Structure of 49607-15-0
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 49607-15-0 |
Formula : | C8H10N2O3 |
M.W : | 182.18 |
SMILES Code : | NCCC1=CC([N+]([O-])=O)=C(C=C1)O |
MDL No. : | MFCD00238620 |
InChI Key : | IUCYCHQMRZWPGT-UHFFFAOYSA-N |
Pubchem ID : | 18958330 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 49.77 |
TPSA ? Topological Polar Surface Area: Calculated from |
92.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.31 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.33 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.8 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.11 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.95 |
Solubility | 2.04 mg/ml ; 0.0112 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.86 |
Solubility | 0.249 mg/ml ; 0.00137 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.65 |
Solubility | 4.04 mg/ml ; 0.0222 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 |
-6.47 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 |
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 |
2.0 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) |
1.71 |
* 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 |
---|---|---|
84% | With hydrogen iodide; hypophosphorous acid; for 1.0h;Reflux; | General procedure: The nitrophenol compounds 8b?13b were then heated under reflux with 57percent HI (10 mL) in thepresence of 30percent H3PO2 (1.0 mL). After 60 min, HPLC analysis confirmed the absence of the nitratedcompounds and the appearance of products corresponding most likely to amino derivatives resultingfrom reduction to amine at the o- (and p-) positions of the hydroxy group. The mixture was evaporated to dryness, taken up in 0.1 M HCl (3 mL) and chromatographed on a Dowex 50W-X2 (200?400 mesh)column (1.8 cm × 31 cm, equilibrated and eluted with 2 M HCl). Fractions of 20 mL were collectedand analyzed by UV spectrophotometry (200?400 nm) and by HPLC. The analytical conditions ofHPLC are described in Section 3.2. After fractions of the target compound were collected,recrystallization of compounds 8c?13c from ethanol (5 mL) plus ether (25 mL) and compound 14cfrom 6 M HCl (3 mL) plus acetone (60 mL) gave colorless crystals as HCl salts. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.3% | With nitric acid; In water; at 20℃; for 0.166667h; | General procedure: An appropriate phenol compound 8a?13a (1 mmol) was mixed with 60percent HNO3 (4.8 mmol). Theresulting suspension was stirred at room temperature for 10 min for 8a and 9a, for 30 min for 10a, 12aand 13a, or overnight for 11a, leading eventually to an intensively dark red solution. HPLC analysisconfirmed the absence of starting material and the presence of 3 major products corresponding mostlikely to nitro derivatives resulting from nitration at the o- and p-positions of the hydroxy group fromthe m-substituted phenols 8a, 10a and 12a, but only one product from the p-substituted phenols 9a,11a and 13a. The crude nitrophenol 8b or 9b was diluted with water (20 mL) and applied onto aDowex 50W-X2 (200?400 mesh) column (1.5 cm × 6 cm, H+ form, equilibrated with water).The column was washed with water (100 mL) and then the product was eluted with 2 M HCl(20 mL/fraction). Fractions containing the target compound were combined and evaporated to drynessto give a yellow powder. After the nitration of phenols 10a, 12a and 13a, the reaction mixture (10b,12b and 13b) was diluted with H2O (20 mL) and extracted with ethyl acetate (2 × 100 mL). Thecombined organic extract was washed with water (2 × 50 mL), dried with Na2SO4 and evaporatedunder reduced pressure. The nitration of 11a afforded 11b as an orange powder in the reaction mixture.After the filtration, the powder was washed with water and dried under reduced pressure to give a darkred powder 11b. |
34% | With nitric acid; In water; at 0 - 20℃; for 0.166667h; | [0228] Synthesis of o-nitrotyramine (S5). This procedure was adapted from Waser and Sommer {Helv. Chim. Acta 1923, 6, 54-61). Tyramine (0.57 g, 4.16 mmol, 1 eq.) in 4 mL of water in a 20 mL scintillation vial was cooled to 0 °C with an ice bath. Nitric acid (2 ml) was added dropwise, and the solution turned reddish brown immediately. After the addition, the reaction was warmed to room temperature and stirred for 10 min. The reaction mixture then stood uncovered at room temperature overnight, at which point the yellow precipitate was collected with a Biichner funnel. This crude product was recrystallized from 3-5 mL of boiling water to afford 0.25 g of papery yellow material (34percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In dimethyl sulfoxide; | EXAMPLE 1 A solution of 17.1 g. (0.1 m.) of benzyl bromide in 100 ml. of dimethylsulfoxide is added slowly to a stirred mixture of 18.2 g. (0.1 m.) of 4-hydroxy-3-nitrophenethylamine in 1 l. of dimethylsulfoxide and 60 ml. of 2N sodium hydroxide at 85°C. After addition is complete the reaction mixture is stirred at 85°C. for an additional two hours, poured into ice-water, saturated with sodium chloride and extracted with ethyl acetate. The organic extract is dried and concentrated to give 4-benzyloxy-3-nitrophenethylamine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In N,N-dimethyl-formamide; for 0.5h; | [0229] Synthesis of Oregon green 514 o-nitrophenol (S6). Oregon green 514 NHS-ester (2.46 mg, 0.004 mmol, 1 eq.) was dissolved in 1 mL of DMF. Compound S5 (1.31 mg, 0.0097 mmol, 2.4 eq.) and triethylamine (8.15 mg, 0.081 mmol, 20 eq.) were added and the reaction was turned end-over-end for 30 min on a laboratory rotisserie. The solvent was removed under reduced pressure, and the crude product mixture was dissolved in 250 °L of methanol. After filtration through a 0.2 mupiiota filter, the o-nitrophenol product was purified via HPLC using an Alltech Econosil CI 8 10 mupiiota column with a gradient of 5-95percent acetonitrile in water with 0.1percent TFA over 1 h. The solvent was removed under reduced pressure, and the dye was stored as a 5 mM solution in 50 iL of DMSO. |
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