Phosphodiesterase-9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of central nervous system diseases and diabetes. Here, we report the discovery of a new category of PDE9 inhibitors by rational design on the basis of the crystal structures. The best compound, (S)-6-((1-(4-chlorophenyl)ethyl)amino)-1-cyclopentyl-1,5,6,7-tetrahydro-4H-pyrazolo[3,4-day]pyrimidin-4-one...

Available surfactants for treatment of respiratory distress syndrome in newborn infants are derived from animal lungs, which limits supply and poses a danger of propagating infectious material. Poly-Val-->poly-Leu analogs of surfactant protein (SP)-C can be synthesized in large quantities and exhibit surface activity similar to SP-C. Here, activity of synthetic surfactants containing a poly-Leu...

Previously unknown metabolites from the two macrolide immunosuppressants rapamycin (sirolimus) and SDZ RAD [40-O-(2-hydroxyethyl)rapamycin] obtained after in vitro incubation with human liver microsomes have been purified. Structure elucidation was performed by nanoelectrospray ionization tandem mass spectrometry applying low energy collision activated dissociation. This ionization method is, a...

The World Health Organization (WHO) estimates that 84 million people will die of cancer between 2005-2015 [1]. According using the WHO mortality database it has been estimated the total number of cancer deaths in the European Union (EU) and in 2012 is predicted to be 1283101, of which 717398 men and 565703 women [2]. The most common types of cancer that will be diagnosed are lung (C33-C34), int...

Three cyclic C33 botryococcenes and one new trimethylsqualene isomer were isolated from the B race, Showa (Berkeley) strain of Botryococcus braunii, which is known to produce large amounts of isoprenoid hydrocarbons ranging in carbon number from 30 to 34. Their purity was determined by GC-MS, and structures were characterized by 1D and 2D NMR. One of these molecules, cyclic C33-1 botryococcene ...

Six mature geldings of light horse breeds (557 ± 37 kg) were randomly assigned to a nontoxic endophyte-infected tall fescue hay (n = 3) or pasture treatment (n = 3) in a crossover design with 14-d periods to estimate DMI with alkane markers and to compare DMI of hay and pasture. When fed pasture, horses were housed in stalls from 0700 to 1300 h daily with access to water and then grazed pasture...

Article history: Received 15 January 2013 Received in revised form 18 April 2014 Accepted 22 April 2014 Available online xxxx JEL classification: C33 D3 D91 J31