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Chemical Structure| 82410-32-0 Chemical Structure| 82410-32-0
Chemical Structure| 82410-32-0

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Ganciclovir

CAS No.: 82410-32-0

,99%

Ganciclovir (BW 759), a nucleoside analogue, is an orally active antiviral agent with activity against CMV. Ganciclovir also exhibits activity in vitro against members of the herpes group and some other DNA viruses. Ganciclovir inhibits the in vitro replication of human herpes viruses (HSV 1 and 2, CMV) and adenovirus serotypes 1, 2, 4, 6, 8, 10, 19, 22, and 28. Ganciclovir has an IC50 of 5.2 μM for feline herpesvirus type-1 (FHV-1) and can diffuse into the brain.

Synonyms: BW 759;2'-Nor-2'-deoxyguanosine;2'-Nor-2'-deoxyguanosine, BW 759, Ganciclovir

4.5 *For Research Use Only !

99%98%
Cat. No.: A2667142 Purity: 99%

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    Product Details of [ 82410-32-0 ]

    CAS No. :82410-32-0
    Formula : C9H13N5O4
    M.W : 255.23
    SMILES Code : O=C1NC(N)=NC2=C1N=CN2COC(CO)CO
    Synonyms :
    BW 759;2'-Nor-2'-deoxyguanosine;2'-Nor-2'-deoxyguanosine, BW 759, Ganciclovir
    MDL No. :MFCD00870588
    InChI Key :IRSCQMHQWWYFCW-UHFFFAOYSA-N
    Pubchem ID :135398740

    Safety of [ 82410-32-0 ]

    GHS Pictogram:
    Signal Word:Danger
    Hazard Statements:H340-H361
    Precautionary Statements:P201-P202-P280-P308+P313-P405-P501

    Calculated chemistry of [ 82410-32-0 ] Show Less

    Physicochemical Properties

    Num. heavy atoms 18
    Num. arom. heavy atoms 9
    Fraction Csp3 0.44
    Num. rotatable bonds 5
    Num. H-bond acceptors 6.0
    Num. H-bond donors 4.0
    Molar Refractivity 61.64
    TPSA ?

    Topological Polar Surface Area: Calculated from
    Ertl P. et al. 2000 J. Med. Chem.

    139.28 Ų

    Lipophilicity

    Log Po/w (iLOGP)?

    iLOGP: in-house physics-based method implemented from
    Daina A et al. 2014 J. Chem. Inf. Model.

    0.16
    Log Po/w (XLOGP3)?

    XLOGP3: Atomistic and knowledge-based method calculated by
    XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

    -1.66
    Log Po/w (WLOGP)?

    WLOGP: Atomistic method implemented from
    Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

    -2.11
    Log Po/w (MLOGP)?

    MLOGP: Topological method implemented from
    Moriguchi I. et al. 1992 Chem. Pharm. Bull.
    Moriguchi I. et al. 1994 Chem. Pharm. Bull.
    Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

    -1.48
    Log Po/w (SILICOS-IT)?

    SILICOS-IT: Hybrid fragmental/topological method calculated by
    FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

    -1.0
    Consensus Log Po/w?

    Consensus Log Po/w: Average of all five predictions

    -1.22

    Water Solubility

    Log S (ESOL):?

    ESOL: Topological method implemented from
    Delaney JS. 2004 J. Chem. Inf. Model.

    -0.42
    Solubility 97.8 mg/ml ; 0.383 mol/l
    Class?

    Solubility class: Log S scale
    Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

    Very soluble
    Log S (Ali)?

    Ali: Topological method implemented from
    Ali J. et al. 2012 J. Chem. Inf. Model.

    -0.75
    Solubility 45.0 mg/ml ; 0.176 mol/l
    Class?

    Solubility class: Log S scale
    Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

    Very soluble
    Log S (SILICOS-IT)?

    SILICOS-IT: Fragmental method calculated by
    FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

    -0.75
    Solubility 45.7 mg/ml ; 0.179 mol/l
    Class?

    Solubility class: Log S scale
    Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

    Soluble

    Pharmacokinetics

    GI absorption?

    Gatrointestinal absorption: according to the white of the BOILED-Egg

    Low
    BBB permeant?

