Structural highlights
Function
PDE5A_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.
Publication Abstract from PubMed
The substituents both at the 6-position of the 5-bromopyrimidinone ring and at the 5'-position of the phenyl ring of 5-bromopyrimidin-4(3H)-ones were explored. 5-Bromo-6-isopropyl-2-(2-propoxy-phenyl)pyrimidin-4(3H)-one was identified as a new scaffold for potent PDE5 inhibitors. The crystal structures of PDE5/2e and PDE5/10a complexes provided a structural basis for the inhibition of 5-bromopyrimidinones to PDE5. In addition, it was also found that there is a great tolerance for the substitution at the 5'-position of the phenyl ring of 5-bormopyrimidinones and the resulted compound 13a has the highest inhibition activity to PDE5 (IC50, 1.7 nM).
Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5.,Gong X, Wang G, Ren J, Liu Z, Wang Z, Chen T, Yang X, Jiang X, Shen J, Jiang H, Aisa HA, Xu Y, Li J Bioorg Med Chem Lett. 2013 Sep 1;23(17):4944-7. doi: 10.1016/j.bmcl.2013.06.062. , Epub 2013 Jun 29. PMID:23867165[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gong X, Wang G, Ren J, Liu Z, Wang Z, Chen T, Yang X, Jiang X, Shen J, Jiang H, Aisa HA, Xu Y, Li J. Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5. Bioorg Med Chem Lett. 2013 Sep 1;23(17):4944-7. doi: 10.1016/j.bmcl.2013.06.062. , Epub 2013 Jun 29. PMID:23867165 doi:http://dx.doi.org/10.1016/j.bmcl.2013.06.062
