Structure of 5'-Tosyladenosine
CAS No.: 5135-30-8
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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.
Synonyms: 5'-Tosyladenosine
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 5135-30-8 |
Formula : | C17H19N5O6S |
M.W : | 421.43 |
SMILES Code : | O=S(C1=CC=C(C)C=C1)(OC[C@H]2O[C@@H](N3C=NC4=C(N)N=CN=C34)[C@H](O)[C@@H]2O)=O |
Synonyms : |
5'-Tosyladenosine
|
MDL No. : | MFCD00005751 |
InChI Key : | CAXLRAROZXYOHH-LSCFUAHRSA-N |
Pubchem ID : | 2724351 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 29 |
Num. arom. heavy atoms | 15 |
Fraction Csp3 | 0.35 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 9.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 100.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
171.06 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.4 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.02 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.25 |
Solubility | 2.35 mg/ml ; 0.00558 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.73 |
Solubility | 0.788 mg/ml ; 0.00187 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.64 |
Solubility | 0.972 mg/ml ; 0.00231 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
Yes |
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 |
-9.15 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
1.0 |
Egan? Egan (Pharmacia) filter: implemented from |
1.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.65 |
* 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 |
---|---|---|
87% | at 20℃; for 120h; | A solution of 3j46 (1.0 g, 2.37 mmol) in 10 mL of 3-(methylamino)propionitrile was stirred at room temperature for 5 days. The reaction mixture was poured into diethyl ether (50 mL). The ether layer was decanted and the resulting syrup was purified by column chromatography (silica gel, elution with 7: 1 :0.1 chloroform:methanol:NH4psiH). The desired fractions were combined, concentrated, and dried in vacuo: yield 685 mg (87percent), MS: m/z 324 (M+H)+; 1HNMR (DMSOd6) delta 8.34 (s, IH, H-8), 8.15 (s, IH, H-2), 7.29 (bs, 2H, 6-NH2), 5.87 (d, IH, H-I', h\\tau = 5.4 Hz), 5.46 (bd, IH, 2'-OH), 5.22 (bd, IH, 3'-OH), 4.65 (m, IH, H-2'), 4.13 (m, IH, H-3'), 3.97-4.03 (m, IH, H-4'), 2.78 (dd, IH, 5'-CH2), 2.58-2.68 (bm, 5H, 5'-CH2, NC- CH2CH2), 2.24 (s, 3eta, N-CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With N-ethyl-N,N-diisopropylamine; at 20℃; for 72h; | Dry aziridine (S. Gabriel, Chem. Ber. 1888, 21, 2664-2669; S. Gabriel, R. Stelzner, Chem. Ber. 1895, 28, 2929-2938) (360 l, 7.2 mmol) was added slowly to a suspension of <strong>[5135-30-8]5'-tosyladenosine</strong> (100 mg, 0.24 mmol, Aldrich) in N-ethyldiisopropylamine (125 l, 0.7 mmol) under an argon atmosphere, and the resulting solution was stirred at room temperature for three days. Any aziridine remaining was removed under reduced pressure, and the crude reaction product was dissolved in water (1 ml) and neutralized with acetic acid (1 M). The solution (100 l at a time) was injected onto a reversed-phase HPLC column (Hypersil-ODS, 5 m, 120 A, 250 x 10 mm, Bischoff, Leonberg, Germany), and the product was eluted with a linear gradient of acetonitrile (7-10percent in 30 min, 2 ml/min) in triethylammonium hydrogencarbonate buffer (0.1 M, pH 8.4). Fractions containing product (retention time 11.3 min, UV detection at 259 nm) were combined, concentrated by lyophilization to 5.5 ml (10.5 mM, using ? = 260, ? = 15400 of adenosine) and stored at -80C. Yield: 0.058 mmol (24percent). For further characterization an aliquot was completely lyophilized to afford compound 2 as a white solid. 1H NMR (500 MHz, D2O): ? = 1.49-1.40 (m, 2H; aziridine-H), 1.85-1.74 (m, 2H; aziridine-H), 2.74 and 2.68 (AB part of ABX-spectrum, 3J = 4.3, 6.6 Hz,2J = 13.3 Hz, 2H; 5'-Ha, 5'-Hb), 4.35 (ddd = dt, 3J = 4.6, 4.6, 6.7 Hz, 1H; 4'-H), 4.46 (dd = t, 3J = 5.1 Hz, 1H; 3'-H), 4.84 (dd = t , 3J = 5.3 Hz, 1H; 2'-H), 6.13 (d, 3J = 5.0 Hz, 1H; 1'-H), 8.30 (s, 1H; 8-H), 8.36 (s, 1H; 2-H). FAB-MS (thioglycolic acid): m/z (percent): 293 (100) [M+ + H], 250 (4) [M+ - C2H4N], 178 (11) [B+ + C2H4O], 167 (34), 165 (5), 164 (5) [B+ + CH2O], 158 (36) [M+ - B], 149 (78), 136 (91) [BH2+], 102 (23); B = deprotonated adenine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: PPN pyrophosphate was prepared as described previously [11]and was dried in a vacuum desiccator over P2O5 (we have alsofound freeze-drying to be effective in other experiments), thendissolved in dry acetonitrile, and stored over activated 4 Amolecular sieves. Tosylated nucleoside 1a?d (0.18 mmol) andPPN pyrophosphate (0.36 mmol) in dry acetonitrile (0.8 mL)were stirred at 30 °C under an inert atmosphere. The reactionprogress was monitored by 31P NMR spectroscopy until nofurther reaction was observed. Sodium iodide (0.149 g) wasdissolved into 9:1 acetone/water (10 mL) and the solution wasadded dropwise with stirring to the crude reaction mixturewhich had been transferred to a centrifuge tube. The solutionwas mixed for 30 minutes at 0 °C and then centrifuged at4,000 rpm for 10 minutes. The supernatant was removed by apipette and the solid residue was dissolved in TEAB buffer(3 mL, 0.1 M, pH 8.0) [4]. Sodium iodide in acetone (5 mL, 0.1 M) was added slowly to the solution and the mixture wasstirred for 30 minutes at 0 °C. Solids were collected by centrifugationat 4,000 rpm for 10 minutes, and the liquid layer wasanalysed by 31P NMR spectroscopy to ensure that selectiveremoval of inorganic pyrophosphate had been achieved. Incases where pyrophosphate ions were still present, an additionalsmall volume (<1 mL) of sodium iodide in acetone was added and the mixture was stirred and solids were collected bycentrifugation as described above. When all pyrophosphate hadbeen removed from the supernatant layer (determined by31P NMR spectroscopy), sodium iodide in acetone (5 mL,0.1 M) was added in order to precipitate the NDP product. Themixture was stirred for 30 minutes at 0 °C and then centrifugedat 4,000 rpm for 10 minutes. The precipitated NDP was washedwith acetone (2 × 2 mL) in order to remove remaining sodiumiodide and dried in a vacuum desiccator to yield a white solid. |