Synthesis and in vitro activity of N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide P2X7 antagonists.
A novel series of cyanoguanidine-piperazine P2X(7) antagonists was designed based upon the structure of A-740003. Structure-activity relationship (SAR) studies focused on the piperazine moiety and the right hand side substitution. Compounds were assayed for activity at human and rat P2X(7) receptors and compound 29 was found to possess potent activity (IC(50)=30-60 nM) at both species.
Morytko
Michael J
MJ
Abbott Bioresearch Center, Department of Medicinal Chemistry, 381 Plantation Street, Worcester, MA 01605, USA.
Betschmann
Patrick
P
Woller
Kevin
K
Ericsson
Anna
A
Chen
Haipeng
H
Donnelly-Roberts
Diana L
DL
Namovic
Marian T
MT
Jarvis
Michael F
MF
Carroll
William A
WA
Rafferty
Paul
P
D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C529337:N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide; C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; D010879:Piperazines; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins