Enhanced pharmacokinetic properties of 1,4-benzodiazepine-2,5-dione antagonists of the HDM2-p53 protein–protein interaction through structure-based drug design

Guided by structure-based drug design, modification of the 1,4-benzodiazepin-2,5-dione lead compound 1 resulted in the discovery of 19, a potent and orally bioavailable antagonist of the HDM2-p53 protein–protein interaction (FP IC50 = 0.7 μM, F ≈ 100%).

Guided by structure-based drug design, modification of the BDP lead compound 1 resulted in the discovery of 19, a potent and orally bioavailable antagonist of the HDM2-p53 protein–protein interaction (FP IC50 = 0.7 μM, F ≈ 100%).Figure optionsDownload as PowerPoint slide