokali K. Zhimomi,&nbsp;Manthae Phom,&nbsp;Khonzani Yanthan,&nbsp;Putusenla Imchen,&nbsp;Shokip Tumtin,&nbsp;Toka Swu,&nbsp;Tovishe Phucho","doi":"10.1002/jhet.4933","DOIUrl":"https://doi.org/10.1002/jhet.4933","url":null,"abstract":"<div>\u0000 \u0000 <p>The synthesis of 1,3-oxazines from 2-naphthol, benzaldehyde, and urea is reported using a simple and efficient microwave-assisted protocol. SiO₂-ZnCl₂ is employed for the first time to synthesize a library of 10 oxazin-3-one compounds, out of which five derivatives are novel. In 30–60 s the products were obtained with simplified work-up, the yield and purity were enhanced, and the reaction time was reduced with the use of microwave assistance. The synthesized oxazines were characterized and evaluated for their in vitro antioxidant properties. The results demonstrated a significant and effective presence of antioxidant capabilities. The compound 1-(4-hydroxy-3-methoxyphenyl)-1,2-dihydro-3<i>H</i>-naphtho[1,2-<i>e</i>][1,3]oxazin-3-one, containing hydroxy and methoxy groups, revealed superior antioxidant activity.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 2","pages":"209-218"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380948","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}