• Synthesis and Characterization:

  A 2011 study published in Microgram Journal details the synthesis, analysis, and characterization of 5- and 6-APDB []. This research provides details on the methods used to produce 6-APDB and techniques for its identification.

• Classification and Effects:

  6-APDB belongs to the class of phenethylamines and acts as a stimulant and entactogen []. Studies suggest it has similar effects to MDMA (3,4-methylenedioxymethamphetamine), but with potential differences in potency and specific mechanisms [].

6-(2-Aminopropyl)-2,3-dihydrobenzofuran, often referred to as 6-(2-aminopropyl)benzofuran, is a compound that belongs to the class of substituted benzofurans. This compound is structurally characterized by a benzofuran ring with a propylamine side chain at the sixth position. Its chemical formula is C11H15NOC11​H15​NO and it has a molecular weight of approximately 179.25 g/mol. The compound has garnered interest in both scientific research and recreational drug use due to its psychoactive properties.

• Oxidation: This compound can undergo oxidation reactions, which may lead to the formation of hydroxylated derivatives or other oxidized products.
• Reduction: It may also participate in reduction reactions, particularly when exposed to reducing agents.
• Rearrangement: Under specific conditions, this compound can undergo rearrangement reactions that alter its structure.

These reactions are essential for understanding the compound’s behavior in biological systems and its potential metabolic pathways .

The biological activity of 6-(2-aminopropyl)-2,3-dihydrobenzofuran is primarily linked to its effects on neurotransmitter systems. It acts as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI), which means it inhibits the reuptake of these neurotransmitters, potentially enhancing their levels in the synaptic cleft. This mechanism is similar to other psychoactive substances and contributes to its empathogenic effects . Additionally, it has been noted for its agonistic activity at serotonin receptors, particularly the 5-HT receptor subtype .

The synthesis of 6-(2-aminopropyl)-2,3-dihydrobenzofuran typically involves several steps:

• Starting Materials: The synthesis often begins with brominated phenols and bromoacetaldehyde diethylacetal.
• Formation of Benzofuran: The brominated phenol is treated with sodium hydride and heated to form a benzofuran structure.
• Amination: The resulting intermediate undergoes reductive amination with an appropriate amine to introduce the 2-aminopropyl group.
• Purification: The final product is purified through techniques such as column chromatography.

This multi-step synthesis highlights the complexity involved in producing this compound and ensures high purity for research purposes  .

6-(2-Aminopropyl)-2,3-dihydrobenzofuran has various applications:

• Research Tool: It is used in pharmacological studies to understand its mechanism of action on neurotransmitter systems.
• Psychoactive Substance: Due to its empathogenic properties, it has been explored as a recreational drug.
• Potential Therapeutic Agent: Research is ongoing into its potential therapeutic applications in treating mood disorders or enhancing emotional processing.

Interaction studies involving 6-(2-aminopropyl)-2,3-dihydrobenzofuran focus on its effects on neurotransmitter transporters and receptors. These studies have shown that the compound interacts with serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), indicating a complex pharmacological profile that may lead to both therapeutic benefits and risks associated with recreational use  .

Several compounds share structural similarities with 6-(2-aminopropyl)-2,3-dihydrobenzofuran. Notable examples include:

These compounds highlight the uniqueness of 6-(2-aminopropyl)-2,3-dihydrobenzofuran due to its specific structural features and resultant pharmacological properties. Its empathogenic effects set it apart from others in its class. Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3, Buy 6-APDB (benzofuran) Cas 152623-93-3

The synthesis of 6-(2-aminopropyl)-2,3-dihydrobenzofuran (6-APDB) originated in the early 1990s through the pioneering work of David E. Nichols at Purdue University. Nichols sought to develop analogs of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) that retained entactogenic properties while minimizing neurotoxic side effects. His strategy involved structural modifications to the phenethylamine core, specifically replacing the methylenedioxy ring with a dihydrobenzofuran moiety. This substitution aimed to reduce oxidative stress associated with catecholamine metabolism, a key factor in MDMA-induced neurotoxicity.

6-APDB emerged alongside its positional isomer 5-APDB during systematic investigations into benzofuran-based phenethylamines. Initial in vitro studies revealed that 6-APDB inhibited serotonin (5-HT), dopamine (DA), and norepinephrine (NE) reuptake with IC~50~ values of 322 nM, 1,997 nM, and 980 nM, respectively. These values suggested a pharmacological profile intermediate between MDA (serotonin-preferring) and MDMA (balanced monoamine activity), positioning 6-APDB as a candidate for further behavioral characterization.

