Design and synthesis of potent and selective macrocyclic thrombin inhibitors

Philippe G. Nantermet; James C. Barrow; Christina L. Newton; Janetta M. Pellicore; Mary Beth Young; S. Dale Lewis; Bobby J. Lucas; Julie A. Krueger; Daniel R. McMasters; Youwei Yan; Lawrence C. Kuo; Joseph P. Vacca; Harold G. Selnick

doi:10.1016/S0960-894X(03)00506-7

Design and synthesis of potent and selective macrocyclic thrombin inhibitors

Philippe G. Nantermet, James C. Barrow, Christina L. Newton, Janetta M. Pellicore, Mary Beth Young, S. Dale Lewis, Bobby J. Lucas, Julie A. Krueger, Daniel R. McMasters, Youwei Yan, Lawrence C. Kuo, Joseph P. Vacca, Harold G. Selnick

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.

Original language	English (US)
Pages (from-to)	2781-2784
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	13
Issue number	16
DOIs	https://doi.org/10.1016/S0960-894X(03)00506-7
State	Published - Aug 18 2003
Externally published	Yes

ASJC Scopus subject areas

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

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10.1016/S0960-894X(03)00506-7

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Nantermet, P. G., Barrow, J. C., Newton, C. L., Pellicore, J. M., Young, M. B., Lewis, S. D., Lucas, B. J., Krueger, J. A., McMasters, D. R., Yan, Y., Kuo, L. C., Vacca, J. P., & Selnick, H. G. (2003). Design and synthesis of potent and selective macrocyclic thrombin inhibitors. Bioorganic and Medicinal Chemistry Letters, 13(16), 2781-2784. https://doi.org/10.1016/S0960-894X(03)00506-7

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abstract = "A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.",

author = "Nantermet, {Philippe G.} and Barrow, {James C.} and Newton, {Christina L.} and Pellicore, {Janetta M.} and Young, {Mary Beth} and Lewis, {S. Dale} and Lucas, {Bobby J.} and Krueger, {Julie A.} and McMasters, {Daniel R.} and Youwei Yan and Kuo, {Lawrence C.} and Vacca, {Joseph P.} and Selnick, {Harold G.}",

year = "2003",

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doi = "10.1016/S0960-894X(03)00506-7",

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T1 - Design and synthesis of potent and selective macrocyclic thrombin inhibitors

AU - Nantermet, Philippe G.

AU - Barrow, James C.

AU - Newton, Christina L.

AU - Pellicore, Janetta M.

AU - Young, Mary Beth

AU - Lewis, S. Dale

AU - Lucas, Bobby J.

AU - Krueger, Julie A.

AU - McMasters, Daniel R.

AU - Yan, Youwei

AU - Kuo, Lawrence C.

AU - Vacca, Joseph P.

AU - Selnick, Harold G.

PY - 2003/8/18

Y1 - 2003/8/18

N2 - A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.

AB - A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.

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U2 - 10.1016/S0960-894X(03)00506-7

DO - 10.1016/S0960-894X(03)00506-7

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AN - SCOPUS:12444322672

SN - 0960-894X

VL - 13

SP - 2781

EP - 2784

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -

Design and synthesis of potent and selective macrocyclic thrombin inhibitors

Abstract

ASJC Scopus subject areas

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