Ganciclovir

Base Information

• Chemical Name: Ganciclovir
• CAS No.: 82410-32-0
• Molecular Formula: C9H13N5O4
• Molecular Weight: 255.233
• Hs Code.: 29335990
• Mol file: 82410-32-0.mol

Synonyms:Gancyclovir;

Chemical Property of Ganciclovir

Chemical Property:

• Appearance/Colour: white powder
• Melting Point: 250 °C
• Refractive Index: 1.7610 (estimate)
• Boiling Point: 675 °C at 760 mmHg
• PKA: 9.33±0.20(Predicted)
• Flash Point: 362 °C
• PSA: 139.28000
• Density: 1.81 g/cm³
• LogP: -1.38970
• Storage Temp.: 2-8°C
• Solubility.: 0.1 M HCl: 10 mg/mL
• Water Solubility.: 3.6g/L(25 oC)

Purity/Quality:

98%-102% , ^*data from raw suppliers

Ganciclovir ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 46-60-61
• Safety Statements: 53-36/37/39-45

MSDS Files:

SDS file from LookChem

Useful:

• Production method: 6-chloro guanine can be taken as raw material. Compound (I) (15 g, 0.088 mol) was suspended in 200 ml of HMDS (1, 1, 1, 3, 3, 3-hexamethyldisilizane), 1.5 g of ammonium sulfate was added and refluxed for 2 h. The reaction solution was concentrated under reduced pressure and mercuric cyanide (24 g, (0.095 mol)) and 250 ml of benzene were added to the remaining yellow solid and the mixture was heated to reflux. A solution of 6-chloroguanine (29.93 g, 0.093 mol) in 250 mL of benzene was added and refluxed under nitrogen for 3 h. The benzene was distilled off under reduced pressure and the residue was stirred with 1.5 L of methylene chloride and filtered. The filtrate was washed twice with 300 ml of 30% potassium iodide aqueous solution, twice with 10% potassium carbonate, twice with 300 ml of water, and with 300 ml of saturated sodium chloride and dried over anhydrous sodium sulfate. Then perform concentration under reduced pressure to obtain 55 g of the crude product of the compound (II). The crude product was dissolved in a minimum amount of dichloromethane and chromatographed on a silica gel column (8.5 cm x 30 cm) eluting first with 2 L of ethyl acetate-hexane (2: 3), then further elute with 3 L of ethyl acetate-hexane 75:25). The compound (II) will be eluted from the second eluent, giving 32 g of the compound (II) with a yield of 80% yield and m.p. of 70-75 ° C. The compound (II) (24g, 0.05mo1) was dissolved in 500ml of methanol, and a solution containing 4.6g of sodium in 200ml of methanol was added, followed by addition of 16 ml of 2-mercaptoethanol and 1ml of water and refluxed inside the nitrogen gas for 1 h. A solution of 3 g sodium dissolved in 50 ml methanol was added and refluxed for 1 h. The reaction solution was concentrated to about 70 ml under reduced pressure, poured into 400 ml of water, and adjusted to pH 6 with glacial acetic acid. The precipitate precipitated was collected by filtration, washed thoroughly with water, washed with ether and dried in vacuo to give 22 g of a solid. The solid was stirred with hot ethyl acetate and the solid was collected by filtration and recrystallized from absolute ethanol to give 16 g of compound (III) with a yield of 70% yield and m.p. of 181-183C. Compound (m) (15.6 g, 36 mmol) was dissolved in 800 ml of refluxing ethanol. 400 ml of cyclohexene and 15 g of platinum black were added and refluxed for 18 h. The catalyst was removed by filtration and washed 5 times with hot dimethylformamide (200 ml, 100 ° C). The washings and filtrate were combined and concentrated. The residue was dissolved in hot ethanol-water (200 ml each) and filtered through 0.5 g of activated charcoal. The filtrate was concentrated under reduced pressure and the residue was crystallized from ethanol-water (4: 1) to give 7.72 g of ganciclovir in a yield of 84%, mp> 285C (decomp).
• Description: Ganciclovir is a synthetic analog of 2''-deoxy-guanosine which is used to treat or prevent cytomegalovirus (CMV) infections. It inhibits the replication of human CMV with an IC50 value of 0.01 μM and is effective against strains of CMV from human, monkey, mouse, and guinea pig. Ganciclovir is a parenterally-active antiviral agent indicated for sight- or life-threatening cytomegalovirus (CMV) infections in immunocompromised patients. Its suppressive effects on bone marrow and renal tubular secretion/absorption are reported to present potential limitations on adjunct therapies involving zidovudine, vincristine, adriamycin and amphotericin B. Recently, the emergence of CMV strains resistant to ganciclovir therapy has been reported.
• Uses: Ganciclovir is a nucleoside analog structurally related to Acyclovir (A192400). Ganciclovir is an antiviral. Ganciclovir may be used as a pharmaceutical reference standard for the determination of the analyte in pharmaceutical formulations by chromatography techniques.
• Indications: Ganciclovir (Cytovene) is an acyclic analogue of 2 deoxyguanosine with inhibitory activity toward all herpesviruses, especially CMV.
• Therapeutic Function: Antiviral
• Clinical Use: Life- or sight-threatening CMV infections in immunocompromised individuals Prevention and treatment of CMV disease in patients receiving immunosuppressive therapy for organ transplantation An ocular implant has been developed for the treatment of CMV retinitis. Use in congenital CMV infections has not yet gained regulatory approval. Intravenous ganciclovir is indicated for the treatment of CMV retinitis in immunocompromised individuals, including those with AIDS, and for the prevention of CMV infection in organ transplant recipients.Oral ganciclovir is less effective than the intravenous preparation but carries a lower risk of adverse effects. It is Intravenous ganciclovir is indicated for the treatment of CMV retinitis in immunocompromised individuals, including those with AIDS, and for the prevention of CMV infection in organ transplant recipients.Oral ganciclovir is less effective than the intravenous preparation but carries a lower risk of adverse effects. It is
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: increased risk of convulsions with imipenem/cilastatin. Antivirals: possibly increased didanosine concentration; profound myelosuppression with zidovudine - avoid if possible. Increased risk of myelosuppression with other myelosuppressive drugs. Mycophenolate: concomitant treatment with ganciclovir and mycophenolate causes increased concentration of ganciclovir and inactive mycophenolate metabolite.

