Structure of 1169748-84-8
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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. : | 1169748-84-8 |
Formula : | C5H7BN2O2 |
M.W : | 137.93 |
SMILES Code : | NC1=CN=CC(B(O)O)=C1 |
MDL No. : | MFCD07374883 |
InChI Key : | RKZHYRRFTYDWTH-UHFFFAOYSA-N |
Pubchem ID : | 52982816 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 38.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
79.37 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.92 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.65 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.98 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-1.28 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.49 |
Solubility | 44.3 mg/ml ; 0.321 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.26 |
Solubility | 75.2 mg/ml ; 0.545 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.53 |
Solubility | 40.9 mg/ml ; 0.296 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 |
-7.79 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 |
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) |
1.97 |
* 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 |
---|---|---|
78% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium hydrogencarbonate; In N,N-dimethyl-formamide; at 70℃; | A 50 mL round bottom flask was charged with 1-(5-(5-iodothiophen-2-yl)-1- methyl-1H-indol-3-yl)ethanone (231 mg, 650 tmol), <strong>[1169748-84-8]3-aminopyridine-5-boronic acid</strong>(171 mg, 780 imol), Pd(dppf)C12 (25 mg, 34.2 tmo1), DMF (12 mL) and 2M KHCO3(3 mL). The mixture was heated to 70C before being quenched with saturated NH4C1(20 mL), diluted with water and extracted with CH2CI2. The organic extracts were driedover MgSO4 and concentrated to give an oil that was further purified by flash columnchromatography (CH2C12IMeOH 98:2 as eluent). The title compound was isolated as anoff-white solid (223 mg, 78%). ?H NMR [400 MHz, CDC13] 88.67 (d, J = 1.3 Hz,1 H),8.35 (br s, 1 H), 8.00 (d, J = 1.9 Hz, I H), 7.74 (s, 1 H), 7.58 (dd, J = 8.6, 1.8 Hz, I H),7.31 (d, J = 8.8 Hz, 1 H), 7.36 (d, J = 3.8 Hz, 1 H), 7.31 (d, J = 3.8 Hz, 1 H), 7.21-7.17(m, I H), 4.17 (t, J 7.2, 7.2 Hz, 2 H), 3.77 (s, 2 H), 2.55 (s, 3 H), 1.89 (td, J = 14.9, 7.5,7.5 Hz, 2 H), 1.40 (qd, J = 14.7, 7.4, 7.4, 7.3 Hz, 2 H), 0.98 (t, J = 7.4, 7.4 Hz, 3 H).LRMS (APCI) calcd for C23H24N30S 390 (MH4), found 390. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; | General procedure: 5-Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solutionof 2 M Na2CO3 (3 mL) and Pd(dppf)Cl2 (94 mg, 0.12 mmol) were added and the entiremixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30mmol) was added and reflux continued under N2 overnight. Upon cooling, the mixture wasdiluted with water (100 mL) and extracted with CH2Cl2 (6x50 mL). The combined organicfractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure togive a crude solid which was purified by flash column chromatography on silica gel (EtOAcas eluant). The title compound was isolated as a light-brown solid (510 mg, 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; | General procedure: 5-Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solutionof 2 M Na2CO3 (3 mL) and Pd(dppf)Cl2 (94 mg, 0.12 mmol) were added and the entiremixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30mmol) was added and reflux continued under N2 overnight. Upon cooling, the mixture wasdiluted with water (100 mL) and extracted with CH2Cl2 (6x50 mL). The combined organicfractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure togive a crude solid which was purified by flash column chromatography on silica gel (EtOAcas eluant). The title compound was isolated as a light-brown solid (510 mg, 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; | General procedure: 5-Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solutionof 2 M Na2CO3 (3 mL) and Pd(dppf)Cl2 (94 mg, 0.12 mmol) were added and the entiremixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30mmol) was added and reflux continued under N2 overnight. Upon cooling, the mixture wasdiluted with water (100 mL) and extracted with CH2Cl2 (6x50 mL). The combined organicfractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure togive a crude solid which was purified by flash column chromatography on silica gel (EtOAcas eluant). The title compound was isolated as a light-brown solid (510 mg, 97%). |