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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology
  • Binding, Competitive
  • Biological Availability
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Molecular Structure
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Protein Binding / drug effects
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors*

Substances

  • Amides
  • Enzyme Inhibitors
  • Naphthalenes
  • Sulfonamides
  • Urokinase-Type Plasminogen Activator