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| Targets |
Rimonabant carboxylic acid functions as a ligand for target proteins in PROTAC technology. The parent compound rimonabant is a cannabinoid CB1 receptor antagonist, and this carboxylic acid derivative retains the pyrazole scaffold that binds to CB1 receptors. In PROTAC applications, this compound serves as the "target ligand" that binds to CB1R, while a separate E3 ligase ligand (e.g., pomalidomide) is connected via a linker. The resulting PROTAC molecule induces ubiquitination and subsequent proteasomal degradation of CB1 receptors.
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| ln Vitro |
In vitro activity of rimonabant carboxylic acid itself has not been extensively characterized. The parent compound rimonabant is a selective CB1 receptor antagonist with Ki values in the low nanomolar range (∼1-10 nM). The carboxylic acid derivative retains the ability to bind to CB1 receptors, as the carboxylic acid group does not disrupt the core pyrazole-CB1 interaction. In PROTAC applications, the compound is conjugated to an E3 ligase ligand to create bivalent molecules that degrade CB1R.
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| ln Vivo |
In vivo activity of rimonabant carboxylic acid has not been reported, as the compound is primarily used as a chemical intermediate. The parent compound rimonabant (Acomplia) was developed as an anti-obesity drug but was withdrawn due to psychiatric side effects. The carboxylic acid derivative is not intended for in vivo administration in its free form; instead, it is incorporated into PROTAC molecules that target CB1R for degradation. These PROTACs may show improved selectivity and reduced side effects compared to the parent antagonist.
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, DMSO-d₆) delta 7.55 (d, 2H, J=8.5 Hz, 4-chlorophenyl), 7.45 (d, 1H, J=2.0 Hz, 2,4-dichlorophenyl H3), 7.35 (dd, 1H, J=8.5, 2.0 Hz, 2,4-dichlorophenyl H5), 7.20 (d, 1H, J=8.5 Hz, 2,4-dichlorophenyl H6), 2.40 (s, 3H, 4-methyl). LC-MS (ESI+) m/z 382.0 [M+H]+, with characteristic isotopic pattern for three chlorine atoms. HPLC-UV on C18 column (acetonitrile/0.1% TFA in water, gradient 40→80% B), detection at 254 nm. Purity >95% by area normalization.
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| Cell Assay |
Cell-based assays for PROTAC efficacy: HEK293 or CB1R-overexpressing CHO cells are treated with PROTAC CB1R Degrader-1 (synthesized using rimonabant carboxylic acid as the target ligand) at concentrations of 0.1-1000 nM for 4-24 h. CB1R protein levels are assessed by Western blot using an anti-CB1R antibody. The DC50 (concentration for 50% degradation) is calculated. Functional CB1R activity is measured using a cAMP assay (forskolin-stimulated cAMP accumulation) or beta-arrestin recruitment assay. Complete degradation is typically observed within 6-12 h at 100 nM. Cytotoxicity is assessed by MTT.
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| Animal Protocol |
Animal study protocol for PROTAC efficacy: Male C57BL/6 mice (n=6 per group) receive PROTAC CB1R Degrader-1 (synthesized from rimonabant carboxylic acid) at 10-50 mg/kg by intraperitoneal injection or oral gavage daily for 5-10 days. Brain and peripheral tissues are collected. CB1R protein levels are measured by Western blot and quantitative immunofluorescence. Functional CB1R occupancy is assessed by ex vivo receptor binding assays using [3H]CP-55,940. Metabolic parameters (body weight, food intake, glucose tolerance) are monitored. The duration of CB1R degradation in the brain is determined.
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| ADME/Pharmacokinetics |
Pharmacokinetic profile: Rimonabant carboxylic acid (MW 381.64) has a high logP value (∼4.5-5.0) due to its highly lipophilic pyrazole-dichlorophenyl structure. Its oral bioavailability is predicted to be moderate (30-50%), with a Tmax of 1-2 h. The terminal half-life is estimated to be 4-8 h. The compound is likely highly plasma protein bound (>95%). Metabolism is predicted to involve aromatic hydroxylation and glucuronidation. Excretion is primarily via the biliary route. As a PROTAC building block, its PK is not directly relevant.
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| Toxicity/Toxicokinetics |
Preclinical toxicology: The parent compound rimonabant has known safety concerns, including depression, anxiety, and suicidal ideation, which led to its withdrawal. Rimonabant carboxylic acid itself is a chemical intermediate and has not been extensively evaluated for toxicity. In PROTAC applications, the carboxylic acid group is conjugated to a linker, resulting in novel chemical entities with potentially improved safety profiles. In silico genotoxicity assessment (DEREK) may flag the polyhalogenated aromatic structure. An Ames test is recommended for impurity qualification.
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| References | |
| Additional Infomation |
Rimonabant carboxylic acid is also known as Rimonabat acomplia and is a ligand for target proteins in PROTAC applications. Storage: store under recommended conditions as specified in the Certificate of Analysis. Soluble in DMSO (≥10 mg/mL). Used for PROTAC synthesis, particularly for PROTAC CB1R Degrader-1, and as a reference standard in chemical research. The compound is also an intermediate for the synthesis of rimonabant. Not for human therapeutic use.
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| Molecular Formula |
C17H11CL3N2O2
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| Molecular Weight |
381.64
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| Exact Mass |
379.989
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| CAS # |
162758-35-2
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| PubChem CID |
1519421
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
459
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(N(N=C1C(=O)O)C2=C(C=C(C=C2)Cl)Cl)C3=CC=C(C=C3)Cl
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| InChi Key |
CYAYCOCJAVHQSD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11Cl3N2O2/c1-9-15(17(23)24)21-22(14-7-6-12(19)8-13(14)20)16(9)10-2-4-11(18)5-3-10/h2-8H,1H3,(H,23,24)
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| Chemical Name |
5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylic acid
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| Synonyms |
Rimonabat acomplia
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6203 mL | 13.1014 mL | 26.2027 mL | |
| 5 mM | 0.5241 mL | 2.6203 mL | 5.2405 mL | |
| 10 mM | 0.2620 mL | 1.3101 mL | 2.6203 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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