Design, synthesis, and preliminary evaluation of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives as potential iNOS inhibitors

Bioorg Med Chem. 2008 Jan 1;16(1):578-85. doi: 10.1016/j.bmc.2007.04.030. Epub 2007 Apr 25.

Abstract

A series of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives were synthesized and evaluated for their abilities to inhibit inducible nitric oxide synthase (iNOS) isoform. All target compounds were prepared in 11 steps from commercially trans-4-hydroxy-L-proline. The preliminary pharmacological test showed that three compounds, 17, 21, and 30, have the good potency (IC(50)=2.36, 2.68, 2.5 microM, respectively) which are compared to the NOS inhibitor N(G)-nitroarginine(L-NNA) (IC(50)=14.74 microM), and could be used as lead compounds for exploring new iNOS inhibitors in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology

Substances

  • Enzyme Inhibitors
  • Pyrrolidines
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II