606488-94-2Relevant articles and documents
Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs
Krall, Jacob,Jensen, Claus Hatt,Bavo, Francesco,Falk-Petersen, Christina Birkedahl,Haugaard, Anne St?hr,Vogensen, Stine Byskov,Tian, Yongsong,Nittegaard-Nielsen, Mia,Sigurdardóttir, Sara Bj?rk,Kehler, Jan,Kongstad, Kenneth Thermann,Gloriam, David E.,Clausen, Rasmus Pr?torius,Harps?e, Kasper,Wellendorph, Petrine,Fr?lund, Bente
, p. 9022 - 9039 (2017/11/14)
γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar Ki) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.
FLT3 INHIBITORS AND USES THEREOF
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Paragraph 00353-00354, (2014/12/12)
The present invention provides methods of using compounds of formula I: or compositions thereof for the inhibition of FLT3, and the treatment of FLT3-mediated disorders.
Degradation of a model naphthenic acid, cyclohexanoic acid, by vacuum UV (172 nm) and UV (254 nm)/H2O2
Drzewicz, Przemyslaw,Afzal, Atefeh,El-Din, Mohamed Gamal,Martin, Jonathan W.
experimental part, p. 12067 - 12074 (2011/02/27)
The mechanism of hydroxyl radical initiated degradation of a typical oil sands process water (OSPW) alicyclic carboxylic acid was studied using cyclohexanoic acid (CHA) as a model compound. By use of vacuum ultraviolet irradiation (VUV, 172 nm) and ultraviolet irradiation in the presence of hydrogen peroxide UV(254 nm)/H2O2, it was established that CHA undergoes degradation through a peroxyl radical. In both processes the decay of the peroxyl radical leads predominantly to the formation of 4-oxo-CHA, and minor amounts of hydroxy-CHA (detected only in UV/H2O 2). In UV/H2O2, additional 4-oxo-CHA may also have been formed by direct reaction of the oxyl radical with H-O 2. The oxyl radical can be formed during decay of the peroxyl-CHA radical or reaction of hydroxy-CHA with hydroxyl radical. Oxo- and hydroxy-CHA further degraded to various dihydroxy-CHAs. Scission of the cyclohexane ring was also observed, on the basis of the observation of acyclic byproducts including heptadioic acid and various short-chain carboxylic acids. Overall, the hydroxyl radical induced degradation of CHA proceeded through several steps, involving more than one hydroxyl radical reaction, thus efficiency of the UV/H 2O2 reaction will depend on the rate of generation of hydroxyl radical throughout the process. In real applications to OSPW, concentrations of H2O2 will need to be carefully optimized and the environmental fate and effects of the various degradation products of naphthenic acids considered.
