胸苷磷酸化酶(TP),也被称为“血小板源性内皮细胞生长因子”是嘧啶补救途径的关键。TP可逆地将胸苷转化为胸腺嘧啶和2-脱氧-D-核糖-1-磷酸(dRib-1-P),进一步降解为2-脱氧-D-核糖(2DDR),具有血管生成和趋化活性。在几种类型的人类癌症中,如乳腺癌和结肠直肠恶性肿瘤,TP在响应缺氧等生物干扰时大量表达,酸中毒,化疗,和放射治疗。TP过表达与血管生成因子如血管内皮生长因子(VEGF)高度相关,白细胞介素(IL),基质金属蛋白酶(MMPs),等。,加速肿瘤发生,入侵,转移,免疫反应逃避,抗凋亡。因此,TP被公认为是开发新抗癌药物的关键靶点。杂环是大多数化学疗法的主要结构元素。甚至75%的含氮杂环化合物对制药业也有贡献。为了创造生物活性分子,药物化学家专注于含氮杂环化合物,如吡咯,吡咯烷,吡啶,咪唑,嘧啶,吡唑,吲哚,喹啉,恶二唑,苯并咪唑,等。恶二唑基序由于其在药物化学中的巨大意义而在所有这些基序中脱颖而出。这篇综述的主要重点领域是探索综合,SAR,以及1,3,4-恶二唑衍生物作为TP抑制剂对其化疗作用的重要作用。
Thymidine phosphorylase (TP), also referred to as \"platelet-derived endothelial cell growth factor\" is crucial to the pyrimidine salvage pathway. TP reversibly transforms thymidine into thymine and 2-deoxy-D-ribose-1-phosphate (dRib-1-P), which further degraded to 2-Deoxy-D-ribose (2DDR), which has both angiogenic and chemotactic activity. In several types of human cancer such as breast and colorectal malignancies, TP is abundantly expressed in response to biological disturbances like hypoxia, acidosis, chemotherapy, and radiation therapy. TP overexpression is highly associated with angiogenic factors such as vascular endothelial growth factor (VEGF), interleukins (ILs), matrix metalloproteases (MMPs), etc., which accelerate tumorigenesis, invasion, metastasis, immune response evasion, and resistant to apoptosis. Hence, TP is recognized as a key target for the development of new anticancer drugs. Heterocycles are the primary structural element of most chemotherapeutics. Even 75% of nitrogen-containing heterocyclic compounds are contributing to the pharmaceutical world. To create the bioactive molecule, medicinal chemists are concentrating on nitrogen-containing heterocyclic compounds such as pyrrole, pyrrolidine, pyridine, imidazole, pyrimidines, pyrazole, indole, quinoline, oxadiazole, benzimidazole, etc. The Oxadiazole motif stands out among all of them due to its enormous significance in medicinal chemistry. The main thrust area of this review is to explore the synthesis, SAR, and the significant role of 1,3,4-oxadiazole derivatives as a TP inhibitor for their chemotherapeutic effects.