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Chemical Structure| 57808-65-8 Chemical Structure| 57808-65-8
Chemical Structure| 57808-65-8

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Closantel

CAS No.: 57808-65-8

Closantel is a salicylanilide anthelmintic compound and exhibits different anthelmintic spectra and apparent toxicity in mammals.

Synonyms: NSC 335306

4.5 *For Research Use Only !

Cat. No.: A220377 Purity: 99+%

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Product Details of [ 57808-65-8 ]

CAS No. :57808-65-8
Formula : C22H14Cl2I2N2O2
M.W : 663.07
SMILES Code : C2=C(C(C1=CC=C(C=C1)Cl)C#N)C(=CC(=C2C)NC(C3=CC(=CC(=C3O)I)I)=O)Cl
Synonyms :
NSC 335306
MDL No. :MFCD00661151
InChI Key :JMPFSEBWVLAJKM-UHFFFAOYSA-N
Pubchem ID :42574

Safety of [ 57808-65-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Calculated chemistry of [ 57808-65-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 30
Num. arom. heavy atoms 18
Fraction Csp3 0.09
Num. rotatable bonds 5
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 137.11
TPSA ?

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

73.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.63
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

7.22
Log Po/w (WLOGP)?

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

6.93
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.

5.71
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

7.56
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

6.21

Water Solubility

Log S (ESOL):?

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

-8.61
Solubility 0.00000161 mg/ml ; 0.0000000024 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.

-8.58
Solubility 0.00000175 mg/ml ; 0.0000000026 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

-10.12
Solubility 0.0000000502 mg/ml ; 0.0000000001 mol/l
Class?

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

Insoluble

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

Yes
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

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.

-5.22 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

2.0
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

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.17

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<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)

3.22

Application In Synthesis [ 57808-65-8 ]

* 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 [ 57808-65-8 ]

[ 57808-65-8 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 78-96-6 ]
  • [ 57808-65-8 ]
  • isopropanolamine closantel salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; acetonitrile; A solution of <strong>[57808-65-8]closantel</strong> in a mixed solvent system of acetonitrile and tetrahydrofuran is treated with an equimolar amount of monoisopropanolamine. The reaction is stirred at 40 C, and then room temperature. Evapoaration of the solvents leads to the isolation of the monoisopropanolamine salt of <strong>[57808-65-8]closantel</strong>. After purification using the standard methods, the salt is characterized.
  • 2
  • [ 6284-40-8 ]
  • [ 57808-65-8 ]
  • N-methylglucamine salt of closantel [ No CAS ]
YieldReaction ConditionsOperation in experiment
In propylene glycol; ethanol; benzyl alcohol; N-methylglucamine is added to a suspension of <strong>[57808-65-8]closantel</strong> in ethanol, benzyl alcohol, and propylene glycol. With stirring, the salt of <strong>[57808-65-8]closantel</strong> forms in situ, forming a solution. Moxidectin is then added, and stirred until solution is obtained. The formulation is then brought to volume with propylene glycol.
  • 3
  • [ 111-42-2 ]
  • [ 57808-65-8 ]
  • diethanolamine closantel salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
In propylene glycol; ethanol; benzyl alcohol; Diethanolamine is added to a suspension of <strong>[57808-65-8]closantel</strong> in ethanol, benzyl alcohol, and propylene glycol. With stirring, the salt of <strong>[57808-65-8]closantel</strong> forms in situ, forming a solution. Moxidectin is then added, and stirred until solution is obtained. The formulation is then brought to volume with propylene glycol.
  • 4
  • [ 141-43-5 ]
  • [ 57808-65-8 ]
  • closantel ethanolamine salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethoxyethoxyethanol; EXAMPLE 1 Preparation Of A Pour-On Formulation Containing An Organic Amine Salt Of <strong>[57808-65-8]Closantel</strong> Ingredients g/200 mL % w/v <strong>[57808-65-8]Closantel</strong> 60.00 30.00 Diethylene glycol 60.0 30.00 Monoethyl ether Ethanol amine 6.6 3.30 Benzyl alcohol 10.0 5.00 Oleic acid 60.0 30.00 Moxidectin 1.04 0.52 Ethanol, USP qs to 200 ml qs to 100 A stirred mixture of <strong>[57808-65-8]closantel</strong> in diethylene glycol monoethyl ether is treated with ethanolamine, and stirring is continued until solution is complete, thus forming the salt in situ. To this solution is then added a solution of moxidectin in benzyl alcohol, followed by the addition of oleic acid and ethanol. Stirring is continued until the mixture is homogeneous.
In 2-pyrrolidinon; polypropylene glycol 400; benzyl alcohol; Ethanolamine is added to a suspension of <strong>[57808-65-8]closantel</strong> in benzyl alcohol, 2- pyrrolidone and polypropylene glycol 400. With stirring, the salt of formed in situ, forming a solution. Moxidectin is then added, and stirred until solution is obtained. The formulation is then brought to volume with PEG 400.
  • 5
  • [ 110-97-4 ]
  • [ 57808-65-8 ]
  • diisopropanolamine closantel salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; acetonitrile; A solution of <strong>[57808-65-8]closantel</strong> in a mixed solvent system of acetonitrile and tetrahydrofuran is treated with an equimolar amount of diisopropanolamine. The reaction is stirred at 40 C, and then room temperature. Evaporation of the solvents leads to the isolation of the diisopropanolamine salt of <strong>[57808-65-8]closantel</strong>. After purification using the standard methods, the salt is characterized.
YieldReaction ConditionsOperation in experiment
0.7 parts (67.5%) EXAMPLE XXXII A warm solution of 1 part of N-{5-chloro-4-[alpha-(4-chlorophenyl)-alpha-cyanomethyl]-2-methylphenyl}-2-hydroxy-3,5-diiodobenzamide, 0.3 parts of sodium hydroxide solution 10N, 8 parts of methanol and 10 parts of water is allowed to crystallize. The product is filtered off, washed with water and dried, yielding 0.7 parts (67.5%)of N-{5-chloro-4-[alpha-(4-chlorophenyl)-alpha-cyanomethyl]-2-methylphenyl}-2-hydroxy-3,5-diiodobenzamide, sodium salt hydrate; mp. 270 -300 C.
  • 7
  • [ 123-91-1 ]
  • [ 42016-91-1 ]
  • [ 61437-85-2 ]
  • [ 57808-65-8 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE X A mixture of 4 parts of 2-hydroxy-3,5-diiodobenzoyl chloride, 2.9 parts of 4-amino-2-chloro-alpha-(4-chlorophenyl)-5-methylbenzeneacetonitrile and 75 parts of 1,4-dioxane is stirred and refluxed for 10 minutes. The reaction mixture is evaporated and the oily residue is crystallized from methanol. The product is filtered off and dried, yielding 5.3 parts of N-{5-chloro-4-[alpha-(4-chlorophenyl)-alpha-cyanomethyl]-2-methylphenyl}-2-hydroxy-3,5-diiodobenzamide; mp. 217.8 C.
  • 8
  • [ 57808-65-8 ]
  • closantel sodium salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
99.3% With sodium hydroxide; In water; at 70.0℃; for 6.0h;Sealed tube; In a 1000 mL sealed four-neck reaction flask, 80 g of sodium hydroxide and 500 mL of water were added and stirred uniformly and was added to the above obtained Example 7 663.1 g of <strong>[57808-65-8]closantel</strong> (IV), and the mixture was heated to 70 C for 6 hours. After cooling to room temperature and filtration, a pale yellow solid <strong>[57808-65-8]closantel</strong> sodium (I) 680.3 g was obtained, yield 99.3%.
  • 9
  • [ 140-53-4 ]
  • [ 57808-65-8 ]
  • 10
  • [ 89-59-8 ]
  • [ 57808-65-8 ]
  • 11
  • [ 844-24-6 ]
  • [ 57808-65-8 ]
  • 12
  • [ 61437-85-2 ]
  • 2-hydroxy-3,5-diiodobenzoyl derivative [ No CAS ]
  • [ 57808-65-8 ]
YieldReaction ConditionsOperation in experiment
89.1% In toluene; at 50.0℃; for 6.0h;Reflux; Sealed tube; In a 1000 mL sealed four-neck reaction flask, 291.2 g of 4-amino-2-chloro-5-methyl-alpha-(4-chlorophenyl)phenylacetonitrile (III) and 500 mL of toluene were added, stirred and dissolved, and the temperature was controlled at 50C, 389.9 g of 2-hydroxy-3,5-diiodobenzoyl chloride in toluene solution was added dropwise, and the dropwise addition time was 1 hour. After the completion of the dropwise addition, the temperature was raised to reflux and stirring was continued for 5 hours.After completion of the reaction, the reaction was completed, and the solvent toluene was recovered to give a pale-yellow solid, closantel (IV), 590.8 g, yield: 89.1%.
 

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