Structure of 27913-99-1
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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. : | 27913-99-1 |
Formula : | C12H16N2O |
M.W : | 204.27 |
SMILES Code : | O=CC1=CC=C(N2CCN(C)CC2)C=C1 |
MDL No. : | MFCD00452233 |
InChI Key : | PFODEVGLOVUVHS-UHFFFAOYSA-N |
Pubchem ID : | 736533 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.42 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 68.09 |
TPSA ? Topological Polar Surface Area: Calculated from |
23.55 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 |
1.32 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.49 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.04 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.68 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.33 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.1 |
Solubility | 1.61 mg/ml ; 0.00791 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.42 |
Solubility | 7.85 mg/ml ; 0.0384 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.52 |
Solubility | 0.615 mg/ml ; 0.00301 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 |
No |
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 |
-6.61 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 |
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) |
1.39 |
* 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 potassium hydroxide; In water; at 60℃; for 12h; | General procedure: To a solution of N-methyl-3-acetylindol (1 mmol) and the benzaldehyde derivative (1 mmol) in methanol (10 ml) was added KOH (1 ml from a 50% solution in H2O). The mixture was heated at 60 C for 12 h then evaporated to dryness. The crude was dissolved in ethyl acetate (30 ml) then washed with HCl (1N, 10 ml) and H2O (10 ml), respectively. The organic layer was separated, dried over Na2SO4 and evaporated. The product was purified by chromatography column eluted with hexane:ethyl acetate (8:2) to yield the title compound as a yellow powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.3% | With sodium cyanoborohydride; zinc(II) chloride; In methanol;Heating; | General procedure: 4.1.52 5-Bromo-1-methyl-3-((5-(1-(oxetan-3-yl)piperidin-4-yl)pyridin-2-yl)amino)pyridin-2(1H)-one (14a) NaBH3CN (40 mg, 1.86 mmol) was added portionwise to a solution of compound 13b (225 mg, 0.62 mmol), oxetan-3-one (22.3 mg, 0.93 mmol) and ZnCl2 (256 mg, 1.86 mmol) in methanol (20 mL) at 0 C. The reaction mixture was stirred at 100 C for 5 h. After cooled down to room temperature, the reaction mixture was diluted with EtOAc and washed with brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue product was purified on a silica gel column using petroleum ether/EtOAc (1:1, v/v) as eluent to afford 14a (160 mg, 61.7%) as a yellow solid. 4.1.48 5-Bromo-1-methyl-3-((4-(4-methylpiperazin-1-yl)benzyl)amino)pyridin-2(1H)-one (12d) Using a method similar to that of 14a, compound 12d was synthesized as a white solid (472 mg, 80.3%). MS (ESI) m/z 391.2 [M+H]+; 1H NMR (400 MHz, CDCl3): delta 7.21 (d, J = 8.60 Hz, 2H), 6.91 (d, J = 8.64 Hz, 2H), 6.73 (d, J = 2.28 Hz, 1H), 6.18 (d, J = 2.24 Hz, 1H), 5.49 (d, J = 4.64 Hz, 1H), 4.20 (d, J = 5.64 Hz, 2H), 3.53 (s, 3H), 3.22 (t, J = 4.88 Hz, 4H), 2.59 (t, J = 4.92 Hz, 4H), 2.36 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With acetic acid; In ethanol; for 2.0h;Reflux; | General procedure: an appropriate 2-((benzazol-2-yl)thio) acetohydrazide 3a-3b (0.002 mol), and a 4-substitutedbenzaldehyde1a-1h (0.002 mol) and a catalytic amount of acetic acid were refluxed in EtOH (30 mL)for 2 h. The mixture was cooled in an ice-bath, and the precipitated product was filtered, dried andrecrystallized from EtOH.2-((1H-Benzimidazol-2-yl)thio)-N0-(4-(4-methylpiperazin-1-yl)benzylidene)acetohydrazide (4a). Yield: 88%,FTIR (ATR, cm-1): 3572 (N-H), 2937 (C-H), 1660 (C=O), 817. 1H-NMR (DMSO-d6): δ= 2.22 (3H, s,-CH3), 2.42-2.45 (4H, m, piperazine), 3.21-3.24 (4H, m, piperazine), 3.37 (2H, s, -CH2), 6.98 (2H, d,J = 8.85 Hz, Ar-H), 7.07 (1H, t, J = 7.80 Hz, Ar-H), 7.19 (1H, t, J = 7.44 Hz, Ar-H), 7.32-7.37 (1H, m,Ar-H), 7.48-7.56 (3H, m, Ar-H), 8.07 (1H, s, Ar-H), 11.56 (1H, br.s, -NH).13C-NMR (DMSO-d6): δ= 40.82,46.20, 47.65, 54.90, 109.68, 110.66, 115.04, 116.72, 121.49, 124.52, 128.31, 145.45, 152.24, 159.99. ESI-MS[M + H]+: 409.00 (100%). |
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