Physicochemical Properties
| Molecular Formula | C11H16N2O5 |
| Molecular Weight | 256.26 |
| Exact Mass | 256.106 |
| Elemental Analysis | C, 51.56; H, 6.29; N, 10.93; O, 31.22 |
| CAS # | 15176-29-1 |
| PubChem CID | 66377 |
| Appearance | Off-white to light yellow solid powder |
| Density | 1.389 g/cm3 |
| Melting Point | 152-153° |
| Index of Refraction | 1.569 |
| LogP | -0.7 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 18 |
| Complexity | 395 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | OC[C@@H]1[C@H](C[C@H](N2C(NC(C(CC)=C2)=O)=O)O1)O |
| InChi Key | XACKNLSZYYIACO-DJLDLDEBSA-N |
| InChi Code | InChI=1S/C11H16N2O5/c1-2-6-4-13(11(17)12-10(6)16)9-3-7(15)8(5-14)18-9/h4,7-9,14-15H,2-3,5H2,1H3,(H,12,16,17)/t7-,8+,9+/m0/s1 |
| Chemical Name | 5-ethyl-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione |
| Synonyms | Edoxudine; CCRIS 2349; CCRIS-2349; CCRIS2349; Edoxudina |
| 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
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Edoxudine cream is able to penetrate the skin in a very rapid manner. This easy penetration allows edoxudine to have a greater activity when compared with other topical antivirals that have better antiviral activity in vitro. In preclinical trials in mice, after intravenous administration of edoxudine, the mean residence time was 25 min. Edoxudine presented a bioavailability of 49% with a Cmax and tmax of 2.4 mcg/g and 31.1 min respectively. The AUC in plasma of edoxudine is significantly higher when administered orally when compared with intravenous administration. This pharmacokinetic property is not available. The plasma clearance of edoxudine is reported to be 85 ml/min. Metabolism / Metabolites In preclinical trials it has been reported that edoxudine presents a biotransformation marked by a cleavage of the glycoside bond. The degradation of edoxudine, after oral administration, seems to be processed by the activity of phosphorylases presented in the gastrointestinal tract and by pre-systemic metabolism. Biological Half-Life In preclinical trials on mice, after intravenous administration, edoxudine presented a very short distribution half-life of 1.4 min. In the same trials, the elimination half-life was reported to be of 24.1 min. |
| Toxicity/Toxicokinetics |
Protein Binding The plasma protein binding of edoxudine is very low and it is reported to be of about 7%. It is mainly found in a bound state to albumin. |
| References |
[1]. Penetration and action of edoxudine in vitro and in vivo. Arzneimittelforschung. 1989 Mar;39(3):366-8. |
| Additional Infomation |
Edoxudine is a pyrimidine 2'-deoxyribonucleoside. Edoxudine is a deoxythymidine analog with activity against herpes simplex virus. It is a potent and selective inhibitor of herpes simplex virus type 1 and 2. The obtained product is an antiviral ointment. The activity of edoxudine against herpes simplex virus was first recognized in 1967. It was later recognized to be effective in vivo in a preclinical model of keratitis caused by herpes virus. It was developed by McNeil Pharmaceutical and approved by Health Canada on December 31, 1992. This medication was later discontinued from the market in 1998. Edoxudine is a deoxythymidine analog with activity against herpes simplex virus. Edoxudine is activated by viral thymidine kinase to the 5'-monophosphate which is further phosphorylated by cellular enzymes to the 5'-triphosphate, a competitive inhibitor of the viral-coded DNA polymerase. Drug Indication Edoxudine was used in Europe, in the form of a topical antiviral, for the treatment of human herpes keratitis. Human herpes keratitis is an inflammation of the cornea in the eye caused by herpes simplex virus infection. This infection is a cause of significant morbidity whose incidence is significantly increased in the presence of recurrent infection and it can even produce corneal blindness. Edoxudine 3% cream was also indicated for the treatment of dermal herpes simplex virus. This virus can produce an infection ubiquitously and it is highly contagious. There are two types of herpes virus, type 1 that is mainly transmitted by oral-to-oral contact and type 2 that is sexually transmitted. Mechanism of Action Edoxudine is a potent inhibitor of the replication of herpes simplex virus type 1 and 2. For the activation of this drug, the action of viral thymidine kinase is required to phosphorylate this molecule in order to form the 5'-monophosphate derivative. Then, it is needed to be further phosphorylated by cellular enzymes until the formation of the 5'-triphosphate derivative which is a competitive inhibitor of the viral-coded DNA polymerase. The advantage of edoxudine is that it is highly selective, this characteristic can be seen by its preferential phosphorylation in herpes-infected cells and its preferential incorporation into viral DNA. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ≥ 125 mg/mL (~487.79 mM ) H2O : ~50 mg/mL (~195.11 mM） |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.12 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 20.8 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: ≥ 2.08 mg/mL (8.12 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 20.8 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: ≥ 2.08 mg/mL (8.12 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.08 mg/mL (8.12 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9023 mL | 19.5114 mL | 39.0229 mL | |
| 5 mM | 0.7805 mL | 3.9023 mL | 7.8046 mL | |
| 10 mM | 0.3902 mL | 1.9511 mL | 3.9023 mL |