Potential Anxiolytic Agents. Part 4: Novel Orally-Active N 5-Substituted Pyrido [1, 2-a] benzimidazoles with High GABA-A Receptor Affinity

…, B Dubinsky, CP Kordik, PJ Sanfilippo, WN Wu…

Index: Jordan, Alfonzo D; Vaidya, Anil H; Rosenthal, Daniel I; Dubinsky, Barry; Kordik, Cheryl P; Sanfilippo, Pauline J; Wu, Wu-Nan; Reitz, Allen B Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 17 p. 2381 - 2386

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Citation Number: 34

Abstract

A series of pyrido [1, 2-a] benzimidazoles (PBIs) with substitution on the N5-nitrogen has been synthesized and found to possess high affinity for the benzodiazepine (BZD) site on the GABA-A receptor. The compounds evaluated include those bearing a heteroalkyl group and heterocyclic rings. The most promising of these compounds is ethoxymethyl analogue 24, which has an IC50 of 0.1 nM for the BZD site on the GABA-A receptor and has been ...