Structure of 171364-78-6
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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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Smolkova, Denisa ; Gregus, Michal ; Cmelik, Richard ; Pizova, Hana ; Jansen-van Vuuren, Ross D ; Bobal, Pavel , et al.
Abstract: This work focuses on profiling N-linked glycans by capillary electrophoresis coupled to mass spectrometry using a novel fluorescent and mass spectrometry (MS) active derivatization tag. The label is based on 2-phenylpyridine bearing tertiary amine and hydrazide functionalities. It provides efficient labeling via hydrazone formation chemistry, promising fluorescence properties, and ionization efficiency in the positive ion MS mode. Electrophoretic analysis in a neutral-coated capillary allowed baseline separation of maltooligosaccharides with limits of detection in nanomolar concentrations. The developed labeling method was successfully applied to the analyses of N-linked glycans released from several glycoproteins such as bovine ribonuclease B, human immunoglobulin G, or chicken albumin.
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Keywords: Oligosaccharides ; Glycans ; Labeling ; Phenylpyridine ; Capillary electrophoresis ; Mass spectrometry
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CAS No. : | 171364-78-6 |
Formula : | C14H22BNO2 |
M.W : | 247.14 |
SMILES Code : | CN(C)C1=CC=C(C=C1)B1OC(C)(C)C(C)(C)O1 |
MDL No. : | MFCD05663854 |
InChI Key : | DGMLJJIUOFKPKB-UHFFFAOYSA-N |
Pubchem ID : | 2758659 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H317 |
Precautionary Statements: | P261-P280 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.57 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 77.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
21.7 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.03 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.67 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.64 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.4 |
Solubility | 0.0993 mg/ml ; 0.000402 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.15 |
Solubility | 0.175 mg/ml ; 0.000706 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.11 |
Solubility | 0.0191 mg/ml ; 0.0000771 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
Yes |
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) |
Yes |
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 |
-5.66 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 |
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) |
2.96 |
* 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 |
---|---|---|
60% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 80℃; for 8h;Inert atmosphere; | It mainly includes the following steps: taking the coumarin derivative (500 mg, 2.2 mmol) after bromination at the 6 position,N,N-dimethylbenzene derivative (618 mg, 2.5 mmol) and K2CO3 (133 mg), which are introduced para-borate borate.The solution was dissolved in a toluene-ethanol mixed solution (3:1, 80 ml).After passing nitrogen gas for 30 min, 15 mg of tetrakistriphenylphosphine palladium catalyst was added to the solvent, and the mixture was heated to 80 C, 1000 r / min, and reacted for 8 hours.After the reaction, it was cooled to room temperature, washed with a large amount of water and extracted with dichloromethane.After removing excess solvent by a rotary evaporator, 100 mL of a dichloromethane solution was added to dissolve the solid, washed with 40 mL of distilled water, and separated.The remaining water was removed with anhydrous sodium sulfate, separated, and dried.The crude product was separated and purified on a 200-300 mesh silica gel column using dichloromethane-n-hexane (volume ratio 2:5) as eluent to afford yellow compound A as shown in Fig. 2.The coumarin-type organic nonlinear optical material compound A obtained by the above production method had a yield of 60%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 80℃; for 12h;Inert atmosphere; | To a solution of 4-bromobenzo[c] [1,2,5]thiadiazole (107 mg,0.50 mmol) and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (124 mg, 0.50 mmol) in toluene-ethanol(30 mL/10 mL), Pd(PPh3)4 (57 mg, 0.05 mmol) and anhydrous K2CO3 (207 mg, 1.5 mmol) were added under an argon flow at room temperature. The mixturewas then heated to 80 °C for12 h. The mixture was quenched with water after cooling back to room temperature and extracted with dichloromethane. The combined extract was dried with anhydrous Na2SO4 and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel with CH2Cl2/petroleum (1:1) to afford NBT as an orange solid. Yield: 49percent. m.p. 128-129 °C. FT-IR (KBr, upsilon/cm-1): 3052.9, 2883.6, 2801.4, 1605.9, 1519.6, 1480.6, 1441.3,1357.3, 1230.9, 1204.9, 1119.8, 1066.0, 948.4, 893.2, 849.0, 825.1, 800.2, 748.4. 1H NMR (CDCl3, 400 MHz): 7.88 (d, J 8.4 Hz, 3H), 7.62(d, J 8.0 Hz, 2H), 6.88 (d, J 8.0 Hz, 2H), 3.03 (s, 6H); 13C NMR (CDCl3, 100 MHz): delta 155.92, 153.86, 150.68, 134.81, 130.17, 129.94, 125.95, 125.34, 119.03, 112.43, 40.54. HRMS (EI mode) (m/z): found(M) 255.0827; calcd for C14H13N3S: 255.0830. |
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