Technology Process of Ganciclovir

There total 35 articles about Ganciclovir 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: 94.0%

N2-acetyl-9-(1,3-dihydroxy-2-propoxymethyl)guanine (84960-04-3) → ganciclovir (82410-32-0)

Guidance literature:

With ammonium hydroxide; In methanol; at 20 ℃; for 17h;

Reference yield: 91.0%

9-(1,3-diacetoxy-2-propoxymethyl)-N2-acetylguanine (86357-14-4) → ganciclovir (82410-32-0)

Guidance literature:

With ammonium hydroxide; for 72h; Ambient temperature;

DOI:10.1055/s-1999-6058

Reference yield: 90.0%

9-<<2-(benzyloxy)-1-<(benzyloxy)methyl>ethoxy>methyl>guanine (82410-31-9) → ganciclovir (82410-32-0)

Guidance literature:

palladium dichloride; In ethanol; cyclohexene; for 5h; Heating;

DOI:10.1002/hlca.19890720710

upstream raw materials:

1-<(1,3-dihydroxy-2-propoxy)methyl>-5-<(thiocarbamoyl)amino>-1H-imidazole-4-carboxamide

C₂₃H₂₁N₅O₆

9-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>-2,6-diamino-purine

9-<<2-benzyloxy-1-(benzyloxymethyl)ethoxy>methyl>guanine

Downstream raw materials:

9-<(1-acetoxy-2-hydroxymethyl)ethoxymethyl>guanine

9-[({1-hydroxy-3-[(4-methoxyphenyl)-diphenylmethoxy]propan-2-yl}oxy)methyl]-2-{[(4-methoxyphenyl)diphenylmethyl]amino}-6,9-dihydro-1H-purin-6-one

9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-2-{[(4-methoxyphenyl)diphenylmethyl]amino}-6,9-dihydro-1H-purin-6-one

Acetic acid 3-acetoxy-2-[6-oxo-2-(trityl-amino)-1,6-dihydro-purin-9-ylmethoxy]-propyl ester

Refernces

• 1、 -. "Preparation method of ganciclovir". Paragraph 0030; 0032; 0034; 0035; 0036; 0038; 0039; 0040. . Retrieved 2018/09/28.
• 2、 Babu, K. Srihari,Srinivas,Madhavi,Babu,Reddy, G. Madhusudhan,Haldar,Rao, P. Narasimha,Krishna,Srinivas,Venkateshwarulu,Reddy, P. Pratap,Anand, R. Vijaya. "A succinct synthesis of valganciclovir hydrochloride, a cytomegalovirus (CMV) retinitis inhibitor". experimental part. p. 199 - 208. Retrieved 2011/05/11.