Fosravuconazole (formerly known as E-1224, BEF-1224, and BMS-379224) is an azole-based antifungal agent that can be potentially used for the treatment of fungal infections. It is a prodrug of ravuconazole with improved water solubility. The phosphonooxymethyl ether fosravuconazole was prepared from ravuconazole and bis-tert-butyl chloromethylphosphate. Fosravuconazole was highly soluble in water and converted to the parent in alkaline phosphatase, and also in vivo (rat). Fosravuconazole has proved to be one of the most promising prodrugs of ravuconazole that were tested, and it is currently in clinical evaluation as an intravenous formulation of the broad spectrum antifungal azole, ravuconazole.
Physicochemical Properties
| Molecular Formula | C23H20F2N5O5PS |
| Molecular Weight | 547.470971107483 |
| Exact Mass | 547.089 |
| CAS # | 351227-64-0 |
| Related CAS # | Fosravuconazole L-lysine ethanolate;914361-45-8 |
| PubChem CID | 9807507 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 4.334 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 37 |
| Complexity | 859 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C[C@@H](C1=NC(=CS1)C2=CC=C(C=C2)C#N)[C@](CN3C=NC=N3)(C4=C(C=C(C=C4)F)F)OCOP(=O)(O)O |
| InChi Key | SYTNEMZCCLUTNX-NPMXOYFQSA-N |
| InChi Code | InChI=1S/C23H20F2N5O5PS/c1-15(22-29-21(10-37-22)17-4-2-16(9-26)3-5-17)23(11-30-13-27-12-28-30,34-14-35-36(31,32)33)19-7-6-18(24)8-20(19)25/h2-8,10,12-13,15H,11,14H2,1H3,(H2,31,32,33)/t15-,23+/m0/s1 |
| Chemical Name | (((2R,3R)-3-(4-(4-cyanophenyl)thiazol-2-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-yl)oxy)methyl dihydrogen phosphate |
| Synonyms | Fosravuconazole; BEF-1224; BMS 379224; E-1224; BEF1224; BMS379224; E 1224; BEF 1224; BMS-379224; E1224. |
| 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 | Strong in vitro antifungal activity of Ravuconodium has been observed against Candida, Aspergillus, and Trichophyton, among other fungi [1]. |
| ln Vivo | In mice infected with the Y strain of Trypanosoma cruzi, treatment with foslaconazole (E-1224; 10-50 mg/kg; oral; daily; for 20 days) lowers parasitemia and averts death [3]. |
| Animal Protocol |
Animal/Disease Models: Swiss female mice (20-24 g) inoculated with trypomastigotes (Y strain) [3]. Doses: 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, 50 mg/kg Route of Administration: Oral; daily; for 20 days Experimental Results: Suppression of parasitemia and prevention of death. |
| References |
[1]. Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study. J Dermatol. 2018 Oct;45(10):1151-1159. [2]. Development of E1224 by leveraging a strategic partnership for the medicines creation against neglected tropical diseases. Parasitol Int. 2020 Dec 25;81:102278. [3]. Outcome of E1224-Benznidazole Combination Treatment for Infection with a Multidrug-Resistant Trypanosoma cruzi Strain in Mice. Antimicrob Agents Chemother. 2018 May 25;62(6):e00401-18. |
| Additional Infomation |
BMS 379224 is an amine. Fosravuconazole is under investigation in clinical trial NCT03378661 (BENDITA BEnznidazole New Doses Improved Treatment and Associations). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~182.66 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8266 mL | 9.1329 mL | 18.2658 mL | |
| 5 mM | 0.3653 mL | 1.8266 mL | 3.6532 mL | |
| 10 mM | 0.1827 mL | 0.9133 mL | 1.8266 mL |