Huang, Luyi published the artcileDiscovery of Pyrrolo[3,2-d]pyrimidin-4-one Derivatives as a New Class of Potent and Cell-Active Inhibitors of P300/CBP-Associated Factor Bromodomain, Category: pyrimidines, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4526-4542, database is CAplus and MEDLINE.
Herein, we report the discovery of a series of new P300/CBP-associated factor (PCAF) bromodomain (BRD) inhibitors, which were obtained through a hit discovery process and subsequent structure-based optimization and structure-activity relationship analyses toward a retrieved hit compound (12). Among these inhibitors, (R,R)-36n is the most potent one with an IC50 of 7 nM in homogeneous time-resolved fluorescence assay and a KD of 78 nM in isothermal titration calorimetry assay. This compound also exhibited activity against GCN5 and FALZ, but weak or no activity against other 29 BRD proteins and 422 kinases, indicating considerable selectivity. X-ray cocrystal structure anal. revealed the mol. interaction mode and the precise stereochem. required for bioactivity. Cellular activity, preliminary RNA-seq anal., and pharmacokinetic properties were also examined for this compound Collectively, this study provides a versatile tool mol. to explore mol. mechanisms of PCAF BRD regulation and also offers a new lead compound for drug discovery targeting PCAF.
Journal of Medicinal Chemistry published new progress about 2351929-82-1. 2351929-82-1 belongs to pyrimidines, auxiliary class Pyrroles, name is 2-Chloro-3-methyl-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, and the molecular formula is C7H6ClN3O, Category: pyrimidines.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia