348-28-7Relevant articles and documents
Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein-Protein Interaction
Chessari, Gianni,Hardcastle, Ian R.,Ahn, Jong Sook,Anil, Burcu,Anscombe, Elizabeth,Bawn, Ruth H.,Bevan, Luke D.,Blackburn, Timothy J.,Buck, Ildiko,Cano, Celine,Carbain, Benoit,Castro, Juan,Cons, Ben,Cully, Sarah J.,Endicott, Jane A.,Fazal, Lynsey,Golding, Bernard T.,Griffin, Roger J.,Haggerty, Karen,Harnor, Suzannah J.,Hearn, Keisha,Hobson, Stephen,Holvey, Rhian S.,Howard, Steven,Jennings, Claire E.,Johnson, Christopher N.,Lunec, John,Miller, Duncan C.,Newell, David R.,Noble, Martin E. M.,Reeks, Judith,Revill, Charlotte H.,Riedinger, Christiane,St. Denis, Jeffrey D.,Tamanini, Emiliano,Thomas, Huw,Thompson, Neil T.,Vinkovi?, Mladen,Wedge, Stephen R.,Williams, Pamela A.,Wilsher, Nicola E.,Zhang, Bian,Zhao, Yan
supporting information, p. 4071 - 4088 (2021/05/04)
Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design of novel isoindolinone-based MDM2 inhibitors. MDM2 X-ray crystallography, quantum mechanics ligand-based design, and metabolite identification all contributed toward the discovery of potent in vitro and in vivo inhibitors of the MDM2-p53 interaction with representative compounds inducing cytostasis in an SJSA-1 osteosarcoma xenograft model following once-daily oral administration.
Anion Recognition in Water by Charge-Neutral Halogen and Chalcogen Bonding Foldamer Receptors
Borissov, Arseni,Marques, Igor,Lim, Jason Y.C.,Félix, Vítor,Smith, Martin D.,Beer, Paul D.
supporting information, p. 4119 - 4129 (2019/03/07)
A novel strategy for the recognition of anions in water using charge-neutral σ-hole halogen and chalcogen bonding acyclic hosts is demonstrated for the first time. Exploiting the intrinsic hydrophobicity of halogen and chalcogen bond donor atoms integrated into a foldamer structural molecular framework containing hydrophilic functionalities, a series of water-soluble receptors was constructed for an anion recognition investigation. Isothermal titration calorimetry (ITC) binding studies with a range of anions revealed the receptors to display very strong and selective binding of large, weakly hydrated anions such as I- and ReO4-. This is achieved through the formation of 2:1 host-guest stoichiometric complex assemblies, resulting in an encapsulated anion stabilized by cooperative, multidentate, convergent σ-hole donors, as shown by molecular dynamics simulations carried out in water. Importantly, the combination of multiple σ-hole-anion interactions and hydrophobic collapse results in I- affinities in water that exceed all known σ-hole receptors, including cationic systems (β2 up to 1.68 × 1011 M-2). Furthermore, the anion binding affinities and selectivity trends of the first example of an all-chalcogen bonding anion receptor in pure water are compared with halogen bonding and hydrogen bonding receptor analogues. These results further advance and establish halogen and chalcogen bond donor functions as new tools for overcoming the challenging goal of anion recognition in pure water.
Enantioselective Construction of Tetrahydroquinazoline Motifs via Palladium-Catalyzed [4 + 2] Cycloaddition of Vinyl Benzoxazinones with Sulfamate-Derived Cyclic Imines
Wang, Chang,Li, Yan,Wu, Yang,Wang, Qijun,Shi, Wangyu,Yuan, Chunhao,Zhou, Leijie,Xiao, Yumei,Guo, Hongchao
supporting information, p. 2880 - 2883 (2018/05/29)
A palladium-catalyzed enantioselective [4 + 2] cycloaddition reaction of vinyl benzoxazinones with sulfamate-derived cyclic imines is described, affording the tetrahydroquinazolines bearing several functional rings in high yields (up to 99% yield) with good to excellent diastereoselectivities and excellent enantioselectivities (up to 96% ee). This reaction represents the first Pd-catalyzed asymmetric decarboxylative cycloaddition of vinyl benzoxazinones with imines.
