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Chemical Structure| 141776-91-2 Chemical Structure| 141776-91-2

Structure of 141776-91-2

Chemical Structure| 141776-91-2

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Product Citations

Product Citations

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.

Alternative Products

Product Details of [ 141776-91-2 ]

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

Safety of [ 141776-91-2 ]

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:

Computational Chemistry of [ 141776-91-2 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.25
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

2.68
Log Po/w (WLOGP)?

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

3.55
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.

3.95
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

3.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.22

Water Solubility

Log S (ESOL):?

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

-3.19
Solubility 0.134 mg/ml ; 0.000646 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.

-2.33
Solubility 0.963 mg/ml ; 0.00465 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

-4.22
Solubility 0.0125 mg/ml ; 0.0000604 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

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)
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

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.

-5.66 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

1.0
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)

1.58

Application In Synthesis of [ 141776-91-2 ]

* 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 [ 141776-91-2 ]

[ 141776-91-2 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 141776-91-2 ]
  • [ 22916-47-8 ]
  • 3-[2-(2,4-dichloro-benzyloxy)-2-(2,4-dichloro-phenyl)-ethyl]-1-(3,5-difluoro-benzyl)-3<i>H</i>-imidazol-1-ium; bromide [ No CAS ]
  • 2
  • [ 50820-65-0 ]
  • [ 141776-91-2 ]
  • [ 691399-51-6 ]
YieldReaction ConditionsOperation 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).
  • 3
  • [ 53241-92-2 ]
  • [ 141776-91-2 ]
  • [ 1345869-53-5 ]
  • 4
  • [ 141776-91-2 ]
  • [ 1201597-22-9 ]
  • 5
  • [ 110-15-6 ]
  • [ 141776-91-2 ]
  • [ 436-77-1 ]
  • C58H54F6N2O6(2+)*C4H4O4(2-) [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 6
  • [ 110-15-6 ]
  • [ 141776-91-2 ]
  • [ 436-77-1 ]
  • C44H44F2N2O6*C4H6O4 [ No CAS ]
YieldReaction ConditionsOperation 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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