发现一种新型 2,3-二甲基咪唑并[1,2-a]吡嗪-6-甲酰胺 M 正变构调节剂（PAM）化学型。
Discovery of a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide M positive allosteric modulator (PAM) chemotype.
机构信息
Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2020 Feb 1;30(3):126812. doi: 10.1016/j.bmcl.2019.126812. Epub 2019 Nov 13.
This Letter details our efforts to discover structurally unique M PAMs containing 5,6-heteroaryl ring systems. In an attempt to improve the DMPK profiles of the 2,3-dimethyl-2H-indazole-5-carboxamide and 1-methyl-1H-benzo[d][1,2,3]triazole-6-carboxamide cores, we investigated a plethora of core replacements. This exercise identified a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide core that provided improved M PAM activity and CNS penetration.
这封信件详细介绍了我们发现含有 5,6-杂芳环系统的结构独特的小分子激活剂（M PAMs）的努力。为了改善 2,3-二甲基-2H-吲唑-5-甲酰胺和 1-甲基-1H-苯并[d][1,2,3]三唑-6-甲酰胺核心的药代动力学性质，我们研究了大量的核心替换。这项研究确定了一个新型的 2,3-二甲基咪唑并[1,2-a]吡嗪-6-甲酰胺核心，它提供了更好的小分子激活剂（M PAM）活性和中枢神经系统穿透性。
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