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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
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Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Structure of 141776-91-2
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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.
4.5
*For Research Use Only !
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Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent
Dube, Phelelisiwe S. ; Angula, Klaudia T. ; Legoabe, Lesetja J. ; Jordaan, Audrey ; Boitz Zarella, Jan M. ; Warner, Digby F. , et al.
Abstract: Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These compounds demonstrate broad-spectrum activities against acid-fast bacterium, Gram-pos. and -neg. bacteria, fungi, and leishmania parasite. Compound 30 maintained antitubercular activity against moxifloxacin-, isoniazid-, and rifampicin-resistant Mycobacterium tuberculosis, while 37 exhibited low micromolar activities (<1 μg/mL) against World Health Organization (WHO) critical pathogens: Cryptococcus neoformans, Acinetobacter baumannii, and Pseudomonas aeruginosa. Compounds in this study are metabolically robust, demonstrating % remnant of >98% after 30 min in the presence of human, rat, and mouse liver microsomes. Several compounds thus reported here are promising leads for the treatment of diseases caused by infectious agents.
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CAS No. : | 141776-91-2 |
Formula : | C7H5BrF2 |
M.W : | 207.02 |
SMILES Code : | FC1=CC(F)=CC(CBr)=C1 |
MDL No. : | MFCD00010304 |
InChI Key : | KVSVNRFSKRFPIL-UHFFFAOYSA-N |
Pubchem ID : | 518896 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H314-H290 |
Precautionary Statements: | P280-P390-P303+P361+P353-P301+P330+P331-P304+P340+P310-P305+P351+P338+P310 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.19 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.25 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.67 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.22 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.19 |
Solubility | 0.134 mg/ml ; 0.000646 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.33 |
Solubility | 0.963 mg/ml ; 0.00465 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.22 |
Solubility | 0.0125 mg/ml ; 0.0000604 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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) |
Yes |
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 |
-5.66 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) |
1.58 |
* 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 |
---|---|---|
84% | Under a nitrogen atmosphere: to a solution of LH-INDOLE-6-CARBOXYLIC acid methyl ester (367 mg, 2.09 mmol) in DMF (10 mL) was added NaH (60% in oil, 101 mg, 2.52 mmol) at room temperature. After stirring for 15 min 1-BROMOMETHYL-3, 5-difluoro- benzene (325 PL, 2.51 mmol) was added and the mixture was stirred at room temperature for 4 h. The reaction was quenched with 3% aqueous citric acid (10 ML) and ethyl acetate (30 mL) was added. The mixture was washed with 3% aqueous citric acid (3X20 mL) and brine (20 mL). The organic phase was dried (MGS04) and concentrated in vacuo to give a pale yellow oil (702 mg). The crude product was purified over a 20 g silica SPE cartridge (ethyl acetate/heptane 1: 9) to give the title compound as a colourless oil, which slowly crystallised on standing (530 mg, yield = 84%). LCMS: 4.08 min (99%, MH+= 302) ; 1H NMR (CDC13) : 8 3.92 (3,3H, CO2CH3), 5.37 (s, 2H, NCH2Ar), 6.54-6. 60 (m, 2H), 6.64 (d, 1H, J = 3.1 Hz), 6.67-6. 74 (m, 1H), 7.27 (d, IH, J = 3.1 Hz), 7.68 (d, 1H, J = 8.6 Hz), 7.83 (d, LH, J = 8. 6 Hz), 8.01 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.25g | Weighing 6.10g of <strong>[436-77-1]fangchinoline</strong>,3.50 g of 3,5-difluorobenzyl bromide and 0.50 g of potassium carbonate dissolved in DMSO 200 mLIn a 500 mL three-necked flask, the mixture was heated and stirred to boiling, and stirred and reacted for 6 hours.The whole reaction of the <strong>[436-77-1]fangchinoline</strong>base was detected by HPLC, the solvent was distilled off under reduced pressure, and the temperature was lowered to room temperature.Add 40% 1,4-succinic acid (to solution pH = 7.5) and stir to boiling for 6 h.Cool to room temperature, add 80 mL of water and extract 3 times with chloroform (300 mL × 3).HPLC separates the separation and purification process of the reaction and the product,The extract was dried over anhydrous Na 2 SO 4 for 8 h, and the chloroform was recovered. The solid was dried at 60 C for 4 h.That is, 6.25 g of a product as a pale yellow powder. The melting point of the desired product: 223.1-224.6 C, TOF-HRMS: M / e (1105.1214), molecular formula: C62H58O10N2F6, that is, Table 2Compound III169. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.95 g | Weigh 6.10g of <strong>[436-77-1]fangchinoline</strong>, 2.10g of 3,5-difluorobenzyl bromide and 1.40g of potassium carbonate dissolved in DMSO 200mLIn a 500 mL three-necked flask, the mixture was heated and stirred to boiling, and stirred and reacted for 6 hours.TLC detection of all reactions of <strong>[436-77-1]fangchinoline</strong>, decompressionEvaporate the solvent and cool to room temperature.20%1,4-succinic acidNeutralize to pH=7.0, add 50 mL of water and extract 3 times with chloroform (150 mL)×3), TLC traces the reaction and the separation and purification process of the product. The extract is dried with anhydrous Na2SO4 for 8 h to recover chloroform.Dry at 60 C for 4 h,That is, 5.95 g of a product as a pale yellow powder. |
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