Cidofovir

Base Information

• Chemical Name: Cidofovir
• CAS No.: 113852-37-2
• Molecular Formula: C8H14N3O6P
• Molecular Weight: 279.189
• Hs Code.: 2933599090
• NSC Number: 742135
• UNII: 768M1V522C
• DSSTox Substance ID: DTXSID3043734
• Nikkaji Number: J407.193J
• Wikipedia: Cidofovir
• Wikidata: Q423445
• NCI Thesaurus Code: C77925
• RXCUI: 1546007
• Metabolomics Workbench ID: 42737
• ChEMBL ID: CHEMBL152
• Mol file: 113852-37-2.mol

Synonyms:1-((3-hydroxy-2-phosphonylmethoxy)propyl)cytosine;1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine;cidofovir;cidofovir anhydrous;cidofovir sodium;cidofovir, (+-)-isomer;cidofovir, (R)-isomer;cidofovir, sodium salt;GS 504;GS-504;GS504;HPMPC;Vistide

Chemical Property of Cidofovir

Chemical Property:

• Appearance/Colour: fluffy white powder
• Vapor Pressure: 2.11E-17mmHg at 25°C
• Melting Point: 260 °C
• Refractive Index: 1.656
• Boiling Point: 609.5 °C at 760 mmHg
• PKA: 2.29±0.10(Predicted)
• Flash Point: 322.4 °C
• PSA: 157.71000
• Density: 1.76 g/cm³
• LogP: -1.08060
• Storage Temp.: room temp
• Solubility.: deionized water: ≥5mg/mL (warmed)
• XLogP3: -3.6
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 6
• Exact Mass: 279.06202217
• Heavy Atom Count: 18
• Complexity: 417

Purity/Quality:

99% ^*data from raw suppliers

Cidofovir hydrate ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 25-38
• Safety Statements: 36-37-45

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: C1=CN(C(=O)N=C1N)CC(CO)OCP(=O)(O)O
• Isomeric SMILES: C1=CN(C(=O)N=C1N)C[C@@H](CO)OCP(=O)(O)O
• Recent ClinicalTrials: Cidofovir Versus Best Supportive Care for Hemorrhagic Cystitis
• Recent EU Clinical Trials: Phase III, random, one-site, pilot, open, parallell group trial for evaluating the eficacy and safety of electrocoagulation vs topic sinecatechins vs topic cidofovir in the High-grade anal intraepithelial neoplasia in HIV homosexuals males
• Recent NIPH Clinical Trials: Cidofovir for laryngeal papillomatosis
• Description: Cidofovir launched as a first-line treatment for CMV retinitis in AIDS patients. It is a nucleotide analog with potent activity against a broad spectrum of DNA viruses, e.g., HSVl, HSV2, CMV, adenovirus and papillomavirus. Cidofovir can be synthesized by a number of methods, the most efficient involves ring openning of (R)-glycidol with cytosine. Metabolically, cidofovir does not require intracellular activation by virally-encoded enzymes like similar compounds, e.g., aciclovir or ganciclovir. It is rapidly converted to its active form, cidofovir diphosphate, which inhibits viral DNA polymerase at concentrations up to 600 fold lower than that required for human DNA polymerase. It is a competitive inhibitor of dCTP incorporation or if incorporated into viral DNA slows down further DNA synthesis and causes the destabilization of the viral DNA. There are three intracellular metabolites which are also active thus giving rise to the long half-life. This results in lower dosing times (once every 1-2 weeks) and the ability to protect previously uninfected cells from subsequent infection.
• Uses: Cidofovir suppresses virus replication by selective inhibition of viral DNA synthesis. Cidofovir, a monophosphorylated nucleotide analog, does not require viral thymidine kinase phosphorylation to act and therefore has activity against herpes simplex infections with deficient or altered thymidine kinase activity. It is ineffective against rare strains with mutations in DNA polymerase. It is administered intravenously, 5 mg/kg/week for acyclovir-resistant infections in immunocompromised hosts. Associated side effects include nephrotoxicity and neutropenia. Concomitant administration of cidofovir with probenecid and saline hydration decreases the nephrotoxicity. Cidofovir resistance has not been documented. An injectable antiviral medication for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It suppresses CMV replication by selective inhibition of viral DNA polymerase and therefore prevention of viral replication and transcription. It is used in the treatment of acyclovir resistant herpes as well as a complementary intralesional therapy against papillomatosis caused by human papillomavirus (HPV).
• Indications: Cidofovir (Vistide) is an acyclic phosphonate cytosine analogue with activity against herpesviruses including CMV, HSV-1, HSV-2, EBV, and VZV. It also inhibits adenoviruses, papillomaviruses, polyomaviruses, and poxviruses. Activation of cidofovir requires metabolism to a diphosphate by host cellular enzymes. Because this activation does not depend upon viral enzymes, similar levels of cidofovir diphosphate are seen in infected and uninfected cells. Cidofovir diphosphate competes with deoxycytidine triphosphate (dCTP) for access to viral DNA polymerase and also acts as an alternative substrate. The incorporation of one cidofovir molecule into the growing DNA chain slows replication; sequential incorporation of two molecules halts DNA polymerase activity.
• Therapeutic Function: Antiviral
• Clinical Use: Treatment of CMV retinitis Because of nephrotoxicity it is a drug of last resort. It has been used experimentally in the treatment of adenovirus pneumonia and BK virus in transplant patients and juvenile laryngeal papillomatosis. Cidofovir is approved for the treatment and prophylaxis of CMV retinitis in AIDS patients. It has also been used in the treatment of acyclovir-resistant (viral thymidine kinase-deficient) HSV infections, polyomavirusassociated progressive multifocal leukoencephalopathy, condylomata acuminata (anogenital warts), and molluscum contagiosum.
• Drug interactions: Potentially hazardous interactions with other drugs Antivirals: avoid concomitant use with tenofovir.

