Discovery of dehydro-oxopiperazine acetamides as novel bradykinin B1 receptor antagonists with enhanced in vitro potency

Wenyuan Qian; Jian Jeffrey Chen; Jason Human; Toshihiro Aya; Jiawang Zhu; Kaustav Biswas; Tanya Peterkin; Randall W Hungate; Leyla Arik; Eileen Johnson; Gondi Kumar; Smriti Joseph; Janan Jona; Hong-Xun Guo; Zufan Wu

doi:10.1016/j.bmcl.2011.11.112

Discovery of dehydro-oxopiperazine acetamides as novel bradykinin B1 receptor antagonists with enhanced in vitro potency

Bioorg Med Chem Lett. 2012 Jan 15;22(2):1061-7. doi: 10.1016/j.bmcl.2011.11.112. Epub 2011 Dec 8.

Authors

Wenyuan Qian¹, Jian Jeffrey Chen, Jason Human, Toshihiro Aya, Jiawang Zhu, Kaustav Biswas, Tanya Peterkin, Randall W Hungate, Leyla Arik, Eileen Johnson, Gondi Kumar, Smriti Joseph, Janan Jona, Hong-Xun Guo, Zufan Wu

Affiliation

¹ Department of Chemistry Research and Discovery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States. wqian@amgen.com

PMID: 22197141
DOI: 10.1016/j.bmcl.2011.11.112

Abstract

In a series of bradykinin B1 antagonists, we discovered that replacement of oxopiperazine acetamides with dehydro-oxopiperazine acetamides provided compounds with enhanced activity against the B1 receptor. The synthesis and SAR leading to potent analogs with reduced molecular weight will be discussed.

MeSH terms

Acetamides / chemical synthesis
Acetamides / chemistry
Acetamides / pharmacology*
Bradykinin B1 Receptor Antagonists*
Dose-Response Relationship, Drug
Humans
Molecular Structure
Piperazines / chemical synthesis
Piperazines / chemistry
Piperazines / pharmacology*
Stereoisomerism
Structure-Activity Relationship

Substances

Acetamides
Bradykinin B1 Receptor Antagonists
Piperazines