Optimization of IRAK1/4/pan-FLT3 kinase inhibitors as treatments for acute myeloid leukemia.

FLT3 kinase inhibitors have been advanced to the clinic as targeted treatments for acute myeloid leukemia (AML). These inhibitors can produce promising initial responses, but patients often relapse with treatment-resistant disease. A significant factor contributing to relapse involves adaptive signaling through an alternative pathway mediated by IRAK1 and IRAK4 kinases.

Radical Reactions with Chiral Acylammonium Salts: Synthesis of Functionalized δ-Lactams through Giese-Initiated Organocascades.

Enantioselective Giese reactions employing chiral α,β-unsaturated acylammonium salts and subsequent diastereoselective trapping followed by lactamization deliver optically active δ-lactams. Alkyl iodides bearing tosylamides undergo radical initiation using triethylborane at low temperatures to provide carbon-centered radicals to initiate the described organocascade. Subsequent diastereoselective inter- or intramolecular trapping of the incipient α-radical leads to highly functionalized, enantioenriched mono- and bicyclic δ-lactams (up to 99:1 er, > 19:1 dr) bearing up to three stereogenic centers.

Zinc-mediated carboxylations of allylic and propargylic halides in flow: synthesis of β-lactones subsequent bromolactonization.

Zinc-mediated carboxylation of allylic halides under flow conditions delivered β,γ-unsaturated carboxylic acids and subsequent bromolactonization provides a streamlined process for the synthesis of γ-bromo-β-lactones. The described process further demonstrates the utility of organozinc reagents prepared by passage of allylic halides through a metallic zinc column integrated into a flow process. Use of a tube-in-tube reactor for efficient CO introduction led to improvements in conversion compared to a batch process and improved overall yields of β-lactones.

Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence -associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia.

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide β-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth.