The discovery of the first selective, small‐molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug‐like agonist with the highest affinity for the AT2R reported to date (K_i = 0.4 nM). Structure‐activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also presented.

中文翻译：

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小分子AT2受体激动剂

描述了第一个选择性的小分子ATR受体（AT2R）激动剂化合物21（C21）（8）的发现，该化合物现已在各种体外和体内模型中进行了广泛研究。的磺酰基氨基甲酸酯衍生物8，包含一个phenylthiofen支架是药物状与用于AT2R最高亲和力激动剂迄今报道的（ķ_我= 0.4纳米）。关于不同的联芳基支架和与这些支架相连的官能团的结构活性关系（SAR），特别关注各种对位取代基取代8位亚甲基咪唑基的影响，进行了讨论。此外，简要讨论了亚甲基咪唑基团迁移的后果和针对分别作为AT2R激动剂（如8）或AT2R拮抗剂（如9）的配体的结构要求。还概述了C21（8）的药理作用。