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.
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.
Amori
L
L
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Italy.
Costantino
G
G
Marinozzi
M
M
Pellicciari
R
R
Gasparini
F
F
Flor
P J
PJ
Kuhn
R
R
Vranesic
I
I
D000818:Animals; D001681:Biological Assay; D016466:CHO Cells; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D003517:Cyclopentanes / Q000138:chemical synthesis*; D018690:Excitatory Amino Acid Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
C415225:1-amino-3-phosphono-3-cyclopentene-1-carboxylic acid; D003517:Cyclopentanes; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D005576:Colforsin