3209-72-1Relevant articles and documents
A new class of phenylhydrazinylidene derivatives as inhibitors of Staphylococcus aureus biofilm formation
Cascioferro, Stella,Maggio, Benedetta,Raffa, Demetrio,Raimondi, Maria Valeria,Cusimano, Maria Grazia,Schillaci, Domenico,Manachini, Barbara,Leonchiks, Ainars,Daidone, Giuseppe
, p. 870 - 878 (2016)
In the struggle against the emergence of the antibiotic resistance, new molecules targeting biofilm formation could be useful as adjuvant of conventional antibiotics. This study focused on a new class of 2-phenylhydrazinylidene derivatives as antivirulence agents. The compound 12e showed interesting activities against biofilm formation of all tested Staphylococcus aureus strains with IC50 ranging from 1.7 to 43 μM; compounds 12f and 13a resulted strong inhibitors of S. aureus ATCC 6538 and ATCC 29213 biofilm formation with IC50 of 0.9 and 0.8 μM, respectively. A preliminary study on the mechanism of action was carried on evaluating the inhibition of sortase A transpeptidase. Compound 12e resulted not to be toxic at 1 mg/ml by using an in vivo model (the wax moth larva model, Galleria mellonella).
Structure-Based Drug Design of Mineralocorticoid Receptor Antagonists to Explore Oxosteroid Receptor Selectivity
Nordqvist, Anneli,O'Mahony, Gavin,Fridén-Saxin, Maria,Fredenwall, Marlene,Hogner, Anders,Granberg, Kenneth L.,Aagaard, Anna,B?ckstr?m, Stefan,Gunnarsson, Anders,Kaminski, Tim,Xue, Yafeng,Dellsén, Anita,Hansson, Eva,Hansson, Pia,Ivarsson, Ida,Karlsson, Ulla,Bamberg, Krister,Hermansson, Majlis,Georgsson, Jennie,Lindmark, Bo,Edman, Karl
supporting information, p. 50 - 65 (2017/01/17)
The mineralocorticoid receptor (MR) is a nuclear hormone receptor involved in the regulation of body fluid and electrolyte homeostasis. In this study we explore selectivity triggers for a series of nonsteroidal MR antagonists to improve selectivity over other members of the oxosteroid receptor family. A biaryl sulfonamide compound was identified in a high-throughput screening (HTS) campaign. The compound bound to MR with pKi=6.6, but displayed poor selectivity over the glucocorticoid receptor (GR) and the progesterone receptor (PR). Following X-ray crystallography of MR in complex with the HTS hit, a compound library was designed that explored an induced-fit hypothesis that required movement of the Met852 side chain. An improvement in MR selectivity of 11- to 79-fold over PR and 23- to 234-fold over GR was obtained. Given the U-shaped binding conformation, macrocyclizations were explored, yielding a macrocycle that bound to MR with pKi=7.3. Two protein–ligand X-ray structures were determined, confirming the hypothesized binding mode for the designed compounds.
Two-step cyanomethylation protocol: Convenient access to functionalized aryl- and heteroarylacetonitriles
Lindsay-Scott, Peter J.,Clarke, Aimee,Richardson, Jeffery
supporting information, p. 476 - 479 (2015/03/05)
A two-step protocol has been developed for the introduction of cyanomethylene groups to metalated aromatics through the intermediacy of substituted isoxazoles. A palladium-mediated cross-coupling reaction was used to introduce the isoxazole unit, followed by release of the cyanomethylene function under thermal or microwave-assisted conditions. The intermediate isoxazoles were shown to be amenable to further functionalization prior to deprotection of the sensitive cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl-substituted acetonitrile building blocks.
