Definition of a pharmacophore for the metabotropic glutamate receptors negatively linked to adenylyl cyclase

(2S,3S,4S)-α-Carboxycyclopropylglycine (l-CCG I) and trans-1-amino-(1S,3R)-cyclopentanedicarboxylic acid ((1S,3R)-ACPD), partially constrained l-glutamate analogs known to be agonists at the metabotropic glutamate receptors (mGluRs) adenylyl cyclase coupled, have been submitted to conformational analysis and the data obtained utilized to define a pharmacophore which takes into account the location of hydrogen bonding donating sites of the receptor. This pharmacophore has been utilized to define the agonist mGluRs↓cAMP bioactive conformation of l-Glu.