Sunifiram (DM-235) Reference Standard — CAS 314728-85-3, C₁₄H₁₈N₂O₂

1. What this material is

This page describes sunifiram supplied as an analytical reference material: a weighed quantity of a single identified substance, intended to serve as the point of comparison against which another sample is measured.

Sunifiram is a 1,4-diacylpiperazine — a saturated piperazine ring carrying a benzoyl group on one nitrogen and a propanoyl group on the other. It was reported in 2000 by the medicinal-chemistry group in Florence as compound 13 in a series obtained by molecular simplification of a bicyclic parent, and it was given the laboratory code DM-235 [21]. It has never been registered as a medicine anywhere. It has no international nonproprietary name and no anatomical-therapeutic-chemical code; it holds no marketing authorisation in Poland [19], no entry of any kind in the European chemicals inventory [8], and no place on the United States schedule of controlled substances [20]. Section 12 sets out each of those measurements with its control. All of its published pharmacology is animal, cell or screening work.

That combination is exactly what makes a reference standard for this compound hard to substitute. A substance with a marketing authorisation acquires a pharmacopoeial monograph, an assay method, a limit test and a chain of official reference standards. Sunifiram acquired none of those, because none of the regulatory machinery ever attached to it — and yet it is a real compound that turns up in real samples. The United States forensic laboratory information system records it as an identified substance from June 2018, in the class reserved for substances that are not scheduled [1]. A forensic, customs or quality-control laboratory that meets it therefore has a genuine identification problem and, as the next sections show, remarkably little public material with which to solve it.

The chemist who first synthesised the compound wrote about exactly this situation. In a 2016 retrospective titled “Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings”, Gualtieri records that the compounds “were not protected by a patent”, that no company took them into development, and that twelve years after publication he “casually found that on the web, there were dozens of sites offering Unifiram and Sunifiram as drugs that improve cognition in healthy individuals even if only few preclinical studies were done and their long-term toxicity was unknown” [28]. That is the author of the molecule describing the distance between what was measured and what is asserted about it. It is quoted here because it is the most authoritative available statement about the limits of the evidence, and because it is the correct frame for what this article is: a chemical, sold to laboratories, for measurement.

The terms on which this and every other reference material here is supplied are collected in the reference standards category.

2. Identity and registry codes

The identity of this compound is unusually well anchored for a substance with so little else on record. The registry number, the structure key and the regulatory substance identifier all agree, and several of the sources carrying them are independent of the compound database itself.

Names that describe a different molecule

Two descriptions of sunifiram circulate widely in secondary and commercial sources, and both are incompatible with the deposited structure. They are set out here because a laboratory that inherits a sample described in those terms needs to know that the description constrains nothing about the chemistry.

“A pyrimidine derivative.” The ring in sunifiram is a piperazine: fully saturated, with nitrogen atoms at the 1 and 4 positions. Pyrimidine is an aromatic 1,3-diazine. The connectivity string in the table above settles the point without interpretation — the fragment ...15-8-10-16(11-9-15)... describes a six-membered ring in which the two nitrogens are separated by two carbons on either side, with every ring carbon carrying two hydrogens. Wrong ring, wrong nitrogen positions, wrong saturation state. The title of the Florence group’s own 2017 paper places the compound in its class without ambiguity: “Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents” [29].

“A homologue of modafinil.” Modafinil is C₁₅H₁₅NO₂S, monoisotopic mass 273.0823 Da, a diphenylmethylsulfinylacetamide carrying a sulfur atom and a stereocentre at that sulfur [1]. Sunifiram is C₁₄H₁₈N₂O₂, 246.1368 Da, contains no sulfur, carries two nitrogens rather than one, and is achiral. Homologues differ by a methylene unit on a preserved skeleton; these two skeletons share no common core. The practical consequence is that no chromatographic or mass-spectrometric expectation transfers between them in either direction — protonated modafinil sits at m/z 274.0896 against 247.1441 for sunifiram, and the two are unrelated in retention behaviour as well as in mass.

Descriptions of this kind are not harmless labelling slips. Section 5 shows that there is a real, registered compound which shares sunifiram’s molecular formula, its exact mass, its polar surface area and its computed partition coefficient, and which differs from it in the position of a single methyl group. Against that background, an identification resting on a name rather than on a measurement is not an identification.

3. Registers that hold nothing, and the controls that prove the search was real

Most of what can be said about the public record of this compound is a list of absences. An absence is the easiest kind of finding to get wrong: a query aimed at the wrong place and a query run against a broken instrument produce the same output, a confident nothing. Every negative result below was therefore paired with the same query run against a substance known to be present, and the negative is reported only where the control came back populated.

Every control fired. The zeros above are therefore findings about the world rather than artefacts of the search. Where a control could not be constructed, the honest verdict is not established, and it appears as such in section 15 rather than being quietly rounded down to none.

Two absences worth naming individually

The cross-reference count. A structure-key lookup across the major chemistry resources returns eight sources for sunifiram and eighteen for piracetam [10]. The ten that piracetam has and sunifiram does not are, precisely: the crystallographic data centre, the binding database, the chemical entities ontology, the clinical-trial index, the drug database, the drug-central index, the pharmacology guide, the human metabolome database, and both protein-structure archives. That list is not a rhetorical flourish. It is a map of the things a laboratory would normally consult and will find empty here: no solved solid-state structure, no measured binding constants, no curated metabolism, no trial record.

The Polish legal position was measured on the law as it currently stands. The consolidated text of the Polish schedules dates from 2024 [16], and it has since been amended twice — by the regulation of 30 April 2025 [17] and by the regulation of 7 July 2026, promulgated on 13 July 2026 [18]. A consolidated text cannot, by construction, show anything added after it was consolidated, so all three documents were searched. Sunifiram, unifiram, the code DM-235 and the CAS number return zero occurrences in each of the three. The controls are described in the table above and in section 12.

