Bioorganic & Medicinal Chemistry Letters 2004-06-21

Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines.

Christopher G Barber, Roger P Dickinson, Paul V Fish

Index: Bioorg. Med. Chem. Lett. 14 , 3227-3230, (2004)

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Abstract

A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA with selectivity over tPA and plasmin. Potency is enhanced by the presence of a 4-halo and a 7-aryl substituent, particularly when substituted by a 3-carboxylic acid group. Compound 13j (UK-356,202) combines excellent potency and selectivity, and has been selected as a candidate for clinical evaluation.