Physicochemical Properties
| Molecular Formula | C20H18CLF2N3O3 |
| Molecular Weight | 421.83 |
| Exact Mass | 421.1 |
| CAS # | 2827061-47-0 |
| PubChem CID | 165412721 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 3.4 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 29 |
| Complexity | 547 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CO[C@H](CNC(=O)C1=NC2=C(C=C(C=C2)Cl)C(=C1)NC3=C(C(=CC=C3)F)F)CO |
| InChi Key | NTOVJWIULULGGI-GFCCVEGCSA-N |
| InChi Code | InChI=1S/C20H18ClF2N3O3/c1-29-12(10-27)9-24-20(28)18-8-17(13-7-11(21)5-6-15(13)25-18)26-16-4-2-3-14(22)19(16)23/h2-8,12,27H,9-10H2,1H3,(H,24,28)(H,25,26)/t12-/m1/s1 |
| Chemical Name | 6-chloro-4-(2,3-difluoroanilino)-N-[(2R)-3-hydroxy-2-methoxypropyl]quinoline-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
| Targets | IC50: 6.3 nM (T. b. brucei 20S proteasome)[1] |
| ln Vitro | Compound 7 (20S Proteasome-IN-4) suppresses T within 24 hours. B. having an EC50 of less than 2.5 nM[1]. brucei growth. |
| ln Vivo | 20S Proteasome-IN-4 (Compound 7) (3 mg/kg; ir; once daily for 4 days) is able to treat a stage I mouse model of African trypanosomiasis in humans[1]. A stage II mouse model of human African trypanosomiasis is cured by 20S Proteasome-IN-4 (15 mg/kg; ir; twice daily for 1 week)[1]. |
| Animal Protocol |
Animal/Disease Models: NMRI mice, hemolymphatic mice model (Stage I)[1] Doses: 3 mg/kg Route of Administration: po (oral gavage) , one time/day for 4 days Experimental Results: Achieved complete cure of the stage I infection. Animal/Disease Models: CD1 mice, meningoncephalic mice model (stage II)[1] Doses: 15 mg/kg Route of Administration: Oral gavage, twice a day for 1 week Experimental Results: Achieved complete cure of the stage II infection. Animal/Disease Models: balb/c (Bagg ALBino) mouse and Wistar rats[1] Doses: 1 mg/kg or 3 mg/kg Route of Administration: intravenous (iv) or oral administration (pharmacokinetic/PK Analysis) Experimental Results: ADME and PK Data for 20S Proteasome-IN-4 (Compound 7)[1] cmp solubility pH 6.8 μM LM CLint (m/r) [μL/min/mg] LM scaled CLint [mL/min/kg] (m/r) fu plasma [%] (m/r) CLp [mL/min/kg] (m/r) CLu [mL/min/kg] (m/r) AUCPO [μM·h] (m/r) AUCIV [μM •h] (m/r) %F m/r 20S Proteasome-IN-4 12 79/66 311/119 1.0/1.6 17/9 1700/563 5.2/17 2.3/4.4 76/128 Solubility: Miniaturized fl shakeask solubility in phosphate buffer; fu,plasma from PPB; LM scaled Clint = (LM Clint·SF1·SF2)/1 |
| References |
[1]. Discovery of Novel Quinoline-Based Proteasome Inhibitors for Human African Trypanosomiasis (HAT). J Med Chem. 2022 Aug 22. |
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 | 2.3706 mL | 11.8531 mL | 23.7062 mL | |
| 5 mM | 0.4741 mL | 2.3706 mL | 4.7412 mL | |
| 10 mM | 0.2371 mL | 1.1853 mL | 2.3706 mL |