Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors.
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Wendt MD, Geyer A, McClellan WJ, Rockway TW, Weitzberg M, Zhao X, Mantei R, Stewart K, Nienaber V, Klinghofer V, Giranda VL
Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors.
Bioorg Med Chem Lett. 2004 Jun 21;14(12):3063-8.
- PubMed ID
- 15149645 [ View in PubMed]
- Abstract
Several 8-substituted 2-naphthamidine-based inhibitors of the serine protease urokinase plasminogen activator (uPA) are described. Direct attachment of five-membered saturated or unsaturated rings improved inhibitor performance; substitution with sulfones further improved binding profiles. Combination of these substituents or of previously described NH-linked heteroaromatic rings with 6-phenyl amide substituents provided further enhancements to potency and selectivity.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 6-(N-Phenylcarbamyl)-2-Naphthalenecarboxamidine Urokinase-type plasminogen activator Ki (nM) 630 N/A N/A Details 6-[(Z)-Amino(Imino)Methyl]-N-[4-(Aminomethyl)Phenyl]-4-(Pyrimidin-2-Ylamino)-2-Naphthamide Urokinase-type plasminogen activator Ki (nM) 0.62 N/A N/A Details 7-Methoxy-8-[1-(Methylsulfonyl)-1h-Pyrazol-4-Yl]Naphthalene-2-Carboximidamide Urokinase-type plasminogen activator Ki (nM) 630 N/A N/A Details 8-(Pyrimidin-2-Ylamino)Naphthalene-2-Carboximidamide Urokinase-type plasminogen activator Ki (nM) 35 N/A N/A Details