62878-96-0Relevant articles and documents
Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent Antimalarials In Vitro
Almolhim, Hanan,Bremers, Emily K.,Butler, Joshua H.,Butschek, Grant J.,Carlier, Paul R.,Cassera, Maria B.,Ding, Sha,Merino, Emilio F.,Rizopoulos, Zaira,Slebodnick, Carla,Totrov, Maxim
supporting information, p. 371 - 376 (2022/03/15)
The tetrahydro-β-carboline scaffold has proven fertile ground for the discovery of antimalarial agents (e.g., MMV008138 (1) and cipargamin (2)). Similarity searching of a publicly disclosed collection of antimalarial hits for molecules resembling 1 drew our attention to N2-acyl tetrahydro-β-carboline GNF-Pf-5009 ((±)-3b). Compound purchase, “analog by catalog”, and independent synthesis of hits indicated the benzofuran-2-yl amide portion was required for in vitro efficacy against P. falciparum. Preparation of pure enantiomers demonstrated the pharmacological superiority of (R)-3b. Synthesis and evaluation of D- and F-ring substitution variants and benzofuran isosteres indicated a clear structure-activity relationship. Ultimately (R)-3b was tested in Plasmodium berghei-infected mice; unfavorable physicochemical properties may be responsible for the lack of oral efficacy.
Benzofuranyl-2-imidazoles as imidazoline I2 receptor ligands for Alzheimer's disease
Brocos-Mosquera, Iria,Callado, Luis F.,Daelemans, Dirk,De Jonghe, Steven,Djikic, Teodora,Escolano, Carmen,Loza, M. Isabel,Molins, Elies,Nikolic, Katarina,Radan, Milica,Vasilopoulou, Foteini,Bagán, Andrea,Brea, José,García-Fuster, M. Julia,García-Sevilla, Jesús A.,Gri?án-Ferré, Christian,Hernández-Hernández, Elena,Martínez, Antón L.,Pérez, Belén,Pallàs, Mercè,Rodriguez-Arévalo, Sergio
, (2021/07/28)
Recent findings unveil the pharmacological modulation of imidazoline I2 receptors (I2-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report the chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico of a family of benzofuranyl-2-imidazoles that exhibit affinity against human brain I2-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2-imidazole, known as LSL60101 (garsevil), showed non-warning properties in the ADMET studies and an optimal pharmacokinetic profile. Moreover, LSL60101 induced hypothermia in mice while decreased pro-apoptotic FADD protein in the hippocampus. In vivo studies in the familial Alzheimer's disease 5xFAD murine model with the representative compound, revealed significant decreases in the protein expression levels of antioxidant enzymes superoxide dismutase and glutathione peroxidase in hippocampus. Overall, LSL60101 plays a neuroprotective role by reducing apoptosis and modulating oxidative stress.
Vinylogous Elimination/C-H Functionalization/Allylation Cascade Reaction of Allenoate Adducts: Synthesis of Ring-Fused Dihydropyridinones
Sun, Manman,Chen, Weida,Wu, Haijian,Xia, Xiangyu,Yang, Jianguo,Wang, Lei,Shen, Guodong,Wang, Zhiming
supporting information, p. 8313 - 8319 (2020/11/03)
A palladium-catalyzed cascade reaction of β′-allenoate adducts with aryl/heteroaryl carboxamides through a vinylogous elimination/C-H functionalization/intramolecular allylation reaction sequence has been developed with high Z stereoselectivity. Various ring-fused dihydropyridinones bearing an α,β-unsaturated ester substituent are obtained. It is the first example of application of the allenoate adducts to C-H functionalization annulations as practical precursors of hard-to-get functionalized electron-deficient 1,3-butadienes. Using air as the terminal oxidant also shows a great advantage in environmental friendliness.
