III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold

  • Bioorg Med Chem Lett. 2011 Dec 1;21(23):6982-6. doi: 10.1016/j.bmcl.2011.09.120.
Seong Heon Kim  1 ,  Gopinadhan N Anilkumar ,  Lisa Guise Zawacki ,  Qingbei Zeng ,  De-Yi Yang ,  Yuefei Shao ,  Guizhen Dong ,  Xiaolian Xu ,  Wensheng Yu ,  Yueheng Jiang ,  Chung-Her Jenh ,  James W Hall 3rd ,  Carolyn Diianni Carroll ,  Doug W Hobbs ,  John J Baldwin ,  Brian F McGuinness ,  Stuart B Rosenblum ,  Joseph A Kozlowski ,  Bandarpalle B Shankar ,  Neng-Yang Shih
Affiliations
PMID: 22018463 DOI: 10.1016/j.bmcl.2011.09.120
Abstract

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. Compound 16e with single-digit CXCR3 affinity, good rat PK and hERG profiles has been identified as a lead for further study.