Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 2

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

doi:10.1016/j.bmcl.2011.10.037

Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 2

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7287-90. doi: 10.1016/j.bmcl.2011.10.037. Epub 2011 Oct 21.

Authors

Stephanie Brumfield¹, Julius J Matasi, Deen Tulshian, Michael Czarniecki, William Greenlee, Charles Garlisi, Hongchen Qiu, Kristine Devito, Shu-Cheng Chen, Yongliang Sun, Rosalia Bertorelli, Justin Ansell, William Geiss, Van-Duc Le, Gregory S Martin, Samuel A Vellekoop, James Haber, Melissa L Allard

Affiliation

¹ Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. Stephanie.Brumfield@merck.com

PMID: 22078214
DOI: 10.1016/j.bmcl.2011.10.037

Abstract

Novel P2X(7) antagonists were developed using a purine scaffold. These compounds were potent and selective at the P2X(7) receptor in human and rodent as well as efficacious in rodent pain models. Compound 15a was identified to have oral potency in several pain models in rodent similar to naproxen, gabapentin and pregabalin. Structure-activity relationship (SAR) development and results of pain models are presented.

MeSH terms

Animals
Humans
Pain / drug therapy*
Purinergic P2X Receptor Antagonists / chemical synthesis*
Purinergic P2X Receptor Antagonists / chemistry
Purinergic P2X Receptor Antagonists / therapeutic use
Purines / chemical synthesis*
Purines / chemistry
Purines / therapeutic use
Rats
Receptors, Purinergic P2X7 / chemistry*
Receptors, Purinergic P2X7 / metabolism
Structure-Activity Relationship

Substances

Purinergic P2X Receptor Antagonists
Purines
Receptors, Purinergic P2X7