    BBB permeation: according to the yolk of the BOILED-Egg

    No
    P-gp substrate?

    P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
    and tested on 415 molecules (test set)
    10-fold CV: ACC=0.72 / AUC=0.77
    External: ACC=0.88 / AUC=0.94

    No
    CYP1A2 inhibitor?

    Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
    and tested on 3000 molecules (test set)
    10-fold CV: ACC=0.83 / AUC=0.90
    External: ACC=0.84 / AUC=0.91

    No
    CYP2C19 inhibitor?

    Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
    and tested on 3000 molecules (test set)
    10-fold CV: ACC=0.80 / AUC=0.86
    External: ACC=0.80 / AUC=0.87

    No
    CYP2C9 inhibitor?

    Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
    and tested on 2075 molecules (test set)
    10-fold CV: ACC=0.78 / AUC=0.85
    External: ACC=0.71 / AUC=0.81

    No
    CYP2D6 inhibitor?

    Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
    and tested on 1068 molecules (test set)
    10-fold CV: ACC=0.79 / AUC=0.85
    External: ACC=0.81 / AUC=0.87

    No
    CYP3A4 inhibitor?

    Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
    and tested on 2579 molecules (test set)
    10-fold CV: ACC=0.77 / AUC=0.85
    External: ACC=0.78 / AUC=0.86

    No
    Log Kp (skin permeation)?

    Skin permeation: QSPR model implemented from
    Potts RO and Guy RH. 1992 Pharm. Res.

    -9.04 cm/s

    Druglikeness

    Lipinski?

    Lipinski (Pfizer) filter: implemented from
    Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
    MW ≤ 500
    MLOGP ≤ 4.15
    N or O ≤ 10
    NH or OH ≤ 5

    0.0
    Ghose?

    Ghose filter: implemented from
    Ghose AK. et al. 1999 J. Comb. Chem.
    160 ≤ MW ≤ 480
    -0.4 ≤ WLOGP ≤ 5.6
    40 ≤ MR ≤ 130
    20 ≤ atoms ≤ 70

    None
    Veber?

    Veber (GSK) filter: implemented from
    Veber DF. et al. 2002 J. Med. Chem.
    Rotatable bonds ≤ 10
    TPSA ≤ 140

    0.0
    Egan?

    Egan (Pharmacia) filter: implemented from
    Egan WJ. et al. 2000 J. Med. Chem.
    WLOGP ≤ 5.88
    TPSA ≤ 131.6

    1.0
    Muegge?

    Muegge (Bayer) filter: implemented from
    Muegge I. et al. 2001 J. Med. Chem.
    200 ≤ MW ≤ 600
    -2 ≤ XLOGP ≤ 5
    TPSA ≤ 150
    Num. rings ≤ 7
    Num. carbon > 4
    Num. heteroatoms > 1
    Num. rotatable bonds ≤ 15
    H-bond acc. ≤ 10
    H-bond don. ≤ 5

    0.0
    Bioavailability Score?

    Abbott Bioavailability Score: Probability of F > 10% in rat
    implemented from
    Martin YC. 2005 J. Med. Chem.

    0.55

    Medicinal Chemistry

    PAINS?

    Pan Assay Interference Structures: implemented from
    Baell JB. & Holloway GA. 2010 J. Med. Chem.

    0.0 alert
    Brenk?

    Structural Alert: implemented from
    Brenk R. et al. 2008 ChemMedChem

    0.0 alert: heavy_metal
    Leadlikeness?

    Leadlikeness: implemented from
    Teague SJ. 1999 Angew. Chem. Int. Ed.
    250 ≤ MW ≤ 350
    XLOGP ≤ 3.5
    Num. rotatable bonds ≤ 7

    No; 1 violation:MW<0.0
    Synthetic accessibility?

    Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
    based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
    trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

    2.61

    Application In Synthesis [ 82410-32-0 ]

    * All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

    • Upstream synthesis route of [ 82410-32-0 ]
    • Downstream synthetic route of [ 82410-32-0 ]

    [ 82410-32-0 ] Synthesis Path-Upstream   1~5

    • 1
    • [ 2466-76-4 ]
    • [ 82410-32-0 ]
    • [ 88110-89-8 ]
    YieldReaction ConditionsOperation in experiment
    75.7%
    Stage #1: With Trimethyl borate In toluene for 5 h; Reflux; Large scale
    Stage #2: at 20℃; for 6 h; Large scale
    Stage #3: at 0 - 20℃; for 2 h; Large scale
    500.0 g (1.96 mol, 1.0 eq) of ganciclovir, 244.4 g (2.35 mol, 1.2 eq) of trimethyl borate,7.5 kg of toluene was added to the reaction vessel, and heated to reflux for 5 hours. The TLC controlled raw material reaction was complete.The temperature was lowered to room temperature, 396.7 g (3.93 mol, 2.0 eq) of triethylamine was added, then 323.7 g (2.94 mol, 1.5 eq) of 1-acetylimidazole was added, and the mixture was stirred at room temperature for 6 hours.The ratio of monoacetyl ganciclovirand N,O-diacetyl ganciclovir in the HPLC was 94/4.The temperature was lowered to 0 to 10 ° C, 2.0 kg of methanol was added dropwise, and the mixture was stirred at room temperature for 2 hours, and the solvent was concentrated under reduced pressure.Add 3.0 kg of ethyl acetate, wash once with 500 g of water, layer, and extract the aqueous layer with 500 g of ethyl acetate.Concentration under reduced pressure, ethanol recrystallization to give colorless crystals 440.9 g, yield 75.7percent, purity 99.2percent,
    75.7%
    Stage #1: With Trimethyl borate In toluene for 5 h; Reflux
    Stage #2: With triethylamine In toluene at 20℃; for 6 h;
    Stage #3: With methanol In toluene at 0 - 20℃; for 2 h;
    500.0g (1.96mol, 1.0eq) of ganciclovir, 244. 4g of trimethyl borate (2·35mol, 1 · 2eq), 7.5kg of toluene were added to the reaction kettle, heated to reflux for 5 hours, controlled by TLC The reaction of the starting material was completed, and the temperature was lowered to room temperature. Triethylamine 396 · 7 g (3 · 93 mol, 2.0 eq) was added, then 1 - acetylimidazole 323 · 7 g (2 · 94 mol, 1.5 eq) was added, and stirred at room temperature for 6 hours, HPLC The ratio of controlled monoacetyl ganciclovir and N,0-diacetyl ganciclovir was 94/4, the temperature was lowered by 0~10 ° C, 2.0 kg of methanol was added dropwise, and the mixture was stirred at room temperature for 2 hours, and concentrated under reduced pressure. the solvent, ethyl acetate was added 3.0kg, 500g once with water, separated and the aqueous layer was extracted with 500g ethyl acetate, the organic layers were combined and concentrated under reduced pressure, and recrystallized from ethanol to give colorless crystals 440.9g, a yield of 75.7percent, Purity 99.2percent
    75.7%
    Stage #1: With Trimethyl borate In toluene for 5 h; Reflux
    Stage #2: With triethylamine In toluene at 20℃; for 6 h;
    Stage #3: With methanol In toluene at 0 - 20℃; for 2 h;
    500.0 g (1.96 mol, 1.0 eq) of ganciclovir, 244.4 g (2.35 mol, 1.2 eq) of trimethyl borate,7.5 kg of toluene was added to the reaction kettle.Heated to reflux for 5 hours,The TLC controlled raw material reaction is complete,Down to room temperature,396.7 g (3.93 mol, 2.0 eq) of triethylamine was added, followed by the addition of 1-acetylimidazole 323.7 g (2.94 mol, 1.5 eq).Stir at room temperature for 6 hours.The ratio of monoacetyl ganciclovir and N,O-diacetyl ganciclovir in the HPLC was 94/4, the temperature was lowered by 0-10 °C, 2.0 kg of methanol was added dropwise, and the dropping was completed.Stir at room temperature for 2 hours.The solvent was concentrated under reduced pressure, and 3.0 kg of ethyl acetate was added, washed once with 500 g of water, and layered.The aqueous layer was extracted with EtOAc (EtOAc).Recrystallization of ethanol gave 440.9 g of colorless crystals.The yield is 75.7percent, the purity is 99.2percent,
    75.7%
    Stage #1: With Trimethyl borate In toluene for 5 h; Reflux
    Stage #2: With triethylamine In toluene at 20℃; for 6 h;
    500.0 g (1.96 mol, 1.0 eq) of ganciclovir, 244.4 g (2.35 mol, 1.2 eq) of trimethyl borate, 7.5 kg of toluene were added to the reaction kettle, and heated to reflux for 5 hours.The TLC controlled raw material reacted completely, dropped to room temperature, and added triethylamine.396.7 g (3.93 mol, 2.0 eq), then added 3-acetylimidazole 323.7 g (2.94 mol, 1.5 eq), stirred at room temperature for 6 hours, HPLC controlled monoacetyl ganciclovir and N, O-diacetyl The ratio of Lovi is 94/4, the temperature is lowered to 0-10 ° C, 2.0 kg of methanol is added dropwise, and the mixture is stirred at room temperature for 2 hours. The solvent is concentrated under reduced pressure. 3.0 kg of ethyl acetate is added, and once with 500 g of water, the layers are separated. The aqueous layer was extracted with 500 g of ethyl acetate and the organic layers were combined.Concentration under reduced pressure, ethanol recrystallization to give colorless crystals 440.9 g, yield 75.7percent, purity 99.2percent,

