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Utilization of the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide scaffold in the design of potential inhibitors of human neutrophil proteinase 3.

ABSTRACT: The S' subsites of human neutrophil proteinase 3 (Pr 3) were probed by constructing diverse libraries of compounds based on the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide using combinational and click chemistry methods. The multiple points of diversity embodied in the heterocyclic scaffold render it well-suited to the exploration of the S' subsites of Pr 3. Molecular modeling studies suggest that further exploration of the S' subsites of Pr 3 using the aforementioned heterocyclic scaffold may lead to the identification of highly selective, reversible competitive inhibitors of Pr 3.

SUBMITTER: Dou D

PROVIDER: S-EPMC2853038 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Utilization of the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide scaffold in the design of potential inhibitors of human neutrophil proteinase 3.

Dou Dengfeng D He Guijia G Li Yi Y Lai Zhong Z Wei Liuqing L Alliston Kevin R KR Lushington Gerald H GH Eichhorn David M DM Groutas William C WC

Bioorganic & medicinal chemistry 20091229 3

The S' subsites of human neutrophil proteinase 3 (Pr 3) were probed by constructing diverse libraries of compounds based on the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide using combinational and click chemistry methods. The multiple points of diversity embodied in the heterocyclic scaffold render it well-suited to the exploration of the S' subsites of Pr 3. Molecular modeling studies suggest that further exploration of the S' subsites of Pr 3 using the aforementioned heterocyclic scaffold may lea ...[more]

PMID: 20061159

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