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Chemical Structure| 99455-15-9 Chemical Structure| 99455-15-9

Structure of 99455-15-9

Chemical Structure| 99455-15-9

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Product Details of [ 99455-15-9 ]

CAS No. :99455-15-9
Formula : C9H5BrClN
M.W : 242.50
SMILES Code : ClC1=NC2=C(C=CC(Br)=C2)C=C1
MDL No. :MFCD06738671
InChI Key :MOEWRAKNXMILKB-UHFFFAOYSA-N
Pubchem ID :14221034

Safety of [ 99455-15-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 99455-15-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 54.45
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.4
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

3.84
Log Po/w (WLOGP)?

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

3.65
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.

3.12
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

3.76
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.35

Water Solubility

Log S (ESOL):?

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

-4.38
Solubility 0.0101 mg/ml ; 0.0000417 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-3.81
Solubility 0.0378 mg/ml ; 0.000156 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

-5.17
Solubility 0.00162 mg/ml ; 0.00000668 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

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.

-5.05 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

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<2.0
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)

1.79

Application In Synthesis of [ 99455-15-9 ]

* 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.

  • Downstream synthetic route of [ 99455-15-9 ]

[ 99455-15-9 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 124-41-4 ]
  • [ 99455-15-9 ]
  • [ 99455-08-0 ]
YieldReaction ConditionsOperation in experiment
98% In methanol; for 16.0h;Reflux; This compound was prepared from 7-bromo-2-chloroquinoline(2) in 98% yield as described for compound 1; Mp 68-69 C; 1HNMR (300 MHz, CDCl3): delta 8.05 (d, 1H, 1.8 Hz), 7.93 (d, 1H, 8.7 Hz),7.57 (d, 1H, 9.0 Hz), 7.47 (dd, 1H, 8.7 Hz and 1.8 Hz), 6.91 (d, 1H,9.0 Hz), 4.00 (s, 3H); MS (APCI, pos. 30 V) m/z: [M+H]+, 239.06.
  • 2
  • [ 99455-15-9 ]
  • [ 94050-90-5 ]
  • (R)-(+)-2-{4-[(7-bromo-2-quinolinyl)oxy]phenoxy}propionic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% Example 7. Preparation of Compound of Formula (I): (2R)-2-{4-[(7-Bromoquinolin-2- yl)oxy]phenoxy}propionic acid. An inerted rector equipped with a mechanical stirrer, a reflux condenser and a temperature probe was charged with 7-bromo-2-chloroquinoline (0.9225 Kg, 3.81 mole), of R-(+)-2-(4-hydroxy-phenoxy) propionic acid (0.721 Kg, 3.81 mole), potassium carbonate (1.319 Kg, 9.48 mole, 2.5 equiv.), and anhydrous dimethylformamide (4.254 Kg) with stirring at 200-300 rpm. The reaction mixture was then heated to 130 to 140C over a period of 1 hour. A temperature of 130 to 14O0C was maintained for a period of 15 hours. The reaction mixture was cooled to 15 to 200C when it became thick. The reactor was then charged with USP purified water (13.84 Kg) and treated slowly by addition of concentrated HCl (834.7 g). At the end of the addition of HCl, a precipitate was observed, and the pH of the mixture was between pH 3 to 4. The solid was extracted with ethyl acetate (8 L), and the ethyl acetate extract was washed with USP purified water (2 x 2L), followed by two washes with 10% citric acid solution. The ethyl acetate solution was then treated with 100 g of Darco G-60 charcoal and stirred for 30 minutes at 22C and filtered through a 10 micron polypropylene filter. The ethyl acetate extract thus obtained was distilled off at reduced (100 mm Hg) pressure. After .4 of the volume of ethyl acetate had distilled out, 6 L of isopropyl alcohol were added and the distillation was continued until another Vi volume of ethyl acetate distilled off. 4 Kg of USP purified water were then added slowly, and cooling was applied at10C/hour to reach a final temperature of 22C. The product crystallized out of the solution. The product was filtered through a polypropylene filter. The wet cake was dried in an isolator at 4O0C in a vacuum oven. The final yield of desired product was 0.753 Kg. A manual sieving was performed though a polyethylene sieve. Yield: 50%.
 

Historical Records

Technical Information

Categories

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[ 99455-15-9 ]

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