ECS modulator (research)
UnscheduledPF-514273
2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-5,6-dihydropyrazolo[3,4-f][1,4]oxazepin-8-one
Aliases.PF 514273 · PF 0514273 · PF514273
A bicyclic-lactam CB1 antagonist, carried into the clinic against obesity then halted along with its whole 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
- C₂₁H₁₇Cl₂F₂N₃O₂
- Molar mass
- 451.07 g·mol⁻¹
- CAS
- 851728-60-4
- PubChem CID
- 11316919
- Origin
- A wholly synthetic compound with no natural occurrence. It was produced within pharmaceutical development and was not commercialised.
- InChIKey
- FJMQJSUOOGOWBD-UHFFFAOYSA-N
In plain terms
PF-514273 blocks the CB1 receptor in order to reduce appetite. It was tested in humans against obesity, following rimonabant. Development of that entire family was abandoned after rimonabant was withdrawn for psychiatric effects.
Receptors and activity
- CB1Antagoniste puissant et sélectif ; activité orale sur la prise alimentaire du rongeur (Dow et coll. 2009)Antagonist
- CB2Sélectivité CB1 revendiquée ; valeur non détaillée dans les sources retenuesModulator
- 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.
- Calm10
- Clarity20
- Sleep10
- Appetite5
- High5
Editorial estimate, not clinical.
Pharmacology
PF-514273 belongs to the second wave of CB1 receptor antagonists intended for the management of obesity. The therapeutic reasoning was sound: activation of CB1 stimulates food intake, a phenomenon that cannabis use makes familiar, and blocking it produces the opposite effect. Rimonabant, the first compound of the class, had obtained a European authorisation in 2006. Dow and colleagues describe in 2009 a new chemical series intended to do better: bicyclic lactams in which the open carboxamide of the first-generation antagonists is replaced by an oxazepinone ring fused to the pyrazole. The compound selected at the end of that optimisation, orally active on rodent food intake, was carried into human clinical trials. The calendar decided the rest. Rimonabant was withdrawn from the European market in 2008 after adverse psychiatric effects were established, including anxiety, depression and suicidal ideation, and the competing programmes of taranabant and otenabant were halted in the same movement. No CB1 antagonist penetrating the central nervous system survived that sequence. The compound went on to a second life as a pharmacological tool: used in mice to test the hypothesis of a role for CB1 in the reinforcing properties of alcohol, it modified neither the acquisition nor the expression of conditioned place preference to ethanol, despite a reduction in locomotor activity.
Key sources.
Origin (research tool)
An entirely chemical route, described here by class only. The molecule is a bicyclic lactam: a pyrazole core is fused to a seven-membered oxazepinone ring, the whole bearing two distinct chlorophenyls and a difluoropropyl chain on the lactam nitrogen. This closed skeleton replaces the open carboxamide of the first-generation antagonists.
Legal framework
France
A substance not listed among narcotics or among psychotropics. CB1 receptor antagonists do not fall under narcotics law, their action being the inverse of that of the agonists targeted by those texts. The compound holds no marketing authorisation.
European Union
Neither controlled nor authorised. Development did not lead to a marketing authorisation. The entire class of CB1 antagonists intended for obesity was halted following the withdrawal of rimonabant from the European market in 2008, prompted by adverse psychiatric effects.
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 was produced within pharmaceutical development and was not commercialised.
- Status
- Unscheduled
References
Structured data
- InChIKey
- FJMQJSUOOGOWBD-UHFFFAOYSA-N
- SMILES
- CC(CN1CCOC2=C(N(N=C2C1=O)C3=CC=CC=C3Cl)C4=CC=C(C=C4)Cl)(F)F
- Formula
- C21H17Cl2F2N3O2
- Molar mass
- 451.07 g·mol⁻¹
- CAS
- 851728-60-4
- PubChem CID
- 11316919
LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.