New Drug Approvals

Home » Uncategorized » Idoxuridine

Idoxuridine

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

Categories

Recent Posts

Blog Stats

  • 3,894,370 hits

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,718 other followers

add to any

Share

 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.[citation needed]

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
Idoxuridine
Idoxuridine - Idoxuridin.svg
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 Yes
ATC code D06BB01 J05AB02,S01AD01
PubChem CID 5905
DrugBank DB00249
ChemSpider 10481938 Yes
UNII LGP81V5245 Yes
KEGG D00342 Yes
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

  1. Jump up^ Prusoff, W.H. (1959) Synthesis and biological activities of iododeoxyuridine, an analog of thymidine. Biochim Biophys Acta. March; 32(1): 295–296.
  2. 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.
  3. ^ 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.
  4. 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.
  5. 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.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

DR ANTHONY CRASTO

Follow New Drug Approvals on WordPress.com

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,718 other followers

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK LIFE SCIENCES LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 PLUS year tenure till date June 2021, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 90 Lakh plus views on dozen plus blogs, 233 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 33 lakh plus views on New Drug Approvals Blog in 233 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

Personal Links

View Full Profile →

TWITTER

bloglovin

Follow my blog with Bloglovin The title of your home page You could put your verification ID in a comment Or, in its own meta tag Or, as one of your keywords Your content is here. The verification ID will NOT be detected if you put it here.
%d bloggers like this: