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Chemical Structure| 36443-68-2 Chemical Structure| 36443-68-2

Structure of TK 12627
CAS No.: 36443-68-2

Chemical Structure| 36443-68-2

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Product Details of [ 36443-68-2 ]

CAS No. :36443-68-2
Formula : C34H50O8
M.W : 586.76
SMILES Code : O=C(OCCOCCOCCOC(CCC1=CC(C)=C(O)C(C(C)(C)C)=C1)=O)CCC2=CC(C)=C(O)C(C(C)(C)C)=C2
MDL No. :MFCD00134694
InChI Key :QSRJVOOOWGXUDY-UHFFFAOYSA-N
Pubchem ID :91620

Safety of [ 36443-68-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 36443-68-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 42
Num. arom. heavy atoms 12
Fraction Csp3 0.59
Num. rotatable bonds 19
Num. H-bond acceptors 8.0
Num. H-bond donors 2.0
Molar Refractivity 166.03
TPSA ?

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

111.52 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

6.33
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

6.85
Log Po/w (WLOGP)?

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

5.99
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.

3.71
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

8.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

6.29

Water Solubility

Log S (ESOL):?

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

-6.75
Solubility 0.000104 mg/ml ; 0.000000177 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.

-9.0
Solubility 0.000000585 mg/ml ; 0.000000001 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

-9.58
Solubility 0.000000154 mg/ml ; 0.0000000003 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

Low
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

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.

-5.02 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

1.0
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

2.0
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<3.0
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)

4.29

Application In Synthesis of [ 36443-68-2 ]

* 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 [ 36443-68-2 ]

[ 36443-68-2 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 6386-39-6 ]
  • [ 51590-67-1 ]
  • [ 856335-90-5 ]
  • [ 36443-68-2 ]
YieldReaction ConditionsOperation in experiment
95% With nitrogen In water; toluene; 2,2'-[1,2-ethanediylbis(oxy)]bisethanol (2)
Into a 1-liter four-necked flask equipped with a stirrer, a condenser, a thermometer, and a nitrogen introducing tube were introduced 327.9 g (1.31 moles) of methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl) propionate, 85.6 g (0.57 mole) of triethylene glycol, and 0.9 g (0.00431 mole) of monobutyltin oxide.
The mixture was allowed to react at 170° C. for 1 hour, and the resulting methanol was distilled off.
The reaction was continued for further 8 hours under a reduced pressure of 60-70 mmHg while bubbling nitrogen gas into the solution and thus completed.
Excess methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl) propionate was distilled off in an amount of 40.5 g at 150°-185° C. under 0.5 -0.2 mmHg by thin film distillation.
This distillate can be reused, as it is, for the next reaction.
Then, the reaction mixture was cooled to 115° C. and returned to atmospheric pressure by the introduction of nitrogen gas, and dissolved homogeneously by adding 260 g of toluene.
The solution was washed with 200 g (0.11 mole) of 5percent oxalic acid water at 80° C. and then with 200 g of water twice for partitioning to two layers.
The toluene layer was concentrated at 120° C. under 30 mmHg to give a pale yellow tacky substance.
The pale yellow tacky substance so obtained was recrystallized from methanol-water to Yield 317.8 g of white crystals of triethylene glycol bis[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate] as intended. Yield: 95percent, residual tin content: 2 ppm.
References: [1] Patent: US5081280, 1992, A, .
[2] Patent: US5081280, 1992, A, .
 

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