205701-85-5Relevant articles and documents
5-HETEROATOM-CONTAINING ALKYL SUBSTITUTED-3-OXO-PYRIDO(1,2-a) BENZIMIDAZOLE-4-CARBOXAMIDE DERIVATIVES USEFUL IN TREATING CENTRAL NERVOUS SYSTEM DISORDERS
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Page 11, (2010/02/05)
A compound of the general formula 1; (1) is disclosed as useful in treating disorders of the central nervous system. Pharmaceutical compositions and methods of treatment are also disclosed.
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 (2013/09/08)
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.