Sarver, Patrick published the artcile6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors, Quality Control of 2055760-88-6, the publication is Journal of Medicinal Chemistry (2019), 62(4), 1793-1802, database is CAplus and MEDLINE.
Protein tyrosine phosphatase SHP2 is an oncoprotein associated with cancer as well as a potential immune modulator because of its role in the programmed cell death PD-L1/PD-1 pathway. In the preceding manuscript, we described the optimization of a fused, bicyclic screening hit for potency, selectivity, and physicochem. properties in order to further expand the chem. diversity of allosteric SHP2 inhibitors. In this manuscript, we describe the further expansion of our approach, morphing the fused, bicyclic system into a novel monocyclic pyrimidinone scaffold through our understanding of SAR and use of structure-based design. These studies led to the identification of SHP394 (1), an orally efficacious inhibitor of SHP2, with high lipophilic efficiency, improved potency, and enhanced pharmacokinetic properties. We also report other pyrimidinone analogs with favorable pharmacokinetic and potency profiles. Overall, this work improves upon our previously described allosteric inhibitors and exemplifies and extends the range of permissible chem. templates that inhibit SHP2 via the allosteric mechanism.
Journal of Medicinal Chemistry published new progress about 2055760-88-6. 2055760-88-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine, name is 2-Chloro-5-iodo-3-methylpyrimidin-4(3H)-one, and the molecular formula is C5H4ClIN2O, Quality Control of 2055760-88-6.
Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com