Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening

With the aim to discover orally active small molecules that stimulate glucose uptake, high throughput screening of a library of 5000 drug-like compounds was conducted in differentiated skeletal muscle cells in presence of insulin. N-Substituted phthalazinone acetamide was identified as a potential glucose uptake modulator. Several novel derivatives were synthesized to establish structure activity relationships. Identified lead thiazolyl-phthalazinone acetamide (7114863) increased glucose uptake (EC₅₀ of 0.07 ± 0.02 μM) in differentiated skeletal muscle cells in presence of insulin. Furthermore, 7114863 was superior to rosiglitazone under similar experimental conditions without inducing PPAR-γ agonist activity thus making it a very interesting scaffold.     

Alpha detection: some comments on Hardt and Kamiya, "Conflicting results in EEG alpha feedback studies".

The problem of defining EEG alpha activity, and of detecting and measuring it, is outlined. Some advantages of a threshold method are presented and compared with an amplitude-integration method. Characteristics of percent-time scoring, based upon observable alpha spindles in the waking EEG, are discussed. A probability distribution of percent-time alpha as a function of detection threshold is derived and compared with empirical data.