Selonabant

CAS 791848-71-0

MF C22H24ClF3N2O2 MW440.89 g/mol

N–tert-butyl-3-[(R)-(4-chlorophenyl)-[2-(trifluoromethyl)phenyl]methoxy]azetidine-1-carboxamide

N-tert-butyl-3-[(R)-(4-chlorophenyl)-[2-(trifluoromethyl)phenyl]methoxy]azetidine-1-carboxamide

(R)-N-(tert-butyl)-3-((4-chlorophenyl)(2-(trifluoromethyl)phenyl)methoxy)azetidine-1-carboxamide

N-tert-butyl-3-{(R)-(4-chlorophenyl)[2-(trifluoromethyl)phenyl]methoxy}azetidine-1-carboxamide
cannabinoid receptor 1 (CB1) antagonist, ANEB 001, V 24343, 4RNU8C6XXW, ANEB001

Drug class: Cannabinoid receptor antagonist (CB1)

The anti-obesity drug, V24343, acts by targeting the CB1 receptor in the brain and suppressing a person’s appetite.

Selonabant (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name; developmental code names ANEB-001, V-24343) is a cannabinoid CB₁ receptor antagonist which is under development for the treatment of acute cannabinoid intoxication.^[1][2][3] It was also previously being developed to treat obesity, but development for this indication was discontinued.^[1] The drug is administered by intravenous infusion.^[1] It dramatically reduced the subjective effects of Δ⁹-tetrahydrocannabinol (THC) in a clinical trial.^[3] Selonabant is being developed by Vernalis and Anebulo Pharmaceuticals.^[1][2] 

1 CLINICAL TRIALS

As of December 2024, it is in phase 2 trials.^[1][2], I.V. Selonabant in Healthy Adult SubjectsCTID: NCT07211607Phase: Phase 1Status: RecruitingDate: 2026-02-12

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CB1 Antagonist ANEB-001 in a THC Challenge TestCTID: NCT05282797Phase: Phase 2Status: CompletedDate: 2023-08-29

Safety and Efficacy of Low Doses of V24343 in Obese SubjectsCTID: NCT00734201Phase: Phase 1Status: CompletedDate: 2011-07-25

A randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single oral doses of CB1 antagonist ANEB-001 in healthy occasional cannabis users

EudraCT: 2021-000305-24

Phase: Phase 2, Status: Completed, Date: 2021-03-18

2. Chemical Structure Features

Key structural motifs:

• Azetidine ring (4-membered nitrogen heterocycle)
• Chiral benzhydryl ether center
• Trifluoromethyl phenyl group
• p-chlorophenyl group
• tert-butyl carboxamide

These motifs are typical of lipophilic GPCR ligands, enabling strong binding to the CB1 receptor.

Key descriptors:

Property	Value
LogP	~4.9
H-bond donors	1
H-bond acceptors	5
TPSA	41.6 Ų
Chiral centers	1

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3. Pharmacological Target

Primary target:

CB1 receptor (CNR1)
• GPCR located in the central nervous system
• Mediates effects of cannabinoids such as THC

Selonabant is a competitive CB1 antagonist.

Mechanism:

1. THC activates CB1 receptor
2. Leads to euphoria, altered cognition, tachycardia
3. Selonabant blocks CB1 binding
4. Reverses or prevents THC effects

---

4. Therapeutic Indication

Main indication

Acute cannabinoid intoxication

Potential clinical uses:

• Cannabis overdose in emergency rooms
• Pediatric accidental cannabis ingestion
• Edible THC overdose
• Severe psychiatric reactions to cannabis

A CB1 antagonist could act as a “cannabis antidote.”

---

5. Clinical Development

Developer:
Anebulo Pharmaceuticals (with earlier work by Vernalis)

Development timeline

Phase	Details
Preclinical	Demonstrated CB1 antagonism
Phase I	Safety and PK studies
Phase II	THC challenge studies

In clinical trials, the drug significantly reduced subjective effects of THC in volunteers.

Status (2024–2025): Phase II development.

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6. Administration

Originally studied as:

• Intravenous infusion for rapid reversal of THC effects

Some reports indicate oral activity in research settings.

The IV route is preferred in emergency settings.

---

7. Comparison with Earlier CB1 Antagonists

Selonabant belongs to the same pharmacological class as:

Drug	Status
Rimonabant	Withdrawn (psychiatric side effects)
Taranabant	Development stopped
Selonabant	Designed for short-term antidote use

Key difference:

Earlier CB1 antagonists were chronic obesity drugs, which caused depression and suicidality.

Selonabant is designed for acute use only, reducing psychiatric risk.

