Novel, selective indole-based ECE inhibitors: lead optimization via solid-phase and classical synthesis

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4201-5. doi: 10.1016/j.bmcl.2005.06.085.

Abstract

A novel class of indole-based endothelin-converting enzyme (ECE) inhibitors was identified by high throughput screening. We report systematic optimization of this compound class by means of classical and solid-phase chemistry. Optimized compounds with a bisarylamide side chain at the 2-position of the indole skeleton exhibit low-nanomolar activity on ECE.

MeSH terms

  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Combinatorial Chemistry Techniques
  • Drug Evaluation, Preclinical / methods
  • Endothelin-Converting Enzymes
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Metalloendopeptidases / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Indoles
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • Endothelin-Converting Enzymes