Structure of 1189207-30-4
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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. : | 1189207-30-4 |
Formula : | C15H9FO |
M.W : | 224.23 |
SMILES Code : | O=CC1=CC=C(F)C=C1C#CC2=CC=CC=C2 |
MDL No. : | MFCD28359714 |
InChI Key : | DQWGIUIRDYPGKU-UHFFFAOYSA-N |
Pubchem ID : | 46913860 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 64.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.66 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.51 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.83 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.49 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.61 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.9 |
Solubility | 0.0284 mg/ml ; 0.000127 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.55 |
Solubility | 0.0629 mg/ml ; 0.000281 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.23 |
Solubility | 0.00131 mg/ml ; 0.00000586 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.18 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 |
2.0 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) |
2.46 |
* 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 |
---|---|---|
48%; 32% | With iodine; In dimethyl sulfoxide; at 100℃; for 3h; | 3-Aminopyrazine-2-carbohydrazide (1, 77mg, 0.5mmol) 4-fluoro-2-(phenyl ethynyl)benzaldehyde (2c, 112mg, 0.5mmol), iodine (13mg, 0.05mmol), and DMSO (5.0mL) was added into a dry 25 mL flask. The reaction mixture was stirred at 100C for 3h. The cooled mixture was poured into 100mL water which was extracted with ethyl acetate (50mL×3). The organic layer was combined and dried by anhydrous Na2SO4. The ethyl acetate was recovered by rotary evaporation, and the residue was purified by column chromatography using ethyl acetate and petroleum ether (1:1) as an eluant to give 4c, 6 in 48% and 32% yields, respectively. 4.3.1 (3-Aminopyrazine-2-carbonyl)(6-fluoro-3-phenylisoquinolin-2-ium-2-yl)amide (6) M.p. 245-246?C; 1H NMR (DMSO-d6, 400?MHz): deltaH 7.15 (s, 2H, NH2), 7.44-7.46 (m, 3H, ArH), 7.64-7.71 (m, 3H, ArH), 7.91 (s, 2H, ArH), 8.10 (d, J?=?9.2?Hz, 1H, ArH), 8.50-8.54 (m, 2H, ArH), 9.87 (s, 1H, ArH). 13C NMR (DMSO-d6, 100?MHz): deltaC 111.5 (d, J(F-C)?=?22.0?Hz), 121.5 (d, J(F-C)?=?27.1?Hz), 125.0, 126.1 (d, J(F-C)?=?5.3?Hz), 128.6, 129.1, 129.8, 130.3, 131.5, 132.0, 133.1 (d, J(F-C)?=?9.8?Hz), 137.7 (d, J(F-C)?=?9.5?Hz), 146.6, 148.8, 155.3, 165.4 (d, J(F-C)?=?253.8?Hz), 167.4, 169.7. HRMS (APCI, m/z): Calcd for C20H15FN5O [M + H]+ 360.1255, found 360.1248. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With iodine; In dimethyl sulfoxide; at 60℃; | General procedure: 3-Aminopyrazine-2-carbohydrazide (77mg, 0.5mmol) 2-(arylethynyl)benzaldehydes (0.5mmol), iodine (7mg, 0.025mmol), and DMSO (5.0mL) was added into a dry 25mL flask. The reaction mixture was stirred at 60C for 2-6h until all the 1 was consumed which was monitored by TLC. Water (about 50mL) was added to the cool mixture, and the pale yellow precipitate formed immediately. The crude product was obtained by filtration and purified by recrystallization from EtOH to give 3. |
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