155202-16-7Relevant academic research and scientific papers
Potential anxiolytic agents. Part 4: Novel orally-active N5-substituted pyrido[1,2-a]benzimidazoles with high GABA-A receptor affinity
Jordan, Alfonzo D,Vaidya, Anil H,Rosenthal, Daniel I,Dubinsky, Barry,Kordik, Cheryl P,Sanfilippo, Pauline J,Wu, Wu-Nan,Reitz, Allen B
, p. 2381 - 2386 (2002)
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 advanced to human clinical trials.
Process research for the synthesis of RWJ-51204, a novel anxiolytic agent
Cohen, Judith H.,Maryanoff, Cynthia A.,Stefanick, Stephen M.,Sorgi, Kirk L.,Villani Jr., Frank J.
, p. 260 - 265 (1999)
RWJ-51204, the lead compound in our pyrido [1,2-α] benzimidazole (PBI) series, was shown to exhibit anxiolytic efficacy in animal models at doses which did not cause central nervous system side effects commonly observed with other anxiolytic agents. To prepare supplies of drug substance for early toxicological and clinical studies, we needed to develop a safe and scaleable synthesis. Our main focus was to improve the last two steps of the process which involved formation of the penultimate carboxamide intermediate followed by alkylation using potentially toxic chloromethyl ethyl ether. Due to safety issues concerning storage and handling of this reagent during the large scale synthesis, we investigated alternate routes to minimize potential exposure risks. The process research carried out for the final steps that led to the safe and cost-effective multi-kilogram synthesis of RWJ-51204 is described herein.
