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