A study of the norcaradiene-cycloheptatriene equilibrium in a series of azulenones by NMR spectroscopy; the impact of substitution on the position of equilibrium.

A systematic investigation of the influence of substitution at positions C-2 and C-3 on the azulenone skeleton, based on NMR characterisation, is discussed with particular focus on the impact of the steric and electronic characteristics of substituents on the position of the norcaradiene-cycloheptatriene (NCD-CHT) equilibrium. Variable temperature (VT) NMR studies, undertaken to enable the resolution of signals for the equilibrating valence tautomers revealed, in addition, interesting shifts in the equilibrium.

Semagacestat, a γ-secretase inhibitor, activates the growth hormone secretagogue (GHS-R1a) receptor.

Objectives: Semagacestat, is a γ-secretase inhibitor, which belongs to a class of drugs that are being developed as therapeutic agents for Alzheimer's disease (AD). This study aims to evaluate another potential effect of semagacestat, namely its ability to stimulate the growth hormone secretagogue receptor (GHS-R1a), which may also contribute to its therapeutic efficacy.

Methods: The GHS-R1a-activating potential of semagacestat and its synthetic precursor was assessed in an in vitro calcium mobilization assay in cells expressing the GHS-R1a receptor and compared with that of the endogenous peptide GHS-R1a agonist, acyl-ghrelin, as well as the non-peptidyl synthetic GHS-R1a agonist, MK0677.