Calmodulin inhibitory activity of the malbrancheamides and various analogs

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6479-81. doi: 10.1016/j.bmcl.2008.10.057. Epub 2008 Oct 17.

Abstract

The preparation and biological activity of various structural analogs of the malbrancheamides are disclosed. The impact of indole chlorination, C-12a relative stereochemistry, and bicyclo[2.2.2]diazaoctane core oxidation state on the ability of these analogs to inhibit calmodulin dependent phosphodiesterase (PDE1) was studied, and a number of potent compounds were identified.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Calmodulin / antagonists & inhibitors*
  • Calmodulin / chemistry*
  • Chlorine / chemistry
  • Chlorpromazine / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 1 / chemistry
  • Drug Design
  • Humans
  • Indole Alkaloids / chemical synthesis*
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / pharmacology*
  • Indoles / chemistry
  • Inhibitory Concentration 50
  • Models, Chemical
  • Oxygen / chemistry
  • Stereoisomerism

Substances

  • Alkaloids
  • Calmodulin
  • Indole Alkaloids
  • Indoles
  • malbrancheamide
  • Chlorine
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • Oxygen
  • Chlorpromazine