ECS modulator (research)
UnscheduledPF-750
N-phenyl-4-(quinolin-3-ylmethyl)piperidine-1-carboxamide
Aliases.PF 750 · PF750
A piperidine urea inhibiting FAAH covalently and with perfect selectivity; a founding compound of its class.
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
- C₂₂H₂₃N₃O
- Molar mass
- 345.40 g·mol⁻¹
- CAS
- -
- PubChem CID
- 25154868
- 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
- BIODYGOZWZNCAG-UHFFFAOYSA-N
In plain terms
PF-750 prevents the destruction of anandamide, a cannabinoid produced by the body. It served to demonstrate that a chemical function reputed to be inert could block that enzyme in a highly targeted way. It has remained a research tool.
Receptors and activity
- FAAHInhibition covalente dépendante du temps ; puissance supérieure aux classes antérieures (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-750 is, together with PF-622, the molecule that established that the urea function could serve as a reactive hinge for inhibiting fatty acid amide hydrolase. The point is counter-intuitive: urea is among the most stable functions in organic chemistry, and a covalent inhibitor is ordinarily designed around a frank electrophilic group, a carbamate, a fluorophosphonate or an activated ketone. Ahn and colleagues nevertheless observed in 2007 that these piperidine ureas inhibit the enzyme in a time-dependent manner, by carbamylating its catalytic serine. Their explanation is that the target enzyme possesses a capability rare among mammalian serine hydrolases, that of cleaving carbon-nitrogen bonds and not only esters; a urea is therefore a plausible substrate for it alone. The measured selectivity confirms the reasoning: proteomic profiling detects the inhibition of no other serine hydrolase, whereas the carbamates of the previous generation hit several off-target enzymes. That conclusion shaped everything that followed in the field, since the urea motif became the hinge of the inhibitors carried into the clinic. It took on particular relief after 2016: the investigation into the accident of the BIA 10-2474 trial in Rennes, which caused one death and irreversible neurological damage, implicated a non-selective inhibition of several brain lipases, that is the exact flaw that the selectivity of this chemotype had made it possible to avoid.
Origin (research tool)
An entirely chemical route, described here by class only. The molecule is a piperidine urea: the piperidine ring links a carboxamide bearing a phenyl to a methylene arm attached to a quinoline substituted at position 3. It differs from PF-622 by the replacement of the piperazine with a piperidine and by the substitution position of the quinoline.
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 entire class of amide hydrolase inhibitors has been subject to reinforced regulatory requirements since the accident of the phase 1 trial of BIA 10-2474 that occurred in Rennes in 2016.
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
- BIODYGOZWZNCAG-UHFFFAOYSA-N
- SMILES
- C1CN(CCC1CC2=CC3=CC=CC=C3N=C2)C(=O)NC4=CC=CC=C4
- Formula
- C22H23N3O
- Molar mass
- 345.40 g·mol⁻¹
- PubChem CID
- 25154868
LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.