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Synthesis of Constrained Heterocycles Employing Two Post-Ugi Cyclization Methods for Rapid Library Generation with In Cellulo Activity.

ABSTRACT: Benzimidazoles and quinoxalinones are present in the core of many pharmacologically relevant compounds. Several combinatorial methods have been developed to attach ring systems to both scaffolds for derivatization at select positions. Herein, we describe the development of novel constrained heterocyclic compounds attached to the N1 position of both benzimidazole and quinoxalinone scaffolds. Utilizing robust post-Ugi cyclization methods, including the Ugi-deprotection-cyclization (UDC) methodology, allows for efficient access to a new area of chemical space. Additionally, molecular modeling and in cellulo screening was employed to therapeutically validate the compounds formed with this method.

SUBMITTER: McConnell N

PROVIDER: S-EPMC6103208 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Synthesis of Constrained Heterocycles Employing Two Post-Ugi Cyclization Methods for Rapid Library Generation with In Cellulo Activity.

McConnell Nicholas N Xu Zhigang Z Kumarasamy Vishnu V Sun Daekyu D Frett Brendan B Li Hong-Yu HY

ChemistrySelect 20171219 35

Benzimidazoles and quinoxalinones are present in the core of many pharmacologically relevant compounds. Several combinatorial methods have been developed to attach ring systems to both scaffolds for derivatization at select positions. Herein, we describe the development of novel constrained heterocyclic compounds attached to the N1 position of both benzimidazole and quinoxalinone scaffolds. Utilizing robust post-Ugi cyclization methods, including the Ugi-deprotection-cyclization (UDC) methodolog ...[more]

PMID: 30140731

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