Structure–Pharmacokinetic Relationships in a Series of Valpromide Derivatives with Antiepileptic Activity

  title={Structure–Pharmacokinetic Relationships in a Series of Valpromide Derivatives with Antiepileptic Activity},
  author={Abdullah I. Haj-Yehia and Meir Bialer},
  journal={Pharmaceutical Research},
The following valpromide (VPD) derivatives were synthesized and their structure–pharmacokinetic relationships explored: ethylbutylacetamide (EBD), methylpentylacetamide (MPD), propylisopropylacetamide (PID), and propylallylacetamide (PAD). In addition, the anticonvulsant activity of these compounds was evaluated and compared to that of VPD, valnoctamide (VCD), and valproic acid (VPA). MPD, the least-branched compound had the largest clearance and shortest half-life of all the amides… 

Pharmacokinetic Analysis of the Structural Requirements for Forming “Stable” Analogues of Valpromide

The antiepileptic potential of stable VPD analogues which may be more potent and less teratogenic than their biotransformed isomers are discussed.

Can we develop improved derivatives of valproic acid?

2-n-propyl-2-pentenoatc and/or a valpromide isomer, which does not undergo amide acid biotransformation and preferably is not an epoxide hydrolase inhibitor, may prove to be improved derivatives of the parent compound valproic acid.

2D and 3D QSAR Analysis of Some Valproic Acid Metabolites and Analogues as Anticonvulsant Agents

It was established that the two approaches—2D and 3D QSAR, prove the importance of the lipophilicity of the compounds foranticonvulsant activity and the results from both the approaches suggest that a substitution at α-position is essential for a higher activity.

Stereoselective Pharmacokinetics and Pharmacodynamics of Propylisopropyl Acetamide, a CNS-Active Chiral Amide Analog of Valproic Acid

R-PID demonstrated better anticonvulsant activity, lower clearance and a longer half-life compared to (S)-PID, and mEH inhibition studies were performed in human liver microsomes, and teratogenicity was evaluated in an inbred susceptible mice strain.

Synthesis and evaluation of antiallodynic and anticonvulsant activity of novel amide and urea derivatives of valproic acid analogues.

A number of VPA analogues and their amide, N-methylamide and urea derivatives, were synthesized and evaluated in animal models of neuropathic pain and epilepsy and indicate strong potential for the above-mentioned novel compounds as candidates for future drug development for the treatment of Neuropathic pain.

Chemical properties of antiepileptic drugs (AEDs).

  • M. Bialer
  • Biology
    Advanced drug delivery reviews
  • 2012

Synthesis and Pharmacological Activity of Two Derivatives of the Amide of Valproic Acid

Two new compounds obtained from VPA are less toxic and more effective in protecting the animals from death caused by PTZ than VPD after intraperitoneal administration to mice.

Valproic acid: Second generation

Potent anticonvulsant urea derivatives of constitutional isomers of valproic acid.

The broad spectrum of anticonvulsant activity of the urea derivatives coupled with their wide safety margin make them potential candidates to become new, potent AEDs.