Inhibition of Sphingosine-1-Phosphate Lyase for the Treatment of Autoimmune Disorders was written by Bagdanoff, Jeffrey T.;Donoviel, Michael S.;Nouraldeen, Amr;Tarver, James;Fu, Qinghong;Carlsen, Marianne;Jessop, Theodore C.;Zhang, Haiming;Hazelwood, Jill;Nguyen, Huy;Baugh, Simon D. P.;Gardyan, Michael;Terranova, Kristen M.;Barbosa, Joseph;Yan, Jack;Bednarz, Mark;Layek, Suman;Taylor, Jerry;Digeorge-Foushee, Ann Marie;Gopinathan, Suma;Bruce, Debra;Smith, Traci;Moran, Liam;O’Neill, Emily;Kramer, Jeff;Lai, Zhong;Kimball, S. David;Liu, Qingyun;Sun, Weimei;Yu, Sean;Swaffield, Jonathan;Wilson, Alan;Main, Alan;Carson, Kenneth G.;Oravecz, Tamas;Augeri, David J.. And the article was included in Journal of Medicinal Chemistry in 2009.Formula: C9H10BrNO2 This article mentions the following:
During nearly a decade of research dedicated to the study of sphingosine signaling pathways, we identified sphingosine-1-phosphate lyase (S1PL) as a drug target for the treatment of autoimmune disorders. S1PL catalyzes the irreversible decomposition of sphingosine-1-phosphate (S1P) by a retro-aldol fragmentation that yields hexadecanaldehyde and phosphoethanolamine. Genetic models demonstrated that mice expressing reduced S1PL activity had decreased numbers of circulating lymphocytes due to altered lymphocyte trafficking, which prevented disease development in multiple models of autoimmune disease. Mechanistic studies of lymphoid tissue following oral administration of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI) showed a clear relationship between reduced lyase activity, elevated S1P levels, and lower levels of circulating lymphocytes. Our internal medicinal chem. efforts discovered potent analogs of 3 bearing heterocycles as chem. equivalent of the pendant carbonyl present in the parent structure. Reduction of S1PL activity by oral administration of these analogs recapitulated the phenotype of mice with genetically reduced S1PL expression. In the experiment, the researchers used many compounds, for example, 2-Bromo-6-(2-methyl-1,3-dioxolan-2-yl)pyridine (cas: 49669-14-9Formula: C9H10BrNO2).
2-Bromo-6-(2-methyl-1,3-dioxolan-2-yl)pyridine (cas: 49669-14-9) belongs to alcohols. Similar to water, an alcohol can be pictured as having an sp3 hybridized tetrahedral oxygen atom with nonbonding pairs of electrons occupying two of the four sp3 hybrid orbitals. Secondary alcohols are easily oxidized without breaking carbon-carbon bonds only as far as the ketone stage. No further oxidation is seen except under very stringent conditions.Formula: C9H10BrNO2
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Alcohols – Chemistry LibreTexts