4. Structure and stereochemistry

Sunifiram is a piperazine ring acylated on both nitrogen atoms: a benzoyl group on one, a propanoyl group on the other. Both nitrogens are therefore amide nitrogens. There is no basic nitrogen anywhere in the molecule and no hydrogen-bond donor of any kind, which has consequences that run through the whole of the analytical discussion below.

The molecule is achiral, and unusually for a compound this thinly documented, that conclusion rests on more than one instrument. Four zeros in the compound record [1]. An explicit ruling in the regulatory substance registration system, which records the substance as achiral, with no optical activity and zero stereocentres — a registrar’s determination rather than an automated count [9]. The identity of the connectivity and stereo-bearing structure strings noted in section 2 [1]. And the absence of any second registry entry that would correspond to a resolved enantiomer [1].

Why there is no stereocentre, and where the one in the parent compound went

Sunifiram was obtained by opening the bicyclic framework of an earlier compound. Its direct predecessor, unifiram (code DM-232), is a 1,4-diazabicyclo[4.3.0]nonanone bearing a stereogenic ring-fusion carbon; simplifying that bicycle to a plain piperazine removed the carbon that carried the stereochemistry [21]. What remains is a ring with a mirror plane through the two nitrogen atoms, two sp² amide nitrogens that cannot invert as chirality elements, and no carbon bearing four different substituents. There is nothing left to be stereogenic.

The contrast with unifiram is not academic. Unifiram is C₁₃H₁₅FN₂O₃S with one undefined atom stereocentre in its record [2], and its enantiomers were prepared separately from (S)- and (R)-5-(hydroxymethyl)-2-pyrrolidinone, resolved to better than 99.9 % enantiomeric excess and checked by capillary electrophoresis; the (R)-(+) form was reported as three- to tenfold more potent than the (S)-(−) form in the animal assay used [25]. That paper is the only stereochemical work in the entire corpus on this compound family, and it is about the other compound.

Achirality also disposes of a class of claim outright. There is no dextrorotatory sunifiram, no laevorotatory form, no R or S designation, no enantiomeric excess to specify, no racemate, and no chiral impurity to control. Any specification, certificate or listing that quotes an optical rotation for this compound is describing something that cannot exist for it. The situation is the reverse of tadalafil, where two defined centres generate four separately registered stereoisomers and the whole analytical burden falls on separating them; here the entire chiral budget is free, and it should be spent on the constitutional problem instead.

5. The isomer with the same mass, the same logP and one extra stereocentre

Accurate mass is the reflex answer to an identity question, and for this compound it is a much weaker answer than it looks. A formula search of the compound registry for C₁₄H₁₈N₂O₂ returns 27 746 records [1]. Every one of them has the monoisotopic mass 246.1368 Da, because they are the same set of atoms. Accurate mass does not identify sunifiram; it narrows the field to roughly twenty-eight thousand candidates.

Most of those are chemically remote and would never be confused with it. A small number are not. Searching that formula space for diacylpiperazines specifically — the same structural class, built from the same two-step chemistry — returns registered compounds that a method built around mass alone will not separate from the target.

Read the second row carefully. 1-(4-Benzoyl-2-methylpiperazin-1-yl)ethanone has the same molecular formula as sunifiram, the same monoisotopic mass to all twelve figures the registry prints, the same topological polar surface area, the same computed partition coefficient to the decimal place, and an InChIKey ending in the same final block [4]. It differs from sunifiram in one respect that a mass spectrometer cannot see: the methyl group that sunifiram carries on the propanoyl chain sits instead on the piperazine ring, at the 2-position. That single relocation creates a stereogenic carbon, which is why its record shows one undefined atom stereocentre where sunifiram shows zero.

Section 7 sets out the second discriminator: the two acyl groups fragment to different ions, and one pair of transitions separates sunifiram from this isomer while another pair does not. Getting that distinction right is the practical content of the whole analytical section.

The label under which this compound travels

Sunifiram is sold, discussed and shipped under the collective label racetams. That label groups compounds with quite different formulas, masses and functional groups, and the grouping is commercial rather than chemical — sunifiram is a diacylpiperazine and contains no 2-pyrrolidinone ring at all, which is the structural feature the name refers to.

Those masses are far apart, and any instrument of ordinary resolving power separates them without effort. That is precisely the point worth making: the risk in this family is not that the measurement cannot distinguish them, but that no measurement is made. When a sample arrives labelled with a trade name and the assignment is taken from the label, the mass differences never come into play. Cohen and colleagues measured what that produces in this exact category of product: of twelve items examined by untargeted liquid chromatography with quadrupole time-of-flight detection, 75 % (9 of 12) of declared quantities were inaccurate, undeclared drugs were present, and declared drugs were absent [33]. Their study looked for omberacetam, aniracetam, phenylpiracetam and oxiracetam — sunifiram was not among the analytes and was neither sought nor found — so it is cited here as a measurement of how reliable labelling is in this product class, not as a finding about this substance.

Two further surveys describe the same market from a different angle. Schifano and colleagues place unifiram analogues among the compounds most often encountered in this space and record that reported benefits in healthy individuals are “uncertain and any reported improvement temporary”, alongside cardiovascular and psychopathological risks [34]. Napoletano and colleagues describe the online supply chain through which these compounds move [35]. A Polish group surveyed the domestic supplement market and catalogued 120 synthetic substances with claimed effects on cognition, 45 of them with unclear status, concluding that the term used to market them “currently serves more as a marketing tool than as a concept describing a group of substances with scientifically proven cognitive effects” [36]. We cite that last work from its abstract only; we were not able to search its full text with a working control, and we do not claim that sunifiram appears in its tables. A separate study on a different compound from the same market demonstrates the analytical approach that such work requires [37].

6. Three spectra, effectively one sample

For a substance sold as an analytical reference material, the state of the deposited spectral record is the most important thing on the page. Here it is short enough to print in full.

The table was read from a complete listing of the record’s sections, not from a keyword search, so the absences are structural rather than inferred: the spectral part of the record contains exactly three subsections, and none of them is an NMR subsection [1].

This is a different kind of gap from a simple absence, and it deserves the distinction. A missing spectrum announces itself: you look, nothing is there, you know where you stand. A spectral record consisting of one sample presented as a reference looks complete from a distance. A laboratory that matches its material against the deposited infrared spectrum and gets a good fit has established that its material resembles the contents of a Sigma-Aldrich container from lot 51K4707 — which is useful, and is not the same as establishing that its material is sunifiram.

The comparison across this catalogue makes the scale clear. Chlodantane has no deposited spectrum of any kind, which at least leaves no room for false confidence. Mebicar has proton NMR, carbon NMR and an electron-ionisation spectrum, but only a vapour-phase infrared, so nothing describes it as a solid. Sunifiram sits between them and is in some ways the more awkward case: it has two solid-phase spectra of good technique, and they share a single origin.

What follows for a laboratory that buys a standard

Because there is no independent reference, the first well-characterised measurement made on authenticated material effectively becomes the reference for the organisation that makes it. Two things follow.

Record more than you normally would. For a compound with a monograph, a retention time and two transitions suffice, because the monograph carries the rest. Here nothing carries the rest. A full set — ¹H and ¹³C with assignments, an accurate-mass measurement, a product-ion spectrum with collision energies, a solid-phase infrared, and a melting range — costs an afternoon and becomes the only description of this substance your organisation will hold. Every one of those measurements is currently absent from the public record, which means yours has value beyond your own laboratory.

Check your first measurement against itself. With no external comparison available, the only available check is agreement between independent techniques on the same material: does the accurate mass match the formula, does the ¹³C spectrum account for all fourteen carbons once the ring symmetry is allowed for — and note that restricted rotation about the two amide bonds commonly broadens or doubles the piperazine ring signals, so a clean count is not guaranteed at room temperature — does the product-ion spectrum show both acyl fragments predicted in section 7, and does a chiral column give one peak. Four techniques that agree constitute an identification. One technique returning an expected number does not — and with an isomer that matches on mass, on polar surface area and on computed logP (section 5), a single expected number is precisely the situation in which a mislabelled vial passes unnoticed.

7. Fragmentation predicted from structure, and the transitions nobody published

Sunifiram has an unusually convenient fragmentation logic and, at present, no published fragmentation data at all. The molecule is a piperazine carrying two different acyl groups. Cleaving either amide bond gives an acylium ion and a complementary protonated amine fragment, so the four principal product ions come in two complementary pairs whose masses add up in a way that can be checked arithmetically.

Note the internal arithmetic: 105.0335 and 143.1179 sum to 248.1514, which is the precursor plus one proton, as they must, because the pair partitions the protonated molecule with charge retention on either side. The same holds for 57.0335 and 191.1179. That consistency is a check you can apply to your own spectrum before you trust it.

Two of those isomers, the toluoyl and the phenylacetyl compounds, give an acylium of the same nominal and the same exact composition, C₈H₇O⁺ at 119.0491, so accurate mass does not separate them from each other either. They should, however, differ in secondary fragmentation: a phenylacetyl group has a benzylic bond and would be expected to give a tropylium ion at 91.0542, while a methylbenzoyl group would not do so readily. That expectation is a structural inference and is not backed by any deposited spectrum, which is exactly the point of this section.

Every number in this section is calculated from the molecular formula using standard nuclide masses, and every one is labelled as such. None of it is a deposited measurement, because no deposited measurement exists. If your spectrum disagrees with these predictions, the first hypothesis to test is that the prediction is incomplete — collision energies, adduct formation and in-source fragmentation all shift what is actually observed — and the way to settle it is the internal-consistency check described in section 6.

8. What works, what fails, and why

The computed descriptors read as an instruction manual for method development if they are read in the right order: XLogP3 1.1, TPSA 40.6 Å², zero hydrogen-bond donors, two acceptors, two rotatable bonds, formal charge zero, and no ionisable group in any ordinary aqueous range [1].

Three of those rows deserve a sentence apiece, because they are the ones most often got wrong.

Zero donors is a structural statement, not a computed guess. The count of zero hydrogen-bond donors follows directly from the structure: both nitrogens carry acyl groups, so neither has a hydrogen. That is why no salt form is possible, why no pH lever exists, and why the exchangeable-proton experiments that resolve many identity questions have nothing to work with here. It is one of the few descriptor values on this page that is not merely a calculation but a direct consequence of the connectivity.

The absent ultraviolet spectrum is a practical obstacle, not a curiosity. Diode-array detection is the default in most quality-control laboratories, and it requires a reference absorption maximum. There is none on record for this compound. You can measure it in an afternoon, and until you do, a peak identified by ultraviolet retention alone has been identified against nothing.

Gas chromatography carries the only deposited mass spectrum. That makes it the technique with a genuine external reference — the single point in this whole discussion where a library comparison is available. Its provenance is not annotated with a sample source, unlike the infrared and Raman entries, so its independence from the same commercial material cannot be established either way.

9. Physicochemical data: computed only

The compound record contains no experimental properties section. Under physical and chemical properties there are computed values and a chemical-class annotation, and nothing else [1]. The national standards database holds nothing for this compound at all: the registry-number lookup returns “Registry Number Not Found”, while the same lookup for formaldehyde returns a full record including phase-change data [7]. There is no melting point, no boiling point, no density, no measured partition coefficient, no pK_a, no vapour pressure, no refractive index, no measured solubility in water or in any organic solvent, and no stability or reactivity study.

Two molecular masses, both defensible

The average molecular mass of this compound is quoted in two forms, and the difference is real rather than a transcription error. The compound record prints 246.30 [1]. Recomputing the formula from the current IUPAC abridged atomic weights — carbon 12.011, hydrogen 1.008, nitrogen 14.007, oxygen 15.999 — gives 246.310, which rounds to 246.31; the bioactivity database independently lists 246.31 [11]. Using an older atomic-weight table (carbon 12.0107, hydrogen 1.00794, nitrogen 14.0067, oxygen 15.9994) reproduces 246.305, which rounds to the registry value. Both numbers are arithmetically correct; they differ because they rest on different editions of the same table.

We print both rather than choosing, because a certificate quoting one and a downstream system reconciling against the other will report a mismatch that is not a mismatch. The monoisotopic mass is unaffected by this and is the value to use for any mass-spectrometric work: 246.1368 Da. The record carries it to twelve significant figures; that precision has no physical meaning for a laboratory measurement and we do not reproduce it in working contexts.

What may and may not be inferred

From the computed set it is legitimate to conclude that the compound is moderately lipophilic, conformationally fairly rigid, incapable of donating a hydrogen bond, and non-ionisable across the usual aqueous range. From the same set it is not legitimate to derive a melting point, a numerical solubility, a density or a shelf life, because those are experimental quantities and no experiment is on record.

10. Eight hundred and seventy screening results, and the seven that are not negative

The only body of experimental data attached to this compound in any public database is high-throughput screening. The bioassay summary for the compound contains 870 rows, distributed as follows [1]:

The counter that produced those figures was checked against piracetam through the same interface, which returns ten active assay identifiers where sunifiram returns seven — so the instrument distinguishes an active outcome from an inactive one, and the number seven is a measurement rather than a default.

Those seven are worth naming, because a screening panel that is 91 % inactive is easy to summarise as “nothing found”, and that summary would be false.

One point about the muscarinic screen is worth recording for completeness, because it is the sort of detail that gets lost when a panel is summarised: the recorded outcome is an antagonist outcome at a cholinergic receptor. The published animal literature on this compound describes activity in the opposite direction, against experimentally induced amnesia including amnesia induced by the muscarinic antagonist scopolamine [22]. An unconfirmed primary screening hit does not overturn a body of animal work, and a body of animal work does not make a screening hit disappear. Both are on the record, they point in different directions, and neither has been followed up. That is the honest state of the evidence.

There is one more absence to record here. A search of the United States adverse-event reporting system returns no reports for this substance, against 111 340 for paracetamol on the same query. That is a fact about reporting rather than about safety: an unapproved substance that is not dispensed as a medicine generates no pharmacovigilance record, whatever its properties. No toxicological package for this compound has been published; the 2016 retrospective by its originator states that long-term toxicity was unknown [28], and the encyclopaedic summary of the compound records that as of 2016 it “had not been subjected to toxicology testing, nor to any human clinical trials, and is not approved for use anywhere in the world” [38].

11. What the literature actually says

The corpus on sunifiram is small enough to count. The biomedical index returns 16 records for the name and every code variant combined; a cross-publisher bibliographic search returns 10. Both counts were reproduced with a working control on the same query form. For comparison, the same index returns 4032 records for piracetam. This is not a body of literature with a review layer, a controversy and a consensus; it is a short shelf, produced almost entirely by one group over about seventeen years.

The primary series

Manetti and colleagues, 2000 [21] is the paper in which the compound first appears, as compound 13 in a series obtained by simplifying a 1,4-diazabicyclo[4.3.0]nonan-9-one framework to a piperazine. The abstract states that compound 13 “shows outstanding potency, being active at a dose of 0.001 mg kg(-1) sc.” in the animal assay used. This is also the most likely location of any physical characterisation of the substance — melting point, synthetic yield, elemental analysis — but the experimental section is behind a paywall and we have not read it, so we quote no number from it.

Ghelardini and colleagues, 2002 [22] is the first full pharmacological description. It reports activity in the mouse passive-avoidance test at 0.001–0.1 mg per kilogram intraperitoneally and 0.01–0.1 mg per kilogram orally, against amnesia induced by scopolamine, mecamylamine, baclofen and clonidine, and states that “its potency is about 1,000 times higher than that of the most active piracetam-like compounds”. Every measurement in it is in mice.

Galeotti and colleagues, 2003 [23] implicates AMPA-receptor activation in the antiamnesic effect of both compounds in the series. Scapecchi and colleagues, 2004 [24] is the structure-activity study and is discussed separately below. Martini and colleagues, 2005 [25] is the enantioselective synthesis of unifiram, discussed in section 4. Romanelli and colleagues, 2006 [26] reviews both compounds, describes them as four orders of magnitude more potent than piracetam in the assays used, and adds a constraint that is easy to miss: they act “although not showing affinity in binding studies for the most important central receptors or channels”.

Moriguchi and colleagues, 2013 [27] reports enhancement of hippocampal synaptic efficacy through the glycine-binding site of the NMDA receptor, with a bell-shaped concentration-response peaking near 10 nM, blocked by 7-chlorokynurenate and unaffected by ifenprodil. Martino and colleagues, 2017 [29] is the most recent synthetic work from the group and carries two mass-spectrometrists among its authors — the closest this corpus comes to analytical chemistry, and a measure of how far from a validated assay it remains.

The literature gets the skeleton wrong too

The 2013 paper referred to above opens by describing sunifiram as a “pyrrolidone nootropic drug” [27]. The compound contains no pyrrolidinone ring; it is a diacylpiperazine, as the group that made it states in the title of its own later paper [29]. The error is minor in its context and does not affect the electrophysiology reported, but it is worth recording for a reason that has nothing to do with criticising the paper: if a peer-reviewed journal can misassign the ring system, then a sample description that names the ring system is not evidence about the ring system. The only durable anchor is the identity chain — CAS 314728-85-3, InChIKey DGOWDUFJCINDGI-UHFFFAOYSA-N, UNII 66924E735K — tied to a material you have measured.

