Abstract: The MDM2 oncoprotein is a cellular inhibitor of the P53 tumor suppressor in that it can bind the transactivation domain of P53 and downregulate its ability to activate transcription. In certain cancers, MDM2 amplification is a common event and contributes to the inactivation of P53. The crystal structure of the MDM2 bound to P53 has been analysised through x-ray crystallography. The crystal structure provides a framework for the discovery of compounds that may prevent the activation of the P53 tumor suppressor by the MDM2 oncogene in cancer. Inhibitors of the MDM2 oncogene have been synthesized on the base of this theory.
All assignments of inhibitors were obtained from ¹H、¹³C、¹H-¹H COSY、HMQC and HMBC spectra. With regarded to count space distance of two benzene rings, three-bond coupling constants were utilized to determine the structure of inhibitors. Sterostructures and relative configurations were discussed, and dominant energy was computed by using Sybyl software.

Key words: Inhibitor of MDM2 oncogene, NMR