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

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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