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Chemical Structure| 589-10-6 Chemical Structure| 589-10-6

Structure of β-Bromophenetole
CAS No.: 589-10-6

Chemical Structure| 589-10-6

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Product Citations

Product Citations

Giri R. Gnawali ; Koichi Okumura ; Karolina Perez ; Rosa Gallagher ; Julia Wulfkuhle ; Emanuel F. Petricoin , et al.

Abstract: Compound VBT-5445 was identified as an inhibitor to block the association of Pim and the protein Enhancer of Decapping 3 (EDC3), a Pim substrate, which normally functions to enhance the decapping of messenger RNA (mRNA). It was also shown to inhibit both the Pim and mTORC protein kinases. The activity of this compound class can be fine-tuned by structural modification. A series of VBT analogs were designed, synthesized, and evaluated. These compounds decrease the growth of multiple cancer types, including pancreas, prostate, breast, lung, and leukemia. Notably, 6-methyl (GRG-1-31, 6d), 4-chloro (GRG-1-34, 6e), 4-Bromo (GRG-1-35, 6f), and phenylthio substituted (GRG-1-104, 6n) derivatives are highly potent at inhibiting tumor growth. The ability of these compounds to block cancer growth in vitro is highly correlated with their activity as mTORC inhibitors. The toxicity of GRG 1–34 is low in mice treated with twice-daily gavage for 30 days and did not induce weight loss. Pharmacokinetics of a single oral dose demonstrated a peak concentration at 0.5 h after gavage. In summary, further development of this compound class has the potential to inhibit important signaling pathways and impact cancer treatment.

Keywords: Quinoline derivatives ; Pim kinase ; Antitumor activity ; mTORC

Alternative Products

Product Details of [ 589-10-6 ]

CAS No. :589-10-6
Formula : C8H9BrO
M.W : 201.06
SMILES Code : BrCCOC1=CC=CC=C1
MDL No. :MFCD00000234
InChI Key :JJFOBACUIRKUPN-UHFFFAOYSA-N
Pubchem ID :68526

Safety of [ 589-10-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362+P364

Computational Chemistry of [ 589-10-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 3
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 45.61
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.31
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

2.6
Log Po/w (WLOGP)?

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

2.46
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.

2.61
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

2.7
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.53

Water Solubility

Log S (ESOL):?

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

-2.97
Solubility 0.215 mg/ml ; 0.00107 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.

-2.44
Solubility 0.725 mg/ml ; 0.00361 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

-3.8
Solubility 0.0316 mg/ml ; 0.000157 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.

-5.68 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<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)

1.37

Application In Synthesis of [ 589-10-6 ]

* 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 [ 589-10-6 ]