One paper in this corpus has been retracted

What the literature does not contain

No validated analytical method. No pharmacokinetic study of any kind. No metabolism or metabolite identification. No toxicological package. No human study. No crystal structure or polymorph screen. No stability or forced-degradation data. Each of those is a measured absence, established as described in section 3, and together they are the reason this page spends more space on how to measure the compound than on what the compound does.

12. Regulatory status

Every statement in this section was measured against a named document with a positive control on the same document. The documents and the controls are listed in section 3.

The Polish position was measured on the law as it currently stands

This deserves setting out in detail, because it is the kind of statement that goes stale silently. The Polish schedules of narcotic drugs, psychotropic substances and new psychoactive substances are published as a regulation of the Minister of Health. The consolidated text in force is that published in 2024 [16]. A consolidated text is a snapshot: it cannot show anything added after the date it was consolidated. Since that date the regulation has been amended twice — by the regulation of 30 April 2025 [17] and by the regulation of 7 July 2026, promulgated on 13 July 2026 [18]. Measuring only the consolidated text would have produced a correct answer for the wrong reason, and would have missed anything added in either amendment.

All three documents were searched. The controls are as follows. In the consolidated text, the amphetamine stem returns 27 occurrences and cocaine 2; six substances that appear only on the new-psychoactive-substances annex — among them 4-CMC, HHC and bromazolam — are all present, which establishes that the annex is included in the document and is searchable rather than an image. In the 2025 and 2026 amendments, which are short instruments listing only changes, the controls are the substances those instruments add. In all three, sunifiram, unifiram, the code DM-235 and the CAS number 314728-85-3 return zero.

Forensic reporting is not scheduling

The compound record carries an entry from the United States drug enforcement administration reading, verbatim, “Sunifiram (Class: Other Substances, Added Date: 06-2018)” [1]. This comes from the national forensic laboratory information system, which is a reporting system: it records what forensic laboratories actually identify in submitted evidence. The class “Other Substances” is the bucket for substances that are not scheduled. An entry there means the compound has been found and identified in casework. It does not mean the compound is controlled, and it confers no schedule. The direct measurement on the schedule listing itself returns zero [20].

For a laboratory, the entry is nonetheless the single most operationally relevant fact on this page: it is documentary evidence that samples containing this substance reach forensic laboratories, and have done since 2018, in a jurisdiction that publishes such counts.

The anti-doping caveat, stated precisely

13. Hazard: no classification exists

There is no hazard classification for sunifiram. Not an incomplete one, not a disputed one, not a single-notifier one: the compound record contains no safety and hazards section whatsoever [1], and the substance has no entry in the European chemicals inventory at all [8]. There is no signal word, no hazard statement, no precautionary statement, no pictogram and no notification count to quote, because there are zero notifications.

The working position we recommend, and apply ourselves, is to handle unclassified material at least as carefully as the most closely comparable classified substance, and to record in the risk assessment that the assessment proceeds by analogy. Treating an unclassified organic solid as though it were at least an irritant, and possibly harmful if swallowed, is a defensible default. Treating it as harmless because the box is empty is not.

14. Handling and storage

15. What we certify and what we do not

16. Terms of supply

This material is supplied as a laboratory reagent and analytical reference material, for in-vitro laboratory use by qualified personnel in an appropriately equipped facility. It is not a medicinal product, not a dietary supplement, not a food, feed or cosmetic ingredient, and it is not supplied for administration to humans or animals in any form or by any route.

Eight pack sizes are catalogued, from 1 g to 100 g. At the time of writing all eight are out of stock; the page remains published so that the identity data, the analytical discussion and the citations stay reachable, and because the specification does not change with stock level. Where a lot is available, lot documentation accompanies the material and names the assay method used.

By ordering, the purchaser confirms that they are a professional user acquiring the material for laboratory purposes; that they will handle it in accordance with section 14 and their own institutional risk assessment, taking specific account of the fact that no hazard classification exists; that they will not administer it to humans or animals, nor supply it to any person who intends to; and that they are responsible for compliance with all laws applicable at the destination.

Nothing on this page is medical advice, and nothing on it is an offer of a medicinal product. Statements in sections 10, 11 and 12 describe published research and the content of named regulatory documents; they describe neither this article nor any use of it.

17. Questions and answers

What reference spectra exist for sunifiram?

Three: a gas-chromatographic mass spectrum, an attenuated-total-reflectance infrared spectrum and a Fourier-transform Raman spectrum. There is no proton NMR, no carbon NMR, no two-dimensional NMR, no LC-MS/MS, no ultraviolet spectrum and no high-resolution mass spectrum. For a substance sold as a reference material this is the single most important fact on the page, which is why it appears in the second paragraph rather than here.

Why does it matter that the infrared and Raman spectra share a lot number?

Because they are then two techniques applied to one sample rather than two independent characterisations. Both are annotated to Sigma-Aldrich catalogue D5689, lot 51K4707. If that material were misidentified or impure, both spectra would carry the error and would agree with each other perfectly. Agreement between an infrared and a Raman spectrum of the same vial says nothing about what is in the vial, and there is no independently sourced solid-phase spectrum in the record to check it against.

Is accurate mass enough to identify it?

No. Roughly 27 700 registered compounds share the molecular formula C₁₄H₁₈N₂O₂ and therefore share the monoisotopic mass 246.1368 Da exactly. At least four of them are diacylpiperazines built from the same chemistry, and one of those matches sunifiram on formula, exact mass, polar surface area and computed logP simultaneously. Accurate mass narrows the field; it does not close it.

Which isomer is the awkward one, and how do I rule it out?

