取代哒嗪-3(2H)-酮作为高效和偏倚的甲酰肽受体激动剂。
Substituted Pyridazin-3(2 H)-ones as Highly Potent and Biased Formyl Peptide Receptor Agonists.
机构信息
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences , Monash University , Parkville , Victoria 3052 , Australia.
Baker Heart and Diabetes Institute , 75 Commercial Road , Melbourne , Victoria 3004 , Australia.
出版信息
J Med Chem. 2019 May 23;62(10):5242-5248. doi: 10.1021/acs.jmedchem.8b01912. Epub 2019 May 13.
Herein we describe the development of a focused series of functionalized pyridazin-3(2 H)-one-based formyl peptide receptor (FPR) agonists that demonstrate high potency and biased agonism. The compounds described demonstrated biased activation of prosurvival signaling, ERK1/2 phosphorylation, through diminution of the detrimental FPR1/2-mediated intracellular calcium (Ca) mobilization. Compound 50 showed an EC of 0.083 μM for phosphorylation of ERK1/2 and an approximate 20-fold bias away from Ca mobilization at the hFPR1.
在此，我们描述了一系列经过精心设计的、基于哒嗪-3(2H)-酮的、具有功能化的、高活性的、偏向性激活的、形式肽受体（FPR）激动剂的发展。这些化合物表现出偏向性激活生存信号，ERK1/2 磷酸化，通过减少有害的 FPR1/2 介导的细胞内钙（Ca）动员。化合物 50 对 ERK1/2 的磷酸化的 EC 为 0.083 μM，并且在 hFPR1 上大约 20 倍地偏向于 Ca 动员。
Zotero 插件