Synthesis of 7-alkylidene-7,12-dihydroindolo[3,2-d]benzazepine-6-(5H)-ones (7-alkylidene-paullones) by N-cyclization-oxidative Heck cascade and characterization as sirtuin modulators

Org Biomol Chem. 2015 Mar 7;13(9):2800-10. doi: 10.1039/c4ob02493a.

Abstract

An extension of our reported protocol to benzofused heterocyclic derivatives (benzofurans, indoles, isochromeneimines), involving a palladium-induced cascade of N-cyclization and oxidative Heck reactions of o-alkynylanilines, has allowed the preparation of indolobenzazepinones (paullones) with an alkylidene group at C7 in just 3-4 steps from ortho-iodoanilines. Some of these compounds behave as Sirt1 activators in biochemical assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzazepines / chemical synthesis
  • Benzazepines / chemistry
  • Benzazepines / pharmacology*
  • Cyclization
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Oxidation-Reduction
  • Sirtuin 1 / chemistry
  • Sirtuin 1 / metabolism*
  • Structure-Activity Relationship
  • U937 Cells

Substances

  • Benzazepines
  • Indoles
  • SIRT1 protein, human
  • Sirtuin 1