1-(4-Benzoyl-2-methylpiperazin-1-yl)ethanone. It carries the same benzoyl group as sunifiram, with the methyl relocated from the propanoyl chain onto the piperazine ring. Two of the four principal product ions are shared, including the obvious 247 → 105 transition. Rule it out with the propanoyl-side pair: sunifiram gives 57.0335 and 191.1179; the isomer gives 43.0178 and 205.1335. Alternatively, run a chiral column — that isomer has a stereocentre and sunifiram does not.

Is sunifiram chiral? Do I need a chiral method?

It is achiral, and you do not need a chiral method to separate anything. You may still want to run one as a check. The compound record shows zero defined and zero undefined stereocentres of both atom and bond type, and the regulatory substance registration system records it explicitly as achiral, with no optical activity and zero stereocentres. Any claim about a dextrorotatory form, an optical rotation or an enantiomeric excess for this compound is fabricated by construction.

Then why would I put an achiral compound on a chiral column?

Because the expected result is one peak, and two peaks are informative. Sunifiram cannot resolve into enantiomers, so a chiral column that gives two peaks has found something else: an impurity, or a different compound — possibly the same-formula isomer above, which does have a stereocentre. It is a cheap correctness test with an unambiguous expected outcome, and it needs a reference material whose achirality is documented.

Does the InChIKey ending in UHFFFAOYSA prove it is achiral?

No, and this is a common trap. Modafinil and unifiram both have an undefined stereocentre and both have InChIKeys ending in the same block. The suffix reflects how the key was generated, not whether the molecule is chiral. What carries the conclusion here is the four zero counts, the registrar’s explicit achiral ruling, and the fact that the record’s connectivity and stereo-bearing structure strings are identical — a comparison that does discriminate, because for a chiral compound the two differ.

Is there a hydrochloride or another salt form?

There cannot be. Both nitrogens are amide nitrogens, there is no basic centre anywhere in the molecule, and the record shows zero hydrogen-bond donors. With no site to protonate, an acid-addition salt is not chemically available. A listing offering a hydrochloride, citrate, fumarate or maleate of this compound is describing a different substance, and the masses quoted here apply to the free base and to nothing else.

What is the melting point?

Unknown to us. The compound record has no experimental properties section at all, and the national standards database has no entry for this compound at all — the registry-number lookup returns “not found”, where the same lookup for formaldehyde returns a full record with phase-change data. A value most plausibly exists in the experimental section of the 2000 synthesis paper, which sits behind a paywall and which we have not read. We do not quote numbers we have not seen. If you measure one on this material, you will have generated a datum that is not currently public.

What hazard classification applies?

None exists. The substance has no entry in the European chemicals inventory, so there are zero notifications, no signal word, no hazard statement and no harmonised classification. That reflects the absence of commercial notification in Europe, not a finding about toxicology. Handle it as an unclassified organic solid, and record in your risk assessment that you are proceeding by analogy.

Is it a controlled substance?

Not in Poland, measured on the consolidated schedules and on both amending regulations issued since, most recently the regulation of 7 July 2026. Not in the United States, measured directly on the alphabetical schedule listing where amphetamine, fentanyl and modafinil all return hits. It does have an entry in the United States forensic reporting system dated June 2018 — that records what laboratories identify in evidence, and it is not a schedule.

Is it prohibited in sport?

It is not listed by name on the 2026 Prohibited List, and the search was verified with controls that fired on bromantan, modafinil and meldonium. That is not the same as permitted. The list contains a class covering non-approved substances — those with no current approval by any governmental health authority for human therapeutic use — and sunifiram has no approval anywhere. Whether it falls inside that class in a given case is a legal determination, not a text search, and we do not make it.

Has it been tested in humans?

No. There is no human study, no pharmacokinetic data and no published toxicological package. Its originator wrote in 2016 that long-term toxicity was unknown, and the encyclopaedic summary of the compound records that as of 2016 it had not been subjected to toxicology testing, nor to any human clinical trials, and was not approved for use anywhere in the world.

Are the screening results a safety assessment?

No. The panel contains 870 rows, of which 793 are inactive, and 7 are active. Five of the seven are mid-micromolar antiplasmodial results from a single published survey; the other two are unconfirmed primary screening hits, one at a muscarinic receptor and one at an enzyme. Primary screening data has a substantial false-positive rate and an unconfirmed hit is a candidate for follow-up, not a property of the molecule. We report all seven because reporting the panel as uniformly negative would be inaccurate, and we draw no pharmacological conclusion from any of them.

Which paper in the bibliography should I not cite?

The 2022 study on sunifiram-carbamate hybrids in the Journal of Enzyme Inhibition and Medicinal Chemistry. It was retracted on 7 August 2026 by a statement of retraction in the same journal, with the retraction confirmed in both directions in the publisher metadata. It is listed in the references below only so that it can be recognised and avoided.

Why is this compound worth holding as a standard if nobody sells a method for it?

That is the reason rather than an objection to it. Where a monograph exists, the monograph carries the identity and a standard mostly confirms it. Here there is no monograph, no validated method, no NMR spectrum, no product-ion spectrum and no independently sourced solid-phase spectrum — so the first well-characterised measurement made on authenticated material becomes the reference for the organisation that makes it. That raises rather than lowers the importance of the material actually being what the label says, because nothing downstream will catch an error.

What purity is guaranteed?

Section 15 sets out exactly what is and is not certified. Purity is stated on the lot documentation together with the method used, and not in catalogue copy. Figures specified to a hundredth of a percentage point circulate in commercial listings for this compound; with no published assay method for it in existence, such precision cannot be supported by anything, and we do not print it.

