36972-73-3Relevant academic research and scientific papers
Synthesis, in vitro activity, and three-dimensional quantitative Structure-activity relationship of novel hydrazine inhibitors of human vascular adhesion protein-1
Nurminen, Elisa M.,Pihlavisto, Marjo,Lázár, László,Szakonyi, Zsolt,Pentik?inen, Ulla,Fül?p, Ferenc,Pentik?inen, Olli T.
experimental part, p. 6301 - 6315 (2010/10/20)
Vascular adhesion protein-1 (VAP-1) belongs to the semicarbazide-sensitive amine oxidases (SSAOs) that convert amines into aldehydes. SSAOs are distinct from the mammalian monoamine oxidases (MAOs), but their substrate specificities are partly overlapping. VAP-1 has been proposed as a target for anti-inflammatory drug therapy because of its role in leukocyte adhesion to endothelium. Here, we describe the synthesis and in vitro activities of novel series of VAP-1 selective inhibitors. In addition, the molecular dynamics simulations performed for VAP-1 reveal that the movements of Met211, Ser496, and especially Leu469 can enlarge the ligand-binding pocket, allowing larger ligands than those seen in the crystal structures to bind. Combining the data from molecular dynamics simulations, docking, and in vitro measurements, the three-dimensional quantitative Structure-activity relationship (3D QSAR) models for VAP-1 (q2LOO: 0.636; r2: 0.828) and MAOs (q2LOO: 0.749, r2: 0.840) were built and employed in the development of selective VAP-1 inhibitors.
Base-Induced Fragmentation of β-Hydroxy Nitrosamines
Loeppky, R. N.,McKinley, W. A.,Hazlitt, L. G.,Outram, J. R.
, p. 4833 - 4841 (2007/10/02)
β-Hydroxy nitrosamines have been found to undergo a base-induced fragmentation reaction.The reaction cleaves the Cα-Cβ bond of the substrate to produce an aldehyde or ketone and a smaller alkylnitrosamine.Rate contants for the fragmentation induced by potassium tert-butoxide in THF or tert-butyl alcohol have been measured for nine substrates at temperatures between 35 and 70 deg C.The rate constants are a function of base concentration and range between 0.15x10-6 and 308x10-6 s-1.Rate constants have been determined for (2-hydroxyethyl)methylnitrosamine,N-nitrosodiethanolamine, (2-hydroxy-2-methylpropyl)methylnitrosamine, (2-hydroxy-2-phenylethyl)methylnitrosamine, N-nitrosoephedrine, (2-hydroxy-2,2-diphenylethyl)methylnitrosamine, and (2-hydroxy-2-phenylpropyl)methylnitrosamine.The nitrosamino alcohol fragmentation rates are in the order tertiary > secondary > primary, and the rate appears to be a function of product stability and steric strain in the substrate.A mechanism which accounts for these observations is proposed.
