Substituted benzothiophene

{{Short description|Class of chemical compounds}}

File:Benzothiophene numbering.svg.]]

The substituted benzothiophenes are a class of chemical compounds based on benzothiophene.{{cite journal | vauthors = Brandt SD, Carlino L, Kavanagh PV, Westphal F, Dreiseitel W, Dowling G, Baumann MH, Sitte HH, Halberstadt AL | title = Syntheses and analytical characterizations of novel (2-aminopropyl)benzo[b]thiophene (APBT) based stimulants | journal = Drug Test Anal | volume = 12 | issue = 8 | pages = 1109–1125 | date = August 2020 | pmid = 32372465 | pmc = 8281332 | doi = 10.1002/dta.2813 | url = }}{{cite journal | vauthors = Rudin D, McCorvy JD, Glatfelter GC, Luethi D, Szöllősi D, Ljubišić T, Kavanagh PV, Dowling G, Holy M, Jaentsch K, Walther D, Brandt SD, Stockner T, Baumann MH, Halberstadt AL, Sitte HH | title = (2-Aminopropyl)benzo[β]thiophenes (APBTs) are novel monoamine transporter ligands that lack stimulant effects but display psychedelic-like activity in mice | journal = Neuropsychopharmacology | volume = 47 | issue = 4 | pages = 914–923 | date = March 2022 | pmid = 34750565 | pmc = 8882185 | doi = 10.1038/s41386-021-01221-0 | url = }} They are closely related to the substituted benzofurans, substituted tryptamines, and to other chemical groups such as the substituted benzodioxoles (or methylenedioxyphenyl compounds).

Substituted benzothiophenes include the (2-aminopropyl)benzo[β]thiophenes (APBTs) 2-APBT, 3-APBT (SKF-6678), 4-APBT, 5-APBT, 5-MAPBT, 6-APBT, 6-MAPBT, and 7-APBT. These drugs have been found to act as serotonin–norepinephrine–dopamine releasing agents (SNDRAs) and, in some cases, as potent serotonin 5-HT₂ receptor agonists, analogously to the entactogen MDMA. They do not produce hyperlocomotion in rodents, suggesting that they lack psychostimulant effects. However, those acting as serotonin 5-HT₂ receptor agonists have been found to induce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.

These findings suggest that substituted benzothiophenes may have entactogenic and/or psychedelic effects in humans whilst lacking stimulant effects and possibly having reduced misuse potential. The substituted benzothiophenes have been little-encountered as designer drugs as of 2022.

Tactogen has patented a number of benzothiophenes as novel entactogens for use as potential medicines.{{cite web | title=Tactogen patents 5-HT1B receptor agonists and MAO-A inhibitors | website=BioWorld | date=7 February 2022 | url=https://www.bioworld.com/articles/687206-tactogen-patents-5-ht1b-receptor-agonists-and-mao-a-inhibitors | access-date=29 January 2025}}{{cite web | title=Advantageous benzothiophene compositions for mental disorders or enhancement | website=Google Patents | date=6 July 2021 | url=https://patents.google.com/patent/EP4175638A1/ | access-date=29 January 2025}}{{cite web | title=2-ethylamine substituted benzofuran and benzothiophene compositions for mental disorders or enhancement | website=Google Patents | date=17 November 2023 | url=https://patents.google.com/patent/WO2024108179A2/ | access-date=29 January 2025}}

{{Gallery

| title = Chemical structures of selected APBTs

| height = 180

| width = 180

| File:2-APBT.svg | 2-APBT

| File:3-APBT.svg | 3-APBT

| File:4-APBT.svg | 4-APBT

| File:5-APBTP structure.png | 5-APBT

| File:6-APBT.svg | 6-APBT

| File:7-APBT.svg | 7-APBT

}}