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Chemical Structure| 6973-51-9

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Product Details of [ 6973-51-9 ]

CAS No. :6973-51-9
Formula : C7H5N3O2S
M.W : 195.20
SMILES Code : NC1=NC2=C([N+]([O-])=O)C=CC=C2S1
MDL No. :MFCD00819610
InChI Key :XPYJFCKUPMJFHE-UHFFFAOYSA-N
Pubchem ID :238934

Safety of [ 6973-51-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 6973-51-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 52.85
TPSA ?

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

112.97 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.18
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

1.86
Log Po/w (WLOGP)?

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

1.79
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.

0.16
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

0.23
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.05

Water Solubility

Log S (ESOL):?

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

-2.67
Solubility 0.419 mg/ml ; 0.00215 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.

-3.85
Solubility 0.0273 mg/ml ; 0.00014 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

-2.0
Solubility 1.97 mg/ml ; 0.0101 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

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)
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

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.

-6.17 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

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

2.0 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)

2.52

Application In Synthesis of [ 6973-51-9 ]

* 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.

  • Upstream synthesis route of [ 6973-51-9 ]

[ 6973-51-9 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 333-20-0 ]
  • [ 88-74-4 ]
  • [ 6973-51-9 ]
YieldReaction ConditionsOperation in experiment
86%
Stage #1: With nano-BF3/SiO2 In acetonitrile for 0.5 h; Cooling with ice
Stage #2: With bromine In acetonitrile at 0 - 20℃; for 5 h;
General procedure: A solution of substituted aniline (2 mmol) in acetonitrile (15 ml) was added to a solution of KSCN (8 mmol) in acetonitrile (15 ml). Then, 0.06 g (30 mol percent BF3) of nano-BF3/SiO2 was added to the mixture, then was placed in a freezing mixture of ice and salt and mechanically stirred for 30 min. Then, bromine (4 mmol, 0.2 ml) in acetonitrile (3 ml) as solvent was added from a dropping funnel at such a rate that the temperature never rose beyond 0°C. After all the bromine was added at 60 min, the solution was stirred for 4 h at room temperature. The progress of the reaction was monitored by TLC. Then, the mixture was poured into water with stirring and the mixture was heated to 70°C on a steam bath and filtered hot to remove the catalyst and the recovered catalyst was washed with acetone and reused in the reaction. The filtrate was neutralized with 10 percent NaOH solution and the precipitate was collected on a filter, dried and recrystallized from ethanol (10 ml) to afford the corresponding products. All of the 2-aminobenzothiazole products were identified by physical and spectroscopic data as reported below, compared and contrasted with authentic samples.#10;Spectral data for selected products#10;6-Bromo-1,3-benzothiazol-2-amine (2e) Yellow solid; Yield = 93 percent; m.p. =202–204°C; (m.p. = 203°C), FT-IR (KBr)/t(cm-1): 3315, 3012, 2835,1580, 1476, 1261, 920, 742, 512. 1H NMR (400 MHz, CDCl3)/d ppm: 5.44 (s, 2H, NH2) 7.4–7.5 (d, 2H, Ar–H), 7.71 (s, 1H, Ar–H); 13C NMR/(100 MHz, DMSO-d6)/d ppm: 119, 120.9, 125.15, 126.07, 133.1, 152.15, 167.75.#10;
References: [1] Synlett, 2012, vol. 23, # 15, p. 2219 - 2222.
[2] Research on Chemical Intermediates, 2016, vol. 42, # 12, p. 7855 - 7868.
  • 2
  • [ 1147550-11-5 ]
  • [ 88-74-4 ]
  • [ 6973-51-9 ]
YieldReaction ConditionsOperation in experiment
41%
Stage #1: at 10℃; for 0.5 h; Cooling with ice
Stage #2: at 0 - 20℃;
General procedure: GP2-1: In a flask were added by ammoniumthiocyanate (2.2 eq) and HOAc (5 volume), bromine (1.1 eq) in HOAc (5 volume)was added dropwise under ice-cooled condition, which was stirred at 10 0Cfor 30 min. After filtering off the solid, the filtrate was collected.In aseparate flask, aniline (1.0 eq) and HOAc (5 volume) were added. Then thefiltrate prepared above was added dropwise under 0 0C within 5 min.The mixture was kept stirring at rt overnight. After removal of solvent underreduced pressure, the residue was diluted with EA, neutralized with saturatedNa2CO3 solution, separated, passed through a pad ofCelite, and concentrated to dryness. The crude was purified by silica gelcolumn.GP2-2: To a round-bottomed flaskwas added 2-aminobenzothiazole (1.0eq) and CuCl2 (1.2 eq) in acetonitrile (10 volume), followed by slowaddition of tert-butyl nitrite (1.2eq). The gas evolved immediately. The reaction was greatly exothermic, and, ifnecessary, ice-water cooling was applied. The mixture was then stirred at rtfor hours, which was monitored by TLC. After completion, the reaction wasquenched by 1M HCl, washed by 1 M HCl twice and extracted by EA. The combinedorganic layer was washed by brine, dried over Na2SO4, concentrated and purifiedby flash column to give the product.
References: [1] Medicinal Chemistry Research, 2011, vol. 20, # 7, p. 1033 - 1041.
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 24, p. 7661 - 7670.
[3] Journal of Enzyme Inhibition and Medicinal Chemistry, 2011, vol. 26, # 4, p. 527 - 534.
  • 3
  • [ 51039-84-0 ]
  • [ 6973-51-9 ]
References: [1] Journal of the Chemical Society, 1927, p. 1190.
[2] Helvetica Chimica Acta, 1940, vol. 23, p. 328,330.
[3] Journal fuer Praktische Chemie (Leipzig), 1974, vol. 316, p. 154 - 158.
[4] Acta Crystallographica Section C: Crystal Structure Communications, 1996, vol. 52, # 4, p. 1040 - 1042.
  • 4
  • [ 2942-08-7 ]
  • [ 6973-51-9 ]
References: [1] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[2] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366.
  • 5
  • [ 88-74-4 ]
  • [ 6973-51-9 ]
References: [1] Chemistry of Heterocyclic Compounds, 2009, vol. 45, # 11, p. 1343 - 1353.
[2] European Journal of Medicinal Chemistry, 2010, vol. 45, # 9, p. 4293 - 4299.
[3] Archiv der Pharmazie, 2010, vol. 343, # 11-12, p. 692 - 699.
  • 6
  • [ 1280582-63-9 ]
  • [ 6973-51-9 ]
References: [1] Letters in Drug Design and Discovery, 2011, vol. 8, # 9, p. 717 - 724.
[2] Letters in Drug Design and Discovery, 2011, vol. 8, # 8, p. 717 - 724.
  • 7
  • [ 88-74-4 ]
  • [ 6973-51-9 ]
References: [1] Letters in Drug Design and Discovery, 2011, vol. 8, # 9, p. 717 - 724.
[2] Letters in Drug Design and Discovery, 2011, vol. 8, # 8, p. 717 - 724.
  • 8
  • [ 95-16-9 ]
  • [ 6973-51-9 ]
References: [1] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[2] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366.
  • 9
  • [ 149-30-4 ]
  • [ 6973-51-9 ]
References: [1] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[2] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366.
  • 10
  • [ 2719-30-4 ]
  • [ 6973-51-9 ]
References: [1] Acta Crystallographica Section C: Crystal Structure Communications, 1996, vol. 52, # 4, p. 1040 - 1042.
 

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