QSAR of the Anticonvulsant Enaminones; Molecular Modeling Aspects and other Assessments

Abstract

The enaminones represent potentially useful agents for the clinical treatment in generalized tonic-clonic seizures (Epilepsia, 1993, 34(6), 1141-1145, Biopharm. Drug Disp. 2003, 397-407). A regression analysis was performed to provide a quantitative structure-activity relationship (QSAR) correlation model for prediction of activity for the anticonvulsant enaminones. Molecular modeling was performed to determine the molecular confluence of the Unverferth model (J. Med. Chem. 1998, 41, 63-73) to the enaminones. Conclusions related to the sodium channel model were assessed.

Enaminones 8: CoMFA and CoMSIA studies on some anticonvulsant enaminones

“…Previously, we reported on the correlation between CLog P and the anticonvulsant activity of our enaminone derivatives. It is known that the lipophilicity of various compounds is associated with the biological activity 18. Thus, the numerical data used in this study to develop the CoMFA and CoMSIA models were the CLog P values for each molecule 8,21.…”

Enaminones: Exploring Additional Therapeutic Activities

“…The anticonvulsants phenytoin and carbamazepine prolong the inactive state of the VGSCs, and more recently, lamotrigine, zonisamide, and rufinamide have appeared and their modes of action suggest an involvement of sodium channel blockade 33. In our studies on the anticonvulsant activity of the enaminones6, 7, 14, 34–44 we found that they act as inhibitors of the VGSCs 31, 38. In our work on analogues of the classic pharmacophore, 35 , it was noted that anticonvulsant activity was maintained when R = H, CH 3 , C 2 H 5 , or C(CH 3 ) 3 and when X = + σ 35.…”

Synthesis and Anticonvulsant Activity of Amino Acid-Derived Sulfamides

“…1 H NMR (CDCl 3 ) δ 5.26 (d broad, J ≈ 7.0 Hz, 2H, NH), 4.10 (m, 2H, CH), 3.77 (s, 6H, O-CH 3 ), 1.45 (d, J ) 7.1 Hz, 6H, CH 3 ). 13…”

“…However, the use of rational methodologies of design that need the knowledge of the mechanism of action of the active compounds is limited because most of the AEDs interact with more than one receptor. The alternative rational design of new AEDs based on pharmacophoric patterns overcome this difficulty as it works on the optimization of the potency of a particular mode of action and is therefore broadly used in the discovery of new chemical entities. − …”

“…The alternative rational design of new AEDs based on pharmacophoric patterns overcome this difficulty as it works on the optimization of the potency of a particular mode of action and is therefore broadly used in the discovery of new chemical entities. [10][11][12][13][14][15] Recent research in our group has analyzed aryl and alkyl sulfamides as new targets of antiepileptic drugs. 16,17 The structures were chosen as potentially active as they comply with the requirements imposed by a pharmacophore for the activity in the maximal electroshock (MES) test, 18 one of the most popular seizure models, usually used together with the subcutaneous pentylenetetrazol (PTZ) test.…”