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Chemical Structure| 959236-59-0 Chemical Structure| 959236-59-0

Structure of 959236-59-0

Chemical Structure| 959236-59-0

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Product Details of [ 959236-59-0 ]

CAS No. :959236-59-0
Formula : C8H5FN2O2
M.W : 180.14
SMILES Code : FC2=C1[NH]N=C(C1=CC=C2)C(=O)O
MDL No. :MFCD07378920
InChI Key :DFOSXJTYCNLCKG-UHFFFAOYSA-N
Pubchem ID :34176082

Safety of [ 959236-59-0 ]

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

Computational Chemistry of [ 959236-59-0 ] 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 4.0
Num. H-bond donors 2.0
Molar Refractivity 43.01
TPSA ?

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

65.98 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.73
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

1.51
Log Po/w (WLOGP)?

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

1.82
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.

1.15
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

1.78
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.4

Water Solubility

Log S (ESOL):?

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

-2.35
Solubility 0.796 mg/ml ; 0.00442 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.

-2.5
Solubility 0.565 mg/ml ; 0.00314 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

-2.56
Solubility 0.493 mg/ml ; 0.00274 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

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

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.

-6.33 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.

0.56

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<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)

1.76

Application In Synthesis of [ 959236-59-0 ]

* 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.

  • Downstream synthetic route of [ 959236-59-0 ]

[ 959236-59-0 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 67-56-1 ]
  • [ 959236-59-0 ]
  • [ 932041-13-9 ]
YieldReaction ConditionsOperation in experiment
64% With sulfuric acid;Reflux; A solution of 30 g <strong>[959236-59-0]7-fluoro-1H-indazole-3-carboxylic acid</strong> in 1200 mL dry methanol was added 8 mL concentrated sulfuric acid. The resulting mixture was heated to reflux and was continued over night. Reaction was allowed to cool to room temperature and was diluted with ethyl acetate (1000 mL). Organic solution was washed with saturated NaHCO3 (2×250 mL), brine (2×250 mL), dried (MgSO4), filtered and concentrated to a brown solid. Crude reaction was purified via MPLC (5%-30% ethyl ether/heptane) to afford 20.74 g (64%) of methyl 7-fluoro-1H-indazole-3-carboxylate as a bright yellow solid. 1H NMR (400 MHz, DMSO-d6) delta 14.49 (br s, 1H), 7.85-7.83 (m, 1H), 7.28-7.21 (m, 2H), 3.92 (s, 3H). MS (ESI) m/z 195 (M+H)+.
7-Fluoro-lH-indazole-3 -carboxylic acid (8.0 g) was dissolved in methanol (500 ml) . To the solution was added concentrated H2S04 (15 ml) at ice temperature, and the mixed solution was stirred under reflux for 7 hours. The solvent was removed under reduced pressure, chloroform was added to the residue, and the resultant was neutralized with saturated sodium bicarbonate aqueous solution. The organic layer was further washed with water, dried, and concentrated under reduced pressure. The residue was purified by silica-gel chromatography (column; Hi-Flash, developing solvent: hexane / ethyl acetate) and then purified again by silica-gel chromatography (column; Hi- Flash, developing solvent: chloroform / methanol) to give methyl 7-fluoro-lH-indazole-3-carboxylate (4.15 g) as a white crystal.
  • 2
  • [ 317-20-4 ]
  • [ 959236-59-0 ]
YieldReaction ConditionsOperation in experiment
47% This compound was prepared following the procedure of Johnson, B. L.; Rodgers, J. D. Syn. Comm. 2005, 35, 2681-2684. A suspension of 5.28 g 7-fluoroisatin in 30 mL of water was added 1.30 g NaOH, in 10 mL water with stirring. The resulting dark red solution was stirred until all of the solids dissolved and was then cooled in an ice water bath. The solution was then slowly added a cooled (ice bath) solution of 2.21 g NaNO2 in 10 mL water. These combined solutions were then added slowly to cooled (ice bath) to solution of aqueous sulfuric acid (3.4 mL H2SO4 in 60 mL water). Ice was added to maintain a temperature of approximately 0 C. After stirring for approximately 10 minutes, this dark red diazonium solution was added slowly to a chilled (0 C., ice bath) solution of 18 g SnCl22H2O in 30 mL concentrated HCl. Ice was again added to maintain a temperature of approximately 0 C. After stirring for approximately 1 hour, the reaction was filtered and the resulting residue was dissolved in 1 N NaOH (60 mL), washed with ether (2×50 mL). The resulting yellow-brown solution was cooled in an ice bath and acidified to a pH3 (litmus paper) with concentrated HCl, which resulted in the formation of a dark yellow precipitate. The precipitate was collected by filtration, washed with water, and dried over night in an oven to give 3.69 g (47%) of 7-fluoro-1H-indazole-3-carboxylic acid as an orange solid. 1H NMR (400 MHz, DMSO-d6) delta 14.35 (br s, 1H), 13.22 (br s, 1H), 7.89-7.87 (m, 1H), 7.26-7.21 (m, 2H). MS (ESI) m/z 181 (M+H)+.
  • 3
  • [ 959236-59-0 ]
  • [ 1185282-09-0 ]
  • 4
  • [ 959236-59-0 ]
  • [ 1185287-57-3 ]
  • 5
  • [ 959236-59-0 ]
  • [ 1185287-58-4 ]
  • 6
  • [ 959236-59-0 ]
  • [ 1117-97-1 ]
  • [ 1415740-61-2 ]
YieldReaction ConditionsOperation in experiment
To a mixed solution of 7-fluoro-lH-indazole-3- carboxylic acid (15.0 g) and tetrahydrofuran (600 ml) were added pyridine (14.8 ml) and N, O-dimethylhydroxylamine (8.94 g) at ice temperature. The mixture was stirred for 1 hour, warmed to room temperature, and further stirred for 1 hour. To the reaction solution were added pyridine (13.4 ml) and l-ethyl-3 - (3 -dimethylaminopropyl) carbodiimide hydrochloride (31.9 g) , and the mixture was stirred at room temperature overnight. After the reaction was completed, the solvent was evaporated under reduced pressure. To the residue was added water (1.0 1), and the resultant crystal was collected on a filter to give 7-fluoro-N-methoxy-N- methyl-lH-indazole-3-carboxamide (12.4 g) as a yellow crystal.
  • 7
  • [ 959236-59-0 ]
  • [ 1415740-46-3 ]
  • 8
  • [ 959236-59-0 ]
  • [ 1415740-63-4 ]
  • 9
  • [ 959236-59-0 ]
  • [ 1415740-62-3 ]
 

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