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Structure of 147200-03-1

Chemical Structure| 147200-03-1

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Product Details of [ 147200-03-1 ]

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

Safety of [ 147200-03-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 147200-03-1 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

168.4 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.34
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-0.22
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.98
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-0.81
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.06
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.27

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.79
Solubility 5.53 mg/ml ; 0.0163 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.86
Solubility 0.468 mg/ml ; 0.00138 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.27
Solubility 1.81 mg/ml ; 0.00536 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-8.52 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

1.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

1.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<0.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

4.13

Application In Synthesis of [ 147200-03-1 ]

* 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.

  • Downstream synthetic route of [ 147200-03-1 ]

[ 147200-03-1 ] Synthesis Path-Downstream   1~8

  • 1
  • cis-(6S)-4-hydroxy-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide [ No CAS ]
  • [ 147200-03-1 ]
  • [ 147128-79-8 ]
YieldReaction ConditionsOperation 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).
  • 2
  • [ 147086-79-1 ]
  • [ 147200-03-1 ]
  • [ 147128-79-8 ]
  • 3
  • [ 1083006-59-0 ]
  • [ 147200-03-1 ]
  • [ 147128-79-8 ]
  • 4
  • [ 1383784-43-7 ]
  • [ 147200-03-1 ]
  • [ 147128-79-8 ]
  • 5
  • [ 154716-03-7 ]
  • [ 147200-03-1 ]
  • [ 147128-79-8 ]
  • 6
  • cis-(6S)-4-hydroxy-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide [ No CAS ]
  • [ 75-05-8 ]
  • [ 147200-03-1 ]
  • [ 147128-79-8 ]
YieldReaction ConditionsOperation 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).
  • 7
  • [ 147200-03-1 ]
  • [ 130693-82-2 ]
  • 8
  • [ 147200-03-1 ]
  • [ 110-16-7 ]
  • 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno<2,3-b>thiopyran-2-sulfonamide 7,7-dioxide maleate salt [ No CAS ]
YieldReaction ConditionsOperation 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).
 

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