The Preparation of Two, Preclinical Amino-quinazolinediones as Antibacterial Agents

Autor:	and Roger V. Parlett, Derek Vrieze, Timothy T. Curran, David C. Boyles, Vladimir Beylin, Dainius Macikenas
Rok vydání:	2007
Předmět:	medicine.drug_class Hydrochloride Organic Chemistry Combinatorial chemistry chemistry.chemical_compound chemistry Nucleophilic aromatic substitution Electrophilic amination Intramolecular force medicine Michael reaction Lactam Side chain Physical and Theoretical Chemistry Topoisomerase inhibitor
Zdroj:	Organic Process Research & Development. 11:441-449
ISSN:	1520-586X 1083-6160
Popis:	This paper describes the synthesis of two amino-quinazolinediones which are potent gyrase/topoisomerase inhibitors and useful as antibacterial agents. The early scale-up work to prepare a chiral side chain on multigram scale and two different amino-quinazolinedione cores is detailed. The enabling synthesis for the side chain employed a previously reported Michael addition of MeNO2 to an enantiomerically enriched δ-amino-enoate and a two-step de-oxygenation of a lactam. Key synthetic steps for core preparation and completion of the amino-quinazolinediones include dianion-promoted cyclization via intramolecular, nucleophilic aromatic substitution, electrophilic amination, nucleophilic aromatic substitution of the side chain to the core, deprotection and isolation of the hydrochloride salt in acceptable yield.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::ea5d3fe864e55136ee5117a27bc2c754 https://doi.org/10.1021/op7000639 Zobrazit plný text záznamu