Structure of 20198-19-0
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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. : | 20198-19-0 |
Formula : | C8H7N3O |
M.W : | 161.16 |
SMILES Code : | O=C1NC(N)=NC2=C1C=CC=C2 |
MDL No. : | MFCD02086153 |
InChI Key : | SDTFBAXSPXZDKC-UHFFFAOYSA-N |
Pubchem ID : | 135403814 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 46.77 |
TPSA ? Topological Polar Surface Area: Calculated from |
71.77 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.36 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.86 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.83 |
Solubility | 2.36 mg/ml ; 0.0147 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.68 |
Solubility | 3.36 mg/ml ; 0.0208 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.87 |
Solubility | 0.22 mg/ml ; 0.00136 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) |
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) |
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 |
-6.86 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 |
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) |
1.63 |
* 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 |
---|---|---|
52% | With copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide at 110℃; for 24 h; | 1.00 g (4.97mmol) of 2-bromobenzoic acid 44, 2.00 g (9.95 mmol) of guanidine hydrochloride, 6.48 g (19.9 mmol) of cesium carbonate and 95 mg (0.497mmol) of copper(I) iodide were dissolved in 20 ml of abs. DMF and stirred at 110 °C for 24 h. The solvent was distilled off in vacuo and the residue filtered through a short pad of silica gel using methanol as eluent. After recrystallization from ethanol 717 mg (52percent) of 2-aminoquinazolone 10 were obtained as a colorless solid. Mp.: >300°C. 1H-NMR(250 MHz, DMSO-d6): / ppm = 10.95 (s, 1H, NH); 7.87 (dd,J =7.9 Hz,J =1.5 Hz, 1H, Ar-H); 7.55 (ddd,J =8.5 Hz,J =7.2 Hz,J =1.6 Hz; 1H, Ar-H); 7.19 (d,J =8.2 Hz, 1H, Ar-H); 7.09 (t,J =7.5 Hz, 1H, Ar-H); 6.34 (br, 2H, NH2). 13C-NMR(75.4 MHz, DMSO-d6): / ppm = 163.2, 152.4, 150.2, 133.9, 125.9, 123.1, 121.4, 117.1. IR: ν = 3581 (w); 3399 (m); 3147 (m); 3063 (m); 2642 (m); 1801 (w); 1689 (m); 1657 (m); 1633 (m); 1608 (s); 1575 (m); 1558 (m); 1511 (m); 1473 (s); 1451 (m); 1402 (m); 1340 (m); 1248 (m); 1166 (m); 1153 (m); 1123 (m); 1041 (m); 1018 (m); 897 (m); 785 (m); 764 (s); 716 (w); 680 (m);623 (m); 591 (m); 537 (s); 491 (m); 465 (m). Anal. calcd. for C8H7N3O*1/3H2O(167,1): C 57.50; H 4.62; N 25.15; found: C 57.65; H 4.41; N 25.30. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | With sodium methylate In methanol; water; butan-1-ol | A. Preparation of 2-amino-4-(3H)-quinazolone Guanidine hydrochloride (47.77 g, 0.5 mol) was added portionwise to a stirred suspension of sodium methoxide (32.42 g, 0.60 mol) in n-butanol (450 ml) at ambient temperature over 0.5 hour. After a further 0.5 hour a solution of methyl anthranilate (15 g, 0.10 mol) in n-butanol (150 ml) was added dropwise and then slowly brought to reflux. After distilling off ca. 100 ml of solvent the reaction mixture was heated under reflux at 116° for 117 hours. The cooled suspension was filtered, excess solvent removed and the residue dissolved in water, acidified to pH 5 and extracted with diethyl ether. The aqueous suspension was reacidified to pH 5, filtered off, washed with water and dried. The solid was then triturated in methanol, filtered, washed with ether and dried to give 2-amino-4-(3H)-quinazolone (3.0 g, 19percent) m.p. >300°. |
19% | With sodium methylate In methanol; water; butan-1-ol | A. Preparation of 2-amino-4-(3H)-quinazolone Guanidine hydrochloride (47.77 g, 0.5 mol) was added portionwise to a stirred suspension of sodium methoxide (32.42 g, 0.60 mol) in n-butanol (450 ml) at ambient temperature over 0.5 hour. After a further 0.5 hour a solution of methyl anthranilate (15 g, 0.10 mol) in n-butanol (150 ml) was added dropwise and then slowly brought to reflux. After distilling off ca. 100 ml of solvent the reaction mixture was heated under reflux at 116°C for 117 hours. The cooled suspension was filtered, excess solvent removed and the residue dissolved in water, acidified to pH 5 and extracted with diethyl ether. The aqueous suspension was reacidified to pH 5, filtered off, washed with water and dried. The solid was then triturated in methanol, filtered, washed with ether and dried to give 2-amino-4-(3H)-quinazolone (3.0 g, 19percent) m.p. >300°C. |
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