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Chemical Structure| 43156-48-5 Chemical Structure| 43156-48-5

Structure of 43156-48-5

Chemical Structure| 43156-48-5

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Product Details of [ 43156-48-5 ]

CAS No. :43156-48-5
Formula : C12H12N2S
M.W : 216.30
SMILES Code : NC1=C(N)C=C(SC2=CC=CC=C2)C=C1
MDL No. :MFCD01073766
InChI Key :YLEPPBFOGUYOEI-UHFFFAOYSA-N
Pubchem ID :3016417

Safety of [ 43156-48-5 ]

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

Computational Chemistry of [ 43156-48-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 0.0
Num. H-bond donors 2.0
Molar Refractivity 65.82
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

77.34 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.85
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

2.72
Log Po/w (WLOGP)?

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

3.02
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.

2.95
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

2.15
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.54

Water Solubility

Log S (ESOL):?

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

-3.35
Solubility 0.0956 mg/ml ; 0.000442 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-4.0
Solubility 0.0217 mg/ml ; 0.0001 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

-4.31
Solubility 0.0105 mg/ml ; 0.0000485 mol/l
Class?

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

Moderately soluble

Pharmacokinetics

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

Yes
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

Yes
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

Yes
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

Yes
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.

-5.69 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

0.0
Egan?

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

0.0
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

0.0
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

1.0 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<1.0
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)

2.06

Application In Synthesis of [ 43156-48-5 ]

* 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 [ 43156-48-5 ]

[ 43156-48-5 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 43156-47-4 ]
  • [ 43156-48-5 ]
YieldReaction ConditionsOperation in experiment
21.2 g With platinum on activated charcoal; hydrogen; In ethanol; at 70 - 90℃; under 7500.75 - 15001.5 Torr; for 8.0h; A 500ml four-necked flask equipped with a thermometer and a stirring device, was added in a weight ratio of 2-nitro-phenylsulfanyl aniline ethanol 4 times, 36.9g of 2-nitro-phenylsulfanyl aniline, weight ratio of 2-nitro-phenylsulfanyl aniline 0.1 times platinum on carbon, turned stirred and heated to 70-90 hydrogen atmosphere, to a pressure 1.0-2.0MPa, hydrogenation reaction of 8 hours, platinum on carbon catalyst was filtered off, The ethanol was evaporated to give 4-phenylthio-o-phenylenediamine 21.2g, was used directly in the next reaction.
  • 2
  • [ 1635-61-6 ]
  • [ 43156-48-5 ]
  • [ 598-52-7 ]
  • [ 108-98-5 ]
  • [ 79-22-1 ]
  • 5-phenylmercapto-benzimidazole-2-methyl-carbaminate [ No CAS ]
  • [ 43156-47-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In N-methyl-acetamide; water; potassium carbonate; acetic acid; EXAMPLE 40 5-Phenylmercapto-benzimidazole-2-methyl-carbaminate 20.9 g Of S-methyl-thiourea were reacted as described in Example 1 in 27 ml of water with 13.5 ml of chloroformic acid methyl ester, 45.7 ml of 25percent sodium hydroxide solution, 27 ml of glacial acetic acid, 100 ml of water and 29 g of 3,4-diaminodiphenyl-thioether. After recrystallization from a mixture of glacial acetic acid and methanol, 14 g of 4-phenylmercapto-benzimidazole-2-methyl-carbaminate melting at 233°C were obtained. For preparing the 3,4-diamino-diphenyl-thioether used as starting material, 22 g of thiophenol were heated for 6 hours under reflux in 100 ml of dimethylformamide with 5-chloro-2-nitroaniline in the presence of 30g of anhydrous potassium carbonate. The whole was allowed to cool, 100 ml of water were added and the crude product was filtered off with suction. After recrystallization from isopropanol, 38 g of 3-amino-4-nitro-diphenyl-thioether melting at 112°C were obtained. 38 g Of the 3-amino-4-nitro-diphenyl-thioether so obtained were added to a solution prepared by dissolving 180 g of crystal-water containing stannous chloride in 200 ml of glacial acetic acid and saturation with gaseous hydrochloric acid at room temperature.
  • 3
  • [ 43156-47-4 ]
  • [ 5443-33-4 ]
  • [ 43156-48-5 ]
YieldReaction ConditionsOperation in experiment
With stannous chloride; sodium; potassium hydrogencarbonate; In hydrogenchloride; chloroform; [This material may also be obtained by reaction of 2-acetamido-4-chloro-1-nitrobenzene with sodium phenylmercaptide essentially as described above for the free amine.] 3.5 G. of <strong>[43156-47-4]2-amino-4-phenylthio-1-nitrobenzene</strong> in 8 ml. conc. hydrochloric acid is treated with a solution of 16 g. of stannous chloride in 8 ml. conc. hydrochloric acid. The mixture is heated for 1 hour on a steam bath, cooled and treated with potassium bicarbonate and chloroform. The mixture is filtered and the chloroform layer evaporated. The residue is triturated with hot cyclohexane yielding 1,2-diamino-4-phenylthiobenzene.
  • 4
  • [ 35266-49-0 ]
  • [ 43156-47-4 ]
  • [ 43156-48-5 ]
  • [ 7439-89-6 ]
  • iron(II) sulfate [ No CAS ]
  • [ 54394-05-7 ]
YieldReaction ConditionsOperation in experiment
In methanol; water; acetone; <strong>[43156-47-4]2-amino-4-phenylthio-1-nitrobenzene</strong> is treated with 2 g. iron powder and 1 g. ferrous sulfate in a refluxing mixture of 160 ml. methanol and 40 ml. water for six hours. The mixture is filtered and concentrated. The residue is extracted with benzene and 1,2-diamino-4-phenylthiobenzene isolated as a gum. 1.6 G. 1,2-diamino-4-phenylthiobenzene is dissolved in 30 ml. acetone and treated with 4 g. methoxycarbonyl isothiocyanate at room temperature overnight. The mixture is concentrated under vacuum and the residue triturated with ether. Recrystallization from methanol-chloroform yields pure 1,2-bis-(3-methoxycarbonyl-2-thioureido)-4-phenylthiobenzene.
  • 5
  • [ 6642-30-4 ]
  • [ 43156-48-5 ]
  • [ 43210-67-9 ]
YieldReaction ConditionsOperation in experiment
86.8% With hydrogenchloride; In toluene; at 20 - 55℃; for 2h; 355.0 g of methyl cyanamidoformate which was cryopreserved in the step 1 was added to a solution of 545.5 g of the intermediate 4 in toluene in the step 5 at room temperature.Raise the temperature to 45-55 C, and add 67.65 g of concentrated hydrochloric acid (36.5%) under stirring. After the addition is completed, stir at 55-60 C for 2 hours.After completion of the reaction, the temperature was lowered to 10-15 C, filtered, and the filter cake was washed with 202.5 g of methanol.The moisture product was dried under hot air at 70 C for 6 hours to obtain 124.5 g of dry product, the purity was 99.7%, and the total yield of the product was 86.8%.
 

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