Synthesis and in vitro activity of N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide P2X7 antagonists

Michael J Morytko; Patrick Betschmann; Kevin Woller; Anna Ericsson; Haipeng Chen; Diana L Donnelly-Roberts; Marian T Namovic; Michael F Jarvis; William A Carroll; Paul Rafferty

doi:10.1016/j.bmcl.2008.01.094

Synthesis and in vitro activity of N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide P2X7 antagonists

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2093-6. doi: 10.1016/j.bmcl.2008.01.094. Epub 2008 Jan 30.

Authors

Michael J Morytko¹, Patrick Betschmann, Kevin Woller, Anna Ericsson, Haipeng Chen, Diana L Donnelly-Roberts, Marian T Namovic, Michael F Jarvis, William A Carroll, Paul Rafferty

Affiliation

¹ Abbott Bioresearch Center, Department of Medicinal Chemistry, 381 Plantation Street, Worcester, MA 01605, USA.

PMID: 18272365
DOI: 10.1016/j.bmcl.2008.01.094

Abstract

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.

MeSH terms

Animals
Humans
In Vitro Techniques
Molecular Structure
Piperazines / chemical synthesis*
Piperazines / pharmacology*
Purinergic P2 Receptor Antagonists*
Rats
Receptors, Purinergic P2 / metabolism
Receptors, Purinergic P2X7
Recombinant Proteins / antagonists & inhibitors*
Recombinant Proteins / metabolism
Structure-Activity Relationship

Substances

N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide
P2RX7 protein, human
P2rx7 protein, rat
Piperazines
Purinergic P2 Receptor Antagonists
Receptors, Purinergic P2
Receptors, Purinergic P2X7
Recombinant Proteins