Crystal structure of (E)-1,2-bis-(4-bromo-2,6-di-fluoro-phen-yl)diazene.

In the crystal, mol-ecules of the centrosymmetric title compound, C12H4Br2F4N2, are linked into strands along [011] by weak C-H⋯F contacts. Furthermore, the mol-ecules are π-π stacked with perpendicular ring distances of 3.4530 (9) Å.

AzoCholine Enables Optical Control of Alpha 7 Nicotinic Acetylcholine Receptors in Neural Networks.

Nicotinic acetylcholine receptors (nAChRs) are essential for cellular communication in higher organisms. Even though a vast pharmacological toolset to study cholinergic systems has been developed, control of endogenous neuronal nAChRs with high spatiotemporal precision has been lacking. To address this issue, we have generated photoswitchable nAChR agonists and re-evaluated the known photochromic ligand, BisQ. Using electrophysiology, we found that one of our new compounds, AzoCholine, is an excellent photoswitchable agonist for neuronal α7 nAChRs, whereas BisQ was confirmed to be an agonist for the muscle-type nAChR. AzoCholine could be used to modulate cholinergic activity in a brain slice and in dorsal root ganglion neurons. In addition, we demonstrate light-dependent perturbation of behavior in the nematode, Caenorhabditis elegans.

Asymmetric hydrogenation of α,ß-unsaturated carboxylic esters with chiral iridium N,P ligand complexes.

Enantioselective conjugate reduction of a wide range of α,ß-unsaturated carboxylic esters was achieved using chiral Ir N,P complexes as hydrogenation catalysts. Depending on the substitution pattern of the substrate, different ligands perform best. α,ß-Unsaturated carboxylic esters substituted at the α position are less problematic substrates than originally anticipated and in some cases α-substituted substrates actually reacted with higher enantioselectivity than their ß-substituted analogues. The resulting saturated esters with a stereogenic center in the α or ß position were obtained in high enantiomeric purity.

Asymmetric hydrogenation of alkenes lacking coordinating groups.

Asymmetric hydrogenation of olefins is one of the most important reactions for the synthesis of optically active compounds, especially in industry. Chiral iridium catalysts based on P,N ligands have strongly expanded their application range. In contrast to rhodium and ruthenium diphosphine complexes they do not require the presence of a coordinating group near the C=C bond and, therefore, allow highly enantioselective hydrogenations of largely unfunctionalized alkenes.

Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers.

The synthesis and structure-activity relationship of a series of arylaminoethyl amide cathepsin S inhibitors are reported. Optimization of P3 and P2 groups to improve overall physicochemical properties resulted in significant improvements in oral bioavailability over early lead compounds. An X-ray structure of compound 37 bound to the active site of cathepsin S is also reported.

Arylaminoethyl carbamates as a novel series of potent and selective cathepsin S inhibitors.

We report a novel series of noncovalent inhibitors of cathepsin S. The synthesis of the peptidomimetic scaffold is described and structure-activity relationships of P3, P1, and P1' subunits are discussed. Lead optimization to a non-peptidic scaffold has resulted in a new class of potent, highly selective, and orally bioavailable cathepsin S inhibitors.

Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 3: heterocyclic P3.

A series of N(alpha)-2-benzoxazolyl-alpha-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure-activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported.