Structure of 59139-93-4
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 59139-93-4 |
Formula : | C11H9NO3 |
M.W : | 203.19 |
SMILES Code : | O=C(O)CN(C=CC1=C2C=CC=C1)C2=O |
MDL No. : | MFCD14551171 |
InChI Key : | SMAQTXRPPCAWTK-UHFFFAOYSA-N |
Pubchem ID : | 641185 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.09 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 56.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
59.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.47 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.24 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.23 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.16 |
Solubility | 1.4 mg/ml ; 0.00691 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.95 |
Solubility | 2.29 mg/ml ; 0.0113 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.57 |
Solubility | 0.552 mg/ml ; 0.00272 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 |
-6.75 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) |
1.83 |
* 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 |
---|---|---|
With trifluoroacetic acid; In dichloromethane; at 20℃;Cooling; | A cold solution of tert-butyl (1 -oxoisoquinolin-2(1 -/)-yl)acetate (1.2 g, 4.6mmol) in dichloromethane (20 mL) was treated with trifluoroacetic acid (10 mL) dropwise. The reaction mixture was then stirred at room temperature for 3h. The solvent was evaporated and the residue was azeotroped with toluene. The solid formed was triturated with ether to afford the title compound. 1 H NMR (400 MHz, DMSO-d6): delta 10.76 (s, 1 H), 8.18-8.20 (m, 1 H), 7.64-7.73 (m, 2H), 7.42- 7.52 (m, 2H), 6.62 (d, J= 8.0 Hz, 1 H), 4.67 (s, 2H). MS (ESI+): 204.3, HPLC (Method A) Rt 2.34 min; HPLC purity 99.3 % |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: A suspension of carboxylic acid 6a (168mg, 0.77mmol) in dry CH2Cl2 was cooled to-5C and HOBt was added (250mg, 1.85mmol). After 20min, the reaction mixture was further cooled to-15C and treated with EDC·HCl (355mg, 1.85mmol). Finally, a cold solution of pinandiol l-leucine boronate trifluoroacetate salt 7 in dry CH2Cl2 (292mg, 0.77mmol) and DIPEA (160muL, 0.92mmol) were added in sequence and the reaction mixture was stirred at-15C for 1h and then at room temperature for 2h. Then, the organic layer was washed with 0.1M KHSO4, 5% NaHCO3, and brine, dried over Na2SO4, filtered, and finally evaporated to give a crude that was triturated in Et2O and filtered, to afford the amide by-product ( 9a) as a solid. The ether solution was evaporated to give crude 8a which was used in the next reaction without further purification (293mg, 82%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With lithium hydroxide; In ethanol; at 0 - 20℃; for 6h; | General procedure: A cooled solution (0C) of 5a (183mg, 0.79mmol) in MeOH (10mL), was treated with 1N LiOH (1.6mL), and the mixture was stirred at room temperature for 6h. After concentration in vacuo, 6N HCl was added to the residual aqueous solution (pH?6.8). Upon evaporation of water at reduced pressure, the residue was purified by column chromatography (3% HCOOH in CHCl3/MeOH 9:1) to yield the title compound 6a as a white powder (168mg, 97%) |
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