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Chemical Structure| 6959-48-4 Chemical Structure| 6959-48-4

Structure of 3-(Chloromethyl)pyridine HCl
CAS No.: 6959-48-4

Chemical Structure| 6959-48-4

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Product Citations

Product Citations

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.

Alternative Products

Product Details of [ 6959-48-4 ]

CAS No. :6959-48-4
Formula : C6H7Cl2N
M.W : 164.03
SMILES Code : ClCC1=CC=CN=C1.[H]Cl
MDL No. :MFCD00012818

Safety of [ 6959-48-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314
Precautionary Statements:P261-P280-P305+P351+P338-P310
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 6959-48-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 40.96
TPSA ?

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

12.89 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

2.06
Log Po/w (WLOGP)?

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

2.47
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.

1.48
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

2.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.68

Water Solubility

Log S (ESOL):?

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

-2.58
Solubility 0.429 mg/ml ; 0.00262 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.

-1.96
Solubility 1.8 mg/ml ; 0.011 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

-3.0
Solubility 0.162 mg/ml ; 0.000989 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

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

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.

-5.84 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

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)

1.17

Application In Synthesis of [ 6959-48-4 ]

* 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 [ 6959-48-4 ]

[ 6959-48-4 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 6959-48-4 ]
  • [ 53052-06-5 ]
  • [ 88594-61-0 ]
  • 2
  • [ 6959-48-4 ]
  • [ 5654-97-7 ]
  • 3
  • [ 6959-48-4 ]
  • [ 39903-01-0 ]
  • [ 941603-84-5 ]
YieldReaction ConditionsOperation in experiment
29% With potassium carbonate; sodium iodide; In acetone;Heating / reflux; 00 suspension of <strong>[39903-01-0]2-amino-5-bromo-pyridin-3-ol</strong> (1.00 g, 5.29 mmol) in acetone (40 mL) was added to a solution of 3-chloromethylpyridine hydrochloride (1.12 g, 6.87 mmol), K2CO3 (2.19 g, 15.8 mmol) and NaI (2.37 g, 15.8 mmol). The mixture was heated to reflux overnight. After cooling, the mixture was dissolved in water and extracted with EtOAc (3x). The combined organics were washed with brine, dried and concentrated. Purification by column chromatography (silica gel, hexanes/EtOAc, 1 :4) gave the title compound (430 mg, 29percent) as a brown oil: 1H NMR (300 MHz, DMSO-^) delta 8.71 (d, J= 1.8 Hz, IH), 8.55 (d, J= 3.0 Hz IH), 7.96-7.92 (m, IH), 7.60 (d, J= 3.0 Hz, IH), 7.45-7.35 (m, IH), 7.34 (d, J= 3.0 Hz, IH), 6.04 (br s, 2H), 5.20 (s, 2H); ESI MS m/z 280 (M + H)+.
  • 4
  • [ 6959-48-4 ]
  • [ 71486-53-8 ]
  • [ 1225498-23-6 ]
YieldReaction ConditionsOperation in experiment
100% With N-ethyl-N,N-diisopropylamine; sodium iodide; In acetonitrile; at 80℃; for 1h; 0.200 g (1.034 mmol) of 1-methyl-4-oxopiperidine-3-carboxylate hydrochloride (commercially available, ABCR), 0.54 mL (3.102 mmol) of diisopropylethylamine, 0.155 g (1.034 mmol) of sodium iodide and 0.170 g (1.034 mmol) of 3-(chloromethyl)pyridine hydrochloride were stirred at 80 °C in 5.0 mL of anhydrous CH3CN.The reaction was monitored by HPLC and UPLC-MS. After 1h at 80°C, the insoluble inorganic materials were filtered off and the filtrate was concentrated in vacuo to give a yellowish residue.This residue was dissolved in CH2C12, washed with brine, H2O, dried over Na2SO4 and concentrated in vacuo to give pure methyl 4-oxo-1-(pyridin-3-ylmethyl)piperidine-3-carboxylate (0.257 g, 1.034 mmol, quantitative yield).The product was used for the next step without further manipulation.
With N-ethyl-N,N-diisopropylamine; sodium iodide; In acetonitrile; at 80℃; for 1h; 0.200 g (1.034 mmol) of l-methyl-4-oxopiperidine-3-carboxylate hydrochloride (commercially available, ABCR), 0.54 mL (3.102 mmol) of diisopropylethylamine, 0.155 g (1.034 mmol) of sodium iodide and 0.170 g (1.034 mmol) of 3- (chloromethyl)pyridine hydrochloride were stirred at 80 °C in 5.0 mL of anhydrous CH3CN. The reaction was monitored by HPLC and UPLC-MS. After lh at 80°C, the insoluble inorganic materials were filtered off and the filtrate was concentrated in vacuo to give a yellowish residue. This residue was dissolved in CH2CI2, washed with brine, H20, dried over Na2S04 and concentrated in vacuo to give pure methyl 4-oxo-l- (pyridin-3-ylmethyl)piperidine-3-carboxylate (0.257 g, 1.034 mmol, quantitative yield). The product was used for the next step without further manipulation
  • 5
  • [ 6959-48-4 ]
  • [ 71486-53-8 ]
  • 2-phenyl-5-(pyridin-3-ylmethyl)-1,4,5,6,7-hexahydro-3H-pyrazolo[4,3-c]pyridin-3-one [ No CAS ]
  • 6
  • [ 6959-48-4 ]
  • [ 71486-53-8 ]
  • [ 1331732-74-1 ]
 

Historical Records

Technical Information

Categories

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