14315-26-5Relevant articles and documents
Elaborate ligand-based pharmacophore exploration and QSAR analysis guide the synthesis of novel pyridinium-based potent β-secretase inhibitory leads
Al-Nadaf, Afaf,Sheikha, Ghassan Abu,Taha, Mutasem O.
experimental part, p. 3088 - 3115 (2010/07/08)
β-Secretase (BACE) inhibitors have potential as anti-Alzheimer's disease treatments prompting us to explore the pharmacophoric space of 129 known BACE inhibitors. QSAR analysis was employed to select optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of explaining bioactivity variation (r2 = 0.88, F = 60.48, rLOO2 = 0.85, rPRESS2 against 25 external test inhibitors = 0.71). We were obliged to use ligand efficiency as the response variable because the logarithmic transformation of bioactivities failed to access self-consistent QSAR models. Three pharmacophoric models emerged in the successful QSAR equation suggesting at least three binding modes accessible to ligands within BACE binding pocket. QSAR equation and pharmacophoric models were validated through ROC curves and were employed to guide synthesis of novel pyridinium-based BACE inhibitors. The best inhibitor illustrated an IC50 value of 1.0 μM against BACE.
The use of formamidine protection for the derivatization of aminobenzoic acids
Zhichkin, Paul E.,Peterson, Lisa H.,Beer, Catherine M.,Rennells, W. Martin
supporting information; experimental part, p. 8954 - 8959 (2009/04/11)
(Chemical Equation Presented) N,N-Dimethylformamidine and novel N,N-diisopropylformamidine protecting groups were used to carry out a one-pot conversion of aminobenzoic acids into the corresponding amides. General conditions for an in situ transformation of aminobenzoic acids and their heterocyclic analogues into the corresponding formamidine-protected acid chlorides were developed. These chlorides were used in reactions with amines, including poorly reactive anilines. The protected amides were then smoothly deprotected by heating with ethylenediamine derivatives, resulting in a general procedure for the one-pot transformation of aminobenzoic acids into their amides. Our one-pot procedure was successfully applied to the preparation of several compounds of pharmaceutical interest.
