Structure of 111296-91-4
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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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CAS No. : | 111296-91-4 |
Formula : | C18H12N2 |
M.W : | 256.30 |
SMILES Code : | N1C2=CC=CC=C2C2=C1C=CC1=C2NC2=CC=CC=C12 |
MDL No. : | MFCD22200776 |
InChI Key : | QQWXDAWSMPLECU-UHFFFAOYSA-N |
Pubchem ID : | 4713445 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 20 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 85.17 |
TPSA ? Topological Polar Surface Area: Calculated from |
31.58 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.13 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.85 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.96 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.63 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.12 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.14 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.22 |
Solubility | 0.00153 mg/ml ; 0.00000596 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.25 |
Solubility | 0.00145 mg/ml ; 0.00000566 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.52 |
Solubility | 0.00000767 mg/ml ; 0.0000000299 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
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) |
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) |
Yes |
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 |
-4.42 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 |
0.55 |
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) |
1.5 |
* 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 |
---|---|---|
67% | With acetic acid; at 118℃; for 8h;Inert atmosphere; | Under a nitrogen atmosphere, 14.1 g (0.061 mol) of the intermediate A, 11.4 g (0.071 mol) ofN,N'-<strong>[3616-56-6]dimethylaminoacetaldehyde diethyl acetal</strong>, and 110.0 g of acetic acid were stirred for 8 hours while being heated at 118°C to reflux. After the reaction solution was cooled to room temperature, the precipitated crystal was collected by filtration and washed with acetic acid (30 ml) . The resultant crystal was subjected to purification by reslurrying to afford 10.4 g (67percent yield) of IC-2 as a white crystal. |
67% | With acetic acid; at 118℃; for 8h;Inert atmosphere; | Under a nitrogen atmosphere, 14.1 g (0.061 mol) of Intermediate C, 11.4 g (0.071 mol) of N,N?-<strong>[3616-56-6]dimethylaminoacetaldehyde diethyl acetal</strong>, and 110.0 g of acetic acid were stirred for 8 hr while being refluxed under heat at 118° C. After the reaction solution had been cooled to room temperature, the precipitated crystal was taken by filtration and washed with acetic acid (30 ml). The resultant crystal was subjected to re-slurry purification to provide 10.4 g (0.041 mol, yield: 67percent) of 5,12-dihydroindolo[3,2-a]carbazole (IC-5) as a white crystal. |
60% | With acetic acid; at 130℃;Inert atmosphere; | (3) 1H,1'H-2,3'-biindole (16.4 g, 70.6 mmol) and 2,2-diethoxy-N,N-dimethylethanamine (14.18 ml, 78 mmol) in glacial acetic acid (160 mL) were refluxed at 130 °C overnight under nitrogen. The reaction solution was cooled to room temperature and filtered. The filtrate was washed with small amount of acetic acid and excess of water. The filtrate was dried in the oven at 65°C overnight affording 10.79 g (60percent) of the 5,12-dihydroindolo[3,2-a]carbazole as gray solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In toluene; for 12h;Inert atmosphere; Reflux; | 10138] A solution of 5,12-dihydroindolo[3,2-a]carbazole (6 g, 23.41 mmol), <strong>[26608-06-0]3-bromodibenzo[b,d]furan</strong> (6.94 g, 28.1 mmol), Pd2(dba)3 (0.21 g, 0.23 mmol), Xphos (0.23 g, 0.47 mmol) and K3P04 (9.94 g, 46.8 mmol) in toluene (100 ml) was refluxed under nitrogen for 12 h. After cooling to room temperature, the solvent was evaporated and the residue was purified by column chromatography on silica gel with heptane/dichloromethane (1/1, v/v) as eluent to yield 5-(dibenzo [b,d]furan-3-yl)-5, 1 2-dihydroindolo[3,2-a]carbazole (6.3 g, 64%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; for 16h;Inert atmosphere; Reflux; | 10141] A solution of 5,12-dihydroindolo[3,2-a]carbazole(2.86 g, 11.16 mmol), <strong>[26608-06-0]3-bromodibenzo[b,d]furan</strong> (6.20 g,25.1 mmol), Pd2(dba)3 (0.20 g, 0.22 mmol), SPhos (0.18 g,0.45 mmol) and tert-8uONa (4.29 g, 44.6 mmol) in xylene(120 ml) was refluxed under nitrogen for 16 h. The solvent was evaporated and the residue was purified by colunm chromatography on silica gel with heptane/dichloromethane (1/1, v/v) as eluent and recrystallized from the same solvent to yield Compound 819 (4.5 g, 69%) as white crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In 5,5-dimethyl-1,3-cyclohexadiene;Inert atmosphere; Reflux; | In a 250 mL three-necked flask, Compound A (1.0 g, 3.9 mmol), Compound B (1.2 g, 4.8 mmol), Pd2 (dba) 3 (0.04 g, 0.039 mmol), sodium t-butoxide (0.75 g. 7.8 mmol) were added. Tri-tert-butylphosphine tetrafluoroborate (0.02g,0.078mmol) and 30ml of xylene, pumping nitrogen three times, heating to reflux temperature under nitrogen protection, cooling after overnight reactionAfter room temperature, it was diluted with toluene, passed through a silica gel column, and then recrystallized from toluene to give a yellow solid (1.4 g, yield: 80percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 95℃; for 24h; | Intermediate 1-3 (10.0 g, 0.031 mol) to intermediate 1-5 (7.9 g, 0.031 mol),Pd (pph3) 4 (1.8 g, 0.0015 mol / P & H TECH),400 ml of TOL was added to potassium carbonate (12.8 g, 0.0935 mol / sigma aldrich) and reacted at 95 C. for 24 hours.After the completion of the reaction, the mixture was cooled and separated by H20: MC, followed by column purification (n-Hexane: MC), to obtain 12.6 g (yield 82%) of intermediate 1-6. |