    References: [1] Patent: CN108383840, 2018, A, . Location in patent: Paragraph 0033; 0034; 0043; 0045; 0050.
    [2] Patent: CN108503642, 2018, A, . Location in patent: Paragraph 0028-0034; 0039; 0040; 0042-0050; 0053; 0054.
    [3] Patent: CN108503641, 2018, A, . Location in patent: Paragraph 0030; 0031; 0033; 0034; 0040-0051; 0054; 0055.
    [4] Patent: CN108409739, 2018, A, . Location in patent: Paragraph 0033; 0034; 0043; 0045; 0050.
    • 2
    • [ 108-05-4 ]
    • [ 82410-32-0 ]
    • [ 88110-89-8 ]
    YieldReaction ConditionsOperation in experiment
    75.2%
    Stage #1: With triethyl borate In 2-methyltetrahydrofuran for 3 h; Reflux; Large scale
    Stage #2: at 20℃; for 6 h; Large scale
    Stage #3: at 0 - 20℃; for 3 h; Large scale
    500.0 g (1.96 mol, 1.0 eq) of ganciclovir, 314.7 g (2.15 mol, 1.1 eq) of triethyl borate,5.0 kg of 2-methyltetrahydrofuran was added to the reaction vessel, and heated to reflux for 3 hours.The TLC controlled raw material reacted completely to room temperature.595.0 g (5.88 mol, 3.0 eq) of triethylamine was added, and then 421.8 g (4.9 mol, 2.5 eq) of vinyl acetate was added, and the mixture was stirred at room temperature for 6 hours.The ratio of monoacetyl ganciclovirand N,O-diacetyl ganciclovir in the HPLC was 93/5, and the temperature was lowered by 0-10 °C.2.0 kg of ethanol was added dropwise, and the mixture was stirred at room temperature for 3 hours, and the solvent was concentrated under reduced pressure.It was washed once with 500 g of water, and the layers were separated.The ethanol was recrystallized to obtain 438.0 g of colorless crystals, the yield was 75.2percent, and the purity was 99.1percent.
    75.2%
    Stage #1: With triethyl borate In 2-methyltetrahydrofuran for 3 h; Reflux
    Stage #2: With triethylamine In 2-methyltetrahydrofuran at 20℃; for 6 h;
    Stage #3: With ethanol In 2-methyltetrahydrofuran at 0 - 20℃; for 2 h;
    500.0g (1.96mol, 1.0eq) of ganciclovir, triethyl borate 314·7g (2·15mol, 1 · leq), 5.0kg of 2-methyltetrahydrofuran was added to the reaction kettle and heated to reflux for 3 hours. The TLC controlled material was completely reacted and cooled to room temperature. Triethylamine 595, 0 g (5.88 mol, 3 · Oeq) was added, then 421,8 g (4.9 mol, 2.5 eq) of vinyl acetate was added, and stirred at room temperature for 6 hours. The ratio of monoacetyl ganciclovir and N,0-diacetyl ganciclovir was 93/5, the temperature was lowered to 0~10 °C, 2.0kg of ethanol was added dropwise, and the mixture was stirred at room temperature for 3 hours, and concentrated under reduced pressure. The solvent ethyl acetate was added 3.0kg, once, partitioned with 500g water, 500g aqueous layer was extracted with ethyl acetate, the organic layers were combined and concentrated under reduced pressure, and recrystallized from ethanol to give colorless crystals 438.0g, 75.2percent yield, purity 99.1percent
    75.2%
    Stage #1: With triethyl borate In 2-methyltetrahydrofuran for 3 h; Reflux
