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Chemical Structure| 437383-99-8 Chemical Structure| 437383-99-8

Structure of 437383-99-8

Chemical Structure| 437383-99-8

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Product Details of [ 437383-99-8 ]

CAS No. :437383-99-8
Formula : C12H9NO3
M.W : 215.21
SMILES Code : N1=CC(=CC=C1)OC2=CC=C(C(=O)O)C=C2
MDL No. :MFCD11182951
InChI Key :JZHQITAPTQQMIF-UHFFFAOYSA-N
Pubchem ID :22261667

Safety of [ 437383-99-8 ]

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

Computational Chemistry of [ 437383-99-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 57.71
TPSA ?

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

59.42 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.77
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

1.91
Log Po/w (WLOGP)?

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

2.57
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.

1.29
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

1.89
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.89

Water Solubility

Log S (ESOL):?

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

-2.73
Solubility 0.397 mg/ml ; 0.00184 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.

-2.78
Solubility 0.356 mg/ml ; 0.00166 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

-3.66
Solubility 0.0468 mg/ml ; 0.000217 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

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.

-6.26 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.

0.56

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)

1.87

Application In Synthesis of [ 437383-99-8 ]

* 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 [ 437383-99-8 ]

[ 437383-99-8 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 877874-61-8 ]
  • [ 437383-99-8 ]
YieldReaction ConditionsOperation in experiment
93% With water; sodium hydroxide In methanol at 75℃; for 1 h; Step 2. Methyl 4-(pyridin-3-yloxy) benzoic acid. To a solution of methyl 4-(pyridin-3- yloxy)benzoate in MeOH (10 mL) was added aq. NaOH (2 mL). The mixture was stirred at 75°C for 1 hr, diluted with IN HC1(10 ml), and extracted with EtOAc. Combined organic layers were dried over anhydrous Na2S04 and concentrated under reduced pressure to give 4-(pyridin-3 -yloxy) benzoic acid (0.8 g, 93percent yield). LC-MS: m/z: 215(M+H)+.
References: [1] Patent: WO2014/176258, 2014, A1, . Location in patent: Page/Page column 37.
  • 2
  • [ 87626-41-3 ]
  • [ 437383-99-8 ]
YieldReaction ConditionsOperation in experiment
54% With Jones reagent In acetone at 0℃; for 2.5 h; 3-(4-Formylphenoxy)pyridine (2.40g, 12.0mmol) and 50mL of acetone were mixed and 2.67mol/L Jones reagent (4.00mL, 10.7mmol) was added under cooling with ice and stirring. After stirring for 30 minutes under cooling with ice, 2.67mol/L Jones reagent (3.00mL, 8.00mmol) was added further and the mixture was stirred for 2 hours under cooling with ice. Water was added to the reaction mixture, which was neutralized with 2mol/L aqueous solution of sodium hydroxide. Then, 100mL of chloroform were added and the solution was filtered through celite. The insolubles were washed with hot chloroform. After the chloroform layer was separated, the aqueous layer was extracted with chloroform. Respective chloroform layers were combined and dried over anhydrous sodium sulfate, then concentrated to obtain 1.40g (54percent) of the title compound as milky white powder.Mass analysis m/z 215(M<+>).
References: [1] Patent: EP1348698, 2003, A1, . Location in patent: Page/Page column 28.
  • 3
  • [ 58835-79-3 ]
  • [ 437383-99-8 ]
References: [1] Patent: WO2014/176258, 2014, A1, .
  • 4
  • [ 626-60-8 ]
  • [ 437383-99-8 ]
References: [1] Archives of Pharmacal Research, 2018, vol. 41, # 12, p. 1149 - 1161.
  • 5
  • [ 120-47-8 ]
  • [ 437383-99-8 ]
References: [1] Archives of Pharmacal Research, 2018, vol. 41, # 12, p. 1149 - 1161.
 

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