Work

Discovery and Structure–Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists

Year: 2024

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide 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 2A R), 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 2A R agonists and detail the structure–activity investigations leading to the identification of LPH-5 [analogue ( S )- 11 ] as a selective 5-HT 2A R agonist with desirable drug-like properties.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/acs.jmedchem.4c00082

Authors: Emil M. Ro̷rsted, Anders A. Jensen, Gints Smits, Karla Frydenvang, Jesper L. Kristensen

Institutions: University of Copenhagen, Latvijas Organiskās Sintēzes Institūts

Language: English

Topic: Psychedelics and Drug Studies

Subfield: Clinical Psychology

Field: Psychology

Domain: Social Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500