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Chemical Structure| 51067-38-0 Chemical Structure| 51067-38-0

Structure of 4-Phenoxyphenylboronic acid
CAS No.: 51067-38-0

Chemical Structure| 51067-38-0

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Product Citations

Product Citations

Pieterse, Lianie ; Beteck, Richard M. ; Baratte, Blandine ; Jesumoroti, Omobolanle J. ; Robert, Thomas ; Ruchaud, Sandrine , et al.

Abstract: Protein kinases, including CDK9/CyclinT and Haspin, are regarded as potential drug targets in cancer therapy. Findings from a previous study suggested 7-azaindole as a privileged scaffold for producing inhibitors of CDK9/CyclinT and Haspin. Inspired by these findings, the current study synthesized and evaluated thirteen (13) C6-substituted 7-azaindole and twenty (20) C4-substituted structurally related 7H-pyrrolo[2,3-d]pyrimidine derivatives against a panel of protein kinases, including CDK9/CyclinT and Haspin. Eleven of the 7H-pyrrolo[2,3-d]pyrimidine derivatives exhibited activity toward CDK9/CyclinT, while 4 of compounds had activity against Haspin. The best CDK9/CyclinT (IC50 of 0.38 μM) and Haspin (IC50 of 0.11 μM) activities were achieved by compounds 7d and 7f, resp. Hence, these compounds may be valuable starting points for development of new anti-cancer drugs.

Keywords: 7-Deazapurine ; Anticancer ; CDK9/CylinT ; Haspin ; Protein kinase

Purchased from AmBeed: ; ; ; ; ;

Alternative Products

Product Details of [ 51067-38-0 ]

CAS No. :51067-38-0
Formula : C12H11BO3
M.W : 214.02
SMILES Code : OB(O)C1=CC=C(OC2=CC=CC=C2)C=C1
MDL No. :MFCD00093312
InChI Key :KFXUHRXGLWUOJT-UHFFFAOYSA-N
Pubchem ID :2734377

Safety of [ 51067-38-0 ]

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

Computational Chemistry of [ 51067-38-0 ] 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 3.0
Num. H-bond donors 2.0
Molar Refractivity 62.78
TPSA ?

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

49.69 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.35
Log Po/w (WLOGP)?

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

1.16
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.

1.53
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

0.42
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.09

Water Solubility

Log S (ESOL):?

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

-3.0
Solubility 0.212 mg/ml ; 0.00099 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.

-3.03
Solubility 0.198 mg/ml ; 0.000926 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

-3.55
Solubility 0.0599 mg/ml ; 0.00028 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.

-5.94 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.

0.55

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<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)

2.19

Application In Synthesis of [ 51067-38-0 ]

* 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 [ 51067-38-0 ]

[ 51067-38-0 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 1920-66-7 ]
  • [ 51067-38-0 ]
  • 4-amino-5-nitro-2-(4-phenoxyphenyl)pyrimidine [ No CAS ]
  • 3
  • [ 19745-07-4 ]
  • [ 51067-38-0 ]
  • [ 76849-86-0 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 85℃; for 2h;Inert atmosphere; To a solution of <strong>[19745-07-4]2,5-dichloropyrazine</strong> (2.91 mmole) in 1,2-dimethoxyethane (9 mL), was added 4-(phenoxyphenyl)lboronic acid (3.49 mmole) and tetrakis(triphenylphosphine)palladium (0.145 mmole) followed by 2M Na2CO3 (3 mL). The resulting mixture was heated at 85 C for 2 hours. The reaction mixture was diluted with ethyl acetate and filtered through celite. The organic extract was dried over Na2SO4 and evaporated in vacuo. The crude product was purifed by biotage chromatography and then with prep TLC eluting with 5percent ethyl acetate and hexane mixture to give 2-chloro-5-(4-phenoxyphenyl)pyrazine.
  • 4
  • [ 38557-72-1 ]
  • [ 51067-38-0 ]
  • [ 1371537-32-4 ]
YieldReaction ConditionsOperation in experiment
89% With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; acetonitrile; for 0.166667h;Inert atmosphere; Microwave irradiation; Example 1Synthesis Example 1Example 1 gives a specific example of the synthesis of the organometallic complex represented by the structural formula (100) in Embodiment 1 which is one embodiment of the present invention, (acetylacetonato)bis[3,5-dimethyl-2-(4-phenoxyphenyl)pyrazinato]iridium(III) (abbreviation: [Ir(dmpoppr)2(acac)]). A structure of [Ir(dmpoppr)2(acac)] is illustrated below. Step 1: Synthesis of 3,5-Dimethyl-2-(4-phenoxyphenyl)pyrazine (abbreviation: Hdmpoppr)First, into a recovery flask equipped with a reflux pipe were placed 1.35 g of <strong>[38557-72-1]2-chloro-3,5-dimethylpyrazine</strong>, 2.02 g of 4-phenoxyphenylboronic acid, 1.00 g of sodium carbonate, 0.043 g of bis(triphenylphosphine)palladium(II)dichloride (abbreviation: Pd(PPh3)2Cl2), 15 mL of water, and 15 mL of acetonitrile, and the air inside the flask was replaced with argon. Heating was performed by microwave irradiation (2.45 GHz, 100 W) of this reaction container for 10 minutes, so that reaction occurred. After that, water was added to this reaction solution, and extraction with dichloromethane was carried out. A solution of the obtained extract was washed with water and dried over magnesium sulfate. After the drying, the solution was filtered. After the solvent of this solution was distilled, the obtained residue was washed with methanol, so that the pyrazine derivative which was the object of the synthesis, Hdmpoppr, was obtained (a white powder in a yield of 89%). Note that a microwave synthesis system (Discover, produced by CEM Corporation) was used for the microwave irradiation. The synthesis scheme of Step 1 is illustrated in the following formulae (e).
  • 7
  • [ 953410-86-1 ]
  • [ 51067-38-0 ]
  • 5-bromo-7-(4-phenoxyphenyl)-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 12h;Inert atmosphere; Compound <strong>[953410-86-1]5-bromo-7-iodo-1H-indazole</strong> 20c (2.0 g, 6.2 mmol), (4-phenoxyphenyl)boric acid (1.46 g, 6.8mmol), cesium carbonate (4.04 g, 12.4 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (453 mg, 0.62 mmol), 1,4-dioxane (50 mL), and water (10 mL) were mixed, degassed, and heated at 100C under nitrogen for 12 hrs. The mixture was cooled to room temperature, and then water (100 mL) was added. Next, the mixture was extracted with ethyl acetate (100 mL*2). The organic phases were combined, and desolventized under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane/methanol = 30/1), to produce a target compound 5-bromo-7-(4-phenoxyphenyl)-1H-indazole 20d (1.6 g, white solid), yield: 71%. MS m/z(ESI):365, 367[M+1]
  • 8
  • [ 31161-46-3 ]
  • [ 51067-38-0 ]
  • C23H16O2S [ No CAS ]
 

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