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Chemical Structure| 86357-13-3 Chemical Structure| 86357-13-3

Structure of 86357-13-3

Chemical Structure| 86357-13-3

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Product Details of [ 86357-13-3 ]

CAS No. :86357-13-3
Formula : C10H16O7
M.W : 248.23
SMILES Code : O=C(OCOC(COC(C)=O)COC(C)=O)C
MDL No. :MFCD08457701
InChI Key :DUOPMEBLLUYTNT-UHFFFAOYSA-N
Pubchem ID :9794888

Safety of [ 86357-13-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319-H335
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 86357-13-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 0
Fraction Csp3 0.7
Num. rotatable bonds 10
Num. H-bond acceptors 7.0
Num. H-bond donors 0.0
Molar Refractivity 55.12
TPSA ?

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

88.13 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.27
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

-0.09
Log Po/w (WLOGP)?

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

0.02
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.

0.23
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

0.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.62

Water Solubility

Log S (ESOL):?

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

-0.66
Solubility 54.0 mg/ml ; 0.218 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.

-1.31
Solubility 12.2 mg/ml ; 0.0491 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

-1.12
Solubility 18.9 mg/ml ; 0.076 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

High
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.

-7.88 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

0.0
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

2.0 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<2.0
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)

2.62

Application In Synthesis of [ 86357-13-3 ]

* 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.

  • Downstream synthetic route of [ 86357-13-3 ]

[ 86357-13-3 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 86357-13-3 ]
  • 9-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-N2-acetylguanine [ No CAS ]
  • [ 86357-17-7 ]
  • [ 86357-14-4 ]
  • [ 13035-61-5 ]
  • 2
  • [ 86357-13-3 ]
  • [ 86357-14-4 ]
  • 3
  • [ 86357-13-3 ]
  • [ 3056-33-5 ]
  • N2-acetyl-7-(1,3-diacetoxy-2-propoxymethyl) guanine [ No CAS ]
  • [ 86357-14-4 ]
YieldReaction ConditionsOperation in experiment
A mixture of diacetyl guanine (25g, 0. 106MOLE), 2-acetoxymethoxy-1,3- diacetoxy propane (40. 0G, 0.161 mole), P-TOLUENE SULFONIC acid monohydrate (0.5g) in N, N-DIMETHYLFORMAMIDE (75ML) is heated at 95°C to 100°C under continuous stirring for 42 hours. After completion of the reaction, the solvents are removed under vacuum yielding a dark brown syrup. The syrup is dissolved by heating in methanol (60ML). The resulting solution is stirred at room temperature, cooled to 0°C, stirred for 30 min. at 0- 5°C. The crystallized material is filtered and washed with methanol (2 x 40ML) to yield N2-ACETYL-7- (1, 3-DIACETOXY-2-PROPOXYMETHYL) guanine (7.67g). The solvent from the filtrate is removed completely by distillation under reduced pressure to give an oily syrup. The oily syrup is dissolved in isopropyl alcohol and filtered through celite. The solvent is distilled off completely under vacuum. The residue is heated with a mixture of METHANOL (20ML) and toluene (150ML) at 60°C, stirred at room temperature and then at 0-5°C for 30 minutes. The product is filtered and washed with a mixture of methanol and toluene (1: 4) to YIELD N2-ACETYL-9- (1, 3-DIACETOXY-2-PROPOXYMETHYL) guanine (11. 0G).
A mixture of diacetyl guanine (100g, 0. 425MOLE), 2-acetoxymethoxy-1,3- diacetoxy propane (150 ML, 0.605 mole), P-TOLUENE SULFONIC acid monohydrate (2. 0G), N2 _ ACETYL-7-(1, 3-DIACETOXY-2-PROPOXYMETHYL) guanine (70G) in N, N- DIMETHYLFORMAMIDE (400ML) IS heated at 90°C to 100°C under continuous stirring for 63 hours. After completion of the reaction, the solvents are removed under vacuum from the reaction mixture, yielding a dark brown syrup. The syrup is dissolved by heating in METHANOL (400M1). The solution is cooled to 0°C, stirred for 1 hour at 0 to 5°C. The crystalline product is filtered and washed with methanol (2 x 100ML) to YIELD N2-ACETYL-7- (1, 3-diacetoxy-2- propoxymethyl) guanine (69. 0G). Solvent is removed completely from the filtrate and METHANOL (100ML) and TOLUENE (800M1) are added to the residue and the mixture is heated to 60°C and then cooled to 5°C and stirred for 30 minutes. The crystalline product is filtered, washed with a mixture of methanol and toluene (1: 4), dried at 60-65°C to afford N2-ACETYL-9- (1, 3-DIACETOXY-2-PROPOXYMETHYL) guanine (107. 0G).
  • 4
  • diacetylguanine [ No CAS ]
  • [ 86357-13-3 ]
  • [ 86357-17-7 ]
  • [ 86357-14-4 ]
YieldReaction ConditionsOperation in experiment
46.7% With phosphoric acid; In chloroform; N,N-dimethyl-formamide; Example 7 Preparation of 9-[2-Acetoxy-1-(acetoxymethyl)ethoxy]methyl}-2-acetamidopurine-6-one (9) and 7-[2-acetoxy-1-(acetoxymethyl)ethoxy]methyl}-2-acetaminopurine-6-one (10) A mixture of diacetylguanine (10.575 g, 45 mmol), 2-acetoxymethoxy-1,3-diacetoxypropane (22.32 g, 90 mmol) and phosphoric acid (0.3 ml) in DMF (45 ml) was heated for three hours at 120° (oil bath 135°) with stirring. The suspension gradually became homogeneous. When TLC indicated the reaction was complete, the reaction solution was evaporated in vacuo to remove solvents yielding a dark-brown syrup. The syrup was dissolved in small amount of CHCl3 and applied to a column (silica gel 60, phi4*27 cm), eluted with CH3 OH:CHCl3 (0-3percent) to give 9 (8.0 g, 46.7percent) and 10 (5.1 g, 29.8percent). Compound 9: mp 165°-7° (ethyl acetate); Rf 0.49 (CH3 OH--CHCl3 =1:9); UV (CH3 OH) lambdamax 254.5, 278.0 (sh); 1 H NMR (DMSO-d6) delta 12.07, 11.78 (NH, s, 2H, D2 O exchangeable), 8.14 (s, H, 8-H), 5.53 (s, 2H, OCH2 N), 4.11-3.94 (m, 5H, (OCH2 CH)2 CH), 2.18 (s, 3H, AcN), 1.88 (s, 6H, AcO). Compound 10: mp 176°-178°; Rf 0.61 (CH3 OH:CHCl3 =1:9); UV (CH3 OH) lambdamax 261.5 nm; 1 H NMR (DMSO-d6) delta 12.18, 11.63 (s, 2H, NH, D2 O exchangeable), 8.38 (s, 1H, 8-H), 5.73 (s, 2H, OCH2 N), 4.14-3.92 (m, 5H, (OCH2 CH)2 CH), 2.17 (s, 3H, AcN), 1.88 (s, 6H, AcO).
  • 5
  • [ 86357-13-3 ]
  • [ 3056-33-5 ]
  • [ 86357-14-4 ]
YieldReaction ConditionsOperation in experiment
85.3% With boron trifluoride diethyl etherate; In N,N-dimethyl-formamide; at 100℃; for 10h;Microwave irradiation; In the first step, 20.0-diacetylguanine 50.0 g (0.21 mol, 1.0 eq), 1,3-diacetoxy-2-(acetoxymethoxy)propane 104.2 g (0.42 mol, 2.0 eq ),3.0 g (0.021 mol, 0.1 eq) of boron trifluoride etherate and 200 g of N,N-dimethylformamide were placed in a microwave reactor, and the mixture was heated to 100 ° C for 10 hours.The solvent was distilled off under reduced pressure, and the mixture was cooled to room temperature. 450 g of ethyl acetate was added and refluxed for 1 hour, and the temperature was lowered to 0 to 5 ° C for 1 hour.After suction filtration and drying, the triacetyl ganciclovir compound (2) 68.3 g, the yield was 85.3percent,The purity was 95.6percent, and the compound (3) was 3.1percent.
 

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