《Rational Design of 2-Chloroadenine Derivatives as Highly Selective Phosphodiesterase 8A Inhibitors》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Huang, Yadan; Wu, Xu-Nian; Zhou, Qian; Wu, Yinuo; Zheng, Dongxiao; Li, Zhe; Guo, Lei; Luo, Hai-Bin. Formula: C6H7Br2N The article mentions the following:
To validate the hypothesis that Tyr748 is a crucial residue to aid the discovery of highly selective phosphodiesterase 8A (PDE8A) inhibitors, we identified a series of 2-chloroadenine derivatives based on the hit clofarabine. Structure-based design targeting Tyr748 in PDE8 resulted in the lead compound 3a (I) (IC50 = 0.010 μM) with high selectivity with a reasonable druglike profile. In the X-ray crystal structure, I bound to PDE8A with a different mode from 3-isobutyl-1-methylxanthine (a pan-PDE inhibitor) and gave a H-bond of 2.7 Å with Tyr748, which possibly interprets the 220-fold selectivity of 3a against PDE2A. Addnl., oral administration of compound I achieved remarkable therapeutic effects against vascular dementia (VaD), indicating that PDE8 inhibitors could serve as potential anti-VaD agents. In the experiment, the researchers used many compounds, for example, 2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8Formula: C6H7Br2N)
2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8) belongs to pyridine. Pyridines are often used as catalysts or reagents; particular notice has been paid recently to how pyridine coordinates to metal centers enabling a wide range of valuable reactions. Formula: C6H7Br2N