85562-26-1Relevant articles and documents
5′-Methylene-triazole-substituted-aminoribosyl uridines as MraY inhibitors: synthesis, biological evaluation and molecular modeling
Fer, Micka?l J.,Bouhss, Ahmed,Patr?o, Mariana,Le Corre, Laurent,Pietrancosta, Nicolas,Amoroso, Ana,Joris, Bernard,Mengin-Lecreulx, Dominique,Calvet-Vitale, Sandrine,Gravier-Pelletier, Christine
, p. 7193 - 7222 (2015/07/01)
The straightforward synthesis of 5′-methylene-[1,4]-triazole-substituted aminoribosyl uridines is described. Two families of compounds were synthesized from a unique epoxide which was regioselectively opened by acetylide ions (for compounds II) or azide ions (for compounds III). Sequential diastereoselective glycosylation with a ribosyl fluoride derivative, Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) with various complementary azide and alkyne partners afforded the targeted compounds after final deprotection. The biological activity of the 16 resulting compounds together with that of 14 previously reported compounds I, lacking the 5′ methylene group, was evaluated on the MraY transferase activity. Out of the 30 tested compounds, 18 compounds revealed MraY inhibition with IC50 ranging from 15 to 150 μM. A molecular modeling study was performed to rationalize the observed structure-activity relationships (SAR), which allowed us to correlate the activity of the most potent compounds with an interaction involving Leu191 of MraYAA. The antibacterial activity was also evaluated and seven compounds exhibited a good activity against Gram-positive bacterial pathogens with MIC ranging from 8 to 32 μg mL-1, including the methicillin resistant Staphylococcus aureus (MRSA).
Zwitterionic sulfobetaine inhibitors of squalene synthase
Spencer, Thomas A.,Onofrey, Thomas J.,Cann, Reginald O.,Russel, Jonathon S.,Lee, Laura E.,Blanchard, Daniel E.,Castro, Alfredo,Gu, Peide,Jiang, Guojian,Shechter, Ishaiahu
, p. 807 - 818 (2007/10/03)
A substantial number of sulfobetaines (e.g., 10) have been synthesized and evaluated as inhibitors of squalene synthase (SS) on the basis of the idea that their zwitterionic structure would have properties conducive both to binding in the active site and to passage through cell membranes. When the simple sulfobetaine moiety is incorporated into compounds containing hydrophobic portions like those in farnesyl diphosphate (1) or presqualene diphosphate (2), inhibition of SS in a rat liver microsomal assay was indeed observed. For example, farnesylated sulfobetaine 10 has IC50 = 10 μM and aromatic derivative 35 has IC50 = 2 μM for SS inhibition. A wide variety of structural modifications, exemplified by compounds 43, 52, 76, 85, 91, 99, 111, and 115, was investigated. Unfortunately, no inhibitors in the submicromolar range were discovered, and exploration of a different type of zwitterion seems necessary if this appealing approach to inhibition of SS is going to provide a potential antihypercholesterolemic agent.
Synthesis of 3- and 4-(ω-Phenylalkyl)catechols, the Sap Exuded from a Burmese Lac Tree, Melanorrhoea Usitate
Miyakoshi, Tetsuo,Du, Yumin,Kumanotani, Ju
, p. 1054 - 1056 (2007/10/02)
The presence of 3- and 4-(ω-phenylalkyl)catechols in Burmese lac has been confirmed by their synthesis. 3-(ω-Phenylalkyl)veratroles were synthesized by alkylation of ω-phenylalkyl bromide with aryl lithium derived from veratrole. 4-(ω-phenylalkyl)veratroles were similarly obtained from w-phenylalkyl bromide and 4-bromoveratrole.Demethylation of 3- and 4-(ω-phenylalkyl)veratroles with boron tribromide gave the corresponding catechols in good yields.
