Structure of 147200-03-1
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 147200-03-1 |
Formula : | C10H14N2O5S3 |
M.W : | 338.42 |
SMILES Code : | CC(N[C@@H](C[C@@H]1C)C(C=C(S(=O)(N)=O)S2)=C2S1(=O)=O)=O |
MDL No. : | MFCD12407171 |
InChI Key : | MQRCTNZVQVRCRD-XNCJUZBTSA-N |
Pubchem ID : | 10449801 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 73.49 |
TPSA ? Topological Polar Surface Area: Calculated from |
168.4 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.98 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.81 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.06 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.27 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.79 |
Solubility | 5.53 mg/ml ; 0.0163 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.86 |
Solubility | 0.468 mg/ml ; 0.00138 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.27 |
Solubility | 1.81 mg/ml ; 0.00536 mol/l |
Class? Solubility class: Log S scale |
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 |
-8.52 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
1.0 |
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 |
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) |
4.13 |
* 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 |
---|---|---|
Methanesulfonic acid (26.0 g, 270.5 mmol) was added dropwise to a suspension of cis-(6S)- 4-hydroxy-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno [2,3 -b]thiopyran-2-sulfonamide (23.0 g, 77.34 mmol) in acetonitrile (29.3 g) at 20 C under nitrogen atmosphere in 20 minutes.The mixture was then diluted with acetonitrile (7.4 g) and heated to 87 C. After 15 hours under reflux, the temperature was lowered to 30 C, and after 3 hours to 10 C. Demineralised water (60.1 g) was added to the mixture at 10 C in 30 minutes. The pH was then adjusted to 7.3 with ammonium hydroxide (16.0 g, 30 % aqueous solution). The temperature was brought to 40 C and the mixture was stirred at this temperature for 30 mm.Demineralised water (60.0 g) was added to the mixture at 40 C in 1 hour. The slurry was then stirred for 30 mm at 40 C and then cooled at 7C for a further 2 hours. The solid was filtered and washed with demineralised water (17.2 g, in 2 portions) and with isopropanol (17.2 g in 2 portions), then dried to give trans-(6S)-4-acetylamino-5,6-dihydro-6-methyl-7,7- dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide (20.6 g, titre cis + trans 91.1 %, de 58 %).Trans diastereoisomer: 1H NMR: H (ppm) (400 MHz, DMSO) 8.6 (1H, m, NH), 8.0 (2H,bs, SO2NH2), 7.4 (1H, s, CH), 5.2 (1H, m, CH), 3.9 (1H, m, CH), 2.45 (1H, m, CH2), 2.30(1H, m, CH2), 1.9 (3H, s, COCH3), 1.37 (3H, s, J= 7 Hz, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 8 trans-(6S)-4-acetylammino-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide Compound of formula (VI) Methanesulfonic acid (26.0 g, 270.5 mmol) was added dropwise to a suspension of cis-(6S)-4-hydroxy-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide (23.0 g, 77.34 mmol) in acetonitrile (29.3 g) at 20 C. under nitrogen atmosphere in 20 minutes. The mixture was then diluted with acetonitrile (7.4 g) and heated to 87 C. After 15 hours under reflux, the temperature was lowered to 30 C., and after 3 hours to 10 C. Demineralised water (60.1 g) was added to the mixture at 10 C. in 30 minutes. The pH was then adjusted to 7.3 with ammonium hydroxide (16.0 g, 30% aqueous solution). The temperature was brought to 40 C. and the mixture was stirred at this temperature for 30 min. Demineralised water (60.0 g) was added to the mixture at 40 C. in 1 hour. The slurry was then stirred for 30 min at 40 C. and then cooled at 7 C. for a further 2 hours. The solid was filtered and washed with demineralised water (17.2 g, in 2 portions) and with isopropanol (17.2 g in 2 portions), then dried to give trans-(6S)-4-acetylamino-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide (20.6 g, titre cis+trans 91.1%, de 58%). Trans diastereoisomer: 1H NMR: deltaH (ppm) (400 MHz, DMSO) 8.6 (1H, m, NH), 8.0 (2H, bs, SO2NH2), 7.4 (1H, s, CH), 5.2 (1H, m, CH), 3.9 (1H, m, CH), 2.45 (1H, m, CH2), 2.30 (1H, m, CH2), 1.9 (3H, s, COCH3), 1.37 (3H, s, J=7 Hz, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.4 g | Example 9 Synthesis of trans-(6S)-4-ethylamino-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide maleate salt Compound of formula (VII) and (VIII) Borane THF (176.9 g, 1M solution in THF) was added dropwise to a suspension of <strong>[147200-03-1]trans-(6S)-4-acetylamino-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide</strong> (20.0 g, 59.1 mmol) in THF (36.7 g) at 38 C. under nitrogen atmosphere in 7 hours. The mixture was left under stirring at 38 C. for 10 hours and was then transferred to a solution of diluted hydrochloric acid at 60 C. The quench suspension was diluted with THF (19.5 g) and stirred under reflux for 1.5 hours. The mixture was then cooled, purified and diluted with THF (41.5 g) and demineralised water (18.7 g). The mixture was concentrated up to a volume of 100 mL, the pH adjusted to 7.5, and lastly the mixture was diluted with ethyl acetate (200.8 g). The aqueous phase was separated and counter-extracted with ethyl acetate (22.7 g). The combined organic phases were washed with demineralised water (17.5 g) and then concentrated under vacuum to a volume of approximately 30 mL. The mixture was then diluted with ethyl acetate (142.6 g) and concentrated to a volume of approximately 30 mL. 1/3 of the solution was subjected to a change of solvent with acetone (102.2 g) by distilling repeatedly up to 10 g of residues. The residue was diluted with acetone (16.0 g), and maleic acid (6.6 g, 20% solution in acetone) was added to the mixture at 40 C. After the addition process, the temperature was brought to 20 C., the solid was filtered and washed with acetone (8.2 g, in 2 portions), then dried to give trans-(6S)-4-ethylamino-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide maleate salt (4.4 g, titre trans+cis 88.3%, de 99.6%, ee 99.9%). 1H NMR: deltaH (ppm) (400 MHz, DMSO) 8.2 (2H, bs, SO2NH2), 7.8 (1H, s, CH), 6.05 (2H, CH=CH), 4.6 (1H, bs, CH), 4.0 (1H, m, CH), 3.2 (1H, m, ½ AB, NH-CH2), 3.0 (1H, m, ½ AB, NH-CH2), 2.7-2.5 (2H, m, CH2), 1.4 (3H, d, J=7 Hz, CH3), 1.2 (3H, m, CH3). |