Aryl sulfones as novel bradykinin B1 receptor antagonists for treatment of chronic pain

Kaustav Biswas; Toshihiro Aya; Wenyuan Qian; Tanya A N Peterkin; Jian Jeffrey Chen; Jason Human; Randall W Hungate; Gondi Kumar; Leyla Arik; Dianna Lester-Zeiner; Gloria Biddlecome; Barton H Manning; Hong Sun; Hong Dong; Ming Huang; Richard Loeloff; Eileen J Johnson; Benny C Askew

doi:10.1016/j.bmcl.2008.07.108

Aryl sulfones as novel bradykinin B1 receptor antagonists for treatment of chronic pain

Bioorg Med Chem Lett. 2008 Sep 1;18(17):4764-9. doi: 10.1016/j.bmcl.2008.07.108. Epub 2008 Jul 31.

Authors

Kaustav Biswas¹, Toshihiro Aya, Wenyuan Qian, Tanya A N Peterkin, Jian Jeffrey Chen, Jason Human, Randall W Hungate, Gondi Kumar, Leyla Arik, Dianna Lester-Zeiner, Gloria Biddlecome, Barton H Manning, Hong Sun, Hong Dong, Ming Huang, Richard Loeloff, Eileen J Johnson, Benny C Askew

Affiliation

¹ Department of Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, MS 29-1-B, Thousand Oaks, CA 91320, USA.

PMID: 18706809
DOI: 10.1016/j.bmcl.2008.07.108

Abstract

We report the development of aryl sulfones as Bradykinin B1 receptor antagonists. Variation of the linker region identified diol 23 as a potent B1 antagonist, while modifications of the aryl moiety led to compound 26, both of which were efficacious in rabbit biochemical challenge and pain models.

Publication types

Comparative Study

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Bradykinin B1 Receptor Antagonists*
Bradykinin B2 Receptor Antagonists
Chronic Disease
Humans
Pain / drug therapy*
Rabbits
Rats
Rats, Sprague-Dawley
Sulfones / administration & dosage
Sulfones / pharmacology*

Substances

Anti-Inflammatory Agents, Non-Steroidal
Bradykinin B1 Receptor Antagonists
Bradykinin B2 Receptor Antagonists
Sulfones