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Structure of 5437-99-0

Chemical Structure| 5437-99-0

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Product Details of [ 5437-99-0 ]

CAS No. :5437-99-0
Formula : C9H6N2O3
M.W : 190.16
SMILES Code : OC1=CC([N+]([O-])=O)=C2N=CC=CC2=C1
MDL No. :MFCD18448969
InChI Key :AZDVQVFOHUFHOP-UHFFFAOYSA-N
Pubchem ID :226259

Safety of [ 5437-99-0 ]

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

Computational Chemistry of [ 5437-99-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 52.59
TPSA ?

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

78.94 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.9
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

1.54
Log Po/w (WLOGP)?

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

1.85
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.

0.1
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

-0.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.83

Water Solubility

Log S (ESOL):?

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

-2.45
Solubility 0.672 mg/ml ; 0.00353 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.

-2.81
Solubility 0.297 mg/ml ; 0.00156 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

-2.51
Solubility 0.589 mg/ml ; 0.0031 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

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.

-6.37 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)

1.88

Application In Synthesis of [ 5437-99-0 ]

* 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 [ 5437-99-0 ]

[ 5437-99-0 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 85-81-4 ]
  • [ 5437-99-0 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: for 16 h; Heating / reflux
Example 35; N-(6-(benzyloxy)quinolin-8-yl)-6-(sulfamoylamino)hexanamide (43) Step 1: 8-nitroquinolin-6-ol (38) 6-methoxy-8-nitroquinoline (2.15 g, 10.51 mmol) was dissolved in 48percent HBr (8.0 mL, 147.20 mmol) and refluxed for 16 hours. The resulting suspension of yellow crystals was cooled down and then filtered. The solid was diluted in water and 15percent NaOH (aq) was added. The suspension was filtered and the aqueous layer was acidified to obtain crystals at pH6. Crystals were washed with water and filtered to afford compound 38 as yellow crystals (1.89 g, 95percent). LRMS (ESI): (calc.) 190.04 (found) 191.1 (MH)+.
74% With hydrogen bromide; acetic acid In water at 130℃; for 48 h; 6-Methoxy-8-nitro-quinoline (2.0 g) was dissolved in a mixed solution of 48percent aq. HBr in HOAc (v/v 3:2) and then the reaction was refluxed at 130 °C for 2 days. The mixture was cooled to rt and filtered to provide a yellow solid, which was then dispensed in sat. NaHCO3 solution (aq.) for 1 h, filtered again and dried over Na2SO4 to afford the desired compound NY-1-31 (1.38 g, 74 percent) as a light yellow solid. 1H NMR 300 MHz, DMSO-c) δ 10.80 (s, 1H), 8.78 (dd, J = 4.2, 1.6 Hz, 1H), 8.35 (dd, J= 8.5, 1.6 Hz, 1H), 7.80 (d, J = 2.6 Hz, 1H), 7.59 (dd, J = 8.4, 4.2 Hz, 1H), 7.45 (d, J = 2.6 Hz, 1H).
References: [1] Patent: US2007/293530, 2007, A1, . Location in patent: Page/Page column 84.
[2] Patent: WO2016/187544, 2016, A1, . Location in patent: Page/Page column 77-78.
[3] Journal of the American Chemical Society, 1946, vol. 68, p. 1569,1570, 1571.
[4] Journal of the American Chemical Society, 1948, vol. 70, p. 3912.
[5] Journal of the American Chemical Society, 1946, vol. 68, p. 1569,1570, 1571.
[6] Journal of Organic Chemistry, 1947, vol. 12, p. 799,804.
[7] Patent: EP1147083, 2004, B1, . Location in patent: Page 46.
  • 2
  • [ 610-81-1 ]
  • [ 107-02-8 ]
  • [ 5437-99-0 ]
YieldReaction ConditionsOperation in experiment
49% With hydrogenchloride; phosphoric acid In water at 80℃; for 4 h; 5.0 g of 4-amino-3-nitrophenol (compound a, 32 mmol), 40 mL of concentrated hydrochloric acid and 15 g of concentrated phosphoric acid were added to a reaction vessel and heated to 80 ° C., 6.5 mL (97 mmol) of acrolein was slowly added added. After reacting for 4 hours, the reaction solution was allowed to cool to room temperature, distilled water was added, and the mixture was filtered through Celite (Celite Corporation). The filtrate was neutralized with aqueous ammonia to give a red precipitate. The precipitate was collected by filtration and dried under vacuum to give a red solid (yield: 3.0 g, yield: 49percent).
References: [1] Chemical Communications, 2015, vol. 51, # 46, p. 9539 - 9542.
[2] Patent: JP2015/20986, 2015, A, . Location in patent: Paragraph 0070.
[3] Inorganic Chemistry, 2010, vol. 49, # 20, p. 9535 - 9545.
  • 3
  • [ 282547-59-5 ]
  • [ 5437-99-0 ]
References: [1] Journal of the American Chemical Society, 1946, vol. 68, p. 781,783.
[2] Zhurnal Obshchei Khimii, 1933, vol. 3, p. 769,776[3] Archiv der Pharmazie (Weinheim, Germany), 1933, vol. 271, p. 359,364[4] Chemisches Zentralblatt, 1934, vol. 105, # II, p. 2227.
  • 4
  • [ 616-86-4 ]
  • [ 5437-99-0 ]
References: [1] Journal of the American Chemical Society, 1946, vol. 68, p. 781,783.
  • 5
  • [ 885-81-4 ]
  • [ 5437-99-0 ]
References: [1] Zhurnal Obshchei Khimii, 1933, vol. 3, p. 769,776[2] Archiv der Pharmazie (Weinheim, Germany), 1933, vol. 271, p. 359,364[3] Chemisches Zentralblatt, 1934, vol. 105, # II, p. 2227.
 

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Technical Information

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