Pharmacokinetic analysis of the structural requirements for forming "stable" analogues of valpromide.

摘要: The following valpromide (VPD) analogues were synthesized and their structure-pharmacokinetic relationships explored: 3-ethyl pentanamide (EPD), methylneopentylacetamide (MND), 1-methyl cyclohexanecarboxamide (MCD), cycloheptanecarboxamide (CHD), t-butylacetamide (TBD). Two aliphatic (EPD MND) two cyclic amides (MCD CHD) underwent complete or partial conversion to corresponding acids. only amide found in this study be “stable” the amide-acid biotransformation was TBD. It also had lowest clearance longest half-life mean residence time. Unlike other investigated amides, TBD contained substitutions of methyl moieties at β position its chemical structure. A analogue must have either position, such as case TBD, a substitution α positions, VPD isomer valnoctamide (VCD). This paper discusses antiepileptic potential stable which may more potent less teratogenic than biotransformed isomers.