Exploring Non-orthosteric Interactions with a Series of Potent and Selective A Antagonists.

A library of potent and highly AAR selective pyrimidine-based compounds was designed to explore non-orthosteric interactions within this receptor. Starting from a prototypical orthosteric AAR antagonist (ISVY130), the structure-based design explored functionalized residues at the exocyclic amide L1 region and aimed to provide additional interactions outside the AAR orthosteric site. The novel ligands were assembled through an efficient and succinct synthetic approach, resulting in compounds that retain the AAR potent and selective profile while improving the solubility of the original scaffold.

Enantioenriched α-Vinyl 1,4-Benzodiazepines and 1,4-Benzoxazepines via Enantioselective Rhodium-Catalyzed Hydrofunctionalizations of Alkynes and Allenes.

Benzofused seven-membered heterocycles such as 1,4-benzo[]diazepines (1,4-BZDs) and 1,4-benzo[]oxazepines (1,4-BZOs) were efficiently synthesized by Rh-catalyzed hydrofunctionalization of internal alkynes and allenes in good to excellent yields. The asymmetric hydroamination of (aminomethyl)anilines gave rise to 3-vinyl-1,4-BZDs with excellent enantioselectivities. Orthogonal -deprotection of 1,4-BZDs allowed an easy entry to an advanced pyrrolobenzodiazepine metabolite of the V-receptor antagonist Lixivaptan.

Anatomical Variations of the Thoracic Duct: A Preliminary Report in Adult and Fetal Specimens.

The study aim is to evaluate anatomical variations of the thoracic duct using a specialized sequential injection procedure. The different types, frequencies, and anatomical topography were recorded and evaluated using 12 adult and 16 fetus specimens. By employing a perfusion pump device, cadavers were sequentially perfused with acrylic colored latex first through the internal marginal vein, then the thoracic duct at the interazygous-aortic recess, and finally through the posterior tibial artery.

Tandem Long Distance Chain-Walking/Cyclization via RuH2(CO)(PPh3)3/Brønsted Acid Catalysis: Entry to Aromatic Oxazaheterocycles.

A novel route to 1,3-oxazaheterocycles based on cooperative Ru-H/Brønsted acid catalysis is reported. The use of the commercially available RuH2(CO)(PPh3)3 complex allows for an efficient long distance chain-walking process while the Brønsted acid is responsible for generation of an electrophilic iminium ion which is trapped intramolecularly by an alcohol moiety. The alcohol, besides its nucleophilic function, also plays an important role in the stabilization of the Ru catalyst.