ECS modulator (research)
UnscheduledPF-622
N-phenyl-4-(quinolin-2-ylmethyl)piperazine-1-carboxamide
Aliases.PF 622 · PF622
A piperazine urea inhibiting FAAH by covalent carbamylation, with complete selectivity across the hydrolase proteome.
Updated on
Level of detail
Harm-reduction warning
No characterised human dose: animal / in vitro data only. Effect profile, safety margin and acute toxicity are not documented in human clinical practice. Extremely potent compound: severe effects, seizures and deaths reported in the literature.
Identifiers
- Formula
- C₂₁H₂₂N₄O
- Molar mass
- 346.40 g·mol⁻¹
- CAS
- -
- PubChem CID
- 11515763
- Origin
- A wholly synthetic compound with no natural occurrence. It is produced as a pharmacology reagent and has not been the subject of clinical development.
- InChIKey
- SNTCRRMCALVGNL-UHFFFAOYSA-N
In plain terms
PF-622 blocks the enzyme that destroys anandamide, one of the cannabinoids made by the body. Its interest lies in being remarkably precise: it touches almost no other enzyme. It has remained a laboratory tool.
Receptors and activity
- FAAHInhibition covalente dépendante du temps par carbamylation de la sérine catalytique (Ahn et coll. 2007)Antagonist
- CB1Effet indirect via l'élévation de l'anandamide ; pas de liaison directeModulator
- Agonist
- Partial agonist
- Antagonist
- Modulator
- Inverse agonist
Hover over a row for the precise value (Ki, EC50…)
Subjective signature
Hover over an axis to read its definition.
- Calm25
- Clarity15
- Sleep20
- Appetite10
- High15
Editorial estimate, not clinical.
Pharmacology
PF-622 was published in 2007 together with PF-750 as the lead of a new mechanistic class of fatty acid amide hydrolase inhibitors. Its discovery rests on a chemical surprise. The urea function is reputed to be one of the most stable in organic chemistry, and nobody expected it to react with an enzyme. Ahn and colleagues nevertheless observed that these piperidine and piperazine ureas inhibit the enzyme in a time-dependent manner, by carbamylating the nucleophilic serine of its active site, that is by binding to it covalently. The explanation put forward by the authors illuminates the whole field: the target enzyme is able to hydrolyse carbon-nitrogen bonds, a rare capability that distinguishes it from almost all other mammalian serine hydrolases, which cleave only esters. A urea is therefore a plausible substrate for it alone. The practical consequence is measured by proteomic profiling: the compound inhibits no other detectable serine hydrolase, a selectivity that the carbamates of the preceding generation did not achieve. That lesson mattered. The urea motif became the chemical hinge of the clinical inhibitors that followed, and retrospective analysis of the BIA 10-2474 accident in 2016 implicated precisely a non-selective inhibition of several brain lipases, confirming that selectivity across the hydrolase proteome, and not potency alone, is the decisive parameter of safety in this family.
Origin (research tool)
An entirely chemical route, described here by class only. The molecule is a piperazine urea: a piperazine ring links on one side a carboxamide bearing a phenyl and on the other a methylene group attached to a quinoline substituted at position 2. It is the urea function, reputed to be chemically inert, that constitutes the reactive group here towards the target enzyme.
Legal framework
France
A substance not listed among narcotics or among psychotropics. It holds no marketing authorisation and is not commercialised; its use falls within research.
European Union
Neither controlled nor authorised. The compound did not lead to a marketing authorisation. The whole class of amide hydrolase inhibitors remains marked by the accident of the phase 1 trial of BIA 10-2474 that occurred in Rennes in 2016, which led European authorities to tighten the requirements applicable to first-in-human trials.
Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.
Structural classification
- Class
- ECS modulator (research)
- Origin
- A wholly synthetic compound with no natural occurrence. It is produced as a pharmacology reagent and has not been the subject of clinical development.
- Status
- Unscheduled
References
Structured data
- InChIKey
- SNTCRRMCALVGNL-UHFFFAOYSA-N
- SMILES
- C1CN(CCN1CC2=NC3=CC=CC=C3C=C2)C(=O)NC4=CC=CC=C4
- Formula
- C21H22N4O
- Molar mass
- 346.40 g·mol⁻¹
- PubChem CID
- 11515763
LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.