Cidofovir

Vistide · Cidovir · cidofovir anhydrous · HPMPC · GS-504 · CS-1956 · CIDOFOVIR · (S)-HPMPC

https://huagongshe.com/en/chemical/60613

Identifiers & Physical Properties

CAS No.	113852-37-2
Molecular formula	C8H14N3O6P
Average molar mass	279.19 g/mol
Monoisotopic mass	279.06202217 g/mol
SMILES	Nc1ccn(C[C@@H](CO)OCP(=O)(O)O)c(=O)n1
InChIKey	VWFCHDSQECPREK-LURJTMIESA-N
PubChem CID	60613
ChEMBL	CHEMBL152
ChEBI	CHEBI:3696
DTXSID	DTXSID3043734

Chemical & Physical Properties

XLogP	-3.6
Topological polar surface area	146
Hydrogen bond donors	4
Hydrogen bond acceptors	6
Rotatable bonds	6
Heavy atoms	18
Formal charge	0
Complexity	417
LogP (partition coefficient)	-3.9log Kow = -3.3 @ pH 7.1
Color/Form	Fluffy white powderWhite crystalline powder
Solubility	=170 mg/mL at pH 6-8Aqueous solubility >=170 mg/ml @ pH 6-81.15e+01 g/Ldeionized water: ≥5mg/mL (warmed)Soluble to 12 mg/mL (42.98 mM) in Water
Melting point	480260 °C (dec)480 °C260° (dec)
Optical Rotation	Specific optical rotation at 20 °C for the D (sodium) line: -97.3 deg (c=0.80 in water)
Physical Description	Solid
Stability/Shelf Life	It is recommended that cidofovir admixtures be administered within 24 hours of preparation and that refrigeration or freezer storage not be used to extend this 24 hour limit.
Other Experimental Properties	UV maximum (pH 2): 279 nm (E 13,000) /Monohydrate/
alpha	D20 -97.3° (c = 0.80 in water)
Boiling point	609.5±65.0 °C(Predicted)
Density	1.76±0.1 g/cm3(Predicted)
Storage conditions	Keep in dark place,Sealed in dry,Store in freezer, under -20°C
Physical state	powder
pKa (acidity coefficient)	2.29±0.10(Predicted)
Color	White to off-white
InChI	InChI=1S/C8H14N3O6P/c9-7-1-2-11(8(13)10-7)3-6(4-12)17-5-18(14,15)16/h1-2,6,12H,3-5H2,(H2,9,10,13)(H2,14,15,16)/t6-/m0/s1
InChIKey	VWFCHDSQECPREK-LURJTMIESA-N
SMILES	P(CO[C@H](CO)CN1C(=O)N=C(N)C=C1)(=O)(O)O
CAS DataBase Reference	113852-37-2(CAS DataBase Reference)
NCI Dictionary of Cancer Terms	cidofovir
FDA UNII	768M1V522C
NCI Drug Dictionary	cidofovir
ATC code	J05AB12
Proposition 65 List	Cidofovir
UNSPSC Code	41116107
NACRES	NA.77
Protein binding	<6%
Excreted unchanged in urine	80-100%
Volume of distribution	0.3-0.8(L/kg)
Biological half-life	1.7-2.7 / 16-25
GHS pictogram	GHS06
Signal word	Danger
GHS hazard statements	H301-H315
GHS precautionary statements	P301+P310+P330-P302+P352
Hazard symbols	T
Risk statements (R)	25-38
Safety statements (S)	36-37-45
UN transport number	UN 2811 6.1 / PGIII
Water hazard class (WGK)	3
RTECS number	SZ6545000
Storage class	6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Hazard class	Acute Tox. 3 OralSkin Irrit. 2
Hazardous substances data	113852-37-2(Hazardous Substances Data)

Safety & Regulations

Regulatory information	Hazard Traits - CarcinogenicityDevelopmental ToxicityReproductive ToxicityAuthoritative List - Prop 65Report - regardless of intended function of ingredient in the product
FDA requirements	The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl cidofovir, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Special Reports	An overview of the pharmacology, pharmacokinetics, efficacy, side effects and dosage of cidofovir for the treatment of cytomegalovirus retinitis.[Levien T, Baker DEHosp Pharm 31: 1604-20 (1996)]
Disposal methods	SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.Partially used vials of cidofovir and diluted solutions should be discarded by high temperature incineration.
Preventive Measures	Caution should be exercised in preparing, administering, and discarding solutions of cidofovir according to guidelines for handling mutagenic substances. If cidofovir concentrate for injection or a dilute solution of the drug comes in contact with the skin or mucosa, the affected area should be washed immediately and thoroughly with soap and water.
Personal Protective Equipment (PPE)	Due to the mutagenic potential of cidofovir, use of appropriate safety equipment is recommended for preparation, administration, and disposal of cidofovir. The National Institutes of Health recommends that cidofovir be prepared in a class II laminar flow biological safety cabinet and that personnel preparing this medication wear surgical gloves and a closed-front surgical-type gown with kint cuffs.
Body burden	Vitreous samples from 9 eyes of 9 patients and plasma samples from 4 patients were assayed with high-performance liquid chromatography to determine cidofovir levels. The only eye that had a detectable vitreous concentration (673.7 ng/ml) was injected with 20 ug 24 hours prior to the surgery. The remaining samples including plasma were below the detection point of the assay (100 ng/ml) and were injected between 5 and 40 days prior to sampling.

Applications & Uses

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

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).

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.

General Description

Cidofovir, (S)-3-hydroxy-2-phosphonomethoxypropyl cytosine(HPMPC, Vistide), is an acyclonucleotide analog thatpossesses broad-spectrum activity against several DNAviruses. Unlike other nucleotide analogs that are activated tonucleoside phosphates, Cidofovir is a phosphonic acid derivative.The phosphonic acid is not hydrolyzed by phosphatasesin vivo but is phosphorylated by cellular kinases to yield adiphosphate. The diphosphate acts as an antimetabolite to deoxycytosinetriphosphate (dCTP). Cidofovir diphosphate is acompetitive inhibitor of viral DNA polymerase and can beincorporated into the growing viral DNA strand, causingDNA chain termination.Cidofovir possesses a high therapeutic index against CMVand has been approved for treating CMV retinitis in patientswith AIDS. Cidofovir is administered by slow, constant intravenousinfusion in a dose of 5 mg/kg over a 1-hour periodonce a week for 2 weeks. This treatment is followed by amaintenance dose every 2 weeks.