Triazine compounds as antagonists at Bv8-prokineticin receptors.
On the basis of a Janssen's patent, we approached a new synthesis of some 1,3,5-triazin-4,6-diones as potential non peptidic prokineticin receptor antagonists, containing the following substitutions: (N(1) and N(5) link a 4-methoxybenzyl and a 4-ethylbenzyl, respectively; C(2) can link an amino-ethyl-guanidine (reference compound 1) or an ethylendiamine (2) or an amino-ethyl-amino-2-imidazoline (3). New compounds were assessed for PKR1 and PKR2 affinity. Antagonist properties were evaluated as inhibition of 1 nM Bv8-induced intracellular Ca2+ mobilization.
Balboni
Gianfranco
G
Department of Pharmaceutical Sciences, University of Ferrara, I-44100 Ferrara, Italy. gbalboni@unica.it
Lazzari
Ilaria
I
Trapella
Claudio
C
Negri
Lucia
L
Lattanzi
Roberta
R
Giannini
Elisa
E
Nicotra
Annalisa
A
Melchiorri
Pietro
P
Visentin
Sergio
S
Nuccio
Chiara De
CD
Salvadori
Severo
S
D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005768:Gastrointestinal Hormones / Q000737:chemistry; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009479:Neuropeptides / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D005768:Gastrointestinal Hormones; D008024:Ligands; D009479:Neuropeptides; C423608:PROK2 protein, human; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D014227:Triazines; D002118:Calcium