Synthesis and evaluation of non-basic inhibitors of urokinase-type plasminogen activator (uPA).

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Venkatraj M, Messagie J, Joossens J, Lambeir AM, Haemers A, Van der Veken P, Augustyns K

Synthesis and evaluation of non-basic inhibitors of urokinase-type plasminogen activator (uPA).

Bioorg Med Chem. 2012 Feb 15;20(4):1557-68. doi: 10.1016/j.bmc.2011.12.040. Epub 2011 Dec 27.

PubMed ID

22285569 [ View in PubMed

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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.

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)	631	N/A	N/A	Details
6-(N-Phenylcarbamyl)-2-Naphthalenecarboxamidine	Urokinase-type plasminogen activator	IC 50 (nM)	13000	N/A	N/A	Details
6-(N-Phenylcarbamyl)-2-Naphthalenecarboxamidine	Urokinase-type plasminogen activator	Ki (nM)	1900	N/A	N/A	Details
6-[N-(4-(Aminomethyl)Phenyl)Carbamyl]-2-Naphthalenecarboxamidine	Urokinase-type plasminogen activator	Ki (nM)	40	N/A	N/A	Details
6-[N-(4-(Aminomethyl)Phenyl)Carbamyl]-2-Naphthalenecarboxamidine	Urokinase-type plasminogen activator	IC 50 (nM)	1200	N/A	N/A	Details