Recent Advances in the Synthesis and Application of SF5-Containing Organic Compounds

It is well known that fluorinated molecules play an important role in daily life. For example, organic molecules bearing either a fluorine atom itself or a short polyfluorinated substituent such as mono-, difluoro-, and trifluoromethyl groups, or pentafluoroethyl and perfluoropropyl groups are already widely used in medicinal and agricultural chemistry. In contrast, molecules with long perfluorinated chains have found vast application in materials science. Among the fluorine-containing moieties, the pentafluorosulfanyl (SF5) substituent occupies a special place.1 The pentafluorosulfanyl group brings unique properties to organic compounds and often improves their biological activities due to the group’s high chemical and metabolic stability, significant lipophilicity, substantial steric effect, unique geometry, and low surface energy. Here we present new routes towards SF5-substituted aliphatic and heterocyclic compounds

Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A)

We report a series of tranylcypromine analogues containing a fluorine in the cyclopropyl ring. A number of compounds with additional m- or p- substitution of the aryl ring were micromolar inhibitors of the LSD1 enzyme. In cellular assays, the compounds inhibited the proliferation of acute myeloid leukemia cell lines. Increased levels of the biomarkers H3K4me2 and CD86 were consistent with LSD1 target engagement

Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin

Sphingosine-1-phosphate (S1P) participates in inflammation;however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P(3)) and G alpha(q), PLC beta and Ca2+. Intraarterial S1P administration increases leukocyte rolling, while S1P(3) deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P(3). Histamine and epinephrine require S1P(3) for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P1 inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific S1P(1)(-/-) mice. In agreement with a dominant pro-rolling effect of S1P(3),FTY720 inhibits rolling in control and S1P(1)(-/-) but not in S1P(3)(-/-) mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action