Structure of 78119-82-1
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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. : | 78119-82-1 |
Formula : | C11H8O2 |
M.W : | 172.18 |
SMILES Code : | O=CC1=CC=C2C=C(O)C=CC2=C1 |
MDL No. : | MFCD03427537 |
InChI Key : | PRYNJOJHKYNLIS-UHFFFAOYSA-N |
Pubchem ID : | 2764110 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 51.36 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.43 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.72 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.36 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.82 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.99 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.49 |
Solubility | 0.552 mg/ml ; 0.0032 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.12 |
Solubility | 1.31 mg/ml ; 0.0076 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.44 |
Solubility | 0.0622 mg/ml ; 0.000361 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) |
Yes |
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 |
-6.13 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) |
1.0 |
* 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 |
---|---|---|
80% | General procedure: Example 1: 4-(((6-(cyclohexyloxy)naphthalen-2-yl)methyl)amino) bicyclo[2.2.2]octane-l-carboxylic acid Step 1: 4-(((6-hvdroxynaphthalen-2-yl methyl amino bicvclor2.2.21octane-l-carboxylate 6-hydroxy-2-naphthaldehyde (520 mg, 3.02 mmol, 1.0 eq) and methyl 4-aminobicyclo[2.2.2]octane-l-carboxylate (663 mg, 3.62 mmol, 1.2 eq) were dissolved in toluene (100 mL). Magnesium sulfate (72 mg, 0.60 mmol, 0.2 eq) was added to the solution and refluxed for 48 h. The solvent was removed in vacuo. The residue was dissolved in THF (150 mL) and sodium cyanoborohydride (571 mg, 9.06 mmol, 3.0 eq) was added. The mixture was refluxed for 24 h. The solvent was removed in vacuo. Water (50 mL) was added to the residue and extracted with EtOAc (2x150 mL). The combined organic phase was washed with brine and dried over Na2S04. The organic phase was concentrated to give methyl 4-(((6-hydroxynaphthalen-2-yl)methyl)amino)bicyclo[2.2.2]octane-l-carboxylate as yellow solid (819 mg, Y: 80%). ESI-MS (M+H)+: 340.2. 1H NMR (400 MHz, DMSO-d6) delta: 9.98 (s, 1H), 8.91 (br, 1H), 7.89 (s, 1H), 7.77 (d, / = 9.2 Hz, 1H), 7.75 (d, / = 8.4 Hz, 1H), 7.47 (dd, /= 8.4, 1.6 Hz, 1H), 7.15 (s, 1H), 7.14 (dd, /= 8.0, 2.4 Hz, 1H), 4.17 (s, 2H), 3.60 (s, 3H), 1.91-1.87 (m, 12H). Step 2: 4-(((6-(cvclohexyloxy naphthalen-2-yl methyl amino bicvclor2.2.21octane-l-carboxylic acid Methyl 4-(((6-hydroxynaphthalen-2-yl)methyl)amino)bicyclo[2.2.2]octane-l-carboxylate (100 mg, 0.295 mmol, 1.0 eq), cyclohexyl methanesulfonate (100 mg, 0.885 mmol, 3.0 eq) and sodium hydroxide (35 mg, 0.875 mmol, 3.0 eq) were dissolved in DMF (2 mL). The mixture was stirred at 100 C for 2 h. After cooling to rt, 1 N HCl was added to adjust pH = 6-7 and extracted with DCM (2x40 mL). The organic phase was washed with brine and dried over Na2S04. After filtration and concentration, the residue was purified by prep-HPLC (65% MeOH/H20) to give 4-(((6-(cyclohexyloxy)naphthalen-2-yl)methyl)amino)bicyclo[2.2.2]octane-l-carboxylic acid as a white solid (40 mg, yield: 33% in two steps). ESI-MS (M+H)+: 408.2. 1H NMR (400 MHz, CD3OD) delta: 7.89 (s, 1H), 7.84 (d, /= 8.4 Hz, 1H), 7.81 (d, /= 8.8 Hz, 1H), 7.49 (dd, /= 8.8, 2.0 Hz, 1H), 7.28 (d, / = 2.0 Hz, 1H), 7.20 (dd, / = 8.8, 2.4 Hz, 1H), 4.52-4.48 (m, 1H), 4.24 (s, 2H), 2.04-1.99 (m, 14H), 1.86-1.83 (m, 2H), 1.63-1.47 (m, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.9 g | With dmap; diisopropyl-carbodiimide; In dichloromethane; | 7.0 g of a compound represented by the formula (I-5-8), 3.7 g of <strong>[430-99-9]2-fluoroacrylic acid</strong>, 0.1 g of N,N-dimethylaminopyridine, and 30 mL of dichloromethane were put into a reactor. 6.7 g of diisopropylcarbodiimide was dropwise added thereto and stirred. After ordinary post-treatment, this was purified through column chromatography and recrystallization to give 3.9 g of a compound represented by the formula (I-5-9). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.4 g | Under a nitrogen atmosphere,To the reaction vessel, 1.0 g of methanesulfonyl chloride,Tetrahydrofuran 5 mL,10 mg of 2,6-di-tert-butyl-4-methylphenol was added.It was cooled to -5 ° C.,A solution prepared by dissolving 2.0 g of the compound represented by the formula (D-2R-4) in 10 mL of tetrahydrofuran and 1.3 g of diisopropylethylamine were added dropwise, followed by stirring at -5 ° C. for 1 hour.9 mL of a tetrahydrofuran solution of 1.2 g of a compound represented by the formula (D-2 R-5)1.3 g of diisopropylethylamine,10 mg of 4-dimethylaminopyridine was added,And the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into water and extracted with dichloromethane.Purification by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane / methanol) gave 2.4 g of a compound represented by the formula (D-2 R-6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3 g | 4 g of compound V and 4.2 g of compound IV, 8.4 g of triphenylphosphine (PPh3) were added to 40 ml of anhydrous tetrahydrofuran.After stirring for 15 minutes, 8.4 mL of diisopropyl azodicarboxylate (DIAD) was added dropwise in small portions to the reaction solution for 10 hours.After thin layer chromatography (TLC), the reaction mixture was poured into 100 mL of water and extracted with ethyl acetate (100 mL×5).The mixture was separated and washed with 5% sodium hydrogencarbonate (NaHCO3) (80 mL×3) and brine (80 mL×3), then dried over anhydrous magnesium sulfate. ester,Subsequent column chromatography V (petroleum ether): V (ethyl acetate)= 10:1 gave a yellow solid III 3g. |