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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Design and synthesis of hydroxyethylene-based peptidomimetic inhibitors of human beta-secretase.

The hydroxyethylene (HE) transition state isostere was developed as a scaffold to provide potent, small molecule inhibitors of human beta-secretase (BACE). The previous work on the statine series proved critical to the discovery of HE structure-activity relationships. Compound 20 with the N-terminal isophthalamide proved to be the most potent HE inhibitor (IC(50) = 30 nM) toward BACE. Unlike the statine series, we identified HE inhibitors without carboxylic acids on the C terminus, leading to enhanced cell penetration and making them attractive candidates for further drug development in Alzheimer's disease.[1]

References

  1. Design and synthesis of hydroxyethylene-based peptidomimetic inhibitors of human beta-secretase. Hom, R.K., Gailunas, A.F., Mamo, S., Fang, L.Y., Tung, J.S., Walker, D.E., Davis, D., Thorsett, E.D., Jewett, N.E., Moon, J.B., John, V. J. Med. Chem. (2004) [Pubmed]
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