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Chemical Structure| 67-36-7 Chemical Structure| 67-36-7

Structure of 4-Phenoxybenzaldehyde
CAS No.: 67-36-7

Chemical Structure| 67-36-7

4-Phenoxybenzaldehyde

CAS No.: 67-36-7

4.5 *For Research Use Only !

Cat. No.: A396423 Purity: 97%

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Product Citations

Product Citations

Christian N. Lotz ; Alina Krollenbrock ; Lea Imhof ; Michael Riscoe ; Jennifer Keiser ;

Abstract: Schistosomiasis caused by Schistosoma spp. is a disease that causes a considerable health burden to millions of people worldwide. The limited availability of effective drugs on the market and the increased risk of resistance development due to extensive usage, highlight the urgent need for new antischistosomal drugs. Recent studies have shown that robenidine derivatives, containing an aminoguanidine core, exhibit promising activities against Plasmodium falciparum, motivating further investigation into their efficacy against Schistosoma mansoni, due to their similar habitat and the resulting related cellular mechanisms like the heme detoxification pathway. The conducted phenotypic screening of robenidine and 80 derivatives against newly transformed schistosomula and adult Schistosoma mansoni yielded 11 candidates with low EC50 values for newly transformed schistosomula (1.12–4.63 μM) and adults (2.78–9.47 μM). The structure-activity relationship revealed that electron-withdrawing groups at the phenyl moiety, as well as the presence of methyl groups adjacent to the guanidine moiety, enhanced the activity of derivatives against both stages of Schistosoma mansoni. The two compounds 2,2′-Bis[(3-cyano-4-fluorophenyl)methylene] carbonimidic Dihydrazide Hydrochloride (1) and 2,2′-Bis[(4-difluoromethoxyphenyl) ethylidene] carbonimidic Dihydrazide Hydrochloride (19), were selected for an in vivo study in Schistosoma mansoni-infected mice based on their potency, cytotoxicity, pharmacokinetic-, and physicochemical properties, but failed to reduce the worm burden significantly (worm burden reduction <20%). Thus, robenidine derivatives require further refinements to obtain higher antischistosomal specificity and in vivo activity.

Keywords: Robenidine derivative ; Aminoguanidine ; Schistosoma mansoni ; Drug discovery ; Structure-activity relationship

Purchased from AmBeed: ; ; ; ; ; ; ;

Alternative Products

Product Details of [ 67-36-7 ]

CAS No. :67-36-7
Formula : C13H10O2
M.W : 198.22
SMILES Code : O=CC1=CC=C(OC2=CC=CC=C2)C=C1
MDL No. :MFCD00003383
InChI Key :QWLHJVDRPZNVBS-UHFFFAOYSA-N
Pubchem ID :66139

Safety of [ 67-36-7 ]

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

Computational Chemistry of [ 67-36-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 58.35
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.28
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

3.07
Log Po/w (WLOGP)?

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

3.29
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

3.22
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.89

Water Solubility

Log S (ESOL):?

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

-3.4
Solubility 0.0795 mg/ml ; 0.000401 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.

-3.29
Solubility 0.102 mg/ml ; 0.000514 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

-4.61
Solubility 0.00489 mg/ml ; 0.0000247 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

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.

-5.33 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)

1.36

Application In Synthesis of [ 67-36-7 ]

* 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 [ 67-36-7 ]

[ 67-36-7 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 67-36-7 ]
  • [ 76-05-1 ]
  • [ 162167-97-7 ]
  • [1-(4-phenoxybenzyl)piperidin-3-yl]methanamine bis(trifluoroacetate) salt [ No CAS ]
  • 2
  • [ 67-36-7 ]
  • [ 3096-81-9 ]
YieldReaction ConditionsOperation in experiment
80% REFERENCE EXAMPLE 34 4-Phenoxybenzonitrile The title compound was obtained from 4-phenoxybenzaldehyde by the method similar to that in Reference Example 32. Yield: 80%. 1H NMR (CDCl3) δ 6.97-7.19 (4H, m), 7.20-7.28 (1H, m), 7.37-7.46 (2H, m), 7.57-7.64 (2H, m).
  • 3
  • [ 67-36-7 ]
  • [ 3096-81-9 ]
  • [ 68-11-1 ]
  • [ 1380593-31-6 ]
YieldReaction ConditionsOperation in experiment
39% With triethylamine; In methanol; for 12h;Reflux; General procedure: A solution of the corresponding aromatic aldehyde (0.8-10.3 mmol), 2-sulfanylacetic acid (1.0-1.3 equiv) and the corresponding aromatic nitrile (1.0-1.3 equiv) and triethylamine (1.5-15.0 equiv) in methanol was refluxed over night. The reaction mixture was evaporated under reduced pressure and the crude product was recrystallized from ethanol and washed with acetone.
  • 4
  • [ 3096-81-9 ]
  • [ 67-36-7 ]
YieldReaction ConditionsOperation in experiment
82% With diisobutylaluminium hydride; at -70 - 20℃;Inert atmosphere; General procedure: To a round bottom flask containing THF, the appropriate aryl nitrileanalogue (1.0 equiv.) was added followed by the addition of nitrogengas. Next, the solution was cooled to 70 C before the addition of aDIBAL-H (1.1 equiv.) solution (1.0 M in THF). After, the mixture wasstirred at 40 C for 5 h under nitrogen until TLC indicated the startingmaterial had been fully consumed. Subsequently, the reaction vessel wasplaced in an ice bath and quenched with 1 mL ethyl acetate and 20 mLHCl (1.0 M). After, the resulting solution was partitioned between EtOAcand brine. Using additional EtOAc, the aqueous brine solution waswashed three times and the combined organic layers were dried overNa2SO4, filtered, and concentrated via vacuum. The resulting concentratewas purified by silica gel chromatography.4.2.6.1. 4-phenoxybenzaldehyde (15a). White solid, yield 82%. 1H NMR(400 MHz, CDCl3) δ: 9.92 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.46 - 7.37(m, 2H), 7.23 (t, J = 7.4 Hz, 1H), 7.09 (dd, J = 8.7, 1.1 Hz, 2H), 7.06 (d,J = 8.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ: 190.9, 163.3, 155.2,132.1, 131.4, 130.3, 125.1, 120.5, 117.7. HRMS (ESI + ) [M + H]+ calcdfor C13H11O2: 199.0754, found: 199.0753.
  • 5
  • [ 67-36-7 ]
  • [ 62-53-3 ]
  • [ 446065-11-8 ]
  • N-(cyclohexyl(4-phenoxyphenyl)methyl)aniline [ No CAS ]
  • 6
  • [ 67-36-7 ]
  • [ 73183-34-3 ]
  • [ 269410-26-6 ]
 

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