Physicochemical Properties
| Molecular Formula | C26H19FN4O2 |
| Molecular Weight | 438.453068971634 |
| Exact Mass | 438.149 |
| CAS # | 167820-10-2 |
| PubChem CID | 10455790 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 759.3±60.0 °C at 760 mmHg |
| Flash Point | 413.0±32.9 °C |
| Vapour Pressure | 0.0±2.6 mmHg at 25°C |
| Index of Refraction | 1.740 |
| LogP | 3.56 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 33 |
| Complexity | 818 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | FC1C=CC=CC=1C1C2=CC=CC3CCN(C([C@H](NC(C4=CC5C=CC=CC=5N4)=O)N=1)=O)C=32 |
| InChi Key | WKJDXKWFGJWGAS-DEOSSOPVSA-N |
| InChi Code | InChI=1S/C26H19FN4O2/c27-19-10-3-2-8-17(19)22-18-9-5-7-15-12-13-31(23(15)18)26(33)24(29-22)30-25(32)21-14-16-6-1-4-11-20(16)28-21/h1-11,14,24,28H,12-13H2,(H,30,32)/t24-/m0/s1 |
| Chemical Name | N-[(11R)-9-(2-fluorophenyl)-12-oxo-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl]-1H-indole-2-carboxamide |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | CHEMBL333994 (Compound 9f, FK-480) potently inhibited the binding of ¹²⁵I-CCK-8 to rat pancreatic membranes in vitro, with an IC₅₀ value of 6.7 × 10⁻¹⁰ M, achieving 95.0% inhibition at 3.2 × 10⁻⁹ M.[1] |
| ln Vivo | CHEMBL333994 (Compound 9f, FK-480) exhibited a potent inhibitory effect on CCK-8-induced delay of charcoal meal gastric emptying in mice following oral administration, with an ED₅₀ value of 0.010 mg/kg and 100% inhibition at 0.1 mg/kg.[1] |
| Enzyme Assay | A rat pancreatic membrane receptor binding assay was performed to evaluate the inhibitory activity of compounds on cholecystokinin receptors. The assay measured the ability of test compounds to compete with ¹²⁵I-CCK-8 for binding sites on the membrane preparation. Specific binding parameters (IC₅₀) were determined.[1] |
| Animal Protocol | The gastric emptying effect was evaluated in mice. The method involved administering a charcoal meal to the animals and measuring the inhibitory effect of the test compound on the delay in gastric emptying induced by exogenous CCK-8 administration. The test compound was administered orally to mice, and the ED₅₀ value (dose producing 50% of the maximal inhibitory effect) was determined.[1] |
| References |
[1]. Studies on a novel, potent and orally effective cholecystokinin A antagonist, FK-480. Synthesis and structure-activity relationships of FK-480 and related compounds. Chem Pharm Bull (Tokyo). 1994 Oct;42(10):2071-83. |
| Additional Infomation |
CHEMBL333994 (Compound 9f, FK-480) is a novel pyrrolo[3,2,1-jk][1,4]benzodiazepine derivative, specifically a (3S)-1-(2-fluorophenyl)-3-[[(2-indolyl)carbonyl]amino]-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzodiazepin-4(3H)-one.[1] It was identified as a potent and selective cholecystokinin receptor antagonist during a structure-activity relationship study of tricyclic 1,4-benzodiazepines.[1] The (S)-enantiomer (CHEMBL333994) was significantly more potent (approximately 50-100 fold) than its corresponding (R)-enantiomer (Compound 9e). It was selected as a candidate compound for further development based on its high in vitro and in vivo potency, as well as the ready availability of its starting material (indoline) and the feasibility of efficient optical resolution of a key synthetic intermediate.[1] The compound containing a 2-fluoro substituent on the phenyl ring at the 5-position was found to be slightly more effective than the unsubstituted analogue.[1] |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2808 mL | 11.4038 mL | 22.8076 mL | |
| 5 mM | 0.4562 mL | 2.2808 mL | 4.5615 mL | |
| 10 mM | 0.2281 mL | 1.1404 mL | 2.2808 mL |