2-Amidino analogs of glycine-amiloride conjugates: Inhibitors of urokinase-type plasminogen activator

Archna P. Massey; William R. Harley; Nagarekha Pasupuleti; Fredric A. Gorin; Michael H Nantz

doi:10.1016/j.bmcl.2011.12.123

2-Amidino analogs of glycine-amiloride conjugates: Inhibitors of urokinase-type plasminogen activator

Archna P. Massey, William R. Harley, Nagarekha Pasupuleti, Fredric A. Gorin, Michael H Nantz

Neurology

Research output: Contribution to journal › Article

4 Scopus citations

Abstract

The relative non-toxicity of the diuretic amiloride, coupled with its selective inhibition of the protease urokinase plasminogen activator (uPA), makes this compound class attractive for structure-activity studies. Herein we substituted the C(2)-acylguanidine of C(5)-glycyl-amiloride with amidine and amidoxime groups. The data show the importance of maintaining C(5)-hydrophobicity. The C(5)-benzylglycine analogs containing either C(2)-acylguanidine or amidine inhibited uPA with an IC ₅₀ ranging from 3 to 7 μM and were cytotoxic to human U87 malignant glioma cells.

Original language	English (US)
Pages (from-to)	2635-2639
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2011.12.123
State	Published - Apr 1 2012

Keywords

Lactate dehydrogenase
Plasminogen activator inhibitor protein-1
Tissue plasminogen activator
Urokinase-type plasminogen activator
Urokinase-type plasminogen activator receptor

ASJC Scopus subject areas

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

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Massey, A. P., Harley, W. R., Pasupuleti, N., Gorin, F. A., & Nantz, M. H. (2012). 2-Amidino analogs of glycine-amiloride conjugates: Inhibitors of urokinase-type plasminogen activator. Bioorganic and Medicinal Chemistry Letters, 22(7), 2635-2639. https://doi.org/10.1016/j.bmcl.2011.12.123

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