Structure of 1103234-56-5
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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. : | 1103234-56-5 |
Formula : | C10H11F2NO4S |
M.W : | 279.26 |
SMILES Code : | O=C(O)C1=C(F)C=CC(NS(=O)(CCC)=O)=C1F |
MDL No. : | MFCD18157658 |
Boiling Point : | No data available |
InChI Key : | RTAWCKGXCGSFJI-UHFFFAOYSA-N |
Pubchem ID : | 46192923 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 61.2 |
TPSA ? Topological Polar Surface Area: Calculated from |
91.85 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.66 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.51 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.62 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.4 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.44 |
Solubility | 1.02 mg/ml ; 0.00364 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.05 |
Solubility | 0.251 mg/ml ; 0.000897 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.5 |
Solubility | 0.0881 mg/ml ; 0.000316 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 |
-6.93 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 |
0.0 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.36 |
* 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 |
---|---|---|
9% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; | 3H-Imidazo[4,5-b]pyridin-6-amine (29 mg, 0.22 mmol), 2,6-difluoro-3-(propylsulfonamido)benzoic acid (60 mg, 0.22 mmol, 1 eq.), EDCI (46 mg, 0.24 mmol, 1.1 eq.), and 1-hydroxybenzotriazole ("HOBT")eta2O (33 mg, 0.22 mmol, 1 eq.) were combined in dry DMF (2 mL) and stirred at room temperature for 16 hours. The reaction mixture was then diluted with brine and extracted with ethyl acetate ("EtOAc"; 2 X). The extracts were washed with water (1 X), dried over sodium sulfate and concentrated under reduced pressure. The resulting crude product was purified by preparative TLC (2 X 0.5 mm plates, 10% MeOH/DCM) to give 2,6-difluoro-N-(3H-imidazo[4,5-b]pyridin-6-yl)-3-(propylsulfonamido)benzamide (7.4 mg, 9%). 1H NMR (400 MHz, DMSOd6) delta 12.63 (br s, IH), 11.03 (br s, IH), 9.81 (br s, IH), 8.43-8.53 (m, 3H), 7.53-7.59 (m, IH), 7.26-7.30 (m, IH), 3.11-3.15 (m, 2H), 1.74-1.80 (m, 2H), 0.98-1.02 (m, 3H); m/z (APCI-pos) M+l = 394.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With triethylamine; In dichloromethane; at 0 - 20℃; | The aniline 76 (1.7 g, 8.8 mmol, 1.0 eq.) was dissolved in DCM(0.25 M), treated with TEA (2.0 g, 19.4 mmol, 2.2 eq.) and cooled to0 C. Propane-1-sulfonyl chloride (2.8 g, 19.4 mmol, 2.2 eq.) wasadded slowly to the solution at 0 C. The ice bath was removed, andthe reaction was stirred at RT until TLC revealed completion of thereaction. Water was added, and the mixture was extracted withEtOAc. The combined organic phases were dried over Na2SO4. Thesolvent was evaporated under reduced pressure, and the intermediaryformed disulfonamide was purified using flash chromatography(SiO2, nHex/EtOAc 9/1, v/v). This intermediatewas suspendedin THF/MeOH (4/1, v/v, 1 M), and aqueous 2 M NaOH solution(13 ml, 26 mmol, 3.0 eq.)was added and stirred at RT overnight. Theorganic solvents were evaporated, and the residue was acidifiedwith aqueous 1 M HCl solution. The thus formed precipitate wasfiltered off, washed with water, and the white solid was dried invacuum to dryness. Yield: 1.7 g, 6.0 mmol, 68% (over two steps). 1HNMR (DMSO-d6, 200 MHz, ppm): d 14.01 (s, 1H), 9.74 (s, 1H), 7.54(dd, J 14.8, 8.7 Hz, 1H), 7.20 (t, J 9.2 Hz, 1H), 3.15e3.02 (m, 2H),1.85e1.63 (m, 2H), 0.97 (t, J 7.4 Hz, 3H); 13C NMR (DMSO-d6,50 Hz, ppm): d 161.8,157.3 (dd, J 174.8, 6.9 Hz),152.3 (dd, J 178.1,6.9 Hz), 129.8 (dd, J 10.2, 2.2 Hz), 122.0 (dd, J 13.5, 3.8 Hz), 112.8 (dd, J 21.3, 19.3 Hz), 112.3 (dd, J 22.6, 4.1 Hz), 53.8, 16.9, 12.6.[M H]-: 278,0. |
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