Idoxuridine, NSC-39661, IdUrd, IDUR, IDU, IUDR, Herpid
Idoxuridine is an anti-herpesvirus antiviral drug.
It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but theiodine atom added to the uracil component blocks base pairing. It is used only topically due to cardiotoxicity. It was synthesized byWilliam Prusoff in the late 1950s.[1] Initially developed as an anticancer drug, idoxuridine became the first antiviral agent in 1962.[2]
Clinical use
Idoxuridine is mainly used topically to treat herpes simplex keratitis.[3] Epithelial lesions, especially initial attacks presenting with a dendritic ulcer, are most responsive to therapy, while infection with stromal involvement are less responsive.[4] Idoxuridine is ineffective against herpes simplex virus type 2 and varicella-zoster.[3]
Side effects
Common side effects of the eye drops include irritation, blurred vision and photophobia.[5] Corneal clouding and damage of the corneal epithelium may also occur.
Formulations and dosage
Idoxuridine is available as either a 0.5% ophthalmic ointment or as a 0.1% ophthalmic solution.[3] The dosage of the ointment is every 4 hours during day and once before bedtime.[3] The dosage of the solution is 1 drop in the conjunctival sac hourly during the day and every 2 hours during the night until definitive improvement, then 1 drop every 2 hours during the day and every 4 hours during the night.[3] Therapy is continued for 3-4 days after healing is complete, as demonstrated by fluorescein staining.[3]
UV - spectrum
 | ||||
| Conditions : Concentration - 2 mg / 100 ml | ||||
| SOLVENT DESIGNATION SCHEDULE | METHANOL  | WATER  | 0.1 M HCL  | 0.1M NAOH  |
|---|---|---|---|---|
| The absorption maximum | 284 nm | 288 nm | 288 nm | 280 nm |
 | 227 | 217 | 217 | 164 |
| ε | 8040 | 7680 | 7680 | 5810 |
IR - spectrum
| WAVELENGTH (ΜM) |
|---|
 |
| WAVENUMBER (CM -1 ) |
ass Spectrum
| SPECTRUM | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
 | ||||||||||
| The 10 largest peaks: | ||||||||||
| PEAK | 28 | 39 | 40 | 43 | 69 | 112 | 127 | 195 | 238 | 254 |
| MEANING | 436 | 291 | 393 | 300 | 295 | 319 | 608 | 570 | 999 | 34 |
Brief background information
| SALT | ATC | FORMULA | MM | CAS |
|---|---|---|---|---|
| - | D06BB01 J05AB02 S01AD01 | C 9 H 11 IN 2 O 5 | 354.10 g / mol | 54-42-2 |
 | |
| SYSTEMATIC (IUPAC) NAME | |
|---|---|
| 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodo-1,2,3,4-tetrahydropyrimidine-2,4-dione | |
| CLINICAL DATA | |
| AHFS/DRUGS.COM | Micromedex Detailed Consumer Information |
| MEDLINEPLUS | a601062 |
| PREGNANCY CAT. | C (US) B1 (topical), B3 (ophthalmologic) [AU] |
| LEGAL STATUS | Prescription Only (S4) (AU) |
| ROUTES | topically |
| IDENTIFIERS | |
| CAS NUMBER | 54-42-2  |
| ATC CODE | D06BB01 J05AB02,S01AD01 |
| PUBCHEM | CID 5905 |
| DRUGBANK | DB00249 |
| CHEMSPIDER | 10481938 |
| UNII | LGP81V5245 |
| KEGG | D00342 |
| CHEMBL | CHEMBL788  |
| NIAID CHEMDB | 001857 |
| SYNONYMS | Iododeoxyuridine; IUdR |
| CHEMICAL DATA | |
| FORMULA | C9H11IN2O5 |
| MOL. MASS | 354.099 g/mol |
Application
- antiviral ( Herpes simplex )
Classes of substances
- Iodine compounds
- Uridine and deoxyuridine
Synthesis pathway
