Classical psychedelics such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) are showing promising results in clinical trials for a range of psychiatric indications, including depression, anxiety, and substance abuse disorder. These compounds are characterized by broad pharmacological activity profiles, and while the acute mind-altering effects can be ascribed to their shared agonist activity at the serotonin 2A receptor (5-HT_2AR), their apparent persistent therapeutic effects are yet to be decidedly linked to activity at this receptor. We report herein the discovery of 2,5-dimethoxyphenylpiperidines as a novel class of selective 5-HT_2AR agonists and detail the structure–activity investigations leading to the identification of LPH-5 [analogue (S)-11] as a selective 5-HT_2AR agonist with desirable drug-like properties.

中文翻译：

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作为选择性血清素 5-HT2A 受体激动剂的 2,5-二甲氧基苯基哌啶的发现及其构效关系

裸盖菇素、麦角酸二乙酰胺 (LSD) 和N,N-二甲基色胺 (DMT)等经典迷幻药在针对一系列精神疾病（包括抑郁症、焦虑症和药物滥用障碍）的临床试验中显示出良好的结果。这些化合物的特点是具有广泛的药理活性，虽然急性改变思维作用可归因于它们对血清素 2A 受体 (5-HT _2A R) 的共同激动剂活性，但它们明显的持久治疗作用尚未明确联系起来。对该受体的活性。我们在此报告了 2,5-二甲氧基苯基哌啶作为一类新型选择性 5-HT _2A R 激动剂的发现，并详细介绍了导致鉴定 LPH-5 [类似物 ( S )- 11 ] 作为选择性 5-HT 2A R 激动剂的结构-活性研究。 -HT _2A R 激动剂，具有理想的药物样特性。