{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"BIODYGOZWZNCAG-UHFFFAOYSA-N","prefName":"PF-750","symbol":"PF-750","iupacName":"N-phenyl-4-(quinolin-3-ylmethyl)piperidine-1-carboxamide","aliases":["PF 750","PF750"],"cas":null,"pubchemCid":"25154868","chebiId":null,"smiles":"C1CN(CCC1CC2=CC3=CC=CC=C3N=C2)C(=O)NC4=CC=CC=C4","molecularFormula":"C22H23N3O","molecularWeight":345.4,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/25154868"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Urée de pipéridine, structure jumelle du PF-622 dont elle diffère par le cycle saturé, pipéridine au lieu de pipérazine, et par la position de rattachement de la quinoléine, en 3 au lieu de 2. Le carboxamide arylé par un phényle est conservé. C'est le fait que les deux variantes produisent le même mécanisme covalent qui a permis d'établir que la réactivité observée relevait du chémotype et non d'une particularité d'un composé isolé."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"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.","originNote":"A wholly synthetic compound with no natural occurrence. It is produced as a pharmacology reagent and has not been the subject of clinical development.","discovered":"Décrit en 2007 par Ahn et collaborateurs, dans le même travail conjoint des laboratoires Pfizer d'Ann Arbor et de l'équipe de Cravatt au Scripps Research Institute qui a introduit le PF-622. Les deux composés sont les chefs de file d'une classe mécanistique nouvelle d'inhibiteurs de l'amidohydrolase des acides gras, fondée sur la réactivité inattendue de la fonction urée vis à vis de cette enzyme."},"pharmacology":{"summaryFr":"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.","receptorSummaryFr":"A covalent inhibitor of fatty acid amide hydrolase, which it inactivates by carbamylating the nucleophilic serine of its active site. Ahn and colleagues report for this compound and for PF-622 an in vitro potency higher than that of the classes of inhibitors established until then, and a time-dependent inhibition characteristic of a covalent mechanism. Activity-based proteomic profiling shows complete selectivity with respect to the other mammalian serine hydrolases. The compound has no described direct action on cannabinoid receptors: its expected effect passes through the elevation of anandamide and the other N-acylethanolamines.","binding":[{"target":"FAAH","efficacy":"antagonist","relativeActivity":90,"reported":"Inhibition covalente dépendante du temps ; puissance supérieure aux classes antérieures (Ahn et coll. 2007)","confidence":"medium"},{"target":"CB1","efficacy":"modulator","relativeActivity":15,"reported":"Effet indirect via l'élévation de l'anandamide ; pas de liaison directe","confidence":"medium"}],"references":[{"label":"Ahn et coll. 2007 : classe mécanistique nouvelle d'inhibiteurs de la FAAH à sélectivité remarquable","pmid":"17949010","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/17949010/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique détaillée n'est publiée pour ce composé, employé comme outil de démonstration mécanistique plutôt que comme candidat au développement. Aucune donnée humaine n'existe et aucune dose humaine n'est caractérisée.","metabolism":"Aucune étude de métabolisme n'est publiée. Le composé se consomme en partie par sa réaction même avec l'enzyme cible, la carbamylation libérant l'amine correspondante. Les hétérocycles azotés sont par ailleurs des substrats habituels des oxydations des cytochromes P450, attente de classe et non résultat mesuré.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. Le suivi de son action passe par la mesure de l'activité enzymatique résiduelle et par le dosage lipidomique des N-acyléthanolamines tissulaires.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":25},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":15},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":20},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":10},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":15}],"doseRanges":null,"humanDataCharacterised":false},"indications":{"approvedMedicines":[]},"harmProfile":{"unstudiedBanner":true,"bannerTextFr":"Aucune dose humaine caractérisée : données animales / in vitro uniquement. Profil d'effet, marge de sécurité et toxicité aiguë non documentés en clinique humaine.","toxicologyFr":"Aucune donnée de toxicologie humaine n'est publiée et aucune dose humaine n'est caractérisée. Le risque pertinent est celui de la classe : l'essai de phase 1 du BIA 10-2474 conduit à Rennes en 2016 a causé un décès et des atteintes neurologiques graves, attribuées par les analyses ultérieures à une inhibition non sélective de plusieurs lipases cérébrales. La sélectivité complète documentée pour ce composé est précisément la propriété dont l'absence a été mise en cause dans cet accident."},"legal":{"scheduleStatus":"unscheduled","scheduleLabel":"Unscheduled","frScheduleStatus":"unscheduled","tiers":[{"jurisdiction":"international","jurisdictionLabel":"International","label":"Non inscrit aux conventions de contrôle","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"eu","jurisdictionLabel":"Union européenne","label":"Non autorisé ; classe sous exigences renforcées depuis 2016","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"Non inscrit ; usage de recherche uniquement","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Ahn et coll. 2007 : classe mécanistique nouvelle d'inhibiteurs de la FAAH à sélectivité remarquable","pmid":"17949010","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/17949010/"}],"meta":{"slug":"pf-750","url":"https://en.phytogrammes.com/wiki/pf-750","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-17","confidence":"medium","dataCompletenessPct":90,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}