Merrell Dow Pharmaceuticals

Richardson-merrell Inc.

Jerry L Adams

Brian W Metcalf

Bruce J Lippert

This application relates to 4-amino-4,5-dihydro-2-thiophenecarboxylic acid, the C.sub.1-6 alkyl esters thereof and to their use in the treatment of epilepsy.

.alpha.-Aminobutyric acid transaminase inhibitors

5-Amino-4-oxo-pentanoic acids of the formula ##STR1## wherein R is CF.sub.3, CHF.sub.2 or CH.sub.2 F; R.sub.1 is H or akyl of 1-4 carbon atoms; and R.sub.2 is H or alkyl or 1-4 carbon atoms or benzyl, which are intermediates to ACE inhibitors or elastase inhibitors, are produced by reacting a 1-(methylthio)-1-methylsulfinyl)-2-R.sub.1 -ethylmetal with an ester of a 3-R-acrylic acid; optionally R.sub.2 -alkylating the thus-produced ester enolate anion of 4-(methylsulfinyl)-4-(methylthio)-5-R.sub.1 R-pentanoic acid followed by splitting off of methylsulfinic acid; reacting the thus-produced 2-R.sub.2 -5-R.sub.1 -4-(methylthio)-3-R-4-pentenoic acid ester with a source of Br.sup.+ to produce a 5-bromo-substituted acid or ester thereof otherwise corresponding to the desired 5-amino-4-oxo-pentanoic acid; and replacing the bromine atom with an amino group, e.g., via the corresponding 5-azido- and 5-N-acylamino- compounds, with hydrolysis of the ester group, if still remaining.

Growing community of inventors

West Chester, OH, United States of America

Jerry L Adams