Improving the inhibitory activity of arylidenaminoguanidine compounds at the N-methyl-D-aspartate receptor complex from a recursive computational-experimental structure-activity relationship study.

Using a combination of both the partial least squares (PLS) and back-propagation artificial neural network (ANN) pattern recognition methods, several models have been developed to predict the activity of a series of arylidenaminoguanidine analogs as inhibitory modulators of the N-methyl-D-aspartate receptor complex. This was done by correlating structural and physicochemical descriptors obtained from computation software with the experimentally observed [(3)H]MK-801 displacement ability of a small library of synthesized and in vitro screened arylidenaminoguanidines. Results for the generated PLS model were r(2)=0.814, rmsd=0.208, rCV(2)=0.714, loormsd=0.261. The ANN model was created utilizing the eleven descriptors from the PLS model for comparison. The quality of the ANN model (r(2)=0.828, rmsd=0.200, rCV(2)=0.721, loormsd=0.257) is similar to the PLS model, and indicates that the feature between the inputs and the output is majorly linear. These computational models were able to predict inhibition of the NMDA receptor complex by this series of compounds in silico, affording a predictive structure-based 'pre-screening' paradigm for the arylideneaminoguanidine analogs.

(4-Methoxy-3-nitrobenzylideneamino)guanidinium chloride.

In the title compound, C(9)H(12)N(5)O(3)(+) x Cl(-), the cation is almost entirely planar. The imine double bond is exclusively in the E geometry.

Novel antiepileptic and anticonvulsive therapeutic agents.

Epilepsy is a broad-reaching central nervous system condition and the underlying pathology suggests a number of pharmacological pathways that can be targeted for drug therapy. These include ion channel modulation, historically the most investigated therapeutic approach, as well as regulation of excitatory and inhibitory neurotransmission. A broad range of drugs that act at each of these targets has been marketed, and promising new drug candidates are being developed constantly. In addition, new drug candidates with novel mechanisms of action are beginning to emerge. This review covers patent literature with the indication for epilepsy between January 2001 and March 2002, and includes brief overviews and backgrounds on currently used anti-epileptic and anticonvulsive drugs.