Structure of 86357-13-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H227-H315-H319-H335 |
Precautionary Statements: | P305+P351+P338 |
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 |
88.13 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.27 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.09 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.67 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.62 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.66 |
Solubility | 54.0 mg/ml ; 0.218 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.31 |
Solubility | 12.2 mg/ml ; 0.0491 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.12 |
Solubility | 18.9 mg/ml ; 0.076 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.88 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.62 |
* 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.
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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. |