Synthesis And Biological Activity Of Pyrrolopyrimidine Compounds

With the deterioration of the environment and changes in people's lifestyles,the number of cancer patients has increased year by year.Currently,approximately 13million cancer patients are diagnosed each year,and approximately 6 million people die from malignant tumors(accounting for approximately 13%of the total deaths).Rate ranked second.Therefore,it is people's eager expectation to develop an anti-tumor drug with high efficacy and low toxicity.it have shown that the Janus kinasee(JAK)/signal transduction and transcription activator signaling pathway is also a common pathway for the signal transduction of many cytokines.They also have significant effects on various solid tumors,lymphoma,leukemia,and inflammatory diseases by negative regulatory factors,interactions with other signaling pathways,and covalent modifications of STATs are involved in human cell proliferation,differentiation,apoptosis,and inflammatory responses.Therefore,it is necessary to search for and develop molecular compounds that are selective for JAK kinase inhibitors.Tofacitinib was chosen as the lead compound in this study.References have been made between Tofacitinib and JAK subtypes.The role of the relationship,the use of bio-electronic isosteresis,and other advantages of molecular splicing strategies such as molecular structure optimization and transformation.This paper aims to synthesize a series of compound based on the active parent nucleus,referring to the relationship between the crystal structure of Tofacitinib and the four JAK subtype interactions,at the same time we optimized structure by using bio-isosteresis,other active molecules and splicing of dominant molecular fragments,etc.After reviewing the related literature about the synthesis of related nitrogen-containing heterocyclic compounds and the existing structure-activity studies.2,5-dibromopyridine was selected as the starting material aim to get key intermediates by the nucleophilic substitution reaction yields the key intermediates,sulfonamide,de-BOC protection and acetylation.and then the key intermediates and the active parent nucleus undergo a Suzuki aryl coupling reaction to synthesis of a series of derivatives with arylsulfonyl,amide,tail different aliphatic ring substituents.The structure was characterized by ~1HNMR and MS.According to the results of the activity test,the anti-tumor activity data of the derivatives were preliminary analyzed and discussed to lay the foundation for the later structural optimization.