References

Compound records: the target and the compounds used for comparison

1. National Center for Biotechnology Information. 2026. "PubChem Compound Summary for CID 4223812, 1-(4-Benzoyl-1-piperazinyl)-1-propanone (Sunifiram)." PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/4223812.
2. National Center for Biotechnology Information. 2026. "PubChem Compound Summary for CID 9861054, Unifiram." PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/9861054.
3. National Center for Biotechnology Information. 2026. "PubChem Compound Summary for CID 2196, Aniracetam." PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/2196.
4. National Center for Biotechnology Information. 2026. "PubChem Compound Summary for CID 10824330, 1-(4-Benzoyl-2-methylpiperazin-1-yl)ethanone." PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/10824330.
5. National Center for Biotechnology Information. 2026. "PubChem Compound Summary for CID 27046747, 1-Acetyl-4-[(4-methylphenyl)carbonyl]piperazine." PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/27046747.
6. National Center for Biotechnology Information. 2026. "PubChem Compound Summaries for CID 71684148, 1-[4-(2-Methylbenzoyl)piperazin-1-yl]ethanone, and CID 71684146, 1-(4-Acetylpiperazin-1-yl)-2-phenylethanone." PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/71684148; https://pubchem.ncbi.nlm.nih.gov/compound/71684146.

Registry, cross-reference and substance-registration sources

7. National Institute of Standards and Technology. 2026. "NIST Chemistry WebBook, SRD 69." https://webbook.nist.gov/chemistry/.
8. European Chemicals Agency. 2026. "Search for Chemicals — ECHA CHEM Substance Inventory." https://chem.echa.europa.eu/.
9. United States Food and Drug Administration. 2026. "Substance Registration System — UNII 66924E735K, Sunifiram." https://precision.fda.gov/uniisearch/srs/unii/66924E735K.
10. European Bioinformatics Institute. 2026. "UniChem — Compound Cross-References." EMBL-EBI. https://www.ebi.ac.uk/unichem/.
11. European Bioinformatics Institute. 2026. "ChEMBL Compound Report Card CHEMBL309176." EMBL-EBI. https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL309176/.
12. United States Environmental Protection Agency. 2026. "CompTox Chemicals Dashboard, DTXSID10400996." https://comptox.epa.gov/dashboard/chemical/details/DTXSID10400996.
13. National Cancer Institute. 2026. "NCI Thesaurus, Concept C220969, Sunifiram." https://ncithesaurus.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C220969.
14. Wikidata. 2026. "Sunifiram (Q6590525)." https://www.wikidata.org/wiki/Q6590525.

Regulatory documents measured for this page

15. World Anti-Doping Agency. 2026. "World Anti-Doping Code International Standard: Prohibited List 2026." WADA. https://www.wada-ama.org/en/prohibited-list.
16. Minister Zdrowia. 2024. "Obwieszczenie Ministra Zdrowia z dnia 17 czerwca 2024 r. w sprawie ogłoszenia jednolitego tekstu rozporządzenia w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych." Dziennik Ustaw 2024, poz. 1139. https://api.sejm.gov.pl/eli/acts/DU/2024/1139/text.pdf.
17. Minister Zdrowia. 2025. "Rozporządzenie Ministra Zdrowia z dnia 30 kwietnia 2025 r. zmieniające rozporządzenie w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych." Dziennik Ustaw 2025, poz. 598. https://api.sejm.gov.pl/eli/acts/DU/2025/598/text.pdf.
18. Minister Zdrowia. 2026. "Rozporządzenie Ministra Zdrowia z dnia 7 lipca 2026 r. zmieniające rozporządzenie w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych." Dziennik Ustaw 2026, poz. 934, promulgated 13 July 2026. https://api.sejm.gov.pl/eli/acts/DU/2026/934/text.pdf.
19. Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych. 2026. "Rejestr Produktów Leczniczych." https://rejestry.ezdrowie.gov.pl/rpl/search/public.
20. United States Drug Enforcement Administration, Diversion Control Division. 2026. "Controlled Substances — Alphabetical Order." https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf.

The primary literature on sunifiram and its immediate series

21. Manetti, Dina, Carla Ghelardini, Alessandro Bartolini, Silvia Dei, Nicoletta Galeotti, Fulvio Gualtieri, Maria Novella Romanelli, and Elisabetta Teodori. 2000. "Molecular Simplification of 1,4-Diazabicyclo[4.3.0]nonan-9-ones Gives Piperazine Derivatives That Maintain High Nootropic Activity." Journal of Medicinal Chemistry 43 (23): 4499–4507. https://doi.org/10.1021/jm000972h.
22. Ghelardini, Carla, Nicoletta Galeotti, Fulvio Gualtieri, Maria Novella Romanelli, Corrado Bucherelli, Elisabetta Baldi, and Alessandro Bartolini. 2002. "DM235 (Sunifiram): A Novel Nootropic with Potential as a Cognitive Enhancer." Naunyn-Schmiedeberg's Archives of Pharmacology 365 (6): 419–426. https://doi.org/10.1007/s00210-002-0577-3.
23. Galeotti, Nicoletta, Carla Ghelardini, Anna Pittaluga, Anna Maria Pugliese, Alessandro Bartolini, Dina Manetti, Maria Novella Romanelli, and Fulvio Gualtieri. 2003. "AMPA-Receptor Activation Is Involved in the Antiamnesic Effect of DM 232 (Unifiram) and DM 235 (Sunifiram)." Naunyn-Schmiedeberg's Archives of Pharmacology 368 (6): 538–545. https://doi.org/10.1007/s00210-003-0812-6.
24. Scapecchi, Serena, Elisabetta Martini, Dina Manetti, Carla Ghelardini, Cecilia Martelli, Silvia Dei, Nicoletta Galeotti, Luca Guandalini, Maria Novella Romanelli, and Elisabetta Teodori. 2004. "Structure–Activity Relationship Studies on Unifiram (DM232) and Sunifiram (DM235), Two Novel and Potent Cognition Enhancing Drugs." Bioorganic & Medicinal Chemistry 12 (1): 71–85. https://doi.org/10.1016/j.bmc.2003.10.025.
25. Martini, Elisabetta, Carla Ghelardini, Carlo Bertucci, Silvia Dei, Fulvio Gualtieri, Luca Guandalini, Dina Manetti, Serena Scapecchi, Elisabetta Teodori, and Maria Novella Romanelli. 2005. "Enantioselective Synthesis and Preliminary Pharmacological Evaluation of the Enantiomers of Unifiram (DM232), a Potent Cognition-Enhancing Agent." Medicinal Chemistry 1 (5): 473–480. https://doi.org/10.2174/1573406054864142.
26. Romanelli, Maria Novella, Nicoletta Galeotti, Carla Ghelardini, Dina Manetti, Elisabetta Martini, and Fulvio Gualtieri. 2006. "Pharmacological Characterization of DM232 (Unifiram) and DM235 (Sunifiram), New Potent Cognition Enhancers." CNS Drug Reviews 12 (1): 39–52. https://doi.org/10.1111/j.1527-3458.2006.00039.x.
27. Moriguchi, Shigeki, Tomoya Tanaka, Toshio Narahashi, and Kohji Fukunaga. 2013. "Novel Nootropic Drug Sunifiram Enhances Hippocampal Synaptic Efficacy via Glycine-Binding Site of N-Methyl-D-Aspartate Receptor." Hippocampus 23 (10): 942–951. https://doi.org/10.1002/hipo.22150.
28. Gualtieri, Fulvio. 2016. "Unifi Nootropics from the Lab to the Web: A Story of Academic (and Industrial) Shortcomings." Journal of Enzyme Inhibition and Medicinal Chemistry 31 (2): 187–194. Published online 2015. https://doi.org/10.3109/14756366.2015.1021252.
29. Martino, Maria Vittoria, Luca Guandalini, Lorenzo Di Cesare Mannelli, Marta Menicatti, Gianluca Bartolucci, Silvia Dei, Dina Manetti, Elisabetta Teodori, Carla Ghelardini, and Maria Novella Romanelli. 2017. "Piperazines as Nootropic Agents: New Derivatives of the Potent Cognition-Enhancer DM235 Carrying Hydrophilic Substituents." Bioorganic & Medicinal Chemistry 25 (6): 1795–1803. https://doi.org/10.1016/j.bmc.2017.02.019.

