Structure of 20474-15-1
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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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CAS No. : | 20474-15-1 |
Formula : | C25H19N |
M.W : | 333.43 |
SMILES Code : | C12=CC=CC=C1C(C3=CC=CC=C3)(C4=CC=CC=C4)C5=C(C=CC=C5)N2 |
MDL No. : | MFCD28127357 |
InChI Key : | HWTHOPMRUCFPBX-UHFFFAOYSA-N |
Pubchem ID : | 13293432 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 26 |
Num. arom. heavy atoms | 24 |
Fraction Csp3 | 0.04 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 110.79 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.03 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
6.59 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.75 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.91 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
5.41 |
Log S (ESOL):? ESOL: Topological method implemented from |
-6.61 |
Solubility | 0.0000818 mg/ml ; 0.000000245 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-6.64 |
Solubility | 0.000076 mg/ml ; 0.000000228 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-10.23 |
Solubility | 0.0000000196 mg/ml ; 0.0000000001 mol/l |
Class? Solubility class: Log S scale |
Insoluble |
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 |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-3.65 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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 |
2.0 |
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 |
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) |
3.44 |
* 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 |
---|---|---|
85% | 2.33 g of 9,9-diphenylacridine,240 mg of 70% oil dispersion of sodium hydride and.20 ml of tetrahydrofuran was added to 50 ml.Liter single-ended round-bottomed flask,After refluxing under argon for 30 minutes, 0.75 g was added.4,7-dichloro-1,10 phenanthroline,Then refluxed at 60 C for 24 hours,After cooling to room temperature, saturated saline was quenched,Extracted with dichloromethane, and dried over anhydrous sodium sulfate.The organic phase was filtered and dried. A methanol: dichloromethane volume ratio of 1:30 to obtain the product 2.15 grams. White solid, Yield.85% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | .33 g of 9,9-diphenylacridine, 240 mg of 70% oil-dispersed sodium hydride and 20 ml of tetrahydrofuran were added to 50 mlLiter single-necked round-bottomed flask, under reflux under an argon atmosphere for 30 minutes, was added 0.75 g of 3,8-dichloro-1,10 phenanthroline,60 C for 24 hours, cooled to room temperature, quenched with saturated brine, extracted with dichloromethane, dried over anhydrous sodium sulfateThe organic phase was filtered and dried. The product was 2.03 g in a ratio of methanol: dichloromethane 1:20 by volume. White solid, Yield.80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110.0℃; for 48.0h; | (2) A mixture of intermediate 2 (1.0 g, 4.76 mmol), 9,9-diphenylacridine (1.75 g, 5.24 mmol), sodium tert-butoxide (0.63 g, 6.56 mmol), palladium acetate (0.025 g, 0.11 mmol), tri-tert-butylphosphine tetrafluoroborate (0.095 g, 0.33 mmol), and toluene 45 mL were charged together into a 100 mL round bottom flask. Refluxed at 110C for 48 hours. The reaction was then quenched with 10 mL of saturated aqueous sodium chloride. After extraction with dichloromethane, dried over anhydrous sodium sulfate. Finally, silica gel column chromatography was carried out using dichloromethane / petroleum ether (v / v = 3: 2) as the eluent to obtain compound 4. Yield: 94%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In tetrahydrofuran; toluene; at 110℃; for 8h;Inert atmosphere; | A mixture of <strong>[171408-84-7]2,7-dibromo-9,9'-spirobi[fluorene]</strong> (SP, 1 g, 1 equiv.), 9,9-diphenyl-9,10 dihydroacridine(1, 1.50 g, 2.1 equiv.), Pd(OAc)2 (0.05 g, 0.1 equiv.), t-Bu3P (10% in toluene, 0.15 mL, 0.03 equiv.), NaOt-Bu(0.81 g, 4 equiv.), anhydrous toluene (80 mL), and dry THF (20 mL) were added together and stirredunder a nitrogen atmosphere for 8 h at 110 C. After completion of the reaction, the crude mixture wasextracted with dichloromethane and water. The organic layer was dried over anhydrous sodium sulphateand concentrated through a rotary evaporation process. The residue was purified by using silica columnchromatography with a n-hexane:dichloromethane (4:1) solvent system to achieve SP1 as a white solid.Yield: 84%; 1H-NMR (CDCl3) delta 7.96-7.98 (d, J = 10 Hz, 2H), 7.74-7.76 (d, J = 10 Hz, 2H), 7.31-7.35 (t, J = 10Hz, 2H), 7.15-7.20 (m, 16H), 6.90-6.98 (m, 18H), 6.79-6.81 (m, 6H), 6.59 (s, 2H), 6.26-6.28 (d, J = 10 Hz, 2H);13C NMR (500MHz, CDCl3) delta 151.91, 147.58, 146.57, 142.14, 141.90, 140.82, 140.75, 130.75, 130.40, 130.10,129.42, 128.16, 128.08, 127.63, 127.57, 126.81, 126.26, 123.62, 122.30, 120.30, 120.15, 114.06, 56.68; GC-MS:978.58 for C75H50N2 [M+ H+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | The 4-benzoyl-4'-bromobiphenyl (0.11 g, 0.3 mmol), 9, 10 - dihydro - 9, 9 - diphenyl acridine (0.23 g, 0 . 66 mmol), tri-tert-butylphosphonium tetrafluoroboronate (0.02 g), sodium tert-butoxide(0.2 g) adding 100 ml three-neck bottle in, vacuum replace the nitrogen three times, added into the dry toluene after 20 ml. Stir at room temperature 15 min, adding Pd2(dba)3(0.02 G), 120 C under stirring 18 h. Ling actually to the room temperature, over-elution column (for eluting DCM), turns on lathe does, [...] powder sample, carrying out column chromatography separation, to obtain white solid 0.21 g (Y=79%). |