{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"WMMMJGKFKKBRQR-UHFFFAOYSA-N","prefName":"Rosonabant","symbol":"Rosonabant","iupacName":"3-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-N-piperidin-1-yl-3,4-dihydropyrazole-5-carboxamide","aliases":["E-6776","E 6776"],"cas":"861151-12-4","pubchemCid":"11316914","chebiId":null,"smiles":"C1CCN(CC1)NC(=O)C2=NN(C(C2)C3=CC=C(C=C3)Cl)C4=C(C=C(C=C4)Cl)Cl","molecularFormula":"C21H21Cl3N4O","molecularWeight":450.078,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/11316914"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Pyrazoline antagoniste du CB1, variante réduite du chémotype pyrazole du rimonabant. Le cycle central porte un dichlorophényle sur l'azote, un chlorophényle sur le carbone adjacent et un carboxamide relié à une pipéridine, triade caractéristique qui porte l'affinité dans toute cette série. La réduction partielle du cycle central introduit un centre stéréogène absent du rimonabant, ce qui distingue chimiquement la molécule sans changer sa logique de reconnaissance."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"An entirely chemical route, described here by class only. The molecule belongs to the pyrazoline antagonists: a pyrazoline ring, the partially reduced form of the pyrazole, bears a dichlorophenyl on the nitrogen, an adjacent chlorophenyl and a piperidine carboxamide. This is the same structural grammar as that of rimonabant, apart from the reduction of the central ring.","originNote":"A wholly synthetic compound with no natural occurrence. It was produced within a pharmaceutical development programme that did not succeed.","discovered":"Développé par le laboratoire espagnol Esteve sous le code E-6776 comme antagoniste du récepteur CB1 destiné au traitement de l'obésité. Janero et Makriyannis le citent en 2009, dans leur revue des antagonistes cannabinoïdes, parmi les composés de suivi du rimonabant effectivement étudiés en clinique. La documentation publique disponible sur cette molécule reste très limitée."},"pharmacology":{"summaryFr":"Rosonabant is a characteristic example of a molecule carried away by the failure of an entire class rather than by a flaw of its own. Developed by the Spanish laboratory Esteve under the code E-6776, this pyrazoline derivative belongs to the same chemical family as rimonabant, the first CB1 receptor antagonist authorised in Europe in 2006 as a treatment for obesity. Janero and Makriyannis mention it in 2009 in their review of the class among the follow-on compounds actually carried into the clinic, alongside taranabant, otenabant, surinabant, SLV-319, AVE-1625 and V-24343. That list is the roll of a complete generation interrupted at the same moment. Rimonabant was withdrawn from the European market in 2008 after adverse psychiatric effects were established, notably anxiety, depression and suicidal ideation, and the authorities took the view that this risk stemmed from the mechanism itself, that is from the blockade of CB1 receptors in the central nervous system, rather than from a peculiarity of one molecule. Competing developments therefore ceased. Rosonabant was never the subject of a detailed pharmacological characterisation in the accessible literature, which makes this entry deliberately sober: what is established concerns its class and its programme, not a set of published measurements. The field subsequently reoriented towards two routes intended to avoid that risk, antagonists restricted to the periphery and genuinely neutral antagonists.","receptorSummaryFr":"An antagonist and inverse agonist of the CB1 receptor, designed as an appetite suppressant through blockade of the endocannabinoid signalling that stimulates food intake. No detailed pharmacological characterisation of the compound, whether affinity values or functional efficacy, is available in the accessible literature retained here: the molecule is identified by its class and by its development programme rather than by a set of published measurements. No action at the CB2 receptor is documented.","binding":[{"target":"CB1","efficacy":"antagonist","relativeActivity":75,"reported":"Antagoniste et agoniste inverse de la série des pyrazolines ; valeurs non publiées dans les sources retenues","confidence":"medium"},{"target":"CB2","efficacy":"modulator","relativeActivity":8,"reported":"Aucune action documentée sur le CB2","confidence":"medium"}],"references":[{"label":"Janero et Makriyannis 2009 : antagonistes des récepteurs cannabinoïdes, opportunités pharmacologiques, expérience clinique et pronostic translationnel","pmid":"19249987","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/19249987/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique n'est publiée dans la littérature accessible retenue ici. Le composé a fait l'objet d'une étude clinique selon la revue de 2009, mais les paramètres correspondants ne sont pas dans le domaine public. Aucune dose humaine n'est caractérisée.","metabolism":"Aucune étude de métabolisme n'est publiée pour cette molécule. La série des pyrazoles et pyrazolines antagonistes est habituellement prise en charge par les oxydations des cytochromes P450, mais aucune voie n'a été mesurée pour ce composé précis.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. Elle n'a jamais été commercialisée ni signalée sur le marché des nouvelles substances psychoactives.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":10},{"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":10},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":5},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":5}],"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 propre à ce composé n'est publiée et aucune dose humaine n'est caractérisée. Le risque déterminant est celui de la classe, et il est la raison même de l'arrêt du programme : le retrait du rimonabant du marché européen en 2008 a été motivé par des effets psychiatriques indésirables comprenant anxiété, dépression et idées suicidaires, et les développements du taranabant et de l'oténabant ont été interrompus pour des motifs comparables. Ce risque est rattaché au blocage des récepteurs CB1 centraux."},"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 ; développement interrompu","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"Non inscrit ; sans autorisation de mise sur le marché","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Janero et Makriyannis 2009 : antagonistes des récepteurs cannabinoïdes, opportunités pharmacologiques, expérience clinique et pronostic translationnel","pmid":"19249987","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/19249987/"}],"meta":{"slug":"rosonabant","url":"https://en.phytogrammes.com/wiki/rosonabant","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."}}