SUBSTRATE RELATED O,O-DIALKYLDIPEPTIDYLY ψ CARBOXYBENZYLPHOSPHONATES, A NEW TYPE OF THROMBIN INHIBITOR

Donovan Green Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London, SW3 6LR, U.K.; University of North London, School of biological and applied Sciences, Faculty of Science, Computing and Engineering, 166-220 Holloway Road, London, N7 8DB, UK

Said Elgendy Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London, SW3 6LR, U.K.

Geeta Patel Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London, SW3 6LR, U.K.

Emmanuel Skordalakes Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London, SW3 6LR, U.K.

Christopher A. Goodwin Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London, SW3 6LR, U.K.

Micheal F. Scully Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London, SW3 6LR, U.K.

Vijay V. Kakkar Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London, SW3 6LR, U.K.

John J. Deadman Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London, SW3 6LR, U.K.

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Abstract

O,O-Dialkyl α-hydroxybenzylphosphonates (1) were coupled to substrate derived dipeptides (2). using an active ester methodology approach to generate a series of phosphonotripeptides (3) with a carboxy ester linkage between the “P1” and “P2” positions of the molecule. These compounds inhibit thrombin in the micromolar range.

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SUBSTRATE RELATED O,O-DIALKYLDIPEPTIDYLY ψ CARBOXYBENZYLPHOSPHONATES, A NEW TYPE OF THROMBIN INHIBITOR

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SUBSTRATE RELATED O,O-DIALKYLDIPEPTIDYLY ψ CARBOXYBENZYLPHOSPHONATES, A NEW TYPE OF THROMBIN INHIBITOR

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