Synthesis and biological evaluation of 2-(3'-(1H-tetrazol-5-yl) bicyclo[1.1.1]pent-1-yl)glycine (S-TBPG), a novel mGlu1 receptor antagonist

Bioorg Med Chem. 2001 Feb;9(2):221-7. doi: 10.1016/s0968-0896(00)00270-4.

Abstract

The design and synthesis of 2-(3'-(1H-tetrazol-5-yl)bicyclo[1.1.1]pent-1-yl)glycine (S-TBPG), a novel mGluR1 antagonist is reported. S-TBPG is characterized by the bioisosteric replacement of the distal carboxy group of 2-(3'-carboxybicyclo [1.1.1]pent-1-yl)glycine (S-CBPG) by a tetrazolyl moiety. Despite a moderate reduction in potency, S-TBPG is a selective mGluR1 antagonist (69 microM), with no activity at other mGluR subtypes. The interesting biological profile of S-TBPG, coupled with its peculiar chemical structure, is discussed in terms of the structure activity relationship (SAR) of mGluR1 antagonists.

MeSH terms

  • Cell Line
  • Glutamine / pharmacology
  • Glycine / analogs & derivatives*
  • Glycine / chemical synthesis
  • Glycine / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Inositol Phosphates / biosynthesis
  • Models, Molecular
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / metabolism
  • Structure-Activity Relationship
  • Tetrazoles / chemical synthesis
  • Tetrazoles / pharmacology*

Substances

  • 2-(3'-(1H-tetrazol-5-yl) bicyclo(1.1.1)pent-1-yl)glycine
  • Inositol Phosphates
  • Receptors, Metabotropic Glutamate
  • Tetrazoles
  • metabotropic glutamate receptor type 1
  • Glutamine
  • (tetrazol-5-yl)glycine
  • Glycine