Abstract
Recent drug discovery programs targeting urokinase plasminogen activator (uPA) have resulted in nonpeptidic inhibitors consisting of amidine or guanidine functional groups attached to aromatic or heteroaromatic scaffolds. There is a general problem of poor oral bioavailability of these charged inhibitors. In this paper, we report the synthesis and evaluation of a series of naphthamide and naphthalene sulfonamides as uPA inhibitors containing non-basic groups as substitute for amidine or guanidine groups.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry
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Amides / pharmacology
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Binding, Competitive
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Biological Availability
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Hydrogen-Ion Concentration
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Inhibitory Concentration 50
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Molecular Structure
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Naphthalenes / chemical synthesis
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Naphthalenes / chemistry
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Naphthalenes / pharmacology
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Protein Binding / drug effects
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
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Urokinase-Type Plasminogen Activator / antagonists & inhibitors*
Substances
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Amides
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Enzyme Inhibitors
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Naphthalenes
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Sulfonamides
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Urokinase-Type Plasminogen Activator