Structure of 5131-60-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Systematic analysis of gut bacterial carcinogen metabolism and its functional consequences
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.
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Purchased from AmBeed: 446-86-6 ; 121-66-4 ; 607-35-2 ; 67-20-9 ; 105650-23-5 ; 59-87-0 ; 117-39-5 ; 57-97-6 ; 5131-60-2 ; 512-56-1 ; 62-44-2 ; 6959-48-4 ; 84-65-1 ; 137-17-7 ; 117-39-5 ; 153-78-6 ; 1614-12-6 ; 298-81-7 ; 404-86-4 ; 320-67-2 ; 99-55-8 ; 94-52-0 ; 2832-40-8 ; 101-61-1 ; 103-33-3 ; 114-83-0 ; 64091-91-4 ; 53-96-3 ; 3817-11-6 ; 90-94-8 ; 613-13-8 ; 56-57-5 ; 91-64-5 ; 26148-68-5 ; 101-80-4 ; 139-65-1 ; 366-70-1 ; 389-08-2 ; 99-59-2 ; 132-32-1 ; 394-69-4 ; 3544-23-8 ; 389-08-2 ; 320-67-2 ; 82-28-0 ; 2475-45-8 ; 129-15-7
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CAS No. : | 5131-60-2 |
Formula : | C6H7ClN2 |
M.W : | 142.59 |
SMILES Code : | NC1=CC=C(Cl)C(N)=C1 |
MDL No. : | MFCD00025284 |
Boiling Point : | No data available |
InChI Key : | ZWUBBMDHSZDNTA-UHFFFAOYSA-N |
Pubchem ID : | 21209 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 40.26 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.04 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.17 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.85 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.52 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.07 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.2 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.75 |
Solubility | 2.52 mg/ml ; 0.0177 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.53 |
Solubility | 4.25 mg/ml ; 0.0298 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.27 |
Solubility | 0.766 mg/ml ; 0.00537 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.57 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.37 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With tin(II) chloride dihdyrate; In ethanol; at 20℃; | A mixture of 1-chloro-2,4-dinitro-benzene (100 mg, 0.5 mmol) and SnCl2.2H2O (1.12 g, 5 mmol) in ethanol (2.5 mL) was stirred at room temperature overnight. Water was added and then the mixture was basified to pH 7-8 with saturated NaHCO3 solution. The solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to yield 4-chloro-benzene-1,3-diamine (D-1) (79 mg, quant.). HPLC ret. time 0.38 min, 10-99% CH3CN, 5 min run; ESI-MS 143.1 m/z (MH+). |
With platinum on activated charcoal; In methanol; at 30℃; under 3750.38 Torr; for 1.5h;Autoclave;Catalytic behavior; | General procedure: PtL1/L2/C (25.0 mg, 1.282 mol of Pt) and the desired amountof substrate were placed in a Teflon-coated stainless steel auto-clave (80.0 mL), equipped with magnetic stirrer, temperature andpressure controller. The autoclave was then sealed and evacu-ated, followed by charging it with deaerated MeOH (10.0 mL)by suction. Afterwards, the autoclave was placed in an oil pathwhich was heated to 30.0C. Once the latter temperature wasreached, the autoclave was pressurized with hydrogen (5.0 bar) and stirred at 800 rpm. After the desired reaction time, the auto-clave was removed from the oil bath and cooled to 20.0C, followedby venting the excess hydrogen. The suspension was centrifugedand the catalytic solution separated from catalyst by decantationin air atmosphere. To the latter solutions n-dodecane (100.0 L,0.44 mmol) was added as external standard and analyzed by GC.Recycling experiments were conducted by using recovered PtL1/2,applying the above descript protocol. The Ptsurface-atom related TOF(h-1) values were calculated according to the following equation:mmol(converted substrate) × [mmol(Ptsurface) × h]-1.The mmolof Ptsurface(i.e. amount of Pt atoms exposed to the substrate)using 25.0 mg of catalyst for the hydrogenation reactions were0.7179 mol for PtL1and 0.7948 mol for PtL2and PtC,according to the percentage of Pt-atoms localized on the NPs? sur-face (i.e. 56% (PtL1) and 62% for PtL2/C), using a HRTEM-basedcalculation [35]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(b) Amino compounds of the formula (XV) and (XV a)1,3-Diamino-benzene, 4-chloro-1,3-diamino-benzene, 2,4-diaminotoluene, 2,6-diamino-toluene, 1,4-diamino-naphthalene, 2,7-diamino-naphthalene, 1,5-diamino-naphthalene-3,7-disulphonic acid, 1,6-diamino-naphthalene-4,8-disulphonic acid, 1,4-diamino-naphthalene-6-sulphonic acid, ... | ||
methylamine, ...2-ethyl-n-butylenediamine, 2-hydroxy-n-propylenediamine, 1,3-diaminobenzene, 1,4-diaminobenzene, 1,3-diamino-4-chlorobenzene, 1,3-diamino-4-methylbenzene, 1,3-diamino-4-ethylbenzene, 1,3-diamino-4-methoxybenzene, ... | ||
...he aromatic nucleus, for example alkyl groups and halogen atoms. ...1,4-phenylenediamine2,4-tolylenediamine2,4-diaminoanisole2,4-diaminochlorobenzene2,5-diaminoanisole1,2-phenylenediamine2,6-tolylenediamine1,4-diaminonaphthalene... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzoyl chloride; triethylamine; In dichloromethane; at 0℃; for 16h; | benzoyl chloride (5.2 ml) was added to a stirred mixture of 2,4-diaminochlorobenzene (6.42 g), triethylamine (12.5 ml) and methylene chloride (100 ml) which had been cooled to 0°C. The mixture was allowed to warm to ambient temperature and was stirred for 16 hours.. The mixture was evaporated and the residue was triturated under a saturated aqueous sodium bicarbonate solution.. The resultant solid was isolated, washed in turn with water and isohexane and dried under vacuum at 55°C. There was thus obtained N-(3-amino-4-chlorophenyl)benzamide as a solid (10.38 g); NMR Spectrum: (DMSOd6) 5.32 (s, 2H), 6.9 (m, 1H), 7.1 (d, 1H), 7.37 (d, 1H), 7.52 (m, 3H), 7.9 (d, 2H), 10.05 (s, 1H). |