Song Buer, Murtazaeva Zarifa, Nie Lifei, Kuryazov Rustamkhon, Gaybullaev Shukhrat, Niu Chao, Bozorov Khurshed, Aisa Haji Akber, Zhao Jiangyu
State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China.
Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan.
Molecules. 2025 Jul 10;30(14):2917. doi: 10.3390/molecules30142917.
The pyrrolo[2,3-]pyrimidine (7-deazapurine) scaffold is a unique heterocyclic system included in the composition of most nucleotides. In this study, series of the pyrrolo[2,3-]pyrimidine-imines and 3--substituted pyrrolo[2,3-]pyrimidines were designed and prepared in high yields. Condensed pyrimidines are obtained via carbonyl-amine condensation and carbon-halogen bond formation. Pyrrolo[2,3-]pyrimidine-imines containing a bromine substituent at position C-4 of the phenyl ring and azepine side-ring exhibited superior antitumor activity on the colon cancer HT-29 cell line; IC values were 4.55 and 4.01 µM, respectively. These results revealed an interesting pattern, where condensed pyrimidinones containing an azepine ring demonstrated selective antitumor activity on the colon cancer cell line HT-29. In addition, the molecular docking results suggest that compound provided a thorough understanding of its interactions with the DDR2 active site. This could pave the way for further development and optimization of DDR-targeting drugs, contributing to advancements in cancer therapeutics. This lead compound may serve as design templates for further studies.
吡咯并[2,3 - ]嘧啶（7 - 脱氮嘌呤）骨架是大多数核苷酸组成中包含的独特杂环系统。在本研究中，设计并高产率制备了一系列吡咯并[2,3 - ]嘧啶 - 亚胺和3 - 取代的吡咯并[2,3 - ]嘧啶。缩合嘧啶通过羰基 - 胺缩合和碳 - 卤键形成获得。在苯环的C - 4位含有溴取代基和氮杂环庚烷侧环的吡咯并[2,3 - ]嘧啶 - 亚胺对结肠癌HT - 29细胞系表现出优异的抗肿瘤活性；IC值分别为4.55和4.01 μM。这些结果揭示了一种有趣的模式，即含有氮杂环庚烷环的缩合嘧啶酮对结肠癌细胞系HT - 29表现出选择性抗肿瘤活性。此外，分子对接结果表明化合物 对其与DDR2活性位点的相互作用提供了全面的理解。这可以为DDR靶向药物的进一步开发和优化铺平道路，有助于癌症治疗的进展。这种先导化合物可作为进一步研究的设计模板。
