{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:32Z","timestamp":1790315972189,"version":"4.1.0"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["COS"],"published-print":{"date-parts":[[2026,9,24]]},"abstract":"\n Introduction:<\/jats:title>\n Pyridine and pyrimidine-based compounds are known to be a part of the\nstructure of DNA and RNA; however, it has been found that these compounds have been incredibly\nuseful in the development of anticancer drugs. The pharmacokinetics of the compounds, along\nwith their potential to target key oncoproteins such as EGFR and VEGFR-2, have made them a\nsubject of research for therapeutic use.<\/jats:p>\n <\/jats:sec>\n \n materials and methods:<\/jats:title>\n A systematic search was performed using scientific databases including PubMed, Scopus, Web of Science, and SpringerLink from 2010\u20132025. Keywords included anticancer agents, kinase inhibitors, pyrimidine derivatives, pyridine scaffolds, SAR analysis, drug resistance, and pharmacokinetics.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n An extensive literature search (2009-2025) has been conducted to obtain information\nabout anticancer compounds based on the pyridine and pyrimidine ring systems. The authors assessed\nstructure-activity relationships, IC50 values, molecular targets, pharmacokinetics, and resistance\nof the compounds.<\/jats:p>\n <\/jats:sec>\n \n results:<\/jats:title>\n Pyrimidines frequently serve as core scaffolds in ATP-competitive inhibitors (e.g., erlotinib, gefitinib, imatinib analogues). SAR analysis reveals:\n\nN1 and N3 positions allow H-bonding critical for anchoring within the hinge region.\n\nElectron-donating groups (EDGs) on the aryl substituents improve kinase affinity.\n\nHalogen substitutions (Cl, F) enhance lipophilicity and improve membrane permeability.\n\nC4\/C6 substitutions modulate selectivity for EGFR, VEGFR, and CDKs.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Pyridine derivatives showed potent inhibitory activity against EGFR, VEGFR-2, and other\nkinases, with good solubility and metabolic stability, and exhibited secondary pharmacological\neffects, such as vasodilation. Pyrimidine derivatives, including hetero-fused compounds, showed\npotent cytotoxic and kinase-inhibitory activity, including against resistant mutants, as well as dual\ninhibition and scaffold-related benefits.<\/jats:p>\n <\/jats:sec>\n \n Discussion:<\/jats:title>\n The results indicate that pyridine and pyrimidine rings are versatile and useful scaffolds\nfor the development of anticancer agents. Their effectiveness in interacting with major molecular\ntargets, overcoming resistance, and having advantageous pharmacokinetic properties makes\nthem promising candidates for addressing unmet medical needs in cancer therapy.<\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Pyridines and pyrimidines are privileged structures in anticancer drug discovery because\nof their high affinity for targets, pharmacokinetic properties, and versatility. SAR and biological\ninformation from scientific literature published from 2009 to 2025 have demonstrated potent\ninhibitory activity against key kinases, including EGFR and VEGFR-2, as well as drug-resistant\nmutants. Based on this information, both structures are potential candidates for the design of nextgeneration\nanticancer agents that can overcome drug resistance.<\/jats:p>\n <\/jats:sec>","DOI":"10.2174\/0115701794467836260911041531","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:22:02Z","timestamp":1790313722000},"source":"Crossref","is-referenced-by-count":0,"title":["A Comprehensive Overview of Pyridine and Pyrimidine Derivatives for Anticancer Drug Development"],"prefix":"10.2174","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9576-6732","authenticated-orcid":true,"given":"Aakash","family":"Sharma","sequence":"first","affiliation":[{"name":"Delhi Pharmaceutical Science and Research University, India (DIPSAR)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7904-6962","authenticated-orcid":true,"given":"Jagdish Kumar","family":"Sahu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura (W), 799022, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2389-0563","authenticated-orcid":true,"given":"Kamal","family":"Shah","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, 281406, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-7819","authenticated-orcid":true,"given":"Shikha","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan, 301028, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","container-title":["Current Organic Synthesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0115701794467836260911041531","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/258723\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0115701794467836260911041531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:22:23Z","timestamp":1790313743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/258723\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":0,"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/0115701794467836260911041531","relation":{},"ISSN":["1570-1794"],"issn-type":[{"value":"1570-1794","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}