    Stage #2: With triethylamine In tetrahydrofuran at 20℃; for 6 h;
    Stage #3: With ethanol In tetrahydrofuran at 0 - 20℃; for 3 h;
    500.0 g (1.96 mol, 1.0 eq) of ganciclovir, 314.7 g (2.15 mol, 1.1 eq) of triethyl borate,5.0 kg of 2-methyltetrahydrofuran was added to the reaction kettle.Heat to reflux for 3 hours,The TLC controlled raw material reacted completely to room temperature.595.0 g (5.88 mol, 3.0 eq) of triethylamine was added, followed by the addition of 421.8 g (4.9 mol, 2.5 eq) of vinyl acetate.Stir at room temperature for 6 hours.The ratio of monoacetyl ganciclovir and N,O-diacetyl ganciclovir in the HPLC was 93/5.Cool down 0~10 °C,Add 2.0kg of ethanol,After the dropwise addition, stir at room temperature for 3 hours.The solvent was concentrated under reduced pressure.Add 3.0 kg of ethyl acetate,It was washed once with 500 g of water, and the layers were separated.Recrystallization of ethanol gave 438.0 g of colorless crystals.The yield is 75.2percent, the purity is 99.1percent
    75.2%
    Stage #1: With triethyl borate In 2-methyltetrahydrofuran for 3 h; Reflux
    Stage #2: With triethylamine In 2-methyltetrahydrofuran at 20℃; for 6 h;
    500.0 g (1.96 mol, 1.0 eq) of ganciclovir, 314.7 g (2.15 mol, 1.1 eq) of triethyl borate, 5.0 kg of 2-methyltetrahydrofuran were added to the reaction kettle, and heated to reflux for 3 hours.The TLC controlled raw material reacted completely to room temperature.Add 595.0 g (5.88 mol, 3.0 eq) of triethylamine, then add 421.8 g (4.9 mol, 2.5 eq) of vinyl acetate, stir at room temperature for 6 hours, and control the monoacetyl ganciclovir and N, O-diacetyl in HPLC. The ratio of ciclovir was 93/5, the temperature was lowered by 0 to 10 ° C, 2.0 kg of ethanol was added dropwise, and the mixture was stirred at room temperature for 3 hours. The solvent was concentrated under reduced pressure. 3.0 kg of ethyl acetate was added and washed once with 500 g of water.The layers were separated, and the aqueous layer was evaporated.The ethanol was recrystallized to obtain 438.0 g of colorless crystals, yield 75.2percent.Purity 99.1percent,

    References: [1] Patent: CN108383840, 2018, A, . Location in patent: Paragraph 0029; 0035; 0036; 0038; 0052.
    [2] Patent: CN108503642, 2018, A, . Location in patent: Paragraph 0028-0031; 0035-0040; 0046; 0047; 0051-0054.
    [3] Patent: CN108503641, 2018, A, . Location in patent: Paragraph 0028-0031; 0036-0039; 0047; 0048; 0052-0055.
    [4] Patent: CN108409739, 2018, A, . Location in patent: Paragraph 0029; 0035; 0036; 0038; 0052.
    • 3
    • [ 1445-45-0 ]
    • [ 82410-32-0 ]
    • [ 88110-89-8 ]
    References: [1] Magnetic Resonance in Chemistry, 2000, vol. 38, # 8, p. 696 - 700.
    • 4
    • [ 1445-45-0 ]
    • [ 82410-32-0 ]
    • [ 88110-89-8 ]
    References: [1] Nucleosides and Nucleotides, 1994, vol. 13, # 4, p. 903 - 913.
    • 5
    • [ 82410-32-0 ]
    • [ 88110-89-8 ]
    References: [1] Synthetic Communications, 2013, vol. 43, # 13, p. 1751 - 1758.
     

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