GABA and L-glutamic acid analogs for antiseizure treatment
AssigneesNorthwestern University, Warner-Lambert Company
InventorsRichard B. Silverman, Ryszard Andruszkiewicz, Po-Wai Yuen, Denis M. Sobieray, Lloyd C. Franklin, Mark A. Schwindt
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Abstract
A compound of the formula ##STR1## wherein R.sub.1 is a straight or branched alkyl group having from 1 to 6 carbon atoms, phenyl, or cycloalkyl having from 3 to 6 carbon atoms; R.sub.2 is hydrogen or methyl; and R.sub.3 is hydrogen, methyl or carboxyl; which is useful in the treatment of seizure disorders. Processes are disclosed for the preparation of the compound. Intermediates prepared during the synthesis of the compound are also disclosed.
Claims1
A process for preparing an S-isomer of a compound of the formula
- wherein R.sub.1 is a straight or branched alkyl of from 1 to 6 carbon atoms, phenyl, or cycloalkyl having from 3 to 6 carbon atoms;
- R.sub.2 is hydrogen, methyl, or carboxyl;
- individual enantiomers thereof;
- and pharmaceutically acceptable salts thereof;
- with the proviso that when R.sub.2 is hydrogen, R.sub.1 is other than methyl;
- said process comprising the steps of forming an acid chloride of an acid of the formula HOC(.dbd.O)CH(R.sub.1)(R.sub.2), the corresponding acid chloride having the formula ClC(.dbd.O)CH(R.sub.1)(R.sub.2), adding the acid chloride to a solution of (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone and n-butyllithium at -78.degree. C. under argon to produce an oxazolidinone derivative of the formula ##STR9## treating the oxazolidinone (II) with benzyl .alpha.-bromoacetate to produce an ester ##STR10## treating the ester (III) with hydrogen peroxide and lithium oxide followed by treatment with sodium metabisulfite to produce a compound of the formula ##STR11## treating the compound (IV) with borane dimethyl sulfide complex to produce the compound ##STR12## forming the corresponding tosylate from the compound (V), forming an azide from the corresponding tosoylate and reducing the azide to the amine of the formula ##STR13## wherein R.sub.1 and R.sub.2 have the meanings defined for formula (I), Ph is phenyl, Me is methyl, and Bn is benzyl.
Dependencies are inferred from the claim text.