{"title":"一步法合成融合异噁唑并[4′,5′:4,5]噻喃并[2,3-d]嘧啶作为有效的表皮生长因子受体靶向抗肺癌药物","authors":"","doi":"10.1016/j.tetlet.2024.155325","DOIUrl":null,"url":null,"abstract":"<div><div>The requirement for scaffolds has prompted synthetic chemists to devise simple and effective methods for optimal synthesis, which are critical in the medical industry. Under comparatively optimized conditions, a click followed by a C<img>C bond coupling reaction between iodoalkyne (4) and substituted nitrile oxide was utilized to explore the synthesis of fused isoxazoles containing thiopyrano[2,3-<em>d</em>]pyrimidine under microwave irradiation. The synthesized compounds were tested for their anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H460 and A549). The compounds <strong>6i</strong> and <strong>6l</strong> have shown more potent activity against both cancer cell lines as compared to standard drugs doxorubicin and erlotinib. And also compounds <strong>6e</strong>, <strong>6j</strong>, and <strong>6k</strong> have shown more potent activity as compared to Doxorubicin and moderate activity compared to erlotinib. Later, <em>in vitro</em> EGFR results of more potent compounds revealed that compounds <strong>6l</strong> and <strong>6k</strong> have shown potent EGFR activity compared to standard erlotinib. To evaluate the molecular interactions of more potent compounds with the human epidermal growth factor receptor. It was observed that all the potent compounds exhibited greater binding energies in comparison to the standard drug erlotinib.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"One-pot synthesis of fused isoxazolo[4′,5′:4,5]thiopyrano[2,3-d]pyrimidines as potent EGFR targeting anti-lung cancer agents\",\"authors\":\"\",\"doi\":\"10.1016/j.tetlet.2024.155325\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The requirement for scaffolds has prompted synthetic chemists to devise simple and effective methods for optimal synthesis, which are critical in the medical industry. Under comparatively optimized conditions, a click followed by a C<img>C bond coupling reaction between iodoalkyne (4) and substituted nitrile oxide was utilized to explore the synthesis of fused isoxazoles containing thiopyrano[2,3-<em>d</em>]pyrimidine under microwave irradiation. The synthesized compounds were tested for their anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H460 and A549). The compounds <strong>6i</strong> and <strong>6l</strong> have shown more potent activity against both cancer cell lines as compared to standard drugs doxorubicin and erlotinib. And also compounds <strong>6e</strong>, <strong>6j</strong>, and <strong>6k</strong> have shown more potent activity as compared to Doxorubicin and moderate activity compared to erlotinib. Later, <em>in vitro</em> EGFR results of more potent compounds revealed that compounds <strong>6l</strong> and <strong>6k</strong> have shown potent EGFR activity compared to standard erlotinib. To evaluate the molecular interactions of more potent compounds with the human epidermal growth factor receptor. It was observed that all the potent compounds exhibited greater binding energies in comparison to the standard drug erlotinib.</div></div>\",\"PeriodicalId\":438,\"journal\":{\"name\":\"Tetrahedron Letters\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-10-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tetrahedron Letters\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0040403924004209\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tetrahedron Letters","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040403924004209","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
One-pot synthesis of fused isoxazolo[4′,5′:4,5]thiopyrano[2,3-d]pyrimidines as potent EGFR targeting anti-lung cancer agents
The requirement for scaffolds has prompted synthetic chemists to devise simple and effective methods for optimal synthesis, which are critical in the medical industry. Under comparatively optimized conditions, a click followed by a CC bond coupling reaction between iodoalkyne (4) and substituted nitrile oxide was utilized to explore the synthesis of fused isoxazoles containing thiopyrano[2,3-d]pyrimidine under microwave irradiation. The synthesized compounds were tested for their anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H460 and A549). The compounds 6i and 6l have shown more potent activity against both cancer cell lines as compared to standard drugs doxorubicin and erlotinib. And also compounds 6e, 6j, and 6k have shown more potent activity as compared to Doxorubicin and moderate activity compared to erlotinib. Later, in vitro EGFR results of more potent compounds revealed that compounds 6l and 6k have shown potent EGFR activity compared to standard erlotinib. To evaluate the molecular interactions of more potent compounds with the human epidermal growth factor receptor. It was observed that all the potent compounds exhibited greater binding energies in comparison to the standard drug erlotinib.
期刊介绍:
Tetrahedron Letters provides maximum dissemination of outstanding developments in organic chemistry. The journal is published weekly and covers developments in techniques, structures, methods and conclusions in experimental and theoretical organic chemistry. Rapid publication of timely and significant research results enables researchers from all over the world to transmit quickly their new contributions to large, international audiences.