Lauflumide (CRL-40940)
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Product Description
Lauflumide, also known as Flmodafinil or CRL-40,940, is a wakefulness-promoting agent and nootropic related to modafinil. Its chemical name is 2-[[bis(4-fluorophenyl)methyl]sulfinyl]acetamide, and it is structurally distinguished by the addition of two fluorine atoms to the phenyl rings of modafinil. First described in the 1960s, Lauflumide was developed by laboratories like Lafon as a potential pharmaceutical for treating conditions such as narcolepsy, chronic fatigue syndrome, and ADHD.
Synthesis Methods
The synthesis of Lauflumide (CRL-40940) involves converting the thioether bond in 2-((Bis(4-fluorophenyl)methyl)thio)acetamide to a sulfinyl group via oxidation. The process includes the following steps:
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Starting Material Selection:
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Use 2-((Bis(4-fluorophenyl)methyl)thio)acetamide (CAS No. 90280-20-9) as the starting material. This compound can be prepared by condensing bis(4-fluorophenyl)methylthiol with chloroacetyl chloride followed by aminolysis.
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Oxidation Reaction Conditions:
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Use hydrogen peroxide (H₂O₂) or m-chloroperbenzoic acid (m-CPBA) as the oxidant.
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Carry out the reaction at a low temperature (0-25°C) to avoid overoxidation to the sulfone.
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Use dichloromethane or acetonitrile as the reaction solvent.
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The reaction time is typically 2-4 hours.
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Purification and Characterization:
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Purify the crude product by silica gel column chromatography using an eluent mixture of ethyl acetate and petroleum ether.
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The final product is a white solid with a melting point of approximately 102°C (decomposition).
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Confirm the structure using nuclear magnetic resonance (¹H NMR) and mass spectrometry (MS). Characteristic peaks include the sulfinyl sulfur atom (δ 2.5-3.5 ppm) and the fluorine substitution signal on the phenyl ring (δ 7.2-7.8 ppm).
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Precautions:
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The oxidant must be prepared fresh to avoid decomposition and decreased yield.
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The reaction system must be strictly dehydrated to prevent hydrolysis of the sulfinyl group.
Uses and Applications
Lauflumide (CRL-40940) is primarily used as a wakefulness-promoting agent (eugeroic) and nootropic. Its applications include:
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Treatment of Sleep Disorders: Investigated for narcolepsy, idiopathic hypersomnia, and shift work sleep disorder. It aims to alleviate excessive daytime sleepiness (EDS) by targeting underlying mechanisms like orexin deficiency.
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Other Therapeutic Research: In preclinical development for chronic fatigue syndrome. Previously explored for attention-deficit/hyperactivity disorder (ADHD) and related conditions involving fatigue or impaired wakefulness.
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Nootropic and Cognitive Enhancement: Commonly sold and used non-medically as a cognitive enhancer in the nootropic community, potentially improving alertness, focus, and mental performance without the intensity of traditional stimulants.
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Research Purposes: Marketed as a "research chemical" for studying dopamine reuptake inhibition and wakefulness pathways, often labeled "not for human consumption" to avoid regulatory restrictions.
Properties and Characteristics
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Chemical Identifiers and Structure:
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Systematic/IUPAC Name: 2-((Bis(4-fluorophenyl)methyl)sulfinyl)acetamide or 2-[bis(4-fluorophenyl)methylsulfinyl]acetamide.
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Common Names/Synonyms: Lauflumide, Bisfluoromodafinil, Flmodafinil, CRL-40940, CRL-40,940.
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InChI: InChI=1S/C15H13F2NO2S/c16-12-5-1-10(2-6-12)15(21(20)9-14(18)19)11-3-7-13(17)8-4-11/h1-8,15H,9H2,(H2,18,19).
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InChIKey: YEAQNUMCWMRYMU-UHFFFAOYSA-N.
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SMILES: C1=CC(=CC=C1C(C2=CC=C(C=C2)F)S(=O)CC(=O)N)F.
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Physical and Chemical Properties:
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XLogP3 (Predicted Octanol-Water Partition Coefficient): 1.9.
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Hydrogen Bond Donor Count: 1.
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Hydrogen Bond Acceptor Count: 5.
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Rotatable Bond Count: 5.
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Exact/Monoisotopic Mass: 309.06350616 Da.
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Topological Polar Surface Area (TPSA): 79.4 Ų.
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Heavy Atom Count: 21.
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Formal Charge: 0.
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Complexity: 356.
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Pharmacological and Biological Properties:
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Mechanism of Action: Acts as a selective atypical dopamine reuptake inhibitor (DRI), blocking the dopamine transporter (DAT) to increase dopamine levels in brain regions like the nucleus accumbens, promoting wakefulness and alertness. May also influence norepinephrine, histamine, and orexin systems. Unlike modafinil, it does not induce cytochrome P450 (CYP) enzymes (e.g., CYP3A4/5) with repeated doses, reducing drug interaction risks.
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Potency and Duration: Preclinical research suggests it is more potent and longer-lasting than modafinil, potentially due to fluorine-induced metabolic stability.
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Comparison to Related Compounds: Fluorinated analog of modafinil (which has a diphenylmethyl group); similar to adrafinil (a prodrug) and armodafinil (R-enantiomer of modafinil). The fluorine atoms may improve potency, half-life, and CNS penetration.
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Safety and Handling
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Safety Profile: Limited rigorous clinical trials exist, so the full safety profile, appropriate dosages, and long-term effects are not well-established. Anecdotal reports from nootropic users suggest side effects similar to but potentially stronger than modafinil, including insomnia, anxiety, headaches, increased heart rate, skin reactions, and overstimulation. As a research chemical, it lacks comprehensive toxicity data; potential risks include addiction (though lower than amphetamines in animal studies), cardiovascular effects, and interactions with other CNS drugs.
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Handling and Storage: Sold as a "research chemical" or "not for human consumption." Handle with standard laboratory precautions: use gloves, avoid inhalation/ingestion, store in a cool, dry place away from light. No specific environmental or disposal guidelines are provided, but follow general chemical handling protocols.
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Legal and Regulatory Status: Not approved for medical use by FDA, EMA, or similar agencies. Unscheduling in the U.S. (unlike modafinil, which is Schedule IV), but may fall under analog laws (e.g., U.S. Federal Analogue Act) due to structural similarity to controlled substances like modafinil. Legal status varies by country; often in a "grey area" for research purposes only. Possession or sale for human consumption could be regulated or prohibited.