Preparation of Trifluoromethyl Lactol Derivatives via Base Initiated Cyclobutanol Ring Opening to a Laterally Lithiated Trifluoromethyl Ketone

Benzocyclobutenone derivatives 4 are converted to the corresponding trifluoromethylcyclobutanols 5 by treatment with trifluoromethyltrimethylsilane in the presence of tetra-n-butylammonium fluoride. These trifluoromethylcyclobutanol derivatives are then treated with LiTMP in the presence of aromatic aldehydes to afford trifluoromethyllactols 6 via a laterally-lithiated trifluoromethylketone intermediate

One-Pot Preparation of 1,3-Dihydro-1- (Trifluoromethyl)isobenzofuran-1-ol Derivatives from 1,2-Dibromobenzene

A one-pot method for the preparation of 1,3-dihydro-1-(trifluoromethyl)isobenzofuran-1-ol derivatives 5from 1,2-dibromobenzene is describe

Synthetic Strategies for the Construction of Enantiomeric Azanoradamantanes

The amino azanoradamantane hexahydro-2,5b-methano-IH-3aS,3aa,6aa-cyclopenta-[clpyrrole-4a-amine 1and the corresponding enantiomer ent-1 have been prepared along with benzamide derivatives SC-52491and SC-52490, respectively, which are of pharmaceutical interest. The key meso-azabicyclo[3.3.0] intermediate 3 was prepared via three separate routes: a [3+2] cycloaddition route, a radical cyclization/ionic cyclization route, and a reductive Pauson-Khand route

Bridgehead-methyl Analog of SC-53116 as a 5-HT4 Agonist

Pyrrolizidine benzamide (±)-2, the bridgehead-methyl analog of SC-53116, was prepared and evaluated for 5-HT4 agonism activity in the rat tunica muscularis (TMM) mucosae assay. Compound (±)-2 has an EC50 of 449 nM in the TMM assay, as compared to 23 nM for SC-53116, and 66 nM for the racemate of SC-53116

Azaadamantane Benzamide 5-HT4 Agonists: Gastrointestinal Prokinetic SC-54750

Azaadamantanone 1 was converted to a series of aminoazaadamantane benzamides 9a–d, which were profiled for serotonin receptor activity. Aminomethylazaadamantane SC-54750 is a potent 5-HT4 agonist and 5-HT3 antagonist with in vivo efficacy in gastroparesis models and also inhibits cisplatin-induced emesis

Dynactin-dependent cortical dynein and spherical spindle shape correlate temporally with meiotic spindle rotation in Caenorhabditis elegans.

Oocyte meiotic spindles orient with one pole juxtaposed to the cortex to facilitate extrusion of chromosomes into polar bodies. In Caenorhabditis elegans, these acentriolar spindles initially orient parallel to the cortex and then rotate to the perpendicular orientation. To understand the mechanism of spindle rotation, we characterized events that correlated temporally with rotation, including shortening of the spindle in the pole-to pole axis, which resulted in a nearly spherical spindle at rotation. By analyzing large spindles of polyploid C. elegans and a related nematode species, we found that spindle rotation initiated at a defined spherical shape rather than at a defined spindle length. In addition, dynein accumulated on the cortex just before rotation, and microtubules grew from the spindle with plus ends outward during rotation. Dynactin depletion prevented accumulation of dynein on the cortex and prevented spindle rotation independently of effects on spindle shape. These results support a cortical pulling model in which spindle shape might facilitate rotation because a sphere can rotate without deforming the adjacent elastic cytoplasm. We also present evidence that activation of spindle rotation is promoted by dephosphorylation of the basic domain of p150 dynactin

(±)-2-exo- and endo-Methylamino-1,2,3,4-tetrahydro-1,4-ethanonapthalene Hydrochloride

This is the published version

Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling

<p>Abstract</p> <p>Background</p> <p>Engineered iron nanoparticles are being explored for the development of biomedical applications and many other industry purposes. However, to date little is known concerning the precise mechanisms of translocation of iron nanoparticles into targeted tissues and organs from blood circulation, as well as the underlying implications of potential harmful health effects in human.</p> <p>Results</p> <p>The confocal microscopy imaging analysis demonstrates that exposure to engineered iron nanoparticles induces an increase in cell permeability in human microvascular endothelial cells. Our studies further reveal iron nanoparticles enhance the permeability through the production of reactive oxygen species (ROS) and the stabilization of microtubules. We also showed Akt/GSK-3β signaling pathways are involved in iron nanoparticle-induced cell permeability. The inhibition of ROS demonstrate ROS play a major role in regulating Akt/GSK-3β – mediated cell permeability upon iron nanoparticle exposure. These results provide new insights into the bioreactivity of engineered iron nanoparticles which can inform potential applications in medical imaging or drug delivery.</p> <p>Conclusion</p> <p>Our results indicate that exposure to iron nanoparticles induces an increase in endothelial cell permeability through ROS oxidative stress-modulated microtubule remodeling. The findings from this study provide new understandings on the effects of nanoparticles on vascular transport of macromolecules and drugs.</p