[ 589-10-6 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 124-22-1 ]
  • [ 589-10-6 ]
  • [ 538-71-6 ]
  • 2
  • [ 112-18-5 ]
  • [ 589-10-6 ]
  • [ 538-71-6 ]
  • 3
  • [ 589-10-6 ]
  • [ 21642-98-8 ]
  • [ 950201-52-2 ]
YieldReaction ConditionsOperation in experiment
97% With potassium carbonate; In acetonitrile; for 16.0h;Heating / reflux; A solution of commercially available 4-methoxy-2-oxo-l,2-dihydro-pyridine-3- carbonitrile (4.0 g, 0.0266 mol), beta-bromophenetole (5.62 g, 0.0279 mol) and K2CO3 (11.0 g, 0.0799 mol) in CH3CN (150 ml) was heated at reflux for 16 hours. The reaction mixture was then filtered off and the filtrate concentrated in vacuo. The residue was recrystallised from ethylether to yield intermediate compound 17 (7 g, 97 percent).
  • 4
  • [ 50820-65-0 ]
  • [ 589-10-6 ]
  • [ 861508-92-1 ]
YieldReaction ConditionsOperation in experiment
75% With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 55℃; for 21h; To a solution of lH-<strong>[50820-65-0]indole-6-carboxylic acid methyl ester</strong> (0.5 g, 2.9 mmol) and l-(2- bromoethoxy)benzene (0.74 g, 3.7 mmol) in DMF (15 mL) was added K2CO3 (1.2 g, 8.6 mmol). After stirring at room temperature for 16 hr, the mixture was heated to 55 0C for 5 hr then cooled to room temperature and diluted with ethyl acetate (100 ml) and washed with water (3 X 50 ml). The organic layer was dried (MgSO4), filtered and concentrated. The remaining residue was subjected to flash chromatography (20% ethyl acetate/hexane, then ethyl acetate) to provide 0.63 g (75%) of methyl l-(2-phenoxyethyl)-lH-indole-6-carboxylate. 1H νMR (300 MHz, DMSO) S 8.26 (d, IH, J <n="142"/>= 1.0 Hz), 7.67-7.62 (m, 3H), 7.23 (td, 2H, J= 7.6 Hz5 J= 1.0 Hz), 6.92-6.84 (m, 3H), 6.55 (dd, IH, J- 3.0 Hz, J= 0.6 Hz), 4.66 (t, 2H, J= 4.9 Hz), 4.28 (t, 2H, J = 4.9 Hz), 3.86 (s, 3H).
  • 5
  • [ 33543-78-1 ]
  • [ 589-10-6 ]
  • [ 1094025-22-5 ]
YieldReaction ConditionsOperation in experiment
93% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 1h; Example 110 N'-[1-imadazol-1-yl-1-[1-(2-phenoxyethyl)imidazol-2-yl]methylidene]-N,N-dimethylhydrazine (compound Nos. 111, 112) To a solution of <strong>[33543-78-1]ethyl imidazole-2-carboxylate</strong> (0.505 g, 3.60 mmol) in N,N-dimethylformamide (6 ml) were added beta-bromophenetole (0.804 g, 4.00 mmol) and potassium carbonate (0.598 g, 4.32 mmol), and the mixture was stirred at 80°C for 1 hr. Ethyl acetate was added to the reaction mixture, the mixture was washed with water, and the organic layer was dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate) to give ethyl 1-(2-phenoxyethyl)imidazole-2-carboxylate (0.869 g, 3.34 mmol, yield 93percent).
  • 6
  • [ 53242-51-6 ]
  • [ 589-10-6 ]
  • 5-(4-methoxyphenyl)-1-(2-phenoxyethyl)pyridin-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% Step 2 : 5-(4-Methoxyphenyl)-l-(2-phenoxyethyl)pyridin-2(lH)-one; According to Scheme 5 Step 2: To a solution of 5-(4-methoxyphenyl)-(lH)-pyridin-2- one (leq, 0.30mmol, 60mg) in TEtaF (3mL) was added K2CO3 (10eq, 3.00mmol, 0.4Ig). The reaction was stirred at room temperature for 30 minutes then l-(2- bromoethoxy)benzene (3eq, 0.90mmol, 0.18g) was added. The reaction was stirred at 60C for 12 hours. After concentration of the solvent, acetonitrile (3mL) was added followed by K2CO3 (10eq, 3.00mmol, 0.4Ig) and l-(2-bromoethoxy)benzene (10eq, 3.00mmol, 0.60g) then the reaction was microwaved for 5 minutes at 180C. The reaction was filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel (AIT Flashsmart prepacked column 10g SiO2) using CEta2Cl2/AcOEt (80/20) as the eluent to afford 5-(4-methoxyphenyl)-l- (2-phenoxyethyl)pyridin-2(lH)-one (0.13mmol, 42mg, 44%) as a yellow oil. Rf= 0.29 (CEta2Cl2/AcOEt 90/10); LC (XTerra RP18, 3.5mum, 3.0x50mm Column): RT = 4.31min; MS m/z (CI) [MH]+= 322; 1H NMR (500MHz, CDCl3) delta 3.86 (s, 3H), 4.33- 4.37 (m, 2H), 4.38-4.43 (m, 2H), 6.67 (d, J=10.1Hz, 1H), 6.87-6.90 (m, 2H), 6.95-6.99 (m, 3H), 7.25-7.30 (m, 2H), 7.32-7.35 (m, 2H), 7.59-7.62 (m, 2H).
