Idoxuridine CAS 54-42-2
Introduction：Basic information about Idoxuridine CAS 54-42-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Idoxuridine Basic information
| Product Name: | Idoxuridine |
| Synonyms: | 5-Indo-2ˊ-deoxyuridine;1-beta-d-2’-deoxyribofuranosyl-5-iodouracil;1beta-D-2'-Deoxyribofuranosyl-5-iodouracil;2’-deoxy-5-iodo-uridin;5-Iodouracil deoxyriboside;5-iodouracildeoxyriboside;5iudr;5-IUdR |
| CAS: | 54-42-2 |
| MF: | C9H11IN2O5 |
| MW: | 354.1 |
| EINECS: | 200-207-8 |
| Product Categories: | Heterocyclic Compounds;Amino Acids;Antivirals for Research and Experimental Use;Biochemistry;Chemical Reagents for Pharmacology Research;Nucleosides and their analogs;Nucleosides, Nucleotides & Related Reagents;Bases & Related Reagents;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals;CYTOVENE;Nucleosides-5-I Nucleosides |
| Mol File: | 54-42-2.mol |
Idoxuridine Chemical Properties
| Melting point | 194 °C (lit.) |
| alpha | 280 º (c=1,1M NaOH) |
| density | 1.7911 (estimate) |
| refractive index | 30 ° (C=1, 1mol/L NaOH) |
| storage temp. | 2-8°C |
| solubility | DMSO (Slightly, Sonicated), Methanol (Slightly, Heated, Sonicated) |
| pka | 8.25(at 25℃) |
| form | Crystalline Powder |
| color | White to slightly beige |
| Optical Rotation | 28.4189°(C=0.8943g/100ml NAOH) |
| biological source | synthetic (organic) |
| Water Solubility | 1.6 g/L (20 ºC) |
| Sensitive | Air & Light Sensitive |
| Merck | 14,4891 |
| BRN | 30397 |
| InChI | 1S/C9H11IN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7+/m0/s1 |
| InChIKey | XQFRJNBWHJMXHO-FSDSQADBSA-N |
| SMILES | OC[C@H]1O[C@H](C[C@@H]1O)N2C=C(I)C(=O)NC2=O |
| CAS DataBase Reference | 54-42-2(CAS DataBase Reference) |
| NIST Chemistry Reference | Uridine, 2'-deoxy-5-iodo-(54-42-2) |
| EPA Substance Registry System | Uridine, 2'-deoxy-5-iodo- (54-42-2) |
Safety Information
| Hazard Codes | T,Xn |
| Risk Statements | 45-46-61-40-68-62-36/37/38-63 |
| Safety Statements | 53-45-36-22-36/37-26 |
| WGK Germany | 3 |
| RTECS | YU7700000 |
| F | 8-23 |
| TSCA | TSCA listed |
| HS Code | 29389090 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Eye Irrit. 2 Muta. 2 Repr. 2 Skin Irrit. 2 STOT SE 3 |
| Hazardous Substances Data | 54-42-2(Hazardous Substances Data) |
| Toxicity | LD50 i.p. in mice: 2.5 g/kg (Prusoff, 1979) |
| Description | 5-Iodo-2'-deoxyuridine is a nucleoside analog that inhibits the replication of viruses and other DNA-containing organisms. 2'-Deoxy-5-iodouridine also has inhibitory properties on cell nuclei, which may be due to its ability to bind with DNA and prevent the synthesis of RNA or protein. |
| Chemical Properties | Crystalline Solid |
| Originator | Dendrid,Alcon,US,1963 |
| Uses | Idoxuridine is an antiviral agent effective against herpes-simplex infections; in ophthalmie eyedrops, ointments, and solutions. |
| Uses | 5-Iodo-2'-deoxyuridine is antitumor nucleoside enantiomer thymidine kinase used as potential antiviral agents. |
| Uses | Antiviral;Nucleic acid synthesis inhibitors |
| Definition | ChEBI: A pyrimidine 2'-deoxyribonucleoside compound having 5-iodouracil as the nucleobase; used as an antiviral agent. |
| Indications | Idoxuridine (Herplex) is a water-soluble iodinated derivativeof deoxyuridine that inhibits several DNA virusesincluding HSV, VZV, vaccinia, and polyoma virus. Thetriphosphorylated metabolite of idoxuridine inhibitsboth viral and cellular DNA synthesis and is also incorporatedinto DNA. Such modified DNA is susceptible tostrand breakage and causes aberrant viral protein synthesis.Because of its significant host cytotoxicity, idoxuridinecannot be used to treat systemic viral infections. Thedevelopment of resistance to this drug is common. |
