638-18-6Relevant articles and documents
Structure-activity relationships of glycogen phosphorylase inhibitor FR258900 and its analogues: A combined synthetic, enzyme kinetics, and computational study
Juhsz, Lszl,Varga, Gergely,Sztankovics, Andrea,Bke, Ferenc,Docsa, Tibor,Kiss-Szikszai, Attila,Gergely, Pl,Ka, Juraj,Tvaroka, Igor,Somsk, Lszl
, p. 1558 - 1568 (2015/02/05)
A series of O- or N-cinnamoylated, p-coumaroylated, feruloylated, phenyl, and substituted phenylpropiolated derivatives of lmalic, 3-hydroxypentanedioic, and l-glutamic acids were synthesized as analogues of the natural product glycogen phosphorylase (GP) inhibitor FR258900 (2,3-bis(4-hydroxycinnamoyloxy) glutaric acid). These compounds proved practically inactive against rabbit muscle glycogen phosphorylase b. A structure-activity study involving previously synthesized tartaric acid analogues of FR258900 revealed that two acyl moieties must be present in the compounds to make a good inhibitor. Molecular modeling methods (docking and quantitative structure-activity relationship (QSAR) calculations) were used to understand the nature of the binding affinities of these GP inhibitors. The generated 3D models for GP-inhibitor complexes showed that both the polar allosteric site pocket and the hydrophobic pocket at the interface of the homodimeric units of GP were important for effective binding of the acyl and aromatic moieties of the inhibitors. The predictive QSAR models consist of empirical and quantum mechanics descriptors and provide good explanatory and predictive abilities (prediction coefficient Q2=0.7-0.9 when cross-validation procedures were performed).
Amidine dications as superelectrophiles
Corr, Michael J.,Roydhouse, Mark D.,Gibson, Kirsty F.,Zhou, Sheng-Ze,Kennedy, Alan R.,Murphy, John A.
supporting information; experimental part, p. 17980 - 17985 (2010/04/01)
2-Dimethylalkylammonium pyridinium and 2-dimethylalkylammonium pyrimidinium ditriflate salts are very powerful methylating agents toward phosphorus (triphenylphosphine) and nitrogen (triethylamine) nucleophiles. In competition experiments with triethylamine as nucleophile, these N-methyl disalts are more reactive methylating agents than dimethyl sulfate. Reaction of the pyridinium dications with water as an oxygen nucleophile leads to attack at the 2-position of the heteroaromatic ring and displacement of an ammonium group; 2-hydroxypyridinium compounds are formed in the first instance, which are easily converted to 2-pyridones. Extending the scope of the reactions, a tricationic 2,6-bis(dimethylalkylammonium) pyridinium salt has also been prepared and characterized and its reactivity as a methylating agent assessed in comparison with that of the dications.
Synthesis of macrocyclic polyhydroxy tetralactams derived from L-tartaric acid and β-hydroxyglutaric acid
Arnaud, Nathalie,Picard, Claude,Cazaux, Louis,Tisnes, Pierre
, p. 13757 - 13768 (2007/10/03)
The synthesis of new 16-, 18-, 19- or 20-membered secondary tetralactams with L-tartaric acid or β-hydroxyglutaric acid moieties is investigated. The stepwise synthesis with an intermediate diamide diamine provides overall good yields (30-55%) compared with other processes using an intermediate diamide diacid or direct macrocyclization. This synthetic pathway leads to symmetrical or unsymmetrical polyhydroxytetralactams with variable hydroxyl group number. Use of mild acylating agents in this approach allows to avoid the protection-deprotection steps of hydroxyl groups.
