《[1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2A Inhibitors: Structure and Free-Energy Perturbation-Guided Exploration》 was written by Tresadern, Gary; Velter, Ingrid; Trabanco, Andres A.; Van den Keybus, Frans; Macdonald, Gregor J.; Somers, Marijke V. F.; Vanhoof, Greet; Leonard, Philip M.; Lamers, Marieke B. A. C.; Van Roosbroeck, Yves E. M.; Buijnsters, Peter J. J. A.. Formula: C3H5N3This research focused ontriazolopyrimidine preparation selective PDE2A inhibitor; structure triazolopyrimidine inhibition phosphodiesterase selectivity; pharmacokinetics CYP inhibition BBB permeability triazolopyrimidine; free energy perturbation optimization triazolopyrimidine substituent phosphodiesterase inhibitor; crystal structure triazolopyrimidine complex phosphodiesterase 2A. The article conveys some information:
We describe the hit-to-lead exploration of a [1,2,4]triazolo[1,5-a]pyrimidine phosphodiesterase 2A (PDE2A) inhibitor arising from high-throughput screening. X-ray crystallog. enabled structure-guided design, leading to the identification of preferred substructural components. Further rounds of optimization used relative binding free-energy calculations to prioritize different substituents from the large accessible chem. space. The free-energy perturbation (FEP) calculations were performed for 265 putative PDE2A inhibitors, and 100 compounds were synthesized representing a relatively large prospective application providing unexpectedly active mols. with IC50’s from 2340 to 0.89 nM. Lead compound 46 originating from the FEP calculations showed PDE2A inhibition IC50 of 1.3 ± 0.39 nM, ~100-fold selectivity vs. other PDE enzymes, clean cytochrome P 450 profile, in vivo target occupancy, and promise for further lead optimization. After reading the article, we found that the author used 1H-Imidazol-2-amine(cas: 7720-39-0Formula: C3H5N3)
1H-Imidazol-2-amine(cas: 7720-39-0) belongs to anime. Examples of direct uses of amines and their salts are as corrosion inhibitors in boilers and in lubricating oils (morpholine), as antioxidants for rubber and roofing asphalt (diarylamines), as stabilizers for cellulose nitrate explosives (diphenylamine), as protectants against damage from gamma radiation (diarylamines), as developers in photography (aromatic diamines), as flotation agents in mining, as anticling and waterproofing agents for textiles, as fabric softeners, in paper coating, and for solubilizing herbicides.Formula: C3H5N3
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem