Synthesis and structure-activity relationships of retro bis-aminopyrrolidine urea (rAPU) derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Part 2

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4922-30. doi: 10.1016/j.bmcl.2006.06.049. Epub 2006 Jul 7.

Abstract

The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited considerable binding affinity (Ki = 1 nM) and functional activity at MCH-R1, acceptable CYP2D6 inhibition, and good rat brain exposure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Inhibitory Concentration 50
  • Molecular Structure
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacokinetics
  • Pyrrolidines / pharmacology*
  • Rats
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Receptors, Somatostatin / metabolism
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis
  • Urea / chemistry
  • Urea / pharmacokinetics
  • Urea / pharmacology

Substances

  • MCHR1 protein, rat
  • Pyrrolidines
  • Receptors, Somatostatin
  • bis-aminopyrrolidine urea
  • Urea