  • 7
  • [ 52427-05-1 ]
  • [ 589-10-6 ]
  • [ 1349821-39-1 ]
YieldReaction ConditionsOperation in experiment
80% With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; General procedure: The mixture of phenol (700 mg, 3.78 mmol), beta-bromophenetole (836 mg, 4.16 mmol) and cesium carbonate (1.838 mg, 5.67 mmol) in DMF (8 mL) was stirred overnight at 50° C. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were dried over sodium sulfate and purified by recrystallization or flash chromatography. The compound 25b was prepared by using the general procedure H, as given in Example 9, starting from compound 25a as pale yellow solid in 80percent yield. 1H NMR (400 MHz, CDCl3) delta 7.86 (d, J=2.3 Hz, 1H), 7.77-7.66 (m, 2H), 7.33-7.26 (m, 2H), 7.00-6.93 (m, 3H), 4.49 (dd, J=5.6, 3.5 Hz, 2H), 4.41 (dd, J=6.0, 3.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) delta 158.37, 133.68, 129.55, 121.38, 120.28, 116.91, 114.73, 108.08, 68.58, 66.18. HRMS (ESI) calculated for C14H12BrNO4 [M+H]+: 359.9842. Found: 359.9855.
50% With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 24h; To a solution of <strong>[52427-05-1]2-bromo-5-nitrophenol</strong> (9g, 0.041 28 mol) in anhydrous DMF (90 mL) at room temperature was added sodium hydride (1.82 g, 0.0454 mol). After stirring the resulting solution for 10 min, (2-bromoethoxy)benzene (9.96g, 0.04954 mol) was added slowly. The reaction was then stirred for 24 h and then quenched with water and diluted with DCM (150 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by recrystallization from ethyl acetate to afford the title compound (6.95 g, 50percent yield). 1H NMR (399 MHz, DMSO) delta 7.94 (s, 1H), 7.87 (d, J=8.1Hz, 1H), 7.76 (d, J=8.3 Hz, 1H), 7.29 (t, J=6.8 Hz, 2H), 6.99 (d, J=7.6 Hz, 2H), 6.95 (s, 1H), 4.57 (s, 2H), 4.37 (s, 2H). 13C NMR (100 MHz, DMSO) delta 158.22, 155.20, 147.77, 133.77, 129.54, 120.87, 119.20, 116.83, 114.56, 108.28, 68.56, 66.10. HRMS (ESI) calcd for C14H12BrNO4 [M+Na]+ 359.9842; found 359.9855.
  • 8
  • [ 589-10-6 ]
  • [ 35344-95-7 ]
  • [ 1396722-54-5 ]
YieldReaction ConditionsOperation in experiment
71% Alternate synthesis: l-(2-phenoxyethyl)-lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong>Sodium hydride (60percent>, 6.3 g, 1.0 eq) was added to a solution of lH-pyrazole-4- carbaldehyde (15 g, 156 mmol) in DMF (150 ml) at 0°C. The mixture was allowed to warm and was stirred at room temperature. (2-Bromoethoxy)benzene (30.2 g, 1 eq) was then added and the resulting mixture was stirred overnight at room temperature. It was quenched by addition of aqueous ammonium chloride, diluted with water and extracted with EtOAc. The combined organic layers were dried over Na2S04, filtered, and concentrated. The residue was purified by column chromatography using a hexane/EtOAc gradient (10: 1 to 0: 100). Pure fractions were combined and evaporated under reduced pressure to yield l-(2-phenoxyethyl)-lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (24 g, 71percent).
71% Sodium hydride (60percent, 6.3 g, 1.0 eq) was added to a solution of <strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (15 g, 156 mmol) in DMF (150 ml) at 0° C. The mixture was allowed to warm and was stirred at room temperature. (2-Bromoethoxy)benzene (30.2 g, 1 eq) was then added and the resulting mixture was stirred overnight at room temperature. It was quenched by addition of aqueous ammonium chloride, diluted with water and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography using a hexane/ EtOAc gradient (10:1 to 0:100). Pure fractions were combined and evaporated under reduced pressure to yield 1-(2-phenoxyethyl)-<strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (24 g, 71percent).
 

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