---

8. Pharmacological Profile

Approximate characteristics (reported in literature):

• High CB1 receptor affinity
• CNS-penetrant
• Rapid onset
• Short therapeutic exposure

Effects in THC challenge studies:

• Reduced intoxication score
• Reduced cognitive impairment
• Reduced subjective “high”

---

9. Chemical Class

Selonabant can be classified as:

Diarylmethoxy-azetidine carbamides

Key scaffold:

Diarylmethanol → ether → azetidine carbamate.

This scaffold appears in several CB1 inverse agonists.

PATENT

WO2005080345

Title: Cannabinoid CB1 receptor antagonists
Assignee: Vernalis (R&D) Ltd
Priority: ~2004

This is the primary patent family covering the scaffold used for Selonabant.

Related Continuation Patent

WO2005080328

Follow-up Patent on CB1 Antagonists

WO2005075450

Later Use Patent (Anebulo)

US11141404

Assignee: Anebulo Pharmaceuticals

Coverage:

• use of Selonabant (ANEB-001)
• treatment of acute cannabinoid overdose
• IV formulations

The patent protection extends to ~2040

Patent Family Map

Main Selonabant IP family:

Patent	Type	Notes
WO2005080345	Composition of matter	core scaffold
WO2005080328	analog compounds	synthetic examples
WO2005075450	optimized CB1 antagonists	SAR
US11141404	method of use	overdose treatment
PCT follow-ups	formulation / delivery	IV use

SYN

https://patents.google.com/patent/US11141404B1/en

SYN

US 7,504,522

https://patentscope.wipo.int/search/en/detail.jsf?docId=US42164596&_cid=P12-MMR5M0-61310-1

Preparation of 2-(trifluoromethyl)-4-chlorobenzhydrol (96)

Magnesium turnings (4.21 g, 170 mmol) were stirred under nitrogen for 10 min. Stirring was halted and a solution of 2-bromobenzotrifluoride (36.37 g, 160 mmol) in dry THF (160 mL) was added via a dropping funnel until the magnesium turnings were just covered. The reaction mixture was heated with a hot-air gun until localised turbidity was observed. At this point, stirring was initiated, and the rate of the reaction was subsequently controlled with intermittent use of an ice-water bath, and varying the rate of addition of the remaining 2-bromobenzotrifluoride solution. After complete addition, the mixture was allowed to stir for 1 h, then used as a ˜0.9 M solution.

To a stirred solution of 4-chlorobenzaldehyde (2.17 g, 15 mmol) in anhydrous THF (10 mL) was added a solution of 2-(trifluoromethyl)phenylmagnesium bromide (0.9 M; 18 mL, 16 mmol) over 2 min. After 16 h, the resultant mixture was partitioned between diethyl ether and 1N HCl. The aqueous phase was extracted with diethyl ether (2×30 mL) and the combined organic extracts were washed with 1N HCl, brine and dried (MgSO 4). Evaporation under reduced pressure afforded the desired product as an amber oil (4.63 g, 100%).

MS 269 [M−OH] +

LC (50/80) 97.6%, 5.47 min

Preparation of 1-benzhydryl-3-[2-(trifluoromethyl)-4′-chlorobenzhydryloxy]azetidine (97)

This material was prepared from 1-benzhydryl-3-azetidinol (1) (40.1 mmol) and 2-(trifluoromethyl)-4-chlorobenzhydrol (96) (80.2 mmol) using the procedure described for compound (3) (13.5 g, 66%).

NMR (400 MHz, d 6-DMSO) δ H 2.74 (1H, br t), 2.86 (1H, br t), 3.20 (1H, br t), 3.29(1H, br t), 4.15 (1H, q, J 6.0 Hz), 4.39 (1H, s), 5.71 (1H, s), 7.16 (2H, m), 7.26 (6H, m), 7.38 (6H, m), 7.54 (1H, m), 7.70 (3H, m)

Preparation of 3-[2-(trifluoromethyl)-4′-chlorobenzhydryloxy]azetidine hydrochloride (98)

This material was prepared from 1-benzhydryl-3-[2-(trifluoromethyl)-4′-chlorobenzhydryloxy]azetidine (97) (25.6 mmol) using the procedure described for compound (9) (8.2 g, 85%).

NMR (400 MHz, d 6-DMSO) δ H 3.78 (1H, m), 3.97 (3H, m), 4.89 (1H, q, J 6.0 Hz), 5.85 (1H, s), 7.33 (2H, m), 7.44 (2H, m), 7.59 (1H, m), 7.76 (3H, m), 8.97 (1H, bs)

Example 81 FINAL MOLECULE

3-[2-(trifluoromethyl)-4′-chlorobenzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide (99)

This material was prepared from 3-[2-(trifluoromethyl)-4′-chlorobenzhydryloxy]azetidine hydrochloride (98) (1.32 mmol) and tert-butyl isocyanate (1.32 mmol) using the procedure described for compound (10) (474 mg, 81%).

