129527-19-1Relevant articles and documents
Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits
Schnute, Mark E.,McReynolds, Matthew D.,Carroll, Jeffrey,Chrencik, Jill,Highkin, Maureen K.,Iyanar, Kaliapan,Jerome, Gina,Rains, John W.,Saabye, Matthew,Scholten, Jeffrey A.,Yates, Matthew,Nagiec, Marek M.
, p. 2562 - 2572 (2017)
Sphingosine kinase (SphK) is the major source of the lipid mediator and G protein-coupled receptor agonist sphingosine-1-phosphate (S1P). S1P promotes cell growth, survival, and migration and is a key regulator of lymphocyte trafficking. Inhibition of S1P signaling has been proposed as a strategy for treatment of inflammatory diseases and cancer. Two different formats of an enzyme-based high-throughput screen yielded two attractive chemotypes capable of inhibiting S1P formation in cells. The molecular combination of these screening hits led to compound 22a (PF-543) with 2 orders of magnitude improved potency. Compound 22a inhibited SphK1 with an IC50 of 2 nM and was more than 100-fold selective for SphK1 over the SphK2 isoform. Through the modification of tail-region substituents, the specificity of inhibition for SphK1 and SphK2 could be modulated, yielding SphK1-selective, potent SphK1/2 dual, or SphK2-preferential inhibitors.
Controlled α-mono- and α,α-di-halogenation of alkyl sulfones using reagent-solvent halogen bonding
Poteat, Christopher M.,Lindsay, Vincent N. G.
, p. 2912 - 2915 (2019/03/17)
The direct and selective α-mono-bromination of alkyl sulfones was achieved through base-mediated electrophilic halogenation. The appropriate combination of solvent and electrophilic bromine source was found to be critical to control the nature of the products formed, where reagent-solvent halogen bonding is proposed to control the selectivity via alteration of the effective size of the electrophilic bromine source. Conversely, the α,α-di-brominated sulfones were selectively obtained in good yields following polyhalogenation followed by selective de-halogenation during workup. Both procedures can be applied on gram scale, and the mono-halogenation was successfully extended to the fully selective α-chlorination, α-iodination and α-fluorination of alkyl sulfones.
Reusable BNPs-SiO2@(CH2)3NHSO3H-catalysed selective oxidation of sulfides to sulfones
Bahrami, Kiumars,Khodamorady, Minoo
, (2018/10/15)
Reusable boehmite nanoparticles–silica–NHSO3H (BNPs-SiO2@(CH2)3NHSO3H) was found to be an efficient heterogeneous nanocatalyst for the selective oxidation of sulfides to sulfones in the presence of H2O2. Excellent yields, easy and quick isolation of products, short reaction times and excellent selectivity are the main advantages of this method. The catalyst was characterized using Fourier transform infrared spectroscopy, energy-dispersive X-ray analysis, X-ray diffraction, and transmission and scanning electron microscopies.
