Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position

Kenneth E. Rittle, James C. Barrow, Kellie J. Cutrona, Kristen L. Glass, Julie A. Krueger, Lawrence C. Kuo, S. Dale Lewis, Bobby J. Lucas, Daniel R. McMasters, Matthew M. Morrissette, Philippe G. Nantermet, Christina L. Newton, William M. Sanders, Youwei Yan, Joseph P. Vacca, Harold G. Selnick

Research output: Contribution to journalArticle

Abstract

Thrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the α-thrombin-hirugen complex provides an explanation for these unanticipated results.

Original languageEnglish (US)
Pages (from-to)3477-3482
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number20
DOIs
StatePublished - Oct 20 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Rittle, K. E., Barrow, J. C., Cutrona, K. J., Glass, K. L., Krueger, J. A., Kuo, L. C., Lewis, S. D., Lucas, B. J., McMasters, D. R., Morrissette, M. M., Nantermet, P. G., Newton, C. L., Sanders, W. M., Yan, Y., Vacca, J. P., & Selnick, H. G. (2003). Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position. Bioorganic and Medicinal Chemistry Letters, 13(20), 3477-3482. https://doi.org/10.1016/S0960-894X(03)00732-7