NMR (400 MHz, d 6-DMSO) δ H 1.20 (9H, s), 3.51 (1H, m), 3.65 (1H, m), 3.84 (2H, m), 4.25 (1H, m), 5.62 (1H, s), 5.73 (1H, s), 7.31 (2H, m), 7.39 (2H, m), 7.57 (1H, m), 7.75 (3H, m)

LC (50/80) 98.6%, 6.93 min

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023064225&_cid=P12-MMR4X9-49599-1

(R)-N-(tert-butyl)-3-((4-chlorophenyl)(2-(trifluoromethyl)phenyl)methoxy)azetidine-1-carboxamide (Compound 1):

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=EP14473050&_cid=P12-MMR4X9-49599-1

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2005080345&_cid=P12-MMR54L-53149-1

The core patent describing the chemistry for Selonabant-type molecules is:

WO2005080345
Title: Cannabinoid receptor antagonists
Assignee: Vernalis plc
Priority: ~2004

for SAR exploration

PATENTS

• Azetidinecarboxamide derivatives and their use in the treatment of cb1 receptor mediated disordersPublication Number: WO-2004096763-A1Priority Date: 2003-05-01
• Azetidinecarboxamide derivatives and their use in the treatment of CB1 receptor mediated disordersPublication Number: NZ-543016-APriority Date: 2003-05-01
• Botulinum neurotoxins for use in therapyPublication Number: US-11260114-B2Priority Date: 2017-03-22Grant Date: 2022-03-01
• Azetidinecarboxamide derivatives and their use in the treatment of cb1 receptor mediated disordersPublication Number: EP-1620395-A1Priority Date: 2003-05-01
• Azetidinecarboxamide derivatives and their use in the treatment of cb1 receptor mediated disordersPublication Number: EP-1620395-B1Priority Date: 2003-05-01Grant Date: 2009-12-30
• Azetidinecarboxamide derivatives and their use in the treatment of cb1 receptor mediated disordersPublication Number: US-7504522-B2Priority Date: 2003-05-01Grant Date: 2009-03-17
• Azetidinecarboxamide derivatives and their use in the treatment of cb1 receptor mediated disordersPublication Number: US-2007054891-A1Priority Date: 2003-05-01
• Botulinum neurotoxins production methodsPublication Number: US-2023016041-A1Priority Date: 2017-04-28
• Initiating neurotoxin treatmentsPublication Number: US-2023058666-A1Priority Date: 2017-04-21
• Initiating neurotoxin treatmentsPublication Number: EP-4137149-A1Priority Date: 2017-04-21
• Botulinum neurotoxins for treating hyperhidrosisPublication Number: US-2022370574-A1Priority Date: 2017-04-20
• Botulinum neurotoxins for use in therapyPublication Number: US-2023027850-A1Priority Date: 2017-03-22

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Clinical data
Other names	ANEB-001; ANEB001; V-24343; V24343
Drug class	Cannabinoid receptor antagonist; Cannabinoid CB1 receptor antagonist; Cannabinoid antidote
Identifiers
IUPAC name
CAS Number	791848-71-0
PubChem CID	68902536
DrugBank	DB18908
ChemSpider	128922145
UNII	4RNU8C6XXW
KEGG	D12875
ChEMBL	ChEMBL5095165
Chemical and physical data
Formula	C22H24ClF3N2O2
Molar mass	440.89 g·mol−1
3D model (JSmol)	Interactive image
SMILES
InChI

References

1.  “Anebulo Pharmaceuticals”. AdisInsight. 26 December 2024. Retrieved 25 February 2025.
2.  “Delving into the Latest Updates on Selonabant with Synapse”. Synapse. 23 January 2025. Retrieved 25 February 2025.
3.  Gorbenko AA, Heuberger JA, Juachon M, Klaassen E, Tagen M, Lawler JF, et al. (February 2025). “CB₁ Receptor Antagonist Selonabant (ANEB-001) Blocks Acute THC Effects in Healthy Volunteers: A Phase II Randomized Controlled Trial”. Clinical Pharmacology and Therapeutics. 117 (5): 1427–1436. doi:10.1002/cpt.3581. PMC 11993283. PMID 39898464.

//////////selonabant, cannabinoid receptor 1 (CB1) antagonist, ANEB 001, V 24343, 4RNU8C6XXW, ANEB001