Expanding Complex Morpholines Using Systematic Chemical Diversity.

The morpholine heterocycle is a structural unit found in many bioactive compounds and FDA-approved drugs, but the generation of more complex C-functionalized morpholine derivatives remains considerably underexplored. Using systematic chemical diversity (SCD), a concept that guides the expansion of saturated drug-like scaffolds through regiochemical and stereochemical variation, we describe the synthesis of a collection of methyl-substituted morpholine acetic acid esters starting from enantiomerically pure amino acids and amino alcohols. In total, 24 diverse substituted morpholines were produced that vary systematically in regiochemistry and stereochemistry (relative and absolute).

The roles of Cyp1a2 and Cyp2d in pharmacokinetic profiles of serotonin and norepinephrine reuptake inhibitor duloxetine and its metabolites in mice.

Duloxetine (DLX) is widely used to treat major depressive disorder. Little is known about the mechanistic basis for DLX-related adverse effects (e.g.

Max-imizing the Attenuation of Myc Using Small Molecules.

It has been a widely held notion within the biomedical research community that the reliable modulation of transcription factors with small molecules would represent a holy grail, given their role in directly potentiating oncogenic programs. Among the transcription factors that have been held in highest regard is Myc, since its dysregulation is among the most recurrent events in human cancer. Despite intense efforts, the ability to identify compounds that bind directly to Myc, resulting in its functional inhibition, have been met with only moderate success.

Update on amino acid transporter functions and on possible amino acid sensing mechanisms in plants.

Amino acids are essential components of plant metabolism, not only as constituents of proteins, but also as precursors of important secondary metabolites and as carriers of organic nitrogen between the organs of the plant. Transport across intracellular membranes and translocation of amino acids within the plant is mediated by membrane amino acid transporters. The past few years have seen the identification of a new family of amino acid transporters in Arabidopsis, the characterization of intracellular amino acid transporters, and the discovery of new roles for already known proteins.