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.
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.
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Italy.
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G
Costantino
K
K
Maltoni
M
M
Marinozzi
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E
Camaioni
L
L
Prezeau
J P
JP
Pin
R
R
Pellicciari
D002460:Cell Line; D005973:Glutamine / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007295:Inositol Phosphates / Q000096:biosynthesis; D008958:Models, Molecular; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000494:pharmacology*
C431766:2-(3'-(1H-tetrazol-5-yl) bicyclo(1.1.1)pent-1-yl)glycine; D007295:Inositol Phosphates; D018094:Receptors, Metabotropic Glutamate; D013777:Tetrazoles; C104077:metabotropic glutamate receptor type 1; D005973:Glutamine; C073649:(tetrazol-5-yl)glycine; D005998:Glycine