三、具有吡嗪基-哌嗪基-哌啶骨架的新型 CXCR3 趋化因子受体拮抗剂的鉴定。
III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold.
机构信息
Merck Research Laboratories, Kenilworth, NJ 07033, USA.
出版信息
Bioorg Med Chem Lett. 2011 Dec 1;21(23):6982-6. doi: 10.1016/j.bmcl.2011.09.120. Epub 2011 Oct 5.
PMID:22018463
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.
摘要
探索了一种新型吡嗪基-哌嗪基-哌啶骨架化合物作为 CXCR3 受体拮抗剂的 SAR。描述了 DMPK 特性的优化和 hERG 抑制的降低。化合物 16e 对 CXCR3 具有单数字亲和力、良好的大鼠 PK 和 hERG 特性，已被确定为进一步研究的先导化合物。
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