Structure of 96797-15-8
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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. : | 96797-15-8 |
Formula : | C22H17IN2 |
M.W : | 436.29 |
SMILES Code : | C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3)[N]4C=C(N=C4)I |
MDL No. : | MFCD02179542 |
InChI Key : | DXJZJYPLPZEYBH-UHFFFAOYSA-N |
Pubchem ID : | 618252 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 25 |
Num. arom. heavy atoms | 23 |
Fraction Csp3 | 0.05 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 109.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.45 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.47 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.59 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.3 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.83 |
Log S (ESOL):? ESOL: Topological method implemented from |
-6.41 |
Solubility | 0.000171 mg/ml ; 0.000000391 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.6 |
Solubility | 0.00109 mg/ml ; 0.0000025 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-8.85 |
Solubility | 0.000000621 mg/ml ; 0.0000000014 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) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-5.08 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 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.14 |
* 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 ethylmagnesium bromide; In diethyl ether; dichloromethane; | EXAMPLE 5 4-[(2,5-dimethylthien-3-yl)methyl]-1H-imidazole Fumarate STR45 To a solution of N-trityl-4-iodo-imidazole (11.8 g, 27 mmol) in dry CH2 Cl2 (200 mL) was added EtMgBr (11.0 mL, 3.0M in Et2 O). After complete halogen-metal exchange this solution was cannulated into a solution of <strong>[26421-44-3]2,5-dimethylthiophene-3-carboxaldehyde</strong> (3.5 g, 25 mmol) in 50 mL of CH2 Cl2. The reaction mixture was stirred at room temperature for 1 hr and then quenched with aqueous NH4 Cl. The mixture was transferred to a separatory funnel and the aqueous layer was extracted with a second portion of CH2 Cl2. The combined extracts were dried (MgSO4) and filtered. The solvent was evaporated in vacuo to give a thick syrup which was triturated with Et2 O to give a solid which was recrystallized from acetone to give (2,5-dimethylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, A5. 1 H NMR (CDCl3) supported the assigned structure. STR46 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Example 1 (step a); Preparation of (2,3-Dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol A solution of isopropylmagnesium bromide in tetrahydrofuran (48 mL, 0.046 mol) was added to a stirred solution of 4-iodo-1-trityl-1 H-imidazole (19.0 g, 0.046 mol) in dichloromethane (180 mL) at 10 to 15°C. The reaction mixture was allowed to warm to the ambient temperature and was stirred at ambient temperature for 1 hour. The reaction mixture was then cooled to 10-15°C, at which point a solution of <strong>[5779-93-1]2,3-dimethylbenzaldehyde</strong> (6.2 mL, 0.046 mol) in dichloromethane (10 mL) was added, while not exceeding 20 to 25°C. After additional stirring for 1 hour at ambient temperature a 10percent aqueous ammonium chloride solution (200 mL) was added to the reaction mixture. The organic layer was separated and washed with an aqueous sodium chloride solution (150 mL), thereafter the organic layer was concentrated to a volume of 40 mL. A precipitate of (2,3-dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol was obtained upon cooling the distillation residue to 4°C and it was separated by filtration, then washed with dichloromethane (50 mL). The intermediate (2,3-dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol was dried at ambient temperature. The yield was 17.4 g (84 percent) of a white or off-white powder, having a melting temperature of 203.0 to 207.0°C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | To a solution of 4-Iodo-1-trityl-1H-imidazole (Synthonix, 2.0 g, 4.58 mmol) in THF (50 mL) at room temperature was added ethylmagnesium bromide (Aldrich, 1.0 M solution in THF, 5.5 mL, 5.50 mmol) under dry conditions. After stirring for 90 minutes, zinc chloride (Aldrich, 0.749. g, 5.50 mmol) was added to the reaction mixture. After stirring for an additional 90 minutes, tetrakis(triphenyl)phosphine)palladium (Strem, 0.529 g, 0.46 mmol) and <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (as prepared in Example 1, step A, 1.29 g, 5.50 mmol) were added to the reaction mixture. The reaction mixture was heated in a 70° C. oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with 0.5 M EDTA buffer (at pH ~9) (2*250 mL) followed by brine (150 mL). The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash silica column chromatography using an 80 g Silicycle.(R). column (elution with 10-30percent ethyl acetate in hexane) which afforded the desired intermediate, 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine, as a white solid (1.38 g, 65percent). Rf 0.87 with 95:5 v/v dichloromethane-methanol; 1H-NMR (400 MHz; DMSO-d6) delta 9.29 (s, 2H), 8.42 (m, 2H), 7.92 (d, 1H), 7.62 (d, 1H), 7.56-7.43 (m, 13H), 7.24-7.22 (m, 6H); MS (ESI-) m/z 463.0 (M-1); H-PGDS FPBA IC50: >20 muM. |
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