Structure of 939-90-2
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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. : | 939-90-2 |
Formula : | C10H10O2 |
M.W : | 162.19 |
SMILES Code : | O=C([C@H]1[C@H](C2=CC=CC=C2)C1)O |
MDL No. : | MFCD00001292 |
InChI Key : | AHDDRJBFJBDEPW-DTWKUNHWSA-N |
Pubchem ID : | 237413 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.49 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.64 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.87 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.89 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.78 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.12 |
Solubility | 1.24 mg/ml ; 0.00764 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.04 |
Solubility | 1.49 mg/ml ; 0.0092 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.13 |
Solubility | 1.21 mg/ml ; 0.00743 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 |
-6.12 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 |
0.56 |
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) |
1.81 |
* 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 ChiralpakAD 5 u; In ethanol; at 35℃; under 75007.5 Torr;Supercritical conditions; Resolution of racemate; | Preparative supercritical fluid chromatography (SFC) was performed on a Berger Multigram II operating at 50 mL/min at 35 C. and 100 bar backpressure using stacked injections. The column was a ChiralpakAD 5 u, 250×21 mm. The eluent was CO2 (70%) and ethanol (30%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Resolution of racemate; | ±trans-2-phenylcyclopropanecarboxylic acid was separated into constituent enantiomers (Intermediate Y and Z) using chiral SFC. Intermediate Y: 1HNMR (300 MHz, CDC13) δ 1HNMR (300 MHz, CDC13) δ 7.35-7.09 (m, 5H), 2.61 (ddd, 1H), 1.91 (dq, 1H), 1.67 (q, 1H), 1.42 (dq, 1H). ESIMS m/z [M-H]+ 161.2. [a]D24 4 -259.546 (c 0.119, MeOH). Absolute stereochemistry assigned by comparison with literature (JMC 2000, p3923; JMC 2011, p957). Intermediate Z: 1HNMR (300 MHz, CDC13) δ 7.35-7.09 (m, 5H), 2.61 (ddd, 1H), 1.91 (dq, J = 4.8, 3.9, 1H), 1.67 (q, 1H), 1.42 (dq, 1H). ESIMS m/z [M-H]+ 161.2. [a]D245 +249.261 (c 0.102, MeOH). Absolute stereochemistry assigned by comparison with literature (JMC 2000, p3923; JMC 2011, p957). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nickel(II) bromide dimethoxyethane; manganese; lithium chloride; 2,9-di-n-hexyl-1,10-phenanthroline; In N,N-dimethyl acetamide; at 30℃; under 760.051 Torr; for 48h;Schlenk technique; | General procedure: An oven-dried Schlenk tube containing a stirring bar was charged with NiBr2·glyme (0.02 mmol, 10 molpercent), L3 (0.05 mmol, 26 molpercent), Mn (0.52 mmol, 2.60 equiv) and LiCl (0.80 mmol, 4 equiv). The Schlenk tube was evacuated and backfilled under CO2 flow (this procedure was repeated three times). Anhydrous DMA (0.50 mL) and the corresponding cyclopropyl bromide 1 (0.20 mmol, 1 equiv) were then added under CO2 flow. The Schlenk tube was next closed at atmospheric pressure of CO2 (1 atm) and the mixture was stirred for 48 h. The mixture was then carefully quenched with 2M HCl to hydrolyze the resulting carboxylate, and extracted several times with EtOAc and CH2Cl2. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The products were purified by flash chromatography (hexanes?EtOAc). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | To 2-phenylcyclopropane-1-carboxylic acid in DMF was added EDC, DMAP and 6- aminoisoquinoline and the solution was stirred overnight at room temperature under N2. The mixture was poured into water and EtOAc and extracted, dried (Na2S04) filtered and evaporated. Column chromatography 0-10percent MeOH-CH2CI2 gave pure N-(isoquinolin-6-yl)-2- phenylcyclopropane-1-carboxamide (E261). |
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