Dihydroquinazolines as a Novel Class of Trypanosoma brucei Trypanothione Reductase Inhibitors: Discovery, Synthesis, and Characterization of their Binding Mode by Protein Crystallography

@inproceedings{Patterson2011DihydroquinazolinesAA,
  title={Dihydroquinazolines as a Novel Class of Trypanosoma brucei Trypanothione Reductase Inhibitors: Discovery, Synthesis, and Characterization of their Binding Mode by Protein Crystallography},
  author={Stephen H Patterson and Magnus S. Alphey and Deuan C. Jones and Emma J. Shanks and Ian P. Street and Julie A. Frearson and Paul G Wyatt and Ian H. Gilbert and Alan H. Fairlamb},
  booktitle={Journal of medicinal chemistry},
  year={2011}
}
Trypanothione reductase (TryR) is a genetically validated drug target in the parasite Trypanosoma brucei , the causative agent of human African trypanosomiasis. Here we report the discovery, synthesis, and development of a novel series of TryR inhibitors based on a 3,4-dihydroquinazoline scaffold. In addition, a high resolution crystal structure of TryR, alone and in complex with substrates and inhibitors from this series, is presented. This represents the first report of a high resolution… CONTINUE READING