Optimization of Novel α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators and the Discovery of a Preclinical Development Candidate Molecule (RGH-560).

During optimization of a previously identified lead compound, attempts were made to optimize the reactive indole structural element, the suboptimal metabolic stability, as well as the low kinetic solubility. It was concluded that the indole was important for activity. With the aim of further improvements, more thorough modifications were also carried out.

Biomimetic synthesis and HPLC-ECD analysis of the isomers of dracocephins A and B.

Starting from racemic naringenin ((±)-), a mixture of dracocephin A stereoisomers 6-(2"-pyrrolidinone-5"-yl)naringenin (±)- and its regioisomer, dracocephin B 8-(2"-pyrrolidinone-5"-yl)naringenin (±)- originally isolated from , have been synthesized in a one-pot reaction. The separation of and was achieved by preparative HPLC. The four stereoisomers of each natural product were separated by analytical chiral HPLC and their absolute configuration was studied by the combination of HPLC-ECD measurements and TDDFT-ECD calculations.