The retracted paper and its retraction notice — listed so they can be recognised, not used

30. Agha, Khalid A., Nader E. Abo-Dya, Abdul Rashid Issahaku, Clement Agoni, Mahmoud E. S. Soliman, Eatedal H. Abdel-Aal, Zakaria K. Abdel-Samii, and Tarek S. Ibrahim. 2022. "RETRACTED ARTICLE: Novel Sunifiram-Carbamate Hybrids as Potential Dual Acetylcholinesterase Inhibitor and NMDAR Co-Agonist: Simulation-Guided Analogue Design and Pharmacological Screening." Journal of Enzyme Inhibition and Medicinal Chemistry 37 (1): 1241–1256. Retracted 7 August 2026. https://doi.org/10.1080/14756366.2022.2068147.
31. Journal of Enzyme Inhibition and Medicinal Chemistry. 2026. "Statement of Retraction: Novel Sunifiram Carbamate Hybrids as Potential Dual Acetylcholinesterase Inhibitor and NMDAR Co-Agonist Simulation-Guided Analogue Design and Pharmacological Screening." 41 (1): 2712703. https://doi.org/10.1080/14756366.2026.2712703.

The screening study behind the antiplasmodial results

32. Yuan, Jing, Ronald L. Johnson, Ruili Huang, Jennifer Wichterman, Hongying Jiang, Karen Hayton, David A. Fidock, Thomas E. Wellems, James Inglese, Christopher P. Austin, and Xin-zhuan Su. 2009. "Genetic Mapping of Targets Mediating Differential Chemical Phenotypes in Plasmodium falciparum." Nature Chemical Biology 5 (10): 765–771. https://doi.org/10.1038/nchembio.215.

The product category, and what measurement finds in it

33. Cohen, Pieter A., Bharathi Avula, Yan Hong Wang, Igor Zakharevich, and Ikhlas A. Khan. 2021. "Five Unapproved Drugs Found in Cognitive Enhancement Supplements." Neurology Clinical Practice 11 (3): e303–e307. https://doi.org/10.1212/CPJ.0000000000000960.
34. Schifano, Fabrizio, Valeria Catalani, Safia Sharif, Flavia Napoletano, John Martin Corkery, Davide Arillotta, Suzanne Fergus, Alessandro Vento, and Amira Guirguis. 2022. "Benefits and Harms of 'Smart Drugs' (Nootropics) in Healthy Individuals." Drugs 82 (6): 633–647. https://doi.org/10.1007/s40265-022-01701-7.
35. Napoletano, Flavia, Fabrizio Schifano, John Martin Corkery, Amira Guirguis, Davide Arillotta, Caroline Zangani, and Alessandro Vento. 2020. "The Psychonauts' World of Cognitive Enhancers." Frontiers in Psychiatry 11: 546796. https://doi.org/10.3389/fpsyt.2020.546796.
36. Pokrywka, Andrzej, Olga Surała, Konstancja Grabowska, Marta Przybyła, Dominika Granda, Andrzej Małecki, Raphael Faiss, and Marta Nowacka-Chmielewska. 2025. "'Brain Doping' Substances: Prohibited or Not in Sports?" Biology of Sport 42 (4): 189–202. https://doi.org/10.5114/biolsport.2025.150047.
37. Upmanis, Toms, Eduards Sevostjanovs, Liga Zvejniece, Helena Kazoka, Vadims Kisis, Osvalds Pugovics, and Maija Dambrova. 2024. "Purchasing 'Nootropics' Online: Identification and Quantification of Ingredients in Phenibut-Containing Products." Medicina 60 (10): 1561. https://doi.org/10.3390/medicina60101561.

Tertiary source, quoted verbatim

38. Wikipedia. 2026. "Sunifiram." https://en.wikipedia.org/wiki/Sunifiram.