Technology Process of Cidofovir

There total 21 articles about Cidofovir which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

(S)-1-<3-Hydroxy-2-<(diethylphosphonyl)methoxy>propyl>cytosine (120362-35-8) → cidofovir (113852-37-2)

Guidance literature:

With trimethylsilyl bromide; In acetonitrile; for 14h; Ambient temperature;

DOI:10.1021/jm00127a010

Reference yield: 80.0%

N4-benzoyl-1-(S)-(3-hydroxy-2-phosphonomethoxypropyl)cytosine (132336-37-9) → cidofovir (113852-37-2)

Guidance literature:

With ammonium hydroxide; at 20 ℃; for 3h;

Reference yield: 71.0%

C10H16N3O7P → cidofovir (113852-37-2)

Guidance literature:

With ammonium hydroxide; at 20 ℃; for 3h;

upstream raw materials:

4-methoxy-2-pyrimidone

(R)-2--3-ytimethylacetyl-1,2,3-propanetriol 1-p-toluenesulfonate

Cytosine

(S)-1-<3-Hydroxy-2-<(diethylphosphonyl)methoxy>propyl>cytosine

Downstream raw materials:

(S)-1-{3-[4,4'-Dimethoxytrityloxy]-2-(phosphonomethoxy)propyl}cytosine

hexadecyloxypropyl-cidofovir

cyclic cidofovir DCMC salt

isopropyl O-[(5S)-5-[(4-amino-2-oxopyrimidin-1(2H)-yl)methyl]-2-oxido-1,4,2-dioxaphosphinan-2-yl]-N-(tert-butoxycarbonyl)-(L)-tyrosinate

Refernces

• 1、 -. "Method for synthesizing antiviral drugs cidofovir and buciclovir". Paragraph 0051; 0052; 0053. . Retrieved 2019/01/06.
• 2、 Tehler, Ulrika,Nelson, Cara H.,Peterson, Larryn W.,Provoda, Chester J.,Hilfinger, John M.,Lee, Kyung-Dall,McKenna, Charles E.,Amidon, Gordon L.. "Puromycin-sensitive aminopeptidase: An antiviral prodrug activating enzyme". experimental part. p. 482 - 489. Retrieved 2010/12/19.