A method for parallel solid-phase synthesis of iodinated analogues of the CB1 receptor inverse agonist rimonabant

Org Lett. 2009 Oct 15;11(20):4760-3. doi: 10.1021/ol902038y.

Abstract

A method for the parallel solid-phase synthesis (SPS) of iodinated analogues of Sanofi-Aventis' type 1 cannabinoid (CB1) receptor inverse agonist rimonabant (acomplia) has been developed. The method allows the synthesis of a range of C3 amide/hydrazide derivatives from a resin-bound C3 ester precursor. The C-Ge linkage to the Hypogel-200 resin is stable to the diversification conditions but allows ipso-iododegermylative cleavage using NaI/NCS even for the products containing the oxidatively labile hydrazide moiety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Inverse Agonism*
  • Halogenation*
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Receptor, Cannabinoid, CB1 / agonists*
  • Rimonabant
  • Structure-Activity Relationship

Substances

  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Rimonabant