Nichols’ team employed drug discrimination paradigms in rats to assess subjective effects, finding that 6-APDB fully substituted for MBDB (N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine) and MMAI (5-methoxy-6-methyl-2-aminoindane), but not for amphetamine or LSD. This specificity indicated a unique receptor interaction pattern distinct from classical stimulants or hallucinogens. Subsequent locomotor activity assays demonstrated 6-APDB-induced hyperlocomotion at doses comparable to MDMA, supporting its entactogen-like behavioral effects.

Table 1: Comparative Pharmacological Profiles of 6-APDB and Related Compounds

Chronological Evolution of Benzofuran-Based Phenethylamine Derivatives

The development of 6-APDB occurred within a broader context of structure-activity relationship (SAR) studies on benzofuran analogs. Following Nichols’ initial synthesis, researchers explored variations in ring saturation and substitution patterns:

• First-Generation Analogs (1990–2000):
  • 5-APDB/6-APDB Pair: The dihydrobenzofuran scaffold allowed direct comparison of oxygen positioning. 5-APDB demonstrated serotonin-selective reuptake inhibition (SERT IC~50~ = 180 nM), while 6-APDB showed balanced monoamine activity.
  • Benzofuran vs. Dihydrobenzofuran: Unsaturated derivatives like 6-APB (benzofuran) exhibited enhanced dopamine release (EC~50~ = 10 nM) compared to 6-APDB (EC~50~ = 1,997 nM).
• Second-Generation Modifications (2000–2010):
  • N-Methylation: Introduction of N-methyl groups produced compounds like 5-MAPB and 6-MAPB. Surprisingly, N-methylation minimally affected transporter inhibition potency but increased 5-HT~2B~ receptor agonism (6-MAPB K~i~ = 2.8 nM).
  • Ring Expansion: Tetrahydrobenzo[1,2-b:4,5-b’]difuran analogs explored conformational restriction, though these showed reduced entactogen activity.
• Third-Generation Hybrids (2010–Present):
  • Benzofuran-Indole Chimeras: Combining benzofuran and tryptamine motifs yielded compounds with mixed 5-HT~2A~/DAT activity, though none surpassed 6-APDB’s balanced profile.

Table 2: Structural Evolution of Benzofuran Phenethylamines

Transition from Experimental Compound to Novel Psychoactive Substance (NPS)

6-APDB’s emergence in recreational markets followed a delayed trajectory compared to its analogs. Three phases characterized this transition:

• Academic to Gray Market (2005–2010):
  • Patent analyses and forensic chemistry publications enabled small-scale synthesis by European research chemical vendors.
  • Initial products appeared as “research chemicals” labeled for in vitro use, circumventing analog legislation.
• UK Proliferation (2011–2013):
  • Marketed as “Benzofury” alongside 5-APB and 6-APB, 6-APDB gained popularity in club scenes due to its MDMA-like effects and legal status.
  • Gas chromatography–mass spectrometry (GC-MS) analyses of seized samples confirmed 6-APDB’s presence in 23% of “Benzofury” products between 2011–2013.
• Regulatory Response (2013–Present):
  • The UK Home Office classified 6-APDB as a Class B drug under the Misuse of Drugs Act 1971 in June 2013, citing structural similarity to MDA.
  • Post-ban forensic prevalence decreased from 18% (2013) to <2% (2015) in European drug seizures, though darknet markets sustained limited availability.

6-(2-Aminopropyl)-2,3-dihydrobenzofuran exhibits potent inhibitory activity across all three major monoamine transporters, demonstrating a triple reuptake inhibition profile that underlies its psychoactive properties [3] [8]. In vitro studies utilizing rat brain synaptosomes have revealed that this compound functions as a substrate-type releaser rather than a simple reuptake inhibitor, distinguishing it from classical stimulants such as cocaine [8].

