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Chemical Structure| 206559-36-6 Chemical Structure| 206559-36-6

Structure of 206559-36-6

Chemical Structure| 206559-36-6

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Product Details of [ 206559-36-6 ]

CAS No. :206559-36-6
Formula : C14H11NOS
M.W : 241.31
SMILES Code : S=C=NC1=CC=CC(OCC2=CC=CC=C2)=C1
MDL No. :MFCD00060374
InChI Key :QJLFNDXMZQJMDL-UHFFFAOYSA-N
Pubchem ID :561446

Safety of [ 206559-36-6 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H331-H302-H312-H314
Precautionary Statements:P261-P273-P280-P305+P351+P338-P310
Class:8(6.1)
UN#:2923
Packing Group:

Computational Chemistry of [ 206559-36-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 12
Fraction Csp3 0.07
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 72.11
TPSA ?

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

53.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.05
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

5.19
Log Po/w (WLOGP)?

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

3.85
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.

4.37
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

5.03
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.3

Water Solubility

Log S (ESOL):?

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

-4.86
Solubility 0.0033 mg/ml ; 0.0000137 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-6.06
Solubility 0.000208 mg/ml ; 0.000000863 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

-5.26
Solubility 0.00132 mg/ml ; 0.00000546 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.

-4.09 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

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

2.0 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)

2.3

Application In Synthesis of [ 206559-36-6 ]

* 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 [ 206559-36-6 ]