| SYNTHESIS A) |
|---|
   |
| SYNTHESIS OF B) |
 |
Idoxuridine can be obtained by several related ways: 1) The reaction of 5-iodouracil (I) with refluxing POCl3 and dimethylaniline gives 2,4-dichloro-5-iodopyrimidine (II), which by reaction with NaOCH3 in refluxing methanol, is converted into 2,4-dimethoxy-5-iodopyrimidine (III). The reaction of (III) with 2-deoxy-3,6-di-Op-toluoyl-D-ribofuranosyl chloride (IV) in acetonitrile yields the ribofuranosyl pyridone (V ), which is demethylated with acetic anhydride - dry HCl to afford 2'-deoxy-5-iodo-3 ', 6'-di-Op-toluoyluridine (VI) Finally, this compound is hydrolyzed with NaOCH3 in methanol 2).. The acetylation of 5-iodouracil (I) with refluxing acetic anhydride gives 1-acetyl-5-iodouracil (VII), which by reaction with mercuric acetate in refluxing methanol is converted into the corresponding mercurium salt (VIII). The condensation of (VIII ) with the ribofuranosyl chloride (IV) in chloroform affords the protected 2'-deoxy-5-iodouridine (VI), already obtained. 3) The iodination of 2'-deoxyuridine (IX) with iodine, iodic acid, acetic anhydride, CCl4 and water gives 2'-deoxy-5,6-diiodo-5,6-dihydrouridine (X), which is then treated with NaOH to eliminate HI. 4) By direct iodination of 2'-deoxyuridine (IX) with iodine and nitric acid in refluxing chloroform.
Reference
Cheong, L .; Rich, MA; Eidinoff, ML; Introduction of the 5-halogenated uracil moiety into deoxyribonucleic acid of mammalian cells in culture J Biol Chem 1960, 235, 5, 1441-7.
Trade Names
| COUNTRY | TRADE NAME | MANUFACTURER |
|---|---|---|
| Germany | Virunguent | Almirall Hermal |
| France | Iduviran | Chauvin |
| United Kingdom | Gerpid | Astellas |
| Italy | Iduher | Farmigea |
| Idustatin | Sanofi-Aventis | |
| Japan | IMU | Kaken |
| I.D.U. | Senju; Takeda | |
| USA | Dendrid | Alcon |
| Gerpleks | Allergan | |
| Stokes | SmithKline & French | |
| Ukraine | No | No |
Formulations
- eye drops 0.1%;
- eye ointment 0.25%;
- Ointment 0.2%, 0.5%;
- solution of 5%, 10%, 40%
Links
- Chang, PK; Welch, AD: J. Med. Chem. (JMCMAR) 6, 428 (1963).
- FR 1,336,866 (Roussel-Uclaf; appl. 27.7.1962).
- GB 1024156 (Roussel-Uclaf; appl. 24.7.1963; F-prior. 27.7.1962).
References
- Jump up^ Prusoff, W.H. (1959) Synthesis and biological activities of iododeoxyuridine, an analog of thymidine. Biochim Biophys Acta. March; 32(1): 295–296.
- Jump up^ Wilhelmus KR (2010). "Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis". Cochrane Database Syst Rev 12: CD002898. doi:10.1002/14651858.CD002898.pub4. PMID 21154352.
- ^ Jump up to:a b c d e f Goodman and Gilman's The Pharmacological Basis of Therapeutics. Edited by Gilman AG, Rall TW, Nies AS, Taylor P. McGraw-Hill. 8th ed. 1990.
- Jump up^ Maxwell E. Treatment of herpes keratitis with 5-iodo-2-deoxyuridine (IDU): a clinical evaluation of 1500 cases. Am. J. Ophthalmol., 1963, 56, 571-573.
- Jump up^ Drugs.com: Idoxuridine ophthalmic
Further Reading
- Seth A, Misra A, Umrigar D (2004). "Topical liposomal gel of idoxuridine for the treatment of herpes simplex: pharmaceutical and clinical implications". Pharm Dev Technol 9 (3): 277–289. doi:10.1081/PDT-200031432. PMID 15458233.
