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Chemical Structure| 1747-60-0 Chemical Structure| 1747-60-0

Structure of 1747-60-0

Chemical Structure| 1747-60-0

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Product Citations

Product Citations

Walczak, Juliusz Maksymilian ; Iwaszkiewicz-Grzes, Dorota ; Ziomkowska, Michalina ; Sliwka-Kaszynska, Magdalena ; Dasko, Mateusz ; Trzonkowski, Piotr , et al.

Abstract: The group of 18 new amide derivatives of mycophenolic acid (MPA) and selected heterocyclic amines was synthesised as potential immunosuppressive agents functioning as inosine-5′-monophosphate dehydrogenase (IMPDH) uncompetitive inhibitors. The synthesis of 14 of them employed uronium-type activating system (TBTU/HOBt/DIPEA) while 4 of them concerned phosphonic acid anhydride method (T3P/Py) facilitating amides to be obtained in moderate to excellent yields without the need of phenolic group protection. Most of optimised protocols did not require complicated reaction work-ups, including chromatographic, solvent-consuming methods. The biological activity assay was performed on the T-Jurkat cell line and peripheral mononuclear blood cells (PBMCs) which are both dedicated for antiproliferative activity determination. Each of designed derivatives was characterised by reduced cytotoxicity and benzoxazole analogue (A2) revealed the most promising activity. Subsequently, an observed structure-activity relationship was discussed.

Keywords: Mycophenolic acid ; amide derivatives ; heterocycles ; benzoxazole ; IMPDH inhibition

Alternative Products

Product Details of [ 1747-60-0 ]

CAS No. :1747-60-0
Formula : C8H8N2OS
M.W : 180.23
SMILES Code : C1=CC(=CC2=C1N=C(N)S2)OC
MDL No. :MFCD00005787
InChI Key :KZHGPDSVHSDCMX-UHFFFAOYSA-N
Pubchem ID :15630

Safety of [ 1747-60-0 ]

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

Computational Chemistry of [ 1747-60-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 9
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 50.52
TPSA ?

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

76.38 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.87
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

2.4
Log Po/w (WLOGP)?

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

1.9
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.

0.97
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

2.38
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.9

Water Solubility

Log S (ESOL):?

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

-2.96
Solubility 0.198 mg/ml ; 0.0011 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.

-3.65
Solubility 0.0408 mg/ml ; 0.000226 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

-2.74
Solubility 0.33 mg/ml ; 0.00183 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

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

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

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.

-5.7 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

0.0 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)

2.13

Application In Synthesis of [ 1747-60-0 ]

* 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 [ 1747-60-0 ]

[ 1747-60-0 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 2293-07-4 ]
  • [ 1747-60-0 ]
YieldReaction ConditionsOperation in experiment
With ammonia; bromine; chlorine; In water; 1,2-dichloro-ethane; EXAMPLE 1 182 parts of p-methoxyphenyl-thiourea are suspended in 2,200 parts of ethylene chloride. To dehydrate the mixture, 200 parts of the solvent are distilled off under atmospheric pressure. The suspension is cooled to 30 C. and 6 parts of bromine are added. 71 parts of chlorine gas are then passed in over 4 hours at the same temperature, whilst cooling the mixture slightly, and the batch is then refluxed for 1 hour. Thereafter it is allowed to cool to about 70 C. and 1,000 parts of water are hereupon added, causing the solid to dissolve. After removing the organic phase, the ethylene chloride emulsified in the aqueous phase is stripped off in steam. The clear solution is then rendered alkaline, at 50 C., with 130 parts of concentrated ammonia. After the mixture has cooled to room temperature, the precipitate is filtered off, washed neutral with water and dried. The yield is 171 parts of 6-methoxy-2-aminobenzothiazole of melting point 163-165 C., corresponding to 95% of theory.
With bromine; acetic acid; at 0 - 15℃; for 2h; General procedure: One of compounds 6a-6d (10 mmol) and ammonium thiocyanate (0.91 g, 12 mmol) were dissolved in glacial acetic acid and the reaction mixture was stirred for 4 h. Bromine (0.6 mL, 11 mmol) in glacial acetic acid (8 mL) was added dropwise to the reaction mixture and it was stirred at 15C for 2 h. Then, the solid was filtered off and dissolved in hot water. The filtrate was quenched with saturated aqueous sodium bicarbonate. The solid residue of the corresponding product 8a-8d was filtered off.
With bromine; In dichloromethane; at 5℃; General procedure: Substituted phenylthiourea (0.1 mol) was taken in CHCl3 and stirred with a mechanical stirrer and bromine (0.1 mol) was added drop by drop for a period of an hour with continuous stirring. The temperature was maintained <5C. After bromine addition, the stirring was maintained for 4-5 hours. The product obtained was dried, followed by SO2 water treatment and filtered. The filtrate obtained was treated with aq. NH3 in neutral conditions. The obtained precipitate was filtered, dried, and recrystallized from absolute alcohol.
  • 2
  • [ 1747-60-0 ]
  • [ 92-55-7 ]
  • 5-Nitro-furfuryliden-(2)-2-amino-6-methoxybenzthiazol [ No CAS ]
  • 3
  • [ 1747-60-0 ]
  • [ 17413-10-4 ]
  • [ 530-62-1 ]
  • 1-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-3-(6-methoxy-benzothiazol-2-yl)-urea [ No CAS ]
  • 5
  • [ 1747-60-0 ]
  • [ 5467-57-2 ]
  • [ 1043056-82-1 ]
  • 7
  • [ 1747-60-0 ]
  • [ 41360-32-1 ]
  • C16H14N2O5S2 [ No CAS ]
 

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