التفاصيل البيبلوغرافية
| العنوان: |
Subtle Structural Changes across the Boundary between A 2A R/A 2B R Dual Antagonism and A 2B R Antagonism: A Novel Class of 2‑Aminopyrimidine-Based Derivatives |
| المؤلفون: |
Haojie Wang, Xinyu Yang, Yan Li, Shuyin Ze, Bo Feng, Yuan Weng, Aoqi Gao, Gaojie Song, Mingyao Liu, Qiong Xie, Yonghui Wang, Weiqiang Lu |
| سنة النشر: |
1753 |
| المجموعة: |
Smithsonian Institution: Figshare |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Neuroscience, Biotechnology, Evolutionary Biology, Cancer, Computational Biology, Chemical Sciences not elsewhere classified, tumor microenvironment exerts, suppress tumor growth, tuning structural modification, 7aj , 7ai , 2b , 2a , position produced potent, 2 ‑ aminopyrimidine, obtaining novel dual, 4 -/ 5, r dual antagonism, novel 2, position 4, indole modification, aminopyrimidine compounds, novel class, work provided, systemic assessment, substituting indole, r antagonists, r antagonism |
| الوصف: |
Aberrantly elevated adenosine in the tumor microenvironment exerts its immunosuppressive functions through adenosine receptors A 2A R and A 2B R. Antagonism of A 2A R and A 2B R has the potential to suppress tumor growth. Herein, we report a systemic assessment of the effects of an indole modification at position 4, 5, 6, or 7 on both A 2A R/A 2B R activity and selectivity of novel 2-aminopyrimidine compounds. Substituting indole at the 4-/5-position produced potent A 2A R/A 2B R dual antagonism, whereas the 6-position of indole substitution gave highly selective A 2B R antagonism. Molecular dynamics simulation showed that the 5-cyano compound 7ai had a lower binding free energy than the 6-cyano compound 7aj due to water-bridged hydrogen bond interactions with E169 or F168 in A 2A R. Of note, dual A 2A R/A 2B R antagonism by compound 7ai can profoundly promote the activation and cytotoxic function of T cells. This work provided a strategy for obtaining novel dual A 2A R/A 2B R or A 2B R antagonists by fine-tuning structural modification. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/media/Subtle_Structural_Changes_across_the_Boundary_between_A_sub_2A_sub_R_A_sub_2B_sub_R_Dual_Antagonism_and_A_sub_2B_sub_R_Antagonism_A_Novel_Class_of_2_Aminopyrimidine-Based_Derivatives/25407367 |
| DOI: |
10.1021/acs.jmedchem.4c00250.s019 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.4c00250.s019 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.967348AC |
| قاعدة البيانات: |
BASE |