| Manufacturing Process | 5 g of 5-iodo-uracil (obtained according to T.B. Johnson et al., J. Biol. Chem.1905/6, 1, 310) in 15 cc of acetic anhydride are heated under reflux for 4,5hours. The acetylated derivative crystallizes on cooling. The crystallizedproduct is chilled for ? hour then filtered with suction, washed with aceticanhydride and then with ether and dried. 4.5 g of 1-acetyl-5-iodo-uracil, MP167°C, are thus obtained. 1.51 g of mercuric acetate are dissolved in 50 cc of methanol under reflux and1.35 g of 1-acetyl-5-iodo-uracilare added. A white precipitate is soon formed.The reaction mixture is kept under reflux for % hour and then allowed to cool to room temperature. The precipitate is then filtered with suction, washedwith methanol and dried. 2.1 g of monomercuric 5-iodo-uracil, MP 280°C, are thus obtained as acolorless powder, insoluble in water and the majority of the usual organicsolvents, such as benzene, chloroform, alcohol, ether and acetone.1.46 g of 5-iodo-uracil monomercuric derivative are introduced into 50 cc ofchloroform and 20 to 30 cc of the solvent are distilled off under normalpressure to ensure good dehydration of the reaction medium. The mixture iscooled to room temperature and 2.59 g of 3,5-di-p-toluyl-desoxy-Dribofuranosyl chloride added. The mixture is agitated for 6 hours with glassballs, filtered, rinsed with chloroform and the filtrate is successively washedwith an aqueous sodium iodide solution, with water, with a saturated solutionof sodium bicarbonate and again with water. The product is dried over sodiumsulfate, filtered and evaporated to dryness. The residue crystallizes in ether and yields about 600 mg of β-3',5'-di-ptoluyl-2'-desoxy-5-iodo-uridine which is recrystallized from toluene. Theproduct is obtained as colorless crystals, soluble in chloroform and pyridine,sparingly soluble in acetone, benzene ether and alcohol, insoluble in water, MP193°C. 206 mg of 3',5'-di-p-toluyl-2'-desoxy-5-iodo-uridineare heated at 80°C with2.5 cc of caustic soda solution (0.4 N) for ? hour. The solution obtained iscooled, filtered and then acidified with acetic acid. The desoxy-iodo-uridineand the p-toluic acid crystallize. Ether is added to dissolve the p-toluic acid,the mixture is chilled, filtered with suction, washed with water and ether, anddried. The residue is recrystallized from water and 100 mg of 5-iodo-2'-desoxy-uridine, are obtained. |
| Brand name | Dendrid (Alcon);Herplex (Allergan); Stoxil (GlaxoSmithKline). |
| Therapeutic Function | Antiviral (ophthalmic) |
| Pharmaceutical Applications | A halogenated pyrimidine analog originally synthesized as ananticancer agent. Formulated in dimethylsulfoxide for topicalapplication and as a solution for ophthalmic use. Activity is largely limited to DNA viruses, primarily HSV-1,HSV-2 and VZV. HSV-1 plaque formation in BHK 21 cellsis sensitive to 6.25–25 mg/L; type 2 microplaques required62.5–125 mg/L. RNA viruses are not affected, with the exceptionof oncogenic RNA viruses such as Rous sarcoma virus.Drug resistance is easily generated in vitro, and may be anobstacle to treatment. However, there is little or no crossresistancewith newer nucleoside analogs. It is poorly soluble in water, and aqueous solutions areineffective against infections other than those localized to theeye. In animals, therapeutic levels are achieved in the corneawithin 30 min of ophthalmic application and persist for 4 h.Penetration is otherwise poor, with only the biologically inactivedehalogenated metabolite uracil entering the eye. The drug is too toxic for systemic administration. Contactdermatitis, punctate epithelial keratopathy, follicular conjunctivitis,ptosis, stenosis and occlusion of the puncta and keratinizationof the lid margins occur in up to 14% of thosereceiving ophthalmic preparations. It is used in herpes keratitis, but has largely been supersededby trifluridine or aciclovir. |
| Biochem/physiol Actions | 5-Iodo-2′-deoxyuridine prevents in vitro DNA viral replication. This is observed in herpesviruses and poxviruses It might possess teratogenic, tumor-promoting, mutagenic, and immunosuppressive properties. 5-Iodo-2′-deoxyuridine, used in topical applications, is effective against epithelial infections. |