- Otto S (1998). "Radiopharmaceuticals (Strontium 89) and radiosensitizers (idoxuridine)". J Intraven Nurs 21 (6): 335–7. PMID 10392098.
- Fauth E, Zankl H (1999). "Comparison of spontaneous and idoxuridine-induced micronuclei by chromosome painting". Mutat Res 440 (2): 147–56. doi:10.1016/s1383-5718(99)00021-2. PMID 10209337.
Title: Idoxuridine
CAS Registry Number: 54-42-2
CAS Name: 2¢-Deoxy-5-iodouridine
Additional Names: 1-(2-deoxy-b-D-ribofuranosyl)-5-iodouracil; 5-iodo-2¢-deoxyuridine; IdU; IdUR; IUdR; IdUrd
Trademarks: Dendrid (Alcon); Emanil; Herpes-Gel (Master); Herplex (Allergan); Idexur; Idoxene (Spodefell); Idulea; Iduridin (Ferring); Kerecid; Ophthalmadine (SAS); Stoxil (SK & F); Virudox (Bioglan)
Molecular Formula: C9H11IN2O5
Molecular Weight: 354.10
Percent Composition: C 30.53%, H 3.13%, I 35.84%, N 7.91%, O 22.59%
Literature References: Cytotoxic nucleoside with antiviral and antineoplastic activity. Prepn: Prusoff, Biochim. Biophys. Acta 32,295 (1959); Cheong et al., J. Biol. Chem. 235, 1441 (1960); Chang, Welch, J. Med. Chem. 6, 428 (1963); Amiard, Torelli, FR1336866 (1963 to Roussel-UCLAF), C.A. 60, 3082g (1964); GB 1024156; Prystas, Sorm, Collect. Czech. Chem. Commun. 29, 121 (1964). Crystal and molecular structure: Camerman, Trotter, Acta Crystallogr. 18, 203 (1965). Review: W. H. Prusoff et al. inAntibiotics vol. 5 (pt. 2), F. E. Hahn, Ed. (Springer-Verlag, New York, 1979) pp 236-261.
Properties: Crystals from water, triclinic, dec 160° (Prusoff; Chang, Welch), 190-195° (Cheong et al.), 240° (Amiard, Torelli), over 175° (Prystas, Sorm). uv max (water): 288 nm (log e 3.87). [a]D25 +7.4° (c = 0.108 in water); [a]D20 +29° (N soda). Physical properties: Ravin, Gulesich, J. Am. Pharm. Assoc. [NS] 4, 122 (1964). pKa 8.25. pH of 0.1% aq soln, about 6. Soly at 25° in mg/ml: 2.0 in water; 2.0 in 0.2N HCl; 74.0 in 0.2N NaOH; 4.4 in methanol; 2.6 in alc; 0.014 in ether; 0.003 in chloroform; 1.6 in acetone; 1.8 in ethyl acetate; 5.7 in dioxane. LD50 i.p. in mice: 2.5 g/kg (Prusoff, 1979).
pKa: pKa 8.25
Optical Rotation: [a]D25 +7.4° (c = 0.108 in water); [a]D20 +29° (N soda)
Absorption maximum: uv max (water): 288 nm (log e 3.87)
Toxicity data: LD50 i.p. in mice: 2.5 g/kg (Prusoff, 1979)
Derivative Type: a-Anomer
Additional Names: 1-(2-Deoxy-a-D-erythro-pentofuranosyl)-5-iodouracil; 1-(2-deoxy-a-D-ribofuranosyl)-5-iodouracil; a-2¢-deoxy-5-iodouridine
Properties: Crystals from water, dec 170°. [a]D25 +21.8° (c = 0.170). uv max (water): 288 nm (log e 3.88).
Optical Rotation: [a]D25 +21.8° (c = 0.170)
Absorption maximum: uv max (water): 288 nm (log e 3.88)
Therap-Cat: Antiviral.
Keywords: Antiviral; Purines/Pyrimidinones.
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