2 research outputs found
Multilayer Silicene Nanoribbons
The synthesis of silicene, graphene-like silicon, has
generated
very strong interest. Here, we reveal the growth of high aspect ratio,
perfectly straight, and aligned silicon nanoribbons, exhibiting pyramidal
cross section. They are multistacks of silicene and show in angle-resolved
photoemission cone-like dispersion of their π and π* bands,
at the <i>XÌ…</i> point of their one-dimensional Brillouin
zone, with Fermi velocity of ∼1.3 × 10<sup>6</sup> m sec<sup>–1</sup>, which is very promising for potential applications
Discovery of a Novel Series of <i>N</i>‑Phenylindoline-5-sulfonamide Derivatives as Potent, Selective, and Orally Bioavailable Acyl CoA:Monoacylglycerol Acyltransferase‑2 Inhibitors
Acyl
CoA:monoacylglycerol acyltransferase-2 (MGAT2) has attracted
interest as a novel target for the treatment of obesity and metabolic
diseases. Starting from <i>N</i>-phenylbenzenesulfonamide
derivative <b>1</b> with moderate potency for MGAT2 inhibition,
we explored an effective location of the hydrophobic group at the
1-position to enhance MGAT2 inhibitory activity. Shifting the hydrophobic
group to the adjacent position followed by introduction of a bicyclic
central core to restrict the substituent orientation produced <i>N</i>-phenylindoline-5-sulfonamide derivative <b>10b</b>, which displayed much improved potency, with an IC<sub>50</sub> value
of 1.0 nM. This compound also exhibited excellent selectivity (greater
than 30,000-fold) against related acyltransferases (MGAT3, DGAT1,
DGAT2, and ACAT1). Subsequent optimization efforts were directed toward
improving pharmacokinetic profiles, which resulted in the identification
of 5-[(2,4-difluorophenyl)Âsulfamoyl]-7-(2-oxopyrrolidin-1-yl)-<i>N</i>-[4-(trifluoromethyl)Âphenyl]-2,3-dihydro-1<i>H</i>-indole-1-carboxamide (<b>24d</b>) endowed with potent MGAT2
inhibitory activity (IC<sub>50</sub> = 3.4 nM) and high oral bioavailability
(<i>F</i> = 52%, mouse). In a mouse oral fat tolerance test,
oral administration of this compound effectively suppressed the elevation
of plasma triacylglycerol levels