| Mechanism of action | Idoxuridine is a nucleoside containing a halogenated pyrimidine and is an analogue of thymidine. Itacts as an antiviral agent against DNA viruses by interfering with their replication based on the similarityof structure between thymidine and idoxuridine. Idoxuridine is first phosphorylated by the host cell virusencoded enzyme thymidine kinase to an active triphosphate form. The phosphorylated drug inhibitscellular DNA polymerase to a lesser extent than HSV DNA polymerase, which is necessary for thesynthesis of viral DNA. The triphosphate form of the drug is then incorporated during viral nucleic acidsynthesis by a false pairing system that replaces thymidine. When transcription occurs, faulty viralproteins are formed, resulting in defective viral particles. |
| Clinical Use | The only FDA-approved use of idoxuridine is in thetreatment of herpes simplex infections of the eyelid, conjunctiva conjunctiva,and cornea. It is most effective against surfaceinfections because it has little ability to penetrate the tissuesof the eye. intravenous idoxuridine was designatedan orphan drug for the treatment of soft tissue sarcoma. |
| Side effects | Idoxuridine may cause local irritation, mild edema, itching,and photophobia. Corneal clouding and small punctatedefects in the corneal epithelium have been reported.Allergic reactions are rare. |
| Safety Profile | Moderately toxic by intraperitoneal route. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental carcinogenic data. Human mutation data reported. When heated to decomposition it emits very toxic fumes of Iand NOx. |
| Synthesis | Idoxuridine, 5-iodo-1-(2-deoxyyribofuranosyl)pyrimidin-2,4-(1H.3H)-dione(36.1.14), is synthesized by the following scheme. 5-Iodouracil is acylated with acetic anhydride to make 1-acetyl-5-iodouracil (36.1.11). Treating this with mercury(II) acetate gives 5-iodomonomercury uracil (36.1.12), which is reacted with 1-bromodidesoxy-D-ribofuranosyl-3,5-bis-(p-toluenesulfonate) to make a ditosyl derivative (36.1.13). Hydrolysis of thetosyl groups using sodium hydroxide and subsequent treatment of the resulting substancewith acetic acid gives the desired product idoxuridine. |
| Veterinary Drugs and Treatments | Idoxuridine (IDU) is chemically similar to thymidine and its substitutioninto viral DNA causes misreading of the viral genetic codethereby inhibiting viral replication. Like trifluridine, IDU is consideredvirostatic rather than viricidal. IDU was found to be secondto trifluridine in efficacy in vitro against common strains of felineherpes virus growing in kidney epithelial cells. IDU is extremelywell tolerated in cats and this feature alone makes it the most popularantiviral currently available for use in cats with presumed orestablished feline herpes virus infection. Although trifluridine wasshown to be more effective in vitro, the topical irritation it inducesin cats frequently negates any beneficial effect that might be notedclinically. Stinging upon application is a rare feature with IDU/artificialtear preparations. |
| Metabolism | Idoxuridine is metabolized rapidly in the body to iodouracil, uracil, and iodide. Metabolites are excreted in the urine. |
Idoxuridine Preparation Products And Raw materials
| Raw materials | Propargyl alcohol-->Oxazole-2-amine-->Cytosine-->L-DIHYDROOROTIC ACID-->Oxazoline-->5-Iodouracil-->Sodium hydroxide-->Acetic acid-->Acetic anhydride-->5-chloromercurio-2-'-deoxyuridine-->1,3,4,6-TETRACHLORO-3ALPHA,6ALPHA-DI-PHENYLGLYCOURIL-->3,5'-Di-O-acetyl-2'-deoxyuridine-->Thymine-->5-(TriMethylstannyl)-2'-deoxyuridine-->4-THIO-2'-DEOXYURIDINE-->3',5'-DIACETYL-5-IODO-2'-DEOXYURIDINE-->2'-Deoxyuridine |
| Preparation Products | Trifluridine-->Brivudine |
