Definition of a pharmacophore for the metabotropic glutamate receptors negatively linked to adenylyl cyclase.
(2S,3S,4S)-alpha-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 decreases cAMP bioactive conformation of L-Glu.
Costantino
G
G
Istituto di Chimica Farmaceutica e Tecnica Farmaceutica, Università degli Studi di Perugia, Italy.
Natalini
B
B
Pellicciari
R
R
Moroni
F
F
Lombardi
G
G
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000600:Amino Acids, Dicarboxylic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005971:Glutamates / Q000737:chemistry / Q000494:pharmacology*; D018698:Glutamic Acid; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D016318:Quisqualic Acid / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000067956:Adenylyl Cyclase Inhibitors; D000600:Amino Acids, Dicarboxylic; D005971:Glutamates; D018094:Receptors, Metabotropic Glutamate; C035261:(alpha-carboxycyclopropyl)glycine; D018698:Glutamic Acid; D016318:Quisqualic Acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases