Structure of 121-66-4
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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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Synthesis and In Vitro Antibacterial Evaluation of Mannich Base Nitrothiazole Derivatives
Phelelisiwe S. Dube ; Dylan Hart ; Lesetja J. Legoabe ; Audrey Jordaan ; Digby F. Warner ; Richard M. Beteck
Abstract: Nitrothiazole derivatives have been reported to exhibit activity against aerobic, anaerobic, and microaerophilic bacteria. This activity profile makes the nitrothiazole compound class an ideal lead source against Mycobacterium tuberculosis, which flourishes in varied environments with different oxygen concentrations. In this work, we investigated six nitrothiazole derivatives for antitubercular activity. The compounds exhibited potent activity, with compounds 9 and 10 possessing an equipotent MIC90 value of 0.24 µM. The compounds were investigated for cytotoxicity against HEK293 cells and hemolysis against red blood cells, and they demonstrated no cytotoxicity nor hemolytic effects, suggesting they possess inherent antitubercular activity.
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Keywords: nitrothiazole ; Mannich bases ; antitubercular activity ; tuberculosis ; Mycobacterium tuberculosis
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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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Nitrothiazole-Thiazolidinone Hybrids: Synthesis and in Vitro Antimicrobial Evaluation
Dylan Hart ; Lesetja J. Legoabe ; Omobolanle J. Jesumoroti ; Audrey Jordaan ; Digby F. Warner ; Rebecca Steventon , et al.
Abstract: Herein we report the synthesis of novel compounds inspired by the antimicrobial activities of nitroazole and thiazolidin-4-one based compounds reported in the literature. Target compounds were investigated in vitro for antitubercular, antibacterial, antifungal, and overt cell toxicity properties. All compounds exhibited potent antitubercular activity. Most compounds exhibited low micromolar activity against S. aureus and C. albicans with no overt cell toxicity against HEK-293 cells nor haemolysis against human red blood cells. Notably, compound 3b exhibited low to sub-micromolar activities against Mtb, MRSA, and C. albicans. 3b showed superior activity (0.25 μg/ml) against MRSA compared to vancomycin (1 μg/ml).
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CAS No. : | 121-66-4 |
Formula : | C3H3N3O2S |
M.W : | 145.14 |
SMILES Code : | NC1=NC=C([N+]([O-])=O)S1 |
MDL No. : | MFCD00005326 |
InChI Key : | MIHADVKEHAFNPG-UHFFFAOYSA-N |
Pubchem ID : | 8486 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 35.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
112.97 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.64 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.83 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.64 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.75 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.38 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.01 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.61 |
Solubility | 3.58 mg/ml ; 0.0247 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.78 |
Solubility | 0.238 mg/ml ; 0.00164 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.29 |
Solubility | 73.8 mg/ml ; 0.508 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 |
No |
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 |
-6.6 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 |
2.0 |
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 |
2.0 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) |
2.76 |
* 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 |
---|---|---|
With sodium nitrite; | Example 12 3-[(5-nitrothiazol-2-yl)mercapto]-5-phenyl-1,2,4-triazole (SU4390) (Compound 7) The key starting material 2-bromo-5-nitrothiazole was prepared by treating 2-amino-5-nitrothiazole (Aldrich) with sodium nitrite and hydrogen bromide (Fr. Demande 2,015,434, 1970). | |
With sodium nitrite; | Example 1 3-[(5-nitrothiazol-2-yl)mercapto]-5-phenyl-1,2,4-triazole (Compound 1) The starting material 2-bromo-5-nitrothiazole was prepared by treating 2-amino-5-nitrothiazole (Aldrich) with sodium nitrite and hydrogen bromide (Fr. Demande 2,015,434, 1970). | |
With sodium nitrite; | Example 1 3-[(5-nitrothiazol-2-yl)mercapto]-5-phenyl-1,2,4-triazole (Compound 7) The starting material 2-bromo-5-nitrothiazole was prepared by treating 2-amino-5-nitrothiazole (Aldrich) with sodium nitrite and hydrogen bromide (Fr. Demande 2,015,434, 1970). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In water; hydrogen bromide; sodium nitrite; | 2-Bromo-5-nitrothiazole To 72.5 g of 2-amino-5-nitrothiazole in 300 mL of 48percent hydrobromic acid and 200 mL of water stirred and cooled to about -10° C. was slowly added, in portions, 51.8 g of sodium nitrite dissolved in 80 mL of water from one addition funnel and 250 mL of n-amyl alcohol from a second addition funnel. The addition of both solutions required about 3 hours. The cooling bath was removed and the mixture allowed to warm to about 15° C. overnight and then stirred at room temperature for 2 hours. The solid was collected by vacuum filtration and steam distilled to give 67 g of crude product. The crude product was recrystallized from hot ethanol to give 61 g (60percent yield) of the 2-bromo-5-nitrothiazole as a yellow solid. |
60% | In water; hydrogen bromide; sodium nitrite; | 2-Bromo-5-nitrothiazole To 72.5 g of 2-amino-5-nitrothiazole in 300 mL of 48percent hydrobromic acid and 200 mL of water stirred and cooled to about -10° C. was slowly added, in portions, 51.8 g of sodium nitrite dissolved in 80 mL of water from one addition funnel and 250 mL of n-amyl alcohol from a second addition funnel. The addition of both solutions required about 3 hours. The cooling bath was removed and the mixture allowed to warm to about 15° C. overnight and then stirred at room temperature for 2 hours. The solid was collected by vacuum filtration and steam distilled to give 67 g of crude product. The crude product was recrystallized from hot ethanol to give 61 g (60percent yield) of the 2-bromo-5-nitrothiazole as a yellow solid. |
60% | In water; hydrogen bromide; sodium nitrite; | 2-Bromo-5-nitrothiazole To 72.5 g of 2-amino-5-nitrothiazole in 300 mL of 48percent hydrobromic acid and 200 mL of water stirred and cooled to about -10° C. was slowly added, in portions, 51.8 g of sodium nitrite dissolved in 80 mL of water from one addition funnel and 250 mL of n-amyl alcohol from a second addition funnel. The addition of both solutions required about 3 hours. The cooling bath was removed and the mixture allowed to warm to about 15° C. overnight and then stirred at room temperature for 2 hours. The solid was collected by vacuum filtration and steam distilled to give 67 g of crude product. The crude product was recrystallized from hot ethanol to give 61 g (60percent yield) of the 2-bromo-5-nitrothiazole as a yellow solid. |
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