Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 1

Julius J Matasi; Stephanie Brumfield; Deen Tulshian; Michael Czarnecki; William Greenlee; Charles G Garlisi; Hongchen Qiu; Kristine Devito; Shu-Cheng Chen; Youngliang Sun; Rosalia Bertorelli; William Geiss; Van-Duc Le; Gregory S Martin; Samuel A Vellekoop; James Haber; Melissa L Allard

doi:10.1016/j.bmcl.2011.04.034

Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 1

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3805-8. doi: 10.1016/j.bmcl.2011.04.034. Epub 2011 Apr 24.

Authors

Julius J Matasi¹, Stephanie Brumfield, Deen Tulshian, Michael Czarnecki, William Greenlee, Charles G Garlisi, Hongchen Qiu, Kristine Devito, Shu-Cheng Chen, Youngliang Sun, Rosalia Bertorelli, William Geiss, Van-Duc Le, Gregory S Martin, Samuel A Vellekoop, James Haber, Melissa L Allard

Affiliation

¹ Merck Research Laboratories, Kenilworth, NJ 07033-0539, USA. Julius.Matasi@merck.com

PMID: 21570840
DOI: 10.1016/j.bmcl.2011.04.034

Abstract

Structure-activity relationship (SAR) efforts around our initial lead compound 1 led to the identification of potent P2X(7) receptor antagonists with improved pharmacokinetic profiles. These compounds were potent and selective at the P2X(7) receptor in both human and rodent. Compound (entry 31) exhibited oral efficacy in the rat MIA and CCI pain models.

MeSH terms

Administration, Oral
Analgesics / chemical synthesis*
Analgesics / chemistry
Animals
Disease Models, Animal
Drug Design*
Humans
Molecular Structure
Pain* / drug therapy
Purinergic P2 Receptor Antagonists / chemical synthesis*
Purinergic P2 Receptor Antagonists / chemistry
Rats
Receptors, Purinergic P2X7 / metabolism
Structure-Activity Relationship

Substances

Analgesics
Purinergic P2 Receptor Antagonists
Receptors, Purinergic P2X7