Synthesis, molecular modeling and preliminary biological evaluation of 1-amino-3-phosphono-3-cyclopentene-1-carboxylic acid and 1-amino-3-phosphono-2-cyclopentene-1-carboxylic acid, two novel agonists of metabotropic glutamate receptors of group III

L Amori; G Costantino; M Marinozzi; R Pellicciari; F Gasparini; P J Flor; R Kuhn; I Vranesic

doi:10.1016/s0960-894x(00)00247-x

Synthesis, molecular modeling and preliminary biological evaluation of 1-amino-3-phosphono-3-cyclopentene-1-carboxylic acid and 1-amino-3-phosphono-2-cyclopentene-1-carboxylic acid, two novel agonists of metabotropic glutamate receptors of group III

Bioorg Med Chem Lett. 2000 Jul 3;10(13):1447-50. doi: 10.1016/s0960-894x(00)00247-x.

Authors

L Amori¹, G Costantino, M Marinozzi, R Pellicciari, F Gasparini, P J Flor, R Kuhn, I Vranesic

Affiliation

¹ Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Italy.

PMID: 10888329
DOI: 10.1016/s0960-894x(00)00247-x

Abstract

On the basis of a pharmacophore definition of mGlu4 agonists, the two novel semi-rigid derivatives 12 and 13 were designed and synthesized. The preliminary biological evaluation demonstrated that both compounds interact with hmGlu4a, while ineffective at group II receptor subtypes. In particular, derivative 13 is a full hmGlu4a agonist with an EC50 = 17 microM.

MeSH terms

Animals
Biological Assay
CHO Cells
Colforsin / pharmacology
Cricetinae
Cyclopentanes / chemical synthesis*
Excitatory Amino Acid Agonists / chemical synthesis*
Excitatory Amino Acid Agonists / metabolism
Excitatory Amino Acid Agonists / pharmacology
Humans
Molecular Structure
Receptors, Metabotropic Glutamate / agonists*
Receptors, Metabotropic Glutamate / genetics
Receptors, Metabotropic Glutamate / metabolism

Substances

1-amino-3-phosphono-3-cyclopentene-1-carboxylic acid
Cyclopentanes
Excitatory Amino Acid Agonists
Receptors, Metabotropic Glutamate
Colforsin