10540-45-1Relevant articles and documents
Rational Design of Selective Small-Molecule Inhibitors for β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interactions
Hoggard, Logan R.,Zhang, Yongqiang,Zhang, Min,Panic, Vanja,Wisniewski, John A.,Ji, Haitao
, p. 12249 - 12260 (2015)
Selective inhibition of α-helix-mediated protein-protein interactions (PPIs) with small organic molecules provides great potential for the discovery of chemical probes and therapeutic agents. Protein Data Bank data mining using the HippDB database indicated that (1) the side chains of hydrophobic projecting hot spots at positions i, i + 3, and i + 7 of an α-helix had few orientations when interacting with the second protein and (2) the hot spot pockets of PPI complexes had different sizes, shapes, and chemical groups when interacting with the same hydrophobic projecting hot spots of α-helix. On the basis of these observations, a small organic molecule, 4′-fluoro-N-phenyl-[1,1′-biphenyl]-3-carboxamide, was designed as a generic scaffold that itself directly mimics the binding mode of the side chains of hydrophobic projecting hot spots at positions i, i + 3, and i + 7 of an α-helix. Convenient decoration of this generic scaffold led to the selective disruption of α-helix-mediated PPIs. A series of small-molecule inhibitors selective for β-catenin/B-cell lymphoma 9 (BCL9) over β-catenin/cadherin PPIs was designed and synthesized. The binding mode of new inhibitors was characterized by site-directed mutagenesis and structure-activity relationship studies. This new class of inhibitors can selectively disrupt β-catenin/BCL9 over β-catenin/cadherin PPIs, suppress the transactivation of canonical Wnt signaling, downregulate the expression of Wnt target genes, and inhibit the growth of Wnt/β-catenin-dependent cancer cells.
Palladium-catalyzed dehydrative aromatization of cyclohexenone oximes to anilines
Matsumoto,Tomizuka,Suzuki
, p. 1441 - 1446 (1994)
Cyclohexenone oximes were smoothly dehydrated to the corresponding anilines by the catalysis of palladium on carbon.
Design, synthesis, molecular modelling and in vitro cytotoxicity analysis of novel carbamate derivatives as inhibitors of Monoacylglycerol lipase
Lauria, Simone,Perrotta, Cristiana,Casati, Silvana,Di Renzo, Ilaria,Ottria, Roberta,Eberini, Ivano,Palazzolo, Luca,Parravicini, Chiara,Ciuffreda, Pierangela
, p. 2561 - 2572 (2018)
Monoacylglycerol lipase (MAGL) has an essential role in the catabolic pathway of the endocannabinoid 2-arachidonoylglycerol, which makes it a potential target for highly specific inhibitors for the treatment of a number of diseases. We designed and synthesized a series of carbamate analogues of URB602. We evaluated their inhibitory activity toward human MAGL in vitro both in cell culture and lysates. The target compounds exhibited moderate to excellent inhibitory activity against MAGL. The most promising compound 2b showed good inhibitory activity with IC50 value of 4.5 ± 0.70 μM reducing MAGL activity to 82% of controls at 10 μM compared to 66% for the parent compound URB602. Interestingly, compounds 2b and 2c induce cell death through the inhibition of MAGL. Molecular modelling approaches and docking studies, used to investigate inhibitory profiles, indicated that trifluoromethyl substitutions of the aryl group and the benzene ring present at the oxygen side of the carbamate molecule had a significant impact on the activity.
Design, synthesis, and structure-activity relationship of 7-propanamide benzoxaboroles as potent anticancer agents
Zhang, Jiong,Zhang, Jinyi,Hao, Guiyun,Xin, Weixiang,Yang, Fei,Zhu, Mingyan,Zhou, Huchen
, p. 6765 - 6784 (2019/08/20)
Benzoxaboroles, as a novel class of bioactive molecules with unique physicochemical properties, have been shown to possess excellent antimicrobial activities with tavaborole approved in 2014 as an antifungal drug. Although urgently needed, the investigation of benzoxaboroles as anticancer agents has been lacking so far. In this study, we report the design, synthesis, and anticancer structure-activity relationship of a series of 7-propanamide benzoxaboroles. Compounds 103 and 115 showed potent activity against ovarian cancer cells with IC50 values of 33 and 21 nM, respectively. Apoptosis was induced by these compounds and colony formation was effectively inhibited. Furthermore, they also showed excellent efficacy in ovarian tumor xenograft mouse model.
