Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti‐inflammatory activity

The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7‐bromo‐2‐(2‐phenylethyl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti‐inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil–endothelial cell interactions. The information obtained from our theoretical and experimental study can be useful in the search for inhibitors of SphK2 that play a prominent role in different diseases, especially in inflammatory and cardiovascular disorders.Fil: Vettorazzi, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Vila, Laura. Universidad de Valencia; EspañaFil: Lima, Santiago. Virginia Commonwealth University School of Medicine; Estados UnidosFil: Acosta, Lina. Universidad Industrial Santander; ColombiaFil: Yépes, Felipe. Universidad Industrial Santander; ColombiaFil: Palma, Alirio. Universidad Industrial Santander; ColombiaFil: Cobo, Justo. Universidad de Jaén; EspañaFil: Tengler, Jan. Medis International a.s.; República ChecaFil: Malik, Ivan. Comenius University; EslovaquiaFil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Marqués, Patrice. Universidad de Valencia; EspañaFil: Cabedo, Nuria. Universidad de Valencia; EspañaFil: Sanz, María J.. Universidad de Valencia; EspañaFil: Jampilek, Josef. Comenius University; EslovaquiaFil: Spiegel, Sarah. Virginia Commonwealth University School of Medicine; Estados UnidosFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Regional Convergence in Germany: a Geographically Weighted Regression Approach

Abstract Regional convergence of German labour markets represents a politically important question. Different studies have examined convergence processes in Germany. We derive equations to estimate the speed of convergence on the basis of an extended Solow model. The technique of geographically weighted regression permits a detailed analysis of convergence processes, which has not been conducted for Germany as yet. It allows the estimation of a separate speed of convergence for every region resulting from the local coefficients of the regression equations. The application of this technique to German labour market regions shows regions moving at different speeds towards their steady states. The half-life periods in the model of conditional convergence disperse less than the same coefficients in the absolute convergence model. Moreover, the speed of convergence is substantially slower in the manufacturing sector than in the service sector.Regional convergence, spatial econometrics, geographically weighted regression, C21, R11, R58,