1353891-99-2Relevant academic research and scientific papers
The hydrophobically-tagged MDM2-p53 interaction inhibitor Nutlin-3a-HT is more potent against tumor cells than Nutlin-3a
Berg, Thorsten,Nietzold, Florian,Rubner, Stefan
, p. 14351 - 14354 (2019)
We present the first application of hydrophobic tagging to a non-covalent inhibitor of protein-protein interactions. Nutlin-3a-HT, created by fusing the hydrophobic tag HyT13 to the MDM2-p53 interaction inhibitor Nutlin-3a, prevented cellular accumulation of MDM2 upon p53 reactivation, and had a stronger effect on cell viability and the induction of apoptosis than Nutlin-3a.
Preparation of (-)-nutlin-3 using enantioselective organocatalysis at decagram scale
Davis, Tyler A.,Vilgelm, Anna E.,Richmond, Ann,Johnston, Jeffrey N.
, p. 10605 - 10616 (2013/11/19)
Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (-)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (-20 C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (-)-Nutlin-3 in a 17 g batch and elimination of all but three chromatographic purifications.
STEREOSELECTIVE METHODS, CATALYSTS AND INTERMEDIATES FOR THE SYNTHESIS OF (-)-NUTLIN-3 AND RELATED COMPOUNDS
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Page/Page column 13, (2012/04/18)
The present invention provides methods and intermediates are provided for the preparation of (?)-Nutlin-3. Methods and intermediates are also provided for the enantioselective addition of aryl nitromethanes to aldimines. Bis(amidine) catalysts for the use
