特殊的麦角生物碱能有效地抑制血液中趋化因子受体 CXCR3。
Special ergolines efficiently inhibit the chemokine receptor CXCR3 in blood.
机构信息
Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, Lichtstrasse 35, CH-4056 Basel, Switzerland.
出版信息
Bioorg Med Chem Lett. 2011 Aug 15;21(16):4745-9. doi: 10.1016/j.bmcl.2011.06.070. Epub 2011 Jun 29.
The structure-activity relationship of highly potent special ergolines which selectively block the chemokine receptor CXCR3 is reported. The most potent compounds showed IC(50) values below 10nM in both ligand binding and Ca(2+)-mobilization assays. However, these compounds were poorly active in an assay that measures receptor occupancy in blood. Introduction of polar substituents led to derivatives with IC(50) values below 10nM in this assay. Among them was compound 11a which showed both a favorable PK profile and cross reactivity with rodent CXCR3 making it a promising tool compound to further explore the role of CXCR3 in animal models.
报道了高活性特殊麦角林类化合物对趋化因子受体 CXCR3 的结构-活性关系。在配体结合和 Ca(2+)-动员测定中，最有效的化合物的 IC(50)值均低于 10nM。然而，这些化合物在测定受体在血液中的占有率的试验中活性较差。引入极性取代基可得到在该试验中 IC(50)值低于 10nM 的衍生物。其中化合物 11a 具有良好的 PK 特征和与啮齿动物 CXCR3 的交叉反应性，使其成为进一步探索 CXCR3 在动物模型中作用的有前途的工具化合物。
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