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

doi:10.1016/S0960-894X(03)00732-7

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 journal › Article › peer-review

25 Scopus citations

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 language	English (US)
Pages (from-to)	3477-3482
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	13
Issue number	20
DOIs	https://doi.org/10.1016/S0960-894X(03)00732-7
State	Published - Oct 20 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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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

Rittle, KE, Barrow, JC, Cutrona, KJ, Glass, KL, Krueger, JA, Kuo, LC, Lewis, SD, Lucas, BJ, McMasters, DR, Morrissette, MM, Nantermet, PG, Newton, CL, Sanders, WM, Yan, Y, Vacca, JP & Selnick, HG 2003, 'Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position', Bioorganic and Medicinal Chemistry Letters, vol. 13, no. 20, pp. 3477-3482. https://doi.org/10.1016/S0960-894X(03)00732-7

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title = "Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position",

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.",

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

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AU - Rittle, Kenneth E.

AU - Barrow, James C.

AU - Cutrona, Kellie J.

AU - Glass, Kristen L.

AU - Krueger, Julie A.

AU - Kuo, Lawrence C.

AU - Lewis, S. Dale

AU - Lucas, Bobby J.

AU - McMasters, Daniel R.

AU - Morrissette, Matthew M.

AU - Nantermet, Philippe G.

AU - Newton, Christina L.

AU - Sanders, William M.

AU - Yan, Youwei

AU - Vacca, Joseph P.

AU - Selnick, Harold G.

PY - 2003/10/20

Y1 - 2003/10/20

N2 - 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.

AB - 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.

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JF - Bioorganic and Medicinal Chemistry Letters

IS - 20

ER -

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

Abstract

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