Design and optimization of antiepileptic drugs

Epilepsy is a group of chronic neurological disorders that are characterized by recurrent unprovoked seizures. There is a need to discover new drugs and a need to improve the design strategies for these drugs. This thesis has addressed this need, achieving the following: (1) Addressing the issue of toxicity, a class of new chemical entities, dioxapiperazines, which are endogenous compounds, has been developed as novel anticonvulsants. Fifteen representative analogues were synthesized and biologically tested. (2) The structure-activity properties of the dioxapiperazines as compared to phenytoin and carbamazepine were evaluated using a comprehensive series of molecular mechanics calculations. (3) Based upon the review of the literature, it is suggested that the dioxapiperazines may have utility in the treatment of either canine or human epilepsy. (4) Pioneering experiments towards developing an innovative way of inactivating pharmaceuticals before they can exert environmental toxicity were completed. Preliminary data are presented and future directions are discussed.