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Structure of 613-13-8

Chemical Structure| 613-13-8

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Boyao Zhang ; George-Eugen Maftei ; Bartosz Bartmanski ; Michael Zimmermann ;

Abstract: Organic carcinogens, in particular DNA-reactive compounds, contribute to the irreversible initiation step of tumorigenesis through introduction of genomic instability. Although carcinogen bioactivation and detoxification by human enzymes has been extensively studied, carcinogen biotransformation by human-associated bacteria, the microbiota, has not yet been systematically investigated. We tested the biotransformation of 68 mutagenic carcinogens by 34 bacterial species representative for the upper and lower human gastrointestinal tract and found that the majority (41) of the tested carcinogens undergo bacterial biotransformation. To assess the functional consequences of microbial carcinogen metabolism, we developed a pipeline to couple gut bacterial carcinogen biotransformation assays with Ames mutagenicity testing and liver biotransformation experiments. This revealed a bidirectional crosstalk between gut microbiota and host carcinogen metabolism, which we validated in gnotobiotic mouse models. Overall, the systematic assessment of gut microbiota carcinogen biotransformation and its interplay with host metabolism highlights the gut microbiome as an important modulator of exposome-induced tumorigenesis.

Vaithilingam Rajendiran ; Ziad El Rassi ;

Abstract: Three LC-based methods, including reversed-phase chromatography (RPC), ion-pair RPC and weak anion-exchange chromatography (WAX), were examined in the separations of precolumn derivatized mono- and oligosaccharides with the following three tagging agents: 1-naphthylamine (1-NA), 2-aminoanthracene (2-AA), and 3-amino-2,7-naphthalenedisulfonic acid (ANDSA). Due to differences in their charges and polarity, the three tagging agents imparted the sugar derivatives varying elution patterns in the three, just mentioned, chromatographic modes. While RPC yielded high resolution separations for 1-NA- and 2-AA-sugar derivatives, ion-pair RPC in the presence of the ion-pairing agent dodecyl trimethylammonium bromide (DTAB) in the mobile phase exhibited far more resolution and selectivity than WAX in the separation of ANDSA-sugar derivatives. This finding portrays the fact that an octadecyl column operating in ion-pair RPC mode can eliminate in most cases the need for an ion-exchange column for bioanalytical separations of ionic or ionizable species. Lastly, the characteristics of each chromatographic mode in the analysis of derivatized sugars are described using various mobile phase compositions.

Keywords: Derivatized sugars ; UV-absorbing tags ; Reversed-phase chromatography ; Ion-pair chromatography ; Anion-exchange chromatography

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Vaithilingam Rajendiran ; Z. El Rassi ;

Abstract: In this research report, an in house developed octadecyl monolithic (ODM) column has been exploited in the reversed-phase capillary electrochromatography (RP-CEC) of precolumn derivatized mono- and oligosaccharides with three different tagging agents, namely 1-naphthylamine (1-NA), 2-aminoanthracene (2-AA) and 3-amino-2,7-naphthalenedisulfonic acid (ANDSA). These three derivatizing agents, which differed in their charges, nonpolar characters and optical absorption properties, led to different RP-CEC elution patterns and UV detection signals. In fact, the limit of detection of the derivatized sugars were 50 µM for the ANDSA- and 1-NA-sugar derivatives and 35 µM for the 2-AA-sugar derivatives due to the presence of three fused aromatic rings in 2-AA versus 2 fused rings in the 1-NA and ANDSA tags. Furthermore, while the longer ANDSA-oligosaccharides eluted later than the shorter ones and the ANDSA-monosaccharides, 1-NA- and 2-AA-sugar derivatives necessitated the presence of borate ions at alkaline pH in the mobile phase to form in situ charged derivatives to facilitate their separation by RP-CEC, and the elution order was the reversal of that observed with the ANDSA-sugar derivatives; that is the mono- eluted later than the larger size oligosaccharides. In addition, plots of log tR vs. number of glucose residues (nGlc) for derivatized glucose and maltooligosaccharides yielded straight lines with slopes representing log η where η is the retention time modulus (i.e., ratio of retention time of two neighboring derivatives differing in one glucosyl residue). In the case of 1-NA and 2-AA derivatives, η was smaller than unity while it was greater than unity in the case of ANDSA-sugar derivatives because the elution occurred in the order of decreasing size of the homologous sugar derivatives in the former than in the later derivatives. The prepared ODM column was stable for more than a month of continuous use, a fact that allowed a good repeatability for intraday and interday analyzes.

Keywords: Reversed phase ; Capillary electrochromatography ; Derivatized mono- and oligosaccharides ; Precolumn derivatization

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Alternative Products

Product Details of [ 613-13-8 ]

CAS No. :613-13-8
Formula : C14H11N
M.W : 193.24
SMILES Code : NC1=CC=C2C=C3C=CC=CC3=CC2=C1
MDL No. :MFCD00003582
InChI Key :YCSBALJAGZKWFF-UHFFFAOYSA-N
Pubchem ID :11937

Safety of [ 613-13-8 ]

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

Computational Chemistry of [ 613-13-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 14
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 1.0
Molar Refractivity 65.86
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.04
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

3.53
Log Po/w (WLOGP)?

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

3.58
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.

3.45
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

3.33
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.19

Water Solubility

Log S (ESOL):?

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

-3.95
Solubility 0.0215 mg/ml ; 0.000112 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.

-3.76
Solubility 0.0335 mg/ml ; 0.000173 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

-5.39
Solubility 0.000784 mg/ml ; 0.00000406 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

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.

-4.97 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

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

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)

1.0

Application In Synthesis of [ 613-13-8 ]

* 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 [ 613-13-8 ]

[ 613-13-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 613-13-8 ]
  • [ 34374-88-4 ]
  • 2,4,6-tris((anthracen-2-ylamino)methylene)cyclohexane-1,3,5-trione [ No CAS ]
 

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