3-氧代-2-哌嗪基乙酰胺类化合物作为强效缓激肽 B1 受体拮抗剂用于治疗疼痛和炎症。
3-Oxo-2-piperazinyl acetamides as potent bradykinin B1 receptor antagonists for the treatment of pain and inflammation.
机构信息
Department of Chemistry Research and Discovery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
出版信息
Bioorg Med Chem Lett. 2011 Jun 1;21(11):3384-9. doi: 10.1016/j.bmcl.2011.03.115. Epub 2011 Apr 7.
The discovery of novel and highly potent oxopiperazine based B1 receptor antagonists is described. Compared to the previously described arylsulfonylated (R)-3-amino-3-phenylpropionic acid series, the current compounds showed improved in vitro potency and metabolic stability. Compound 17, 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide, showed EC(50) of 10.3 nM in a rabbit biochemical challenge model. The practical syntheses of chiral arylsulfonylated oxopiperazine acetic acids are also described.
新型高活性氧代哌嗪基 B1 受体拮抗剂的发现。与先前描述的芳基磺酰化（R）-3-氨基-3-苯基丙酸系列相比，当前的化合物显示出体外活性和代谢稳定性的提高。化合物 17，2-((2R)-1-((4-甲基苯基)磺酰基)-3-氧代-2-哌嗪基)-N-((1R)-6-(1-哌啶基甲基)-1,2,3,4-四氢-1-萘基)乙酰胺，在兔生物化学挑战模型中显示出 10.3 nM 的 EC50。也描述了手性芳基磺酰化氧代哌嗪基乙酸的实用合成方法。
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