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Chemical Structure| 942189-39-1 Chemical Structure| 942189-39-1

Structure of 942189-39-1

Chemical Structure| 942189-39-1

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Product Details of [ 942189-39-1 ]

CAS No. :942189-39-1
Formula : C26H18BrN3O2
M.W : 484.34
SMILES Code : O=[N+](C1=CC2=C(N(C(C3=CC=CC=C3)(C4=CC=CC=C4)C5=CC=CC=C5)N=C2Br)C=C1)[O-]
MDL No. :MFCD17169854
InChI Key :PDUHZXZECHMGLL-UHFFFAOYSA-N
Pubchem ID :58946443

Safety of [ 942189-39-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Computational Chemistry of [ 942189-39-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 32
Num. arom. heavy atoms 27
Fraction Csp3 0.04
Num. rotatable bonds 5
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 130.86
TPSA ?

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

63.64 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.62
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

7.2
Log Po/w (WLOGP)?

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

6.55
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.

5.81
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

3.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.4

Water Solubility

Log S (ESOL):?

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

-7.67
Solubility 0.0000103 mg/ml ; 0.0000000212 mol/l
Class?

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

Poorly soluble
Log S (Ali)?

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

-8.36
Solubility 0.00000212 mg/ml ; 0.0000000044 mol/l
Class?

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

Poorly 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

-9.76
Solubility 0.0000000851 mg/ml ; 0.0000000002 mol/l
Class?

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

Poorly 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

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

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

Yes
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.

-4.14 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

1.0
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

1.0
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<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)

3.54

Application In Synthesis of [ 942189-39-1 ]

* 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 [ 942189-39-1 ]

[ 942189-39-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 481681-02-1 ]
  • [ 942189-39-1 ]
  • [ 1093064-47-1 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 80℃; A suspension of 3-bromo-5-nitro-1-trityl-1 H-indazole 1 (6 g, 12.41 mmol), 4- fluoro-3-hydroxymethylphenylboronic acid 10AV (2 g, 12.87 mmol), Pd(dppf)CI2 (800 mg, 0.98 mmol) and K3PO4 (6 g, 28.30 mmol) in 124 ml_ of dioxane/H2O (25:6) was heated to 80C for overnight. After removal of most of the solvent, the black residue was diluted with EtOAc (250 ml_) and H2O (60 ml_). The resulting mixture was filtered through a pad of Celite. Additional 150 ml_ of EtOAc was used to wash the Celite cake. The filtrates were combined. The aqueous layer was separated and the organic layer was washed with brine, dried (MgSO4) and concentrated to give crude 3-(4- fluoro-3-hydroxymethylphenyl)-5-nitro-1-trityl-1 H-indazole 11AV (8.2 g) as a greenish yellow solid.
  • 2
  • [ 942189-39-1 ]
  • [ 612845-44-0 ]
  • [ 1184174-51-3 ]
YieldReaction ConditionsOperation in experiment
89% With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 90℃; for 18h;Inert atmosphere; Example 11Synthesis of 3-Methoxy-1 -(2-f 4-r°-d -methyl-1 H-F1 ,2,41triazol-3-yl)-phenv?-3.6- dihvdro-2H-pyridin-1 -yl)-2-oxo-ethyl)-pyrrolidine-3-carboxylic acid r3-(6-ethoxy- pyridin-3-yl)-1 H-indazol-5-yll-amide (Example 1) Step 1 : A mixture of <strong>[612845-44-0]6-ethoxypyridine-3-boronic acid</strong> (2.5 g, 14.97 mmol), bromoindazole 3Bl (7.25 g, 14.97 mmol), potassium carbonate (6.2 g, 44.91 mmol), PdCI2(dppf)2.CH2Cl2 (1.22 g, 1.497 mmol), 1 ,4-dioxane (40 ml_) and water (10 rriL), was purged with nitrogen for 15 min at r.t. and then heated at 90 0C for 18 hrs and cooled to r.t. Water (100 ml_) and ethyl acetate (300 ml_) were added. Solids were filtered through Celite. Layers were separated and the separated organic layer was washed with water (100 ml_). The combined organic layers were dried (Na2SO4), filtered and solvents were removed in vacuum. Column purification [Hexanes-ethyl acetate = 9:1 (Wv)] gave Compound 2BU (7 g, 89%).
 

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Technical Information

Categories

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