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Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).

ABSTRACT: Human African trypanosomiasis (HAT) is a parasitic neglected tropical disease that affects 10,000 patients each year. Current treatments are sub-optimal, and the disease is fatal if not treated. Herein, we report our continuing efforts to repurpose the human phosphodiesterase 4 (hPDE4) inhibitor piclamilast to target trypanosomal phosphodiesterase TbrPDEB1. We prepared a range of substituted heterocyclic replacements for the 4-amino-3,5-dichloro-pyridine headgroup of piclamilast, and found that these compounds exhibited weak inhibitory activity of TbrPDEB1.

SUBMITTER: Woodring JL

PROVIDER: S-EPMC3825250 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).

Woodring Jennifer L JL Bland Nicholas D ND Ochiana Stefan O SO Campbell Robert K RK Pollastri Michael P MP

Bioorganic & medicinal chemistry letters 20130821 21

Human African trypanosomiasis (HAT) is a parasitic neglected tropical disease that affects 10,000 patients each year. Current treatments are sub-optimal, and the disease is fatal if not treated. Herein, we report our continuing efforts to repurpose the human phosphodiesterase 4 (hPDE4) inhibitor piclamilast to target trypanosomal phosphodiesterase TbrPDEB1. We prepared a range of substituted heterocyclic replacements for the 4-amino-3,5-dichloro-pyridine headgroup of piclamilast, and found that ...[more]

PMID: 24042005

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