[ 206559-36-6 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 206559-36-6 ]
  • [ 959938-92-2 ]
  • methyl [trans-4-(4-[(5-[3-(benzyloxy)phenyl]amino}-1,3,4-oxadiazol-2-yl)carbonyl]amino}-3-nitrophenyl)cyclohexyl]acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% Intermediate 21 : Methyl fcralpha«s-4-(4-([(5-{f3-(benzyloxy)phenyI1amino|-l,3,4- oxadiazol-2-yl)carbonilamino}-3-nitrophenvi)cyclohexyllacetate; l-(Benzyloxy)-3-isothiocyanatobenzene (290 mg, 1.2 mmol) was added in one portion to a stirred solution of methyl [/ralpha«5-4-(4-[hydrazino(oxo)acetyl]amino}-3- nitrophenyl)cyclohexyl]acetate (Intermediate lvi, 378 mg, 1.0 mmol) in DMA (5 mL) and the reaction mixture was stirred at ambient temperature for 4 h. EDCI (288 mg, 1.5 mmol) was added in one portion and the reaction mixture was heated in a microwave at 80C for 10 mins. Water (15 mL) was added and the mixture was filtered to leave a solid, which was washed with water to give the title compound as a solid (470mg, 80%). 'H NMR deltal.Odelta-l^l (2H, m), 1.46-1.6 (2H, m), 1.73-1.9 (5H, m), 2.27 (2H, d), 2.6-2.7(IH, m), 3.61 (3H, s), 5.12 (2H, s), 6.76 (IH, dd), 7.17 (IH, dd), 7.25-7.5 (7H, m), 7.7 (IH, dd), 7.92-8.05 (2H, m), 11.05 (IH, s), 11.4 (IH, s); MS m/e MH+ SSO.
  • 3
  • [ 1484-26-0 ]
  • [ 6160-65-2 ]
  • [ 206559-36-6 ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; EXAMPLE 1. PREPARATION OF 1- (3-BENZYLOXY) PHENYLTHIOUREA (Compound 1); 1. I 02N X 1. 2. 1. TCD ., base >, I Compound 1 [0114] 3-Nitrophenol (X) is converted to ether (Y) by sequential treatment with sodium hydride and benzylbromide. Reduction of the aniline with tin chloride provides aniline (Z). In certain circumstances the reduction may be accomplished using a hydrogen/Pd catalyst system when the substituent on the aryl group does not include an aryl group. [0115] The final product, Compound 1 is obtained by treatment of Z with thiocarbonyl di- imidazole followed by ammonia. 3-Benzyloxyaniline (5 g, 25 mmol) is added dropwise over a one minute period to 4.94 g (27.6 mmol) thiocabonyl di-imidazole in methylene chloride (150 ml). The resulting mixture is stirred at room temperature overnight. An additional 400 mg thiocarbonyl di- imidazole (TCDI) is added and the reaction is continued for 2 hours more. The reaction is diluted with hexane and filtered through silica. Concentration provides 5.1 g of the desired 3- benzyloxyphenyl isothiocyanate. [0116] A portion of this isothiocyanate (50 mg, 0.21 mmol) in 1 ml methylene chloride is mixed with 0.5 ml of 2 M ammonia in methanol. After 30 minutes the reaction is concentrated to provide Compound 1 in quantitative yield. [0117] Alternatively thiocarbonyl di-imidazole (1.1 mmol, 196 mg) is added to a solution of 3-benzyloxyaniline (1 mmol, 199 mg) in dichloromethane (5 mL). The reaction is stirred at room temperature until the aniline is consumed, about 1 hour. A solution of methanolic ammonia (2 M, 2 mL) is added and the stirring continued for 2 hours. Solvent is evaporated and the residue purified by chromatography on silica gel to give 150 mg of (3-benzyloxyphenyl) thiourea. [0118] NMR (CDCI3) D : 5.08 (s, 2H), 6.03 (brs, 2H), 6.8 (M, 2H), 6.93 (m, 1H), 7. 3- 7. 47 (M, 6H), 7.82 (brs, 1H). MS (APCI) : M++1 = 259.
  • 4
  • [ 206559-36-6 ]
  • [ 117174-83-1 ]
YieldReaction ConditionsOperation in experiment
100% With ammonia; In methanol; dichloromethane; for 0.5h;Product distribution / selectivity; EXAMPLE 1. PREPARATION OF 1- (3-BENZYLOXY) PHENYLTHIOUREA (Compound 1); 1. I 02N X 1. 2. 1. TCD ., base >, I Compound 1 [0114] 3-Nitrophenol (X) is converted to ether (Y) by sequential treatment with sodium hydride and benzylbromide. Reduction of the aniline with tin chloride provides aniline (Z). In certain circumstances the reduction may be accomplished using a hydrogen/Pd catalyst system when the substituent on the aryl group does not include an aryl group. [0115] The final product, Compound 1 is obtained by treatment of Z with thiocarbonyl di- imidazole followed by ammonia. 3-Benzyloxyaniline (5 g, 25 mmol) is added dropwise over a one minute period to 4.94 g (27.6 mmol) thiocabonyl di-imidazole in methylene chloride (150 ml). The resulting mixture is stirred at room temperature overnight. An additional 400 mg thiocarbonyl di- imidazole (TCDI) is added and the reaction is continued for 2 hours more. The reaction is diluted with hexane and filtered through silica. Concentration provides 5.1 g of the desired 3- benzyloxyphenyl isothiocyanate. [0116] A portion of this isothiocyanate (50 mg, 0.21 mmol) in 1 ml methylene chloride is mixed with 0.5 ml of 2 M ammonia in methanol. After 30 minutes the reaction is concentrated to provide Compound 1 in quantitative yield. [0117] Alternatively thiocarbonyl di-imidazole (1.1 mmol, 196 mg) is added to a solution of 3-benzyloxyaniline (1 mmol, 199 mg) in dichloromethane (5 mL). The reaction is stirred at room temperature until the aniline is consumed, about 1 hour. A solution of methanolic ammonia (2 M, 2 mL) is added and the stirring continued for 2 hours. Solvent is evaporated and the residue purified by chromatography on silica gel to give 150 mg of (3-benzyloxyphenyl) thiourea. [0118] NMR (CDCI3) D : 5.08 (s, 2H), 6.03 (brs, 2H), 6.8 (M, 2H), 6.93 (m, 1H), 7. 3- 7. 47 (M, 6H), 7.82 (brs, 1H). MS (APCI) : M++1 = 259.
  • 5
  • [ 206559-36-6 ]
  • C24H26ClN2Pol [ No CAS ]
  • C38H37ClN3OPolS [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; for 4h; Step b): General procedure for the preparation of the N-(3-amino-propyl)-N'-(benzyloxyphenyl)thiourea resins; A 0.24 M solution of benzyloxyphenyl isothiocyanate in dichloromethane (4.5 ml; 6 eq.) is added to a reactor containing the 1,3-propane-diamine resin (180 umol; 1 eq.). The suspension is stirred for 4 hours at room temperature. The resin is then washed with dichloromethane (3x5 ml) and N-methylpyrrolidone (NMP; 3x5 ml). The resin is stored as a suspension in NMP (1 ml) and then used in the following reaction.
  • 6
  • [ 206559-36-6 ]
  • [ 892491-52-0 ]
  • 5-[3-(benzyloxy)phenyl]amino}-N-(6-morpholin-4-ylpyridin-3-yl)-1,3,4-oxadiazole-2-carboxamide [ No CAS ]
  • 7
  • [ 206559-36-6 ]
  • [ 32315-10-9 ]
  • C15H11F4NO2 [ No CAS ]
  • 8
  • [ 206559-36-6 ]
  • C23H18F3NO2 [ No CAS ]
 

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Technical Information

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