3,3-Dialkyl- and 3-alkyl-3-benzyl-substituted 2-pyrrolidinones: A new class of anticonvulsant agents

P. Amruta Reddy, Bonnie C.H. Hsiang, Tammy N. Latifi, Matthew W. Hill, Karen E. Woodward, Steven M. Rothman, James A. Ferrendelli, Douglas F. Covey

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

A series of 3,3-dialkyl- and 3-alkyl-3-benzyl-substituted 2- pyrrolidinones (lactams) have been prepared and evaluated for their anticonvulsant activities. In the pentylenetetrazole mouse seizure model, 3,3-diethyl lactam 7c and 3-benzyl-3-ethyl lactam 7j are the most effective anticonvulsants (ED50 = 46 and 42 mg/kg, respectively) and have protective index (PI = TD50/ED50) values of 5.65 and 3.00, respectively. These protective index values compare favorably to those of the clinically used antiepileptic drugs ethosuximide (ED50 = 161 mg/kg), phenobarbital (ED50 = 22 mg/kg), and valproic acid (ED50 = 133 mg/kg), which have PI values of 2.35, 4.00, and 2.12, respectively. The benzyl compounds [3-substituents are Bn, H (7h); Bn, Me (7i); and Bn, Et (7j)] are also very effective anticonvulsants against seizures induced by maximal electroshock (ED50 = 41, 55, and 74 mg/kg, respectively) and have PI values of 3.51, 3.04, and 1.70, respectively. The corresponding PI values for phenobarbital and valproic acid are 1.37 and 5.18, respectively. As a class of anticonvulsants, the 3,3-disubstituted 2-pyrrolidinones have a broad spectrum of action and may be useful for the treatment of human epilepsies.

Original languageEnglish
Pages (from-to)1898-1906
Number of pages9
JournalJournal of Medicinal Chemistry
Volume39
Issue number9
DOIs
StatePublished - Apr 26 1996

Fingerprint

Dive into the research topics of '3,3-Dialkyl- and 3-alkyl-3-benzyl-substituted 2-pyrrolidinones: A new class of anticonvulsant agents'. Together they form a unique fingerprint.

Cite this