Serotonin Transporter Interactions

The compound demonstrates significant potency at the serotonin transporter with an inhibitory concentration fifty (IC50) value of 322 nanomolar [3]. This potency represents approximately 8.5-fold greater activity compared to 3,4-methylenedioxyamphetamine, indicating enhanced serotonergic activity [8]. In release assays conducted in rat brain synaptosomes, 6-(2-Aminopropyl)-2,3-dihydrobenzofuran produced concentration-dependent release of [³H]5-hydroxytryptamine with an effective concentration fifty (EC50) of 36 nanomolar, achieving 100% efficacy relative to maximal release [8].

Dopamine Transporter Dynamics

At the dopamine transporter, 6-(2-Aminopropyl)-2,3-dihydrobenzofuran exhibits an IC50 value of 1,997 nanomolar for uptake inhibition, demonstrating preferential activity for serotonergic over dopaminergic systems [3]. However, the compound functions as a potent dopamine releaser with an EC50 of 10 nanomolar, representing 10-fold greater potency than 3,4-methylenedioxyamphetamine [8]. This substrate-type releasing activity at the dopamine transporter involves reversal of normal transporter flux, consistent with the molecular mechanism observed for ring-substituted amphetamines [8].

Norepinephrine Transporter Modulation

The norepinephrine transporter represents an intermediate target for 6-(2-Aminopropyl)-2,3-dihydrobenzofuran, with an IC50 value of 980 nanomolar for uptake inhibition [3]. Release studies demonstrate an EC50 of 14 nanomolar for norepinephrine efflux, indicating potent substrate activity at this transporter [8]. The compound achieves 98% efficacy relative to maximal norepinephrine release, suggesting full substrate properties at the norepinephrine transporter [8].

Comparative Transporter Activity Profile

The transporter selectivity profile indicates non-selective substrate activity across all three monoamine transporters, with calculated ratios suggesting balanced effects on multiple neurotransmitter systems [8]. This pharmacological profile distinguishes 6-(2-Aminopropyl)-2,3-dihydrobenzofuran from selective serotonin reuptake inhibitors and demonstrates its classification as a broad-spectrum monoamine releaser [8].

Serotonergic Receptor Agonism: 5-Hydroxytryptamine2A/2B/2C Binding Affinity Landscapes

6-(2-Aminopropyl)-2,3-dihydrobenzofuran demonstrates significant agonist activity at multiple serotonin receptor subtypes, with particularly pronounced effects at the 5-hydroxytryptamine2B receptor [12] [16]. These receptor interactions contribute to the compound’s complex pharmacological profile and distinguish it from pure transporter inhibitors

152623-93-3

Post Buying Request

• 

• Basic information

  1. Product Name: 6-(2-aminopropyl)-2,3-dihydrobenzofuran
  2. Synonyms: 6-(2-aminopropyl)-2,3-dihydrobenzofuran;6-APDB;6-BenzofuranethanaMine,2,3-dihydro-a-Methyl-;1-(2,3-dihydrobenzofuran-6-yl)propan-2-amine;6-APDB lila@tuskwei.com whatsapp:+8615230133735
  3. CAS NO:152623-93-3
  4. Molecular Formula: C11H15NO
  5. Molecular Weight: 177.11
  6. EINECS: N/A
  7. Product Categories: pharmaceutical intermediate
  8. Mol File: 152623-93-3.mol

• Chemical Properties

  1. Melting Point: N/A
  2. Boiling Point: 292.868 °C at 760 mmHg
  3. Flash Point: 134.233 °C
  4. Appearance: /
  5. Density: 1.088 g/cm³
  6. Vapor Pressure: 0.00179mmHg at 25°C
  7. Refractive Index: 1.565
  8. Storage Temp.: N/A
  9. Solubility: N/A
  10. CAS DataBase Reference: 6-(2-aminopropyl)-2,3-dihydrobenzofuran(CAS DataBase Reference)
  11. NIST Chemistry Reference: 6-(2-aminopropyl)-2,3-dihydrobenzofuran(152623-93-3)
  12. EPA Substance Registry System: 6-(2-aminopropyl)-2,3-dihydrobenzofuran(152623-93-3)

• Safety Data

  1. Hazard Codes: N/A
  2. Statements: N/A
  3. Safety Statements: N/A
  4. WGK Germany:
  5. RTECS:
  6. HazardClass: N/A
  7. PackingGroup: N/A
  8. Hazardous Substances Data: 152623-93-3(Hazardous Substances Data)

5-Hydroxytryptamine2B Receptor Interactions