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Chemical Structure| 149104-88-1 Chemical Structure| 149104-88-1

Structure of 149104-88-1

Chemical Structure| 149104-88-1

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Product Citations

Product Citations

Paul Getreuer ; Laura Marretta ; Emine Toyoglu ; Orsolya Dömötör ; Michaela Hejl ; Alexander Prado-Roller , et al.

Abstract: In this contribution we report the synthesis, characterization and in vitro anticancer activity of novel cyclometalated 4-phenylthiazole-derived ruthenium(II) (2a–e) and osmium(II) (3a–e) complexes. Formation and sufficient purity of the complexes were unambigiously confirmed by 1H-, 13C- and 2D-NMR techniques, X-ray diffractometry, HRMS and elemental analysis. The binding preferences of these cyclometalates to selected amino acids and to DNA models including structures were analyzed. Additionally, their stability and behaviour in aqueous solutions was determined by UV-Vis spectroscopy. Their cellular accumulation, their ability of inducing , as well as their interference in the were studied in SW480 colon cancer cells. The anticancer potencies were investigated in three human cancer cell lines and revealed IC50 values in the low micromolar range, in contrast to the biologically inactive ligands.

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Product Details of [ 149104-88-1 ]

CAS No. :149104-88-1
Formula : C7H9BO4S
M.W : 200.02
SMILES Code : C1=C([S](=O)(=O)C)C=CC(=C1)B(O)O
MDL No. :MFCD01630820
InChI Key :VDUKDQTYMWUSAC-UHFFFAOYSA-N
Pubchem ID :2734364

Safety of [ 149104-88-1 ]

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

Computational Chemistry of [ 149104-88-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 49.36
TPSA ?

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

82.98 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

0.06
Log Po/w (WLOGP)?

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

-0.15
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.

-0.22
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

-1.42
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.34

Water Solubility

Log S (ESOL):?

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

-1.33
Solubility 9.41 mg/ml ; 0.047 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.36
Solubility 8.81 mg/ml ; 0.0441 mol/l
Class?

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

Very 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

-1.61
Solubility 4.96 mg/ml ; 0.0248 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

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.

-7.48 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

0.0
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)

2.14

Application In Synthesis of [ 149104-88-1 ]

* 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 [ 149104-88-1 ]

[ 149104-88-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1010120-55-4 ]
  • [ 149104-88-1 ]
  • [ 1257704-24-7 ]
YieldReaction ConditionsOperation in experiment
33% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; N,N-dimethyl-formamide; at 80℃; for 18h;Inert atmosphere; Sealed tube; A dry tube was charged with tetrakis(triphenylphopshine)palladium(0) (1.29 g, 1.1 mmol), 5-bromo-[l,2,4]triazolo[l,5-a]pyridin-2-ylamine (2.98 g, 14.0 mmol), (4- methylsulfonylphenyl) boronic acid (3.08 g, 15.4 mmol), sodium carbonate (3.26 g, 31.04 mmol), dioxane (30 mL), N,N-dimethylformamide (60 mL) and water (30 mL). The tube was evacuated with a high vacuum and backflushed under a stream of nitrogen three times. The mixture was stirred for 2 minutes at room temperature under nitrogen then the tube was sealed and heated at 800C for 18 hours. The mixture was transferred to a round bottom flask and evaporated under reduced pressure. Water (100 mL) was added and solution extracted with dichloromethane (3 portions of 50 mL). The combined organic was dried over magnesium sulfate, filtered and evaporated. The solid was triturated with ether/dichloromethane (4:1; 10 mL), filtered and rinsed with ether. The recovered material was consistent for 5-(4-methanesulfonyl-phenyl)-[l,2,4]triazolo[l,5-a]pyridin-2-ylamine (1.3 g, 33%). 1H NMR (400 MHz, CDCl3, delta, ppm): 8.21 (d, J = 8.0 Hz, 2H) 8.08 (d, J = 8.0 Hz, 2H), 7.55 (m, IH), 7.44 (d, J = 9.1 Hz, IH), 7.13 (d, J = 7.5 Hz, IH), 6.10 (br s, 2H) 3.31 (s, 3H). MS = 289 (MH)+.
  • 2
  • [ 138006-41-4 ]
  • [ 149104-88-1 ]
  • [ 202409-86-7 ]
 

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Technical Information

Categories

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