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Structure—Activity Relationships of Analogues of NF449 Confirm NF449 as the Most Potent and Selective Known P2X1 Receptor Antagonist
- Source :
- ChemInform. 35
- Publication Year :
- 2004
- Publisher :
- Wiley, 2004.
-
Abstract
- NF449 [4,4',4",4"'-(carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino)))tetrakisbenzene-1,3-disulfonic acid-octasodiumsalt)] was recently described to inhibit recombinant rP2X(1) receptors (Naunyn Schmiedeberg's Arch. Pharmacol. 364 (2001) 285). The purpose of this study was to examine structure-activity-relationships at P2 receptors of a series of NF449 analogues. Thus, compounds containing various arylaminemono-, di-, or trisulfonic acids and a replacement of the central urea bridge were synthesized. NF449 displayed a pIC(50) at P2X(1) receptors (rat vas deferens) of 6.31 +/- 0.04 being at least 19-fold more potent at P2X(1) than at P2X(3), P2Y(1), P2Y(2), or P2Y(11). Any deletion or change of position of sulfonic acid groups or replacing the central urea bond by the bisamide of terephthalic acid reduced the potency at P2X(1) by at least 90%. All compounds were very weak antagonists at P2Y(2) or P2Y(11) receptors (pIC(50)4.5). In conclusion, NF449 remains the most potent and selective P2X(1) antagonist known. Potential lead compounds among the suramin class for P2X(3) (16d) and P2Y(1) (16a) receptors were identified.
- Subjects :
- Male
Stereochemistry
Suramin
Guinea Pigs
Uridine Triphosphate
Sulfonic acid
Chemical synthesis
Cell Line
Lethal Dose 50
Structure-Activity Relationship
chemistry.chemical_compound
Adenosine Triphosphate
Vas Deferens
P2x1 receptor
Ileum
Drug Discovery
Purinergic P2 Receptor Antagonists
medicine
Animals
Humans
Structure–activity relationship
PPADS
Receptor
Suramin Sodium
Pharmacology
chemistry.chemical_classification
Dose-Response Relationship, Drug
Receptors, Purinergic P2
Chemistry
Benzenesulfonates
Organic Chemistry
Antagonist
General Medicine
Rats
Receptors, Purinergic P2X
Urea
medicine.drug
Subjects
Details
- ISSN :
- 15222667 and 09317597
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- ChemInform
- Accession number :
- edsair.doi.dedup.....773611b30b2b5719c31a98811bdd6766