Orally Active 7-Substituted (4-Benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as Active-Site Inhibitors of Sphingosine 1-Phosphate Lyase for the Treatment of Multiple Sclerosis was written by Weiler, Sven;Braendlin, Nadine;Beerli, Christian;Bergsdorf, Christian;Schubart, Anna;Srinivas, Honnappa;Oberhauser, Berndt;Billich, Andreas. And the article was included in Journal of Medicinal Chemistry in 2014.HPLC of Formula: 149554-29-0 This article mentions the following:
Sphingosine 1-phosphate (S1P) lyase has recently been implicated as a therapeutic target for the treatment of multiple sclerosis (MS), based on studies in a genetic mouse model. Potent active site directed inhibitors of the enzyme are not known so far. Here we describe the discovery of (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile 5 in a high-throughput screen using a biochem. assay, and its further optimization. This class of compounds was found to inhibit catalytic activity of S1PL by binding to the active site of the enzyme, as seen in the cocrystal structure of derivative 31 with the homodimeric human S1P lyase. 31 induces profound reduction of peripheral T cell numbers after oral dosage and confers pronounced protection in a rat model of multiple sclerosis. In conclusion, this novel class of direct S1P lyase inhibitors provides excellent tools to further explore the therapeutic potential of T cell-targeted therapies in multiple sclerosis and other autoimmune and inflammatory diseases. In the experiment, the researchers used many compounds, for example, 6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0HPLC of Formula: 149554-29-0).
6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.HPLC of Formula: 149554-29-0
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics