Structure of 1849-55-4
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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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High-throughput screening of α-chiral-primary amines to determine yield and enantiomeric excess
Moor, Sarah R. ; Howard, James R. ; Herrera, Brenden T. ; Anslyn, Eric V. ;
Abstract: A novel screening protocol was developed using a combination of a fluorescent indicator displacement assay and a CD (CD) active Fe(II) complex to determine concentration and enantiomeric excess (ee) of α-chiral amines, resp. The analyte concentration is quantified with a pre-formed non-fluorescent imine, where transmission with the chiral amine results in displacement of the fluorophore 2-naphthylamine. After discerning the concentration of amine via fluorescence in a well-plate reader, the analyte is then incorporated into a three-component octahedral Fe(II) assembly for ee determination using an EKKO CD plate-reader. With these two assays, both the ee and yield of asym. transformations of 192 samples could be determined with acceptable errors in under 15 min (not counting the preparation time). This combined speed and accuracy provides an attractive solution to overcoming anal. bottlenecks when creating α-chiral amines.
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Keywords: Circular Dichroism ; Fluorescence ; High-throughput screening ; Indicator displacement assay
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CAS No. : | 1849-55-4 |
Formula : | C6H5NO2 |
M.W : | 123.11 |
SMILES Code : | O=CC1=NC=CC=C1O |
MDL No. : | MFCD06245505 |
InChI Key : | ICDSWZBXIZCMHR-UHFFFAOYSA-N |
Pubchem ID : | 2737332 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.65 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.84 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.84 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.43 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.56 |
Solubility | 3.39 mg/ml ; 0.0276 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.48 |
Solubility | 4.11 mg/ml ; 0.0334 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.35 |
Solubility | 5.46 mg/ml ; 0.0444 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 |
Yes |
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 |
-6.45 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 |
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) |
1.07 |
* 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 |
---|---|---|
In chloroform; at 20℃; for 0.5h; | General procedure: Lambda-[Ir(ppy)2(MeCN)2](PF6) (0.0072g, 0.01mmol), 3-hydroxypyridine-2-carboxaldehyde (0.0012g, 0.01mmol) and amine or amino derivative (0.01mmol) was added to a CHCl3 (3 mL) solution sequentially. The solution was stirred at room temperature for 30min. Then the solvent was removed and the mixture was transferred to a NMR tube with 0.5mL CDCl3 for 1H NMR determination. For 3-aminopropane-1,2-diol experiment, CH3OH and CD3OD solvents were used. |
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