Rapid and efficient synthesis of a novel series of substituted aminobenzosuberone derivatives as potent, selective, non-peptidic neutral aminopeptidase inhibitors

Bioorg Med Chem. 2012 Aug 15;20(16):4942-53. doi: 10.1016/j.bmc.2012.06.041. Epub 2012 Jun 28.

Abstract

Racemic 5-substituted 7-aminobenzocyclohepten-6-one were synthesized and evaluated for their ability to inhibit metalloaminopeptidase activities. Unexpectedly, 5-thio substituted compounds showed enhanced inhibition potency with K(i) values in the nanomolar range against the 'one zinc' aminopeptidases from the M1 family, while most of them were rather poor inhibitors of the 'two zincs' enzymes from the M17 family. This interesting selectivity profile may guide the design of new, specific inhibitors of target mammalian aminopeptidases with one active site zinc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / antagonists & inhibitors*
  • Aminopeptidases / metabolism
  • Animals
  • Anisoles / chemical synthesis
  • Anisoles / chemistry
  • Anisoles / pharmacology*
  • Cycloheptanes / chemical synthesis
  • Cycloheptanes / chemistry
  • Cycloheptanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Kidney / enzymology
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship
  • Swine

Substances

  • Anisoles
  • Cycloheptanes
  • Enzyme Inhibitors
  • amino-benzosuberone
  • Aminopeptidases