Synthesis of boronic acid analogs of L-arginine as alternate substrates or inhibitors of nitric oxide synthase

Bioorg Med Chem Lett. 1998 Sep 22;8(18):2573-6. doi: 10.1016/s0960-894x(98)00455-7.

Abstract

The asymmetric synthesis of an unprotected alpha-amino boronic acid analog of L-arginine 1a (boroarg-OH. 2 HCl) and its N alpha-acetyl derivative 1b (Ac-boroarg-OH. HCl) is described. These compounds were evaluated as substrates and inhibitors of recombinant nitric oxide synthases (NOS). Boroarg-OH 1a selectively inhibited inducible NOS (IC50 = 50 microM) compared to the neuronal isoform (IC50 = 300 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Boronic Acids*
  • Citrulline / metabolism
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Models, Chemical
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / metabolism*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism

Substances

  • Boronic Acids
  • Enzyme Inhibitors
  • Recombinant Proteins
  • Citrulline
  • Arginine
  • Nitric Oxide Synthase