Article

Pyrrolopyrimidines: Design, Synthesis and Antitumor Properties of Novel Tricyclic Pyrrolo [2,3-d]pyrimidine Derivatives

Buer SongState 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, ChinaZarifa MurtazaevaDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanLifei NieState 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, ChinaRustamkhon KuryazovDepartment of Chemistry, Urgench State University, Kh. Olimjon st. 14, Urgench 220100, UzbekistanShukhrat GaybullaevDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanChao NiuState 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, ChinaKhurshed BozorovDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanHaji Akber AisaState 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, ChinaJiangyu ZhaoState 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

Moleculesjournal2025en

ABI

Abstract

The pyrrolo[2,3-d]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-d]pyrimidine-imines and 3-halo-substituted pyrrolo[2,3-d]pyrimidines were designed and prepared in high yields. Condensed pyrimidines are obtained via carbonyl-amine condensation and carbon-halogen bond formation. Pyrrolo[2,3-d]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; IC50 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 8g 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.

Topics

Synthesis and Reactivity of Heterocycles HIV/AIDS drug development and treatment Quinazolinone synthesis and applications

Identifiers

DOI: 10.3390/molecules30142917

Citations and references

Cited by 1 69 references

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