Structure of 182247-45-6
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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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CAS No. : | 182247-45-6 |
Formula : | C12H14O4 |
M.W : | 222.24 |
SMILES Code : | O=C(O)C[C@H](CC1=CC=CC=C1)C(OC)=O |
MDL No. : | MFCD01311761 |
InChI Key : | BUNMUVFKMIOEQU-JTQLQIEISA-N |
Pubchem ID : | 7006556 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 58.5 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.74 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.49 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.85 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.71 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.07 |
Solubility | 1.89 mg/ml ; 0.00852 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.48 |
Solubility | 0.728 mg/ml ; 0.00327 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.71 |
Solubility | 0.43 mg/ml ; 0.00194 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 |
-6.56 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 |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 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) |
2.16 |
* 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% | With boron trifluoride diethyl etherate; In tetrahydrofuran; for 1.0h;Inert atmosphere; | To a solution of <strong>[182247-45-6](S)-3-benzyl-4-methoxy-4-oxobutanoic acid</strong> (0.5g, 2.25mmol) and tert-butyl-2,2,2-trichloroacetimidate (0.8mL, 4.51mmol) in anhydrous THF (4mL) under Ar at 0C was added BF3.OEt2 (42muL, 0.34mmol) dropwise. The reaction mixture was stirred for 1h at 0C. Since conversion was incomplete (LCMS), additional tert-butyl-2,2,2-trichloroacetimidate (0.8mL, 4.51mmol) was added and mixture stirred for a further hour at 0C. Saturated NaHCO3 (5mL) was carrefully added and mixture extracted with EtOAc (2*10mL). The combined organic layer was dried over MgSO4, filtered and concentrated to dryness. The residue was then purified by flash chromatography on silica gel (5% EtOAc in cyclohexane) providing 4-(tert-butyl)-1-methyl-(S)-2-benzylsuccinate (0.54g, 87%). LCMS (Method B) m/z 223 (M+1 - tBu). HPLC purity>95% (254nm). 1H NMR (CDCl3) delta: 7.41 - 7.01 (m, 5H), 3.66 (s, 3H), 3.20 - 2.90 (m, 2H), 2.73 (m, 1H), 2.60 (dd, J=16.5, 9.1Hz, 1H), 2.33 (dd, J=16.5, 4.7Hz, 1H), 1.41 (s, 9H). To a solution of 4-(tert-butyl)-1-methyl-(S)-2-benzylsuccinate (0.54g, 1.93mmol) in THF/water (1/1, 8mL) was added LiOH (185mg, 7.73mmol) and the reaction mixture stirred at rt for 14h whereupon HCl (3M) was added to adjust pH to 1. Thereafter, the mixture was extracted with DCM (3*10mL) and the combined extracts dried (MgSO4), filtered and concentrated to dryness. The crude residue was purified by flash chromatography (40% EtOAc in cyclohexane) providing (S)-2-benzyl-4-(tert-butoxy)-4-oxobutanoic acid (18) (0.43g, 85%). LCMS (Method B) m/z 209 (M+1 - tBu). HPLC purity>98% (254nm). 1H NMR (CDCl3) delta: 10.49 (bs, 1H), 7.38 - 7.24 (m, 5H), 3.20 - 3.13 (m, 2H), 2.83 (dd, J=15.4, 10.4Hz, 1H), 2.62 (dd, J=16.6, 8.6Hz, 1H), 2.41 (dd, J=16.6, 4.6Hz, 1H), 1.48 (s, 9H). |
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