Department of Pharmaceutical Analysis, ISF College of Pharmacy, Moga, Punjab, India.
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.
Mini Rev Med Chem. 2024;24(19):1746-1783. doi: 10.2174/0113895575296174240323172754.
Non-small cell Lung cancer (NSCLC) is the most common type of lung cancer, which is caused by high consumption of tobacco and smoking. It is an epithelial lung cancer that affects about 2.2 million people across the globe, according to International Agency for Research on Cancer (IARC). Non-small cell lung cancer is a malignant tumor caused by EGFR mutation that occurs in the in-frame deletion of exon 19 and L858R point mutation in exon 21. Presently, clinically available inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific and responsible for undesirable adverse effects. Moreover, to solve this problem search for newer EGFR inhibitors is the utmost need for the treatment and/or management of increasing lung cancer burden. The discovery of therapeutic agents that inhibit the specific target in tumorous cells, such as EGFR, is one of the successful strategies in treating many cancer therapies, including lung cancer. The exhaustive literature survey (2018-2023) has shown the importance of medicinally privileged pyrimidine derivatives together, fused and/or clubbed with other heterocyclic rings to design and develop novel EGFR inhibitors. Pyrimidine derivatives substituted with phenylamine, indole, pyrrole, piperazine, pyrazole, thiophene, pyridine and quinazoline derivatives substituted with phenylamine, pyrimidine, morpholine, pyrrole, dioxane, acrylamide, indole, pyridine, furan, pyrimidine, pyrazole etc. are privileged heterocyclic rings shown promising activity by inhibiting EGFR and TKIs. The present review summarizes the structure-activity relationship (SAR) and enzyme inhibitory activity, including IC values, percentage inhibition, and kinetic studies of potential compounds from various literature. The review also includes various aspects of molecular docking studies with compounds under clinical trials and patents filed on pyrimidine-based EGFR inhibitors in treating non-small cell lung cancer. The present review may benefit the medicinal chemist for developing novel compounds such as EGFR inhibitors.
非小细胞肺癌（NSCLC）是最常见的肺癌类型，由高烟草消费和吸烟引起。根据国际癌症研究机构（IARC）的数据，它是一种上皮性肺癌，影响全球约 220 万人。非小细胞肺癌是一种由 EGFR 突变引起的恶性肿瘤，这种突变发生在第 19 外显子的框内缺失和第 21 外显子的 L858R 点突变。目前，临床上可用的 EGFR 抑制剂（包括厄洛替尼、拉帕替尼、吉非替尼、塞尔美替尼等）并不特异，会引起不良的不良反应。此外，为了解决这个问题，寻找新的 EGFR 抑制剂是治疗和/或管理不断增加的肺癌负担的当务之急。发现能够抑制肿瘤细胞中特定靶标的治疗剂，如 EGFR，是治疗许多癌症疗法（包括肺癌）的成功策略之一。从 2018 年到 2023 年的详尽文献调查表明，将具有药用特权的嘧啶衍生物一起融合和/或组合到其他杂环中，对于设计和开发新型 EGFR 抑制剂具有重要意义。用苯甲胺、吲哚、吡咯、哌嗪、吡唑、噻吩、吡啶和喹唑啉衍生物取代的嘧啶衍生物，以及用苯甲胺、嘧啶、吗啉、吡咯、二氧六环、丙烯酰胺、吲哚、吡啶、呋喃、嘧啶、吡唑等取代的嘧啶衍生物，都是具有药用特权的杂环，通过抑制 EGFR 和 TKI 显示出有希望的活性。本综述总结了来自不同文献的潜在化合物的结构-活性关系（SAR）和酶抑制活性，包括 IC 值、百分比抑制和动力学研究。综述还包括了与临床试验中的化合物和已提交专利的嘧啶基 EGFR 抑制剂在治疗非小细胞肺癌方面的分子对接研究的各个方面。本综述可能有益于药物化学家开发新型化合物，如 EGFR 抑制剂。
