Structure of 59944-76-2
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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. : | 59944-76-2 |
Formula : | C8H5NO2S |
M.W : | 179.20 |
SMILES Code : | O=C(C1=CC2=CC=CN=C2S1)O |
MDL No. : | MFCD07371381 |
InChI Key : | XGCSHAYMNOFFNA-UHFFFAOYSA-N |
Pubchem ID : | 7162095 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.58 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.43 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.99 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.03 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.49 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.76 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.74 |
Solubility | 0.328 mg/ml ; 0.00183 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.34 |
Solubility | 0.0827 mg/ml ; 0.000461 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.34 |
Solubility | 0.815 mg/ml ; 0.00455 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 |
-5.93 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 |
0.56 |
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) |
1.98 |
* 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 |
---|---|---|
85% | With hydrogenchloride; sodium hydroxide; In methanol; water; | C101 (0.700 g, 3.63 mmol) is dissolved in MeOH (15 mL) and 3 mL H2O. 2N NaOH (1.82 mL, 3.63 mmol) is added drop-wise, and the reaction is stirred at rt for 24 h. The reaction is concentrated in vacuo, and H2O (40 mL) is added to dissolve the residue. The resulting solution is acidified to pH 4 using concentrated HCl, and the precipitate is isolated by filtration, yielding thieno[2,3-b]pyridine-2-carboxylic acid (C102) as a white powder (85% yield). MS (EI) for C8H5NO2S, M/z: 179 (M)+. |
85% | With hydrogenchloride; sodium hydroxide; In methanol; water; | C101 (0.700 g, 3.63 mmol) is dissolved in MeOH (15 mL) and 3 mL water. 2N NaOH (1.82 mL, 3.63 mmol) is added drop-wise, and the reaction is stirred at rt for 24 h. The reaction is concentrated in vacuo, and water (40 mL) is added to dissolve the residue. The resulting solution is acidified to pH 4 using concentrated HCl, and the precipitate is isolated by filtration, yielding thieno[2,3-b]pyridine-2-carboxylic acid (C102) as a white powder (85% yield). MS (EI) for C8H5NO2S, m/z: 179 (M)+. |
78% | With water; sodium hydroxide; In methanol; at 20℃; for 5h; | Thieno[2,3-b]pyridine-2-carboxylic acid (147-C). To a solution of compound 147-B (0.508 g, 2.63 mmol) in a mixture of MeOH (15 mL) and H2O (3 mL) was added 3N NaOH (1.9 mL, 5.66 mmol) and the reaction mixture was stirred at ambient temperature for 5 h. The solvent was evaporated under reduced pressure, the residue dissolved in H2O, and acidified with 1N HCl. The precipitate was filtered, washed with H2O, and dried under vacuum to afford compound 147-C as a white solid (0.366 g, 78%). MS: m/z 180.0 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9% | Coupling: Example 13 is obtained as a white salt (9% yield) using acid C102 according to Method A with non-critical changes. HRMS (FAB) calculated for C15H17N3OS+H: 288.1170, found 288.1175 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With diphenyl phosphoryl azide; N-ethyl-N,N-diisopropylamine; In dichloromethane; for 16h;Reflux; | Thieno[2,3-b]pyridin-2-yl-carbamic acid tert-butyl ester (147-D) A solution of compound 147-C (0.36 g, 2.00 mmol), N,N-diisopropylethylamine (0.385 mL, 2.21 mmol) and diphenyl phosphoryl azide (0.536 mL, 2.41 mmol) in t-butanol (3.6 mL) was heated at reflux for 16 h. The solvent was evaporated in vacuo, the residue dissolved in dichloromethane, washed with 1 N NaOH, brine, dried with Na2SO4, filtered, and evaporated to afford a residue. Flash column chromatography (SiO2) eluting with dichloromethane afforded compound 147-D as a white solid (0.25 g, 50%). 1H-NMR (CDCl3): delta 1.55 (s, 9H), 6.60 (s, 1H), 7.20 (dd, 1H), 7.80 (d, 1H), 8.40 (d, 1H); MS: m/z 251.2 (MH+). |
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