Structure of 59483-84-0
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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. : | 59483-84-0 |
Formula : | C13F10O3 |
M.W : | 394.12 |
SMILES Code : | O=C(OC1=C(F)C(F)=C(F)C(F)=C1F)OC2=C(F)C(F)=C(F)C(F)=C2F |
MDL No. : | MFCD00368353 |
InChI Key : | IOVVFSGCNWQFQT-UHFFFAOYSA-N |
Pubchem ID : | 2734833 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 26 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 13.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 59.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
35.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.87 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.64 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
8.86 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
6.87 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
6.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
6.0 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.28 |
Solubility | 0.00205 mg/ml ; 0.0000052 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.11 |
Solubility | 0.00304 mg/ml ; 0.00000772 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.06 |
Solubility | 0.000034 mg/ml ; 0.0000000863 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-5.41 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
1.0 |
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 |
3.0 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) |
2.6 |
* 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 |
---|---|---|
In tetrahydrofuran; at 20℃; for 18h; | Fmoc-NHNH2 (750 mg, 2.95 MMOL) and bis (pentafluorophenyl) carbonate (1221 mg, 3.1 MMOL) were stirred in dry THF (15 mL) at rt for 18 h. The reaction mixture was diluted with water (50 mL) and extracted with EA (x3). The combined organic fractions were washed with 1 M HCI (X1) and brine (X1), dried (MgSO4), and concentrated to give a clear oil, which solidified in vacuo. Off- white solid. Yield : 1.32 g (96percent). Rf = 0.4 (PE: EA 3: 1). This compound was used crude, since it was partially unstable to purification by both recrystallization and silica chromatography |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | [00275j Synthesis of N- [(CR2)5 COO-t-Buj -N?-Boc-N?-methyl-ethylene-diamine 6- hydroxybenzo [dj thiazole-2-carbonitrile-carbamate. To the mixture of 2-cyano-6- hydroxybezothiazole (0.366 g, 2.08 mmol) and bis(pentafluorophenyl) carbonate (0.902 g, 2.29 mmol) in 20 ml of dry THF, TEA (580 uL, 4.16 mmol) was added at room temperature under nitrogen. The mixture was stirred for 30 mm minutes, and N-[(CH2)5-COO-t-Bu]-N?-Boc-N?- methyl-ethylenediamine (1.43 g, 4.16 mmol) in 10 mL dry THF was added. The resulting mixture was stirred at room temperature for over 30 minutes. The solvent was removed, and then the product mixture was dissolved in methylene chloride and washed with saturated K2C03 solution 3 times and once with water. The organic layer was dried over Na2SO4, and the solvent was removed. The compound was purified by flash column chromatography using heptane/ethyl acetate as eluent to give the product in a yield of 77 percent (0.875 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | [00243j Synthesis of N- [(PEG)2 COO-t-Buj -N?-Boc-N?-methyl-ethylene-diamine 6- hydroxybenzo [dj thiazole-2-carbonitrile- carbamate. To the mixture of 2-cyano-6- hydroxybezothiazole (0.803 g, 4.56 mmol) and bis(pentafluorophenyl) carbonate (1.98 g, 5.02 mmol) in 40 ml of dry THF, TEA (0.293 g, 2.89 mmol) was added at room temperature under nitrogen. The mixture was stirred for 1 hour, and N-t-butylCOO (PEG)3-N?-BOC-N?-methyl ethylenediamine (3 .56g, 9.12 mmol) in 18 mL dry THF was added. The resulting mixture was stirred at room temperature for over 30 minutes after which the solvent was removed. The product mixture was dissolved in methylene chloride and washed with sat K2C03 solution three times and once with water, then the organic layer was dried over Na2SO4. The compound was purified by flash column chromatography using heptane/ethyl acetate as eluent to give the product in a yield of 70 percent (1.90 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | [002591 Synthesis of N- [(CR2)3 COO-t-Buj -N?-Boc-N?-methyl-ethylene-diamine 6- hydroxybenzo [dl thiazole-2-carbonitrile-carbamate. To the mixture of 2-cyano-6- hydroxybezothiazole (0.5 87 g, 3.33 mmol) and bis(pentafluorophenyl) carbonate (1.44 g, 3.66 mmol) in 30 ml of dry THF, TEA (930 iL, 6.66 mmol) was added at room temperature under nitrogen. The mixture was stirred for 30 mm minutes, and N-[(CH2)3-COO-t-Bu]-N?-Boc-N?- methyl-ethylenediamine (2.11 g, 6.66 mmol) in 20 mL dry THF was added. The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was then dried down, and the product mixture was dissolved in methylene chloride and washed with saturated K2C03 solution 3 times and once with water, then dried over Na2SO4. The solvent was removed, and the compound was purified by flash column chromatography using heptane/ethyl acetate as eluent to give the product in a yield of 86 percent (1.5 g) |