A facile synthetic route to diazepinone derivatives via ring closing metathesis and its application for human cytidine deaminase inhibitors

Chem Commun (Camb). 2012 Dec 4;48(93):11443-5. doi: 10.1039/c2cc35484e. Epub 2012 Oct 19.

Abstract

A variety of diazepinone derivatives were prepared from α-amino acids and amino alcohols by a new synthetic methodology based on ring closing metathesis as a key step. The diazepinones were coupled with ribose derivatives to afford novel diazepinone nucleosides. Among them, (4R)-1-ribosyl-4-methyl-3,4-dihydro-1H-1,3-diazepin-2(7H)-one (3) showed a potent inhibitory effect (K(i) = 145.97 ± 4.87 nM) against human cytidine deaminase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azepines / chemical synthesis*
  • Azepines / chemistry
  • Azepines / pharmacology*
  • Chemistry Techniques, Synthetic
  • Cytidine Deaminase / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans

Substances

  • Azepines
  • Enzyme Inhibitors
  • Cytidine Deaminase