Celontin (methsuximide) / Pfizer - LARVOL DELTA

Nonsilyl bicyclic secondary amine catalyzed Michael addition of nitromethane to β,β-disubstituted α,β-unsaturated aldehydes. (PubMed, Org Biomol Chem) - "The scalability of this methodology was demonstrated at the 5.1 mmol scale. The synthetic utility of this methodology is showcased through the concise asymmetric synthesis of methsuximide, an anticonvulsant drug."

Journal

From barbiturates to ganaxolone: The importance of chirality in drug development and in understanding the actions of old and new antiseizure medications. (PubMed, Pharmacol Ther) - "Out of 37 antiseizure medications (ASMs) currently in the market, 17 are chiral molecules and an additional one (oxcarbazepine) is a prodrug of the chiral compound licarbazepine. Of the 17 chiral ASMs, six (ethosuximide, fenfluramine, methsuximide, mephobarbital, stiripentol and vigabatrin) are marketed as racemates, and the remainder are licensed as enantiomerically pure medicines...We identified a number of critical knowledge gaps that are relevant to the use of chiral drugs in epilepsy, including a remarkable lack of published information on the comparative pharmacokinetics, toxicity and antiseizure activity of the enantiomers of most racemic ASMs. The importance of chirality aspects in understanding the clinical actions of racemic ASMs is discussed, together with the rationale for the development of enantiomerically pure follow-up compounds with potentially improved efficacy, safety and commercial viability."

Journal